Ophthalmology Explorer 1st Edition

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Ophthalmology Explorer 1st Edition Dhaval Patel

MD (AIIMS)

Ophthalmology Post-PG Examination Guide

Ophthalmology Explorer Ophthalmology Post-PG Examination Guide Dhaval Patel MD (AIIMS) [email protected] by ophthalmologyexplorer.blogspot.com 1st edition, April 2014

This is a compilation effort from my preparation notes and other sources, thus any contributions or comments are welcomed in the effort to improve this book. Therefore, feel free to e-mail me at [email protected]

Ophthalmology Explorer

Dhaval Patel MD

PREFACE

The CLASS is knowing what to say, when to say and when to stop.

Dear Friends, If you are reading this, then either you are approaching your final ophthalmology exams or you are preparing for further study courses in ophthalmology. So first thing I want you to know is the course for this exam include all aspects of ophthalmology in different amounts and nobody knows it perfectly. This preparation manual I have prepared during my residency and added up while preparing for senior residency/ fellowship examinations preparation which may serve as a small guide to your preparation. It will also serve as a good collection of facts which we might forget/neglect during overall MD/MS exam preparation. So whatever it may serve you, I am proud of what I have prepared and I feel it worth sharring with all emerging ophthalmologist friends. All the Best..!!

-Dhaval Patel MD

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Ophthalmology Explorer

Dhaval Patel MD

INDEX

Exploring EYE .................................. 6 Basic Sciences ............................... 90 Optics & Refraction ......................... 122 Cornea........................................ 160 Lens ........................................... 192 Glaucoma .................................... 205 Retina ......................................... 226 Uvea .......................................... 264 Strabismus ................................... 275 Neurophthalmology ......................... 284 Oculoplasty .................................. 310 Community Ophthalmology................ 337 Miscellaneous ............................... 342 Lateral Thinking ............................. 356 The Class Questions ....................... 364 Important History ............................ 369 Recalls from previous papers ............. 370

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Ophthalmology Explorer

Dhaval Patel MD

Exploring EYE .................................. 6

Genes ....................................... 29

AAO Color Codes of Topical Medication: 6

Giant Cells .................................. 35

Age Related Changes ...................... 6

Growth Factors ............................ 35

Aquaporins ................................... 7

Half Life ..................................... 36

Acquisition time .............................. 7

HLA .......................................... 37

Axis and Angles ............................. 8

HLA wise Diseases ..................... 37

Bimodal Age Distribution ................... 8

Disease wise HLAs ..................... 37

Blocks ......................................... 9

Host Cell Receptors ....................... 38

Cell Cycle Phase Facts ..................... 9

Host for Parasites ......................... 39

Collagen Collection ....................... 10

Hypersensitivity in Eye .................... 39

Contents of Important Fluids ............ 11

IHC Markers ................................ 40

Chromosomes for Eye .................... 13

Inheritence .................................. 41

Connexins .................................. 19

Inside Retinal Layers ...................... 42

Craniosynostosis .......................... 20

Interferons Therapy & Eye ............... 43

Diameters .................................. 20

Intraocular Gases .......................... 44

Drug Resistance ........................... 21

Intracameral Dosages .................... 44

Dye for Eye................................. 21

Intrastromal Dosages ..................... 45

Electromagnetic Spectrum ............... 21

Intravitreal Dosages ....................... 45

Evolutions of anesthetic techniques for cataract surgery ........................... 22

Intravitreal Implants ....................... 46

FDA Approved Drugs ..................... 23 FDA Device Classification ............... 26 Field of View ............................... 27 First in Genetics ........................... 27 Fellow Eye Risk ........................... 28 Frequency of Probes ..................... 29

Iris Nodules & Pathology ................. 48 Laser Facts ................................. 48 Brief History.............................. 48 Instrument Wavelengths ............... 49 Therapeutic Wavelengths ............. 49 Laser settings for glaucoma ........... 50 Laser settings in Retina ................ 51 3

Ophthalmology Explorer

Dhaval Patel MD

Laser Parameters for PTK ............ 51

DME ...................................... 74

Modes of Laser ......................... 51

ROP....................................... 76

Laser Mediums ......................... 52

ARMD .................................... 77

Laser Safety Classification ............ 52

Vitreomacular interface (VMI) diseases ............................................ 81

Latest Drugs ............................... 53 Mechanism of Action ..................... 57 MIP .......................................... 58 MMPs ....................................... 58 Molecular Weights ........................ 59 MUCins ..................................... 59 NV % ........................................ 60 OCT Review ............................... 61 Optic Nerve Segments ................... 62 Orders of Abberations .................... 63 Percentages % Primer ................... 63 Phacomatosis .............................. 65 Principles ................................... 66 Radiation and Eye......................... 67 Rates ........................................ 67 Recurrence %.............................. 68 Refractive Indices ......................... 69 Resolutions................................. 70 RB Stats .................................... 71 Racial predilection of Diseases ......... 72 Studies and Trials ......................... 72 DR ........................................ 72

Glaucoma ................................ 82 ON ........................................ 83 NAION .................................... 83 MISC ...................................... 83 Surface Tension ........................... 84 Specific Gravity ............................ 84 Surface Area ............................... 85 Survival Rates.............................. 85 Test Distances ............................. 86 Thickness ................................... 87 VEGF Facts ................................ 88 Vitreous cavity volume displacement ... 89 Water Content.............................. 89 Basic Sciences ............................... 90 Optics & Refraction ........................ 122 Cornea ....................................... 160 Lens .......................................... 192 Glaucoma ................................... 205 Retina ........................................ 226 Uvea.......................................... 264 Strabismus .................................. 275 4

Ophthalmology Explorer

Dhaval Patel MD

Neurophthalmology ......................... 284

Lateral Thinking ............................ 356

Oculoplasty .................................. 310

The Class Questions....................... 364

Community Ophthalmology ................ 337

Important History ........................... 369

Miscellaneous ............................... 342

Recalls from previous papers ............ 370

5

Ophthalmology Explorer

Dhaval Patel MD

Exploring EYE

AAO Color Codes of Topical Medication: Based on the American Academy of Ophthalmology recommendations to the FDA to aid patients in distinguishing among drops and thus minimize the chance of using an incorrect medication 

Purple Cap: Alpha-Adrenergic Receptor Agonists



Yellow or Blue Cap: Beta-Blockers



Green Cap: Cholinergic Agonists, Miotics



Orange Cap: Carbonic Anhydrase Inhibitors



Turquoise/Teal Cap: Prostaglandin Analogues



Red Cap: Mydriatic/ cycloplegic agents



Tan Cap: Anti-infectives



Pink Cap: Steroids/ Anti-inflammatory



Gray Cap: Nonsteroidal anti-inflammatories



Dark Blue: beta-blocker combination

Age Related Changes 

Ganglion cell loss: 5000/year



Endothelial cell loss: 0.6%/year



Decrease in ACD due to increase LT: 20 microns/year



Age related loss of VF sensitivity: 1 db/year



15.6-μm decrease in choroidal thickness for each decade of life



LENS thickness increases 0.2 mm per 10 year. 20 year: 3.8 mm 40 year: 4.4 mm 6

Ophthalmology Explorer

Dhaval Patel MD

60 year: 4.8 mm 80 year: 5.2 mm 

central anterior chamber depth decreases 0.01 mm/year

Aquaporins



Water channels are known as aquaporins and lens epithelial cells contain an abundance of these.



MIP26 is believed to be a very old (and not very efficient) member of the aquaporin family and is termed aquaporin O.



Types o

AQP0 (MIP) in lens fiber

o

AQP1 in cornea endothelium, ciliary and lens epithelia and trabecular meshwork

o

AQP2 is not present in eye and is restricted to the kidney collecting duct

o

AQP3 in conjunctiva

o

AQP4 in ciliary epithelium and retinal Müller cells

o

AQP5 in corneal and lacrimal gland epithelia



AQP1 protects against vascular leakage by stabilizing the formed vessels.



NMO-IgG is a disease-specific autoantibody for neuromyelitis optica (NMO) and its target antigen is aquaporin-4 (AQP4) water channel.

Acquisition time 

Pentacam: 2 sec



OCT: 1 to 5 sec



Visante ASOCT: 3.3 sec o

Anterior segment scan ( 16×6mm): 256 A-scan/ 0.125 sec

o

High resolution scan: 512 A-scan/ 0.25 sec 7

Ophthalmology Explorer o

Dhaval Patel MD

Pachymetry scan: 128 A-scans/0.5 sec



Dynamic light scattering DLS for lens pathology: 5 sec



CSLO: 1.6 sec

Axis and Angles Axis of the Eye FOVea o

Fixation Axis: This is a straight line that joins center of rotation of eyeball with fixation point

o

Optical Axis: A line passing through center of cornea, center of lens and posterior pole of retina is the optical axis of eyeball

o

Visual Axis: A line joining point of fixation with fovea and passing through nodal point of eyeball is called visual axis. Nodal point of eyeball is just anterior to posterior capsule of lens. Fixation point is the point which is being seen with fovea at any particular moment.

o

Pupillary Line: This is a straight line that passes through center of pupil

Angles of the Eye o

Angle Alpha is the angle formed between optical axis and visual axis. AOV

o

Angle Kappa is the angle formed between visual axis and pupillary axis. KaVPa

o

Angle Gamma is the angle formed between optical axis and fixation axis. GOF

POsitive angle Kappa results in pseudoeXotropia. K-POX

Bimodal Age Distribution 

Craniopharyngioma (peaking in the first 2 decades and again in the years 50 to 70



Thyroid orbitopathy (for women occur from ages 40 to 44 years and 60 to 64 years; for men from ages 45 to 49 years and 65 to 69 years)



Hodgkin's lymphoma (early peak at 15 to 35 years of age and a second peak after 50) 8

Ophthalmology Explorer 

Glaucoma in SWS: (early-onset/congenital-type and later-onset)



Ocular Trauma

Dhaval Patel MD

Blocks

Facial Blocks: LOAN 

van Lint‘s block: Blocking the peripheral branches of facial nerve



O‘Brien‘s block: Facial nerve trunk block at the neck of mandible



Atkinson‘s block: In it superior branches of the facial nerve are blocked by injecting anaesthetic solution at the inferior margin of the zygomatic bone.



Nadbath block: facial nerve is blocked as it leaves the skull through the stylomastoid foramen.

Other Blocks 

Retrobulbar block was introduced by Herman Knapp in 1884



Peribulbar block was described in 1986 by Davis and Mandel

Cell Cycle Phase Facts 

Thymocyte- T cells: G0 arrest



Stem Cells: G0 arrest



Endothelial Cells: G1 arrest



central zone epithelial cells of lens capsule: G0 arrest



In the G1 phase of the cell cycle, the RB-protein is hypophosphorylated. In S, G2, and M, it is hyperphosphorylated. 9

Ophthalmology Explorer

Dhaval Patel MD



p53 mediates arrest of the cell cycle in the G1 phase after sublethal DNA damage



Rb gene arrests cells in the G1 or G1/S-phase of the cell cycle, and stops further proliferation.



Mitomycin C acts on all phases of cell cycle.

Collagen Collection 

Type 1: corneal stroma, tarsal plate



Type 2: vitreous



Type 3: ciliary process



Type 4: Descemet membrane, lens capsule, PNBZ, basal lamina of corneal epithelium



Type 5: Bowman membrane



Type 7: ABZ



Cornea total Collagen 15% o

o

fibrous collagens types I, II, III and V 

Type I 50-55%



Type III ~ 1%



Type VI 25-30%

non-fibrous collagen type IV 

Type IV 8-10%

o

filamentous collagens types VI, VIII, IX and X

o

basal lamina of the epithelium contains type IV collagen

o

Bowman‘s layer: type V

o

predominant collagen (about 90%) of the stroma is type I

o

Descemet's membrane contains predominantly type IV collagen, with about 10% type V 10

Ophthalmology Explorer

Dhaval Patel MD



BM of ciliary process and ciliary muscles ECM: laminin and collagen types I, III, and IV



human trabecular meshwork: collagen types I and III and elastin



Juxtacanalicular Tissue: collagen type III but no collagen type I or elastin



steroid-induced glaucoma shows increase in fine fibrillar material stains for collagen type IV in the subendothelial region of the Schlemm canal



anterior uveitis: reducing the density of collagen type I in the extracellular matrix of the ciliary body leading to increase in uveoscleral flow



lamina cribrosa of the human optic nerve head: collagen types I through VI, laminin, and fibronectin



Topical prostaglandin F2alpha treatment reduces collagen types I, III, and IV in the monkey uveoscleral outflow pathway

Contents of Important Fluids



BSS: Na, K, Ca, Mg, Cl, Citrate, Acetate BSS plus: ―+ HCO3, PO4, Glucose, Glutathione Aqueous: ―+ Lactate, Ascorbate, Protein



M.K. Media (4days): Tc199, Dextran, PH 7.0-7.5, Osmolality 295-355, gentamycin sulphate 75-150 micro gm/ml, HEPES as buffer, Phenol red as indicator



K-Sol: Tc 199, MEM & Earles media, HEPES, Gentamicin, Chondroin sulphate 2.5%



Dexol: MEM, 1.35% Chondrotin Sulphate, 1mM Sodium pyruvate, 1mM non- essential amino acids, Antioxidants, 1% dextran40.



Optisol GS: MEM, 1.35% Chondrotin Sulphate, 1mM Sodium pyruvate, 1 mM non-essential aminoacids, Antioxidants, 1% dextran40, ATP, Iron, cholestrol, L-hydroxyproline, Vitamins, 2 antibiotics- Gentamycin, Streptomycin



Procell: MEM,1.35%chondrotin sulphate,1mM sodium pyruvate1mM,Non-essential aminoacids,Antioxidants,Dextran40, Humen insulin 10 ug/ml & Human epidermal growth factor hEGF 10ng/ml to improve long term endothelial survival after PKP



Eusol-C: Store at 4 deg.C, Dextran, Sodium Piruvate, Glucose, Essential & non-essential aminoacids, mineral salts, Vitamins, Gentamin, hepes buffer, Bicarbonate, Phenol Red 11

Ophthalmology Explorer

Dhaval Patel MD



Organ culture medium: Fetal Bovine Serum, L-Glutamine, Earle's salts and 0.44% Mercaptoethanol in addition to the other constituents present in most intermediate storage media



Aqueous contents Relative to plasma, aqueous humor has



o

Slight hypertonicity and acidity (pH 7.2 in AC)

o

Marked excess of ascorbate (15 times greater than arterial plasma)

o

Marked deficit of protein (0.02% in aqueous vs. 7% in plasma)

o

Only calcium and phosphorus are in concentrations of about one-half that in plasma.

o

Chloride and bicarbonate vary from 20% to 30% above or below plasma levels.

o

Sight excess of lactic acid

o

Slight deficit of sodium, bicarbonate, carbon dioxide, and glucose

o

Protein and antibodies in aqueous equilibrate with those in serum when a plasmoid aqueous occurs with an anterior uveitis

o

Albumin/globulin ratio is similar to plasma, although there is less gamma globulin

Tear contents o

Lipid layer 

o

Wax, cholesterol, fatty acid esters

Aqueous layer 

Water



electrolytes (Na+, K+ Cl–, HCO3–, Mg2+)



proteins (albumin, lysozyme, lactoferrin,transferrin, ceruloplasmin),



immunoglobulins (IgA, IgG, IgE, IgM)



cytokines



growth factors (EGF, TGF-α, TGF-β1, TGF-β2, bFGF, HGF, VEGF, substance P) 12

Ophthalmology Explorer  o

others (glucose, vitamins)

Mucinous layer 

o

Dhaval Patel MD

Sulfomucin, cyalomucin, MUC1, MUC4, MUC5AC

IgD has not been detected in any study of human tears.

Chromosomes for Eye Chromosome 1: 

Fuch‘s dystrophy, COL8A2, AD



Posterior polymorphous dystrophy, PPCD2, AD



Stickler syndrome, COL2A, AD



Gelatinous drop like dystrophy, TYACSTD, AR



Schnyder corneal dystrophy, MJNFR, AD



EDS, EDS6, AR



Congenital glaucoma, GLC3B, AR



JOAG, Myocillin, AD



Stargardt‘s, ABCA4, AR



ARMD, CFH1



Usher syndrome, AR



Chediak higashi syndrome, LYST, AR



Leber‘s congenital amaurosis, RPE65, AR

Chromosome 2: 

Congenital Glaucoma, CYP1B1, AR



Oguchi‘s disease, Arrestin, AR 13

Ophthalmology Explorer 

PXE, laminin/fibrillin, AR



Autosomal dominant drusen, EFEMP1, AD



Fleck dystrophy, PIP5K3, AD

Dhaval Patel MD

Chromosome 3: 

BPES 1 (with premature ovarian failure) and BPES 2 (without premature ovarian failure) are caused by type 1 mutations in FOXL2 gene



Von Hippel–Lindau syndrome Inheritance is AD condition caused by a mutation of the VHL gene clusterin



Retinitis pigmentosa, Rhodopsin, AD



Xeroderma pigmentosa, NER enzyme, AR



Alkaptonuria, homogentisate 1-2 dihydroxygenase, AR



Kjer autosomal dominant optic atrophy, OPA1, AD

Chromosome 4: 

Axenfield Rieger syndrome, PITX2, AD



CSNB, PDE6, AR



Wolfram syndrome, WFS1, AR



Hurler syndrome, alpha L iduronidase, AR



Bietti dystrophy, CYP4V2, AR



Fraser syndrome, FRAS1, AR

Chromosome 5: 

Treacher Collins syndrome (mandibulofacial dysostosis) Inheritance is AD with high penetrance and variable expressivity, although 60% of cases occur with no family history and are thought to arise by de novo mutation. The gene involved is the ‗treacle‘ gene TCOF1 on chromosome 5q. 14

Ophthalmology Explorer

Dhaval Patel MD



Cri du chat syndrome (partial deletion of 5p)



Mutations in TGFB1 on chromosome 5 cause CDB1, CDB2, lattice type 1, lattice type 3A, Avellino, and granular dystrophy. These are therefore allelic variants.

Chromosome 6: 

Adult-onset macular vitelliform dystrophy is caused by mutation in the RDS gene on chrn Dysromosome 6p, as well as the BEST1 gene in common with juvenile-onset Best dystrophy.



VEGF



Pattern dystrophy, RDS/ peripherin, AD



Axennfeld reiger syndrome, FOXC1, AD

Chromosome 7: 

Galactosemia classic, galactose 1 phosphate uridyl transaferase, AR



Pigment dispersion syndrome, AD

Chromosome 8:

Chromosome 9: 

Lattice 2, gelsolin, AR



Nevoid BCC syndrome, PTCH, AD



Rilet Day syndrome, IKBKAP, AR

Chromosome 10: 

Crouzon syndrome Inheritance is usually AD, but 25% of cases represent a fresh mutation. The gene (FGFR2) has been isolated to chromosome 10.



Thiel behnke dystrophy, AD 15

Ophthalmology Explorer 

MEN2B, RET proto-oncogene, AD



Gyrate atrophy, OAT, AR



NTG-COAG, optineurin, AD

Dhaval Patel MD

Chromosome 11: 

Aniridia, peter‘s, AD keratitis, Axenfed reiger: PAX6, AD



Nanophthalmos, NNO1, AD



Best disease, 11q13 bestrophin, AD



FEVR, frizzled 4 gene, AD



OCA, TYR/OCA2, AR



CFEOM2: 11q13

Chromosome 12: 

CFEOM-1:



Cornea plana, KERA, AR



CHSD, DCN, AD



Meesman dystrophy, KRT3, AD



Fundus albipunctatous, RDH5, AR

Chromosome 13: 

Retinoblastoma, 13q14, AD



Sclerocornea, HCCS, AD



Microphthalmos, Trisomy 13



Congenital microcornea, AD



Oguchi disease, rhodopsin kinase, AR 16

Ophthalmology Explorer 

Late onset fuchs dystrophy, FECD2, AD



CFEOM-3

Dhaval Patel MD

Chromosome 14: 

Oculopharyngeal dystrophy Inheritance is AD caused by mutation on chromosome 14q.

Chromosome 15: 

Marfan syndrome: FBN1, AD

Chromosome 16: 

Posterior Polar Cataract: mutation of PITX3 gene



Macular dystrophy, CHST6, AR



Pseudo xantoma elasticum, ABCC6, AR



Fish eye disease, LCAT, AR



Tyrosenemia, tyrosine amino transferase, AR

Chromosome 17: 

Meesman dystrophy, AD



NF1, NF1, AD



Cystinosis, CTNS, AR

Chromosome 18: 

Edwards syndrome (trisomy 18)



Transthyretin

17

Ophthalmology Explorer

Dhaval Patel MD

Chromosome 19:

Chromosome 20: 

CHED AD, CHED1 20911, AD



CHED AR< CHED2 20p13, AR



PPMD2, VSX1, AD

Chromosome 21: 

Down syndrome (trisomy 21)



Homocystinuria: Inheritance is AR with the gene locus on chromosome 21q.22.3.

Chromosome 22: 

NF2, NF2, AD



Sorsby dystrophy, TIMP3, 22q13, AD

Chromosome X: XR 

Fabry disease, alpha galactokinase



CSNB, calcium channels



Megalocornea, LTBP2



Coat‘s disease, NDP



FEVR, NDP



Retinitis pigmentosa, RPGR



Choroderemia, REP1



Norrie disease, NDP gene on chromosome Xp11. 18

Ophthalmology Explorer

Dhaval Patel MD

XD 

Lowe syndrome, OCRL1



Alport‘s syndrome, COL4A3



Aicardi syndrome



Incontinentia pigmenti: NEMO gene on chromosome Xq28.



Ichthyosis, STS

Chromosome Y:

Connexins 

At electrical synapses a cytoplasmic bridge is formed by specialized proteins called connexins. Six connexins form a hexagonal tube that projects out of the plane of the plasma membrane of one participating cell; this unit is called a connexon.



Connexin 43:



o

gap junctions of lateral membranes of lens epithelial cells

o

oculodentodigital syndrome

Connexin 46 and 50: o

Transmembrane proteins forming lens fiber gap junction is typically 16 nm thick

o

connexin 50 or MP70 is most prevalent in outer cortical fibers, where it undergoes age-related degradation to MP38, which continues in functional gap junctions.



connexin mutations can give rise to congenital cataracts



Connexin 50, connexin 37, and connexin 40 are all encoded by genes consisting of a single exon on chromosome 1q21



A zonular pulverulent cataract has been localized to chromosome 13 near the connexin 46 gene.

19

Ophthalmology Explorer

Dhaval Patel MD

Craniosynostosis

SPOT: Scaphocephaly: sagittal suture closure (aka 'dolichocephaly') Plagiocephaly: unilateral Coronal suture (anterior) or Lamboid (posterior) Oxycephaly: coronal suture plus any other suture, like the lambdoid Trigonocephaly: metopic suture closure

Syndromes Apert syndrome Crouzon syndrome Pfeiffer syndrome Saethre-Chotzen syndrome

Diameters



Collagen fibres in corneal stroma: 25 nm diameter, 60 nm spacing between each pair



Collagen fibres in vitreous: 10 nm diameter



Lens fibre diameter: 10.5 um



Zonular fibres: 70-80 nm diameter, grouped into bundles of 5-50 um diameter



Cone diameter: 2 um with 0.3 um spacing



Cochet and Bonnet esthesiometer wire: 0.12 mm

20

Ophthalmology Explorer

Dhaval Patel MD

Drug Resistance 

CMV UL97 mutations (a CMV DNA polymerase mutation that confers ganciclovir resistance) were detected in 3% of patients treated with ganciclovir over 3 months and in none treated less than 3 months.

Dye for Eye





Anterior Segment (Capsule staining) o

0.5% indocyanine green

o

0.15% trypan blue (less costly when compared to the cost of ICG)

Posterior Segment o

ICG: ILM staining  0.05%

o

IFCG: 0.05%

o

TB: ERM stain  0.06%

o

BBG: ILM staining  0.05%, 0.025%

o

TA

o

PB

o

BrB

o

NaF

Electromagnetic Spectrum (part of spectrum which is important in ophthalmology) 21

Ophthalmology Explorer

Dhaval Patel MD



Ultraviolet C rays: This band is blocked by the ozone layer of atmosphere.



Ultraviolet B rays: This band is responsible for snow blindness and photo keratitis caused by welding arc. Prolonged exposure to these rays can cause formation of pingicula and pterigium.



Ultraviolet A rays: This band of UV rays is absorbed by crystalline lens and thus retina is protected against their bad effects. Prolonged exposure to these rays causes cataract formation. IOLs implanted during cataract surgery have chromophores [inhibitors of UV rays] to protect retina against UV rays.



Visible Rays: VIBGYOR



Infrared A rays are responsible for macular burn in solar eclipse [photo retinitis].



Infrared rays B and C can cause corneal opacity and cataract formation on prolonged exposure.

Evolutions of anesthetic techniques for cataract surgery



General anesthesia 1846



Topical cocaine 1881 Koller



Injectable retrobulbar cocaine 1884 Knapp



OrbicuIaris akinesia 1914 Van lint, O'Briens Atkinson



Hyaluronidase 1948 Atkinson



Peribulbar 1970 kelman (but not published)



Posterior peribulbar 1985 Davis and Mandel



limbal 1990 Furata et al.



Anterior peribulbar 1991 Bloomberg



Pinpoint anesthesia 1992 Fukasawa and Furata



Topical tetracaine 1992 Fichman



Topical plus intracameral 1995 Gills



No anesthesia 1998 Agarwal 22

Ophthalmology Explorer 

Cryoanalgesia 1999 Gutierrez-Carmona



Xylocaine jelly 1999 Koch and Assia



Hypothesis, no anesthesia 2001 Pandey and Agarwal



Viscoanesthesia 2001 Werner, Pandey, Apple et al

Dhaval Patel MD

FDA Approved Drugs

Drugs Approved in 2012 

Cystaran (cysteamine hydrochloride); Sigma Tau Pharmaceuticals; For the treatment of corneal cystine crystal accumulation due to cystinosis, Approved October 2012



Jetrea (ocriplasmin); Thrombogenics; For the treatment of symptomatic vitreomacular adhesion, Approved October 2012



Lucentis (ranibizumab injection); Genentech; For the treatment of diabetic macular edema, Approved August 2012



Zioptan (tafluprost ophthalmic solution); Merck; For the treatment of elevated intraocular pressure, Approved February 2012

Drugs Approved in 2011 

Eylea (aflibercept); Regeneron Pharmaceuticals; For the treatment of neovascular (wet) age-related macular degeneration, Approved November 2011

Drugs Approved in 2010 

Zymaxid (gatifloxacin ophthalmic solution); Allergan; For the treatment of bacterial conjunctivitis, Approved May 2010

Drugs Approved in 2009 

Acuvail (ketorolac tromethamine); Allergan; For the treatment of pain and inflammation following cataract surgery., Approved July 2009



Bepreve (bepotastine besilate ophthalmic solution); Ista Pharmaceuticals; For the treatment of itching associated with allergic conjunctivitis, Approved September 2009



Besivance (besifloxacin 0.6% ophthalmic suspension); Bausch & Lomb; For the treatment of bacterial conjunctivitis, Approved June 2009 23

Ophthalmology Explorer

Dhaval Patel MD



Ozurdex (dexamethasone); Allergan; For the treatment of macular edema following branch retinal vein occlusion or central retinal vein occlusion, Approved June 2009



Zirgan (ganciclovir ophthalmic gel); Sirion Therapeutics; For the treatment of acute herpetic keratitis, Approved September 2009

Drugs Approved in 2008 

Akten (lidocaine hydrochloride); Akorn; For anesthesia during ophthalmologic procedures, Approved October 2008



Astepro (azelastine hydrochloride nasal spray); Meda Pharmaceuticals Inc.; For the treatment of seasonal and perennial allergic rhinitis, Approved October 2008



Durezol (difluprednate); Sirion Therapeutics; For the treatment of inflammation and pain associated with ocular surgery, Approved June 2008

Drugs Approved in 2007 

AzaSite (azithromycin); InSite Vision; For the treatment of bacterial conjunctivitis, Approved April 2007

Drugs Approved in 2006 

Lucentis (ranibizumab); Genentech; For the treatment of neovascular (wet) age related macular degeneration, Approved June 2006

Drugs Approved in 2004 

Macugen (pegaptanib); Pfizer / Eyetech Pharmaceuticals; For the treatment of wet agerelated macular degeneration., Approved December 2004

Drugs Approved in 2002 

Restasis (cyclosporine ophthalmic emulsion); Allergan; For the treatment of low tear production., December 2002

Drugs Approved in 2001 

Lumigan (bimatoprost ophthalmic solution); Allergan; For the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension, Approved March 2001



Travatan (travoprost ophthalmic solution); Alcon; For the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension, Approved March 2001

24

Ophthalmology Explorer 

Dhaval Patel MD

Valcyte (valganciclovir HCl); Roche; For the treatment of cytomegalovirus retinitis in patients with AIDS, Approved March 2001

Drugs Approved in 2000 

Betaxon; Alcon; For lowering IOP in patients with chronic open-angle glaucoma or ocular hypertension, Approved February 2000



Quixin (levofloxacin); Santen; For treatment of bacterial conjunctivitis, Approved August 2000



Rescula (unoprostone isopropyl ophthalmic solution) 0.15%; Ciba Vision; For the treatment of open-angle glaucoma or ocular hypertension, Approved August 2000



Visudyne (verteporfin for injection); QLT; For the treatment of wet age-related macular degeneration (wet AMD), Approved April 2000

Drugs Approved in 1999 

Alamast; Santen; pemirolast potassium ophthalmic solution, Approved September 1999



ZADITOR; Ciba Vision; Treatment for the prevention of itching of the eye, Approved July 1999

Drugs Approved in 1998 

Alrex; Bausch & Lomb, Pharmos; Treatment for seasonal allergic conjunctivitis, Approved March 1998



Cosopt; Merck; Treatment for glaucoma or ocular hypertension, Approved April 1998



Lotemax; Bausch & Lomb, Pharmos; Treatment for post-operative eye inflammation, Approved March 1998



Salagen Tablets; MGI Pharma; Treatment for Sjogren's Syndrome, Approved February 1998



Viroptic; King Pharmaceuticals; Treatment for inflammation of the cornea in children due to herpes simplex virus, Approved February 1998



Vitravene Injection; Isis Pharmaceuticals; Treatment for CMV in AIDS patients, Approved August 1998

Drugs Approved in 1997 

Acular (ketorolac tromethamine ophthalmic solution) 0.5%; Allergan; Treatment for postoperative inflammation in patients who have undergone cataract extraction, Approved January 1997 25

Ophthalmology Explorer

Dhaval Patel MD



Acular (ketorolac tromethamine ophthalmic solution) 0.5%; Allergan; Treatment for postsurgical inflammation following cataract extraction, Approved November 1997



BSS Sterile Irrigating Solution; Alcon; Treatment during ocular surgical procedures, Approved December 1997

Drugs Approved in 1996 

AK-Con-A (naphazoline ophthalmic); Akorn; Over-the-counter combination vasoconstrictor/antihistamine product for opthalmic use, Approved January 1996



Alphagan (brimonidine); Allergan; Treatment for open-angle glaucoma and ocular hypertension, Approved September 1996



Ocuflox (ofloxacin opthalmic solution) 0.3%; Allergan; Treatment for corneal ulcers, Approved May 1996



OcuHist; Pfizer; Over-the-counter antihistamine eye drop, Approved January 1996



Vistide (cidofovir); Gilead; Treatment for cytomegalovirus (CMV) retinitis, Approved June 1996



Vitrasert Implant; Chiron; Drug delivery system for the treatment of cytomegalovirus, Approved March 1996

FDA Device Classification 3 classes of ophthalmology devices 1. Class I devices (eg, refractometers, perimeters, sunglasses, visual acuity charts) are usually considered minimal-risk devices. Although these devices are subject to general controls, most of them are exempt from premarket review by the FDA. With few exceptions, manufacturers can go directly to market with a class I device. 2. Class II devices (eg, phacoemulsification units, tonometers, vitrectomy machines, dailywear contact lenses) are usually considered moderate-risk devices. Class II devices are those for which general controls alone are insufficient to ensure safety and effectiveness and for which methods exist to provide such assurances. These devices, in addition to general controls, are subject to special controls, which may include special labeling requirements) mandatory performance standards, and postmarket su rveillance. With few exceptions, class II devices requi re premarket review by the FDA. 26

Ophthalmology Explorer

Dhaval Patel MD

3. Class III devices (eg, excimer lasers, intraocular lenses, extended -wear contact lenses, intraocular fl uids) are considered significant-risk devices that present a potential unreasonable risk of illness or injury. Class III devices are those for which insufficient information exists to ensure safety and effectiveness solely through general or special controls. Class III devices cannot be marketed in the United States until the FDA determines that there is a reasonable assurance of safety and effectiveness when used accordi ng to the approved indications for use. Most class III devices come to market through the premarket approval (PMA) process and require an extensive review by the FDA before approval is granted for marketing.

Field of View 

Standard Fundus Camera: 20, 30 and 50 degrees



RetCam: 130 degrees



Optos: 200 degrees of retina (equator is at 180 degrees)



First in Genetics

Wow…!! It’s amazing that all of following diseases first described in each category has an eye manifestation…!!! (Ref: Alex Levin MD, WEI, PA, USA)

1st AD: Piebaldism 1st AR: alkaptonuria 1st XR: red green colour deficiency 1st XD: Incontigenta pigmenti 1st Mitochondrial: LHON 1st digenic: RP 1st trigenic: bardet biedel 27

Ophthalmology Explorer

Dhaval Patel MD

1st two-hit hypothesis: Retinoblastoma 1st contiguous gene deletion syndrome: anridia syndrome of wagner

Fellow Eye Risk



Keratoconus: 50% of normal fellow eyes will progress to keratoconus within 16 years



PXG: A patient with unilateral PXG and only PXF in the fellow eye is at high risk (50% in 5 years) of developing glaucoma in the fellow eye. A patient with unilateral PXG who does not have PXF in the fellow eye has only a low risk of developing glaucoma in the normal eye.



Patients with advanced AMD (late ARM) in one eye, or even moderate vision loss due to non-advanced AMD in one eye, have about a 50% chance of developing advanced AMD in the fellow eye within 5 years.



In Age related Macular Hole, risk of involvement of the fellow eye at 5 years is around 10%.



In NAION, Involvement of the fellow eye occurs in about 10% of patients after 2 years and 15% after 5 years.



AAION affects 30–50% of untreated patients of which one-third develop involvement of the fellow eye, usually within 1 week of the first.



7% of patients with CRVO develop a nonsimultaneous venous occlusion of the fellow eye within 2 years



The risk of any vascular occlusion in the fellow eye is estimated to be 0.9% per year.



The Macular Photocoagulation Study (MPS) reported that the 5-year risk of neovascularization in fellow eyes of individuals with unilateral neovascular AMD was 10% in those without large drusen and 30–46% in those with large drusen



POHS with CNVM, 20% risk over a 2-3-year period of developing choroidal neovascularization in the macula of the fellow eye



50-75% of patients with angle closure in one eye will have an attack in the fellow eye often within 1 year (up to 10years) despite miotic treatment. Prophylactic laser iridotomy in fellow eyes of patients presenting with unilateral acute PAC also appears to be safe and effective in preventing acute PAC in 100%, and in preventing long-term rise in IOP in 89%

28

Ophthalmology Explorer

Dhaval Patel MD



Acute retinal necrosis may occur in the fellow eye in approximately 30% of patients at an average interval of 4 weeks.



Chances of RD in fellow eye varies from 9-40%.

Frequency of Probes 

USG: 10 MHz



Ultrasonic Pachymetry: 10-20 MHz



UBM: 50 MHz



HI-SCAN: 35 MHz

Genes 

Genotypic heterogeneity: multiple genes causing single disease



Phenotypic heterogeneity: single gene causing multiple disease



PXF: LOX L1



BPES: FOX L2



Pterygium: KL-6



Lowe‘s syndrome: OCRL1 gene



TGFB1: aka BIGH3 o

5q31.2

o

Protein produced by corneal epithelium

o

Phenotypic heterogeneity GREAT 

Granular



Reis Buckler 29

Ophthalmology Explorer







EBMD



lAttice



Thiel Behnke

Dhaval Patel MD

PAX6, 11p13: phenotypic heterogeneity o

Aniridia

o

Gillespe

o

WAGR

Axenfield Reiger Spectrum (AD) – genotypic heterogeneity, multiple genes causing same disease o

GJA1 (connexin 43)  6p21

o

FKHL7/ FOXC1  6p25

o

PITX2/ RIEG1 4q25

o

RIEG2  13q14

o

COL4A1  13q34 (MCQ: all except type question, so remember its Chromosomes 4, 6 and 13)



Fuchs: genetic heterogeneity o

Following all genes do cause Fuchs and other diseases mentioned below. 

COL8A2: PPMD



SLC4A11: CHED



ZEB1: PPMD



PITX2: homeobox gene  Peters, ARS, AN, Iris hypoplasia



KCNJ13: upregulates ZEB1

30

Ophthalmology Explorer 

Dhaval Patel MD

Keratin genes: cytokeratin 12 + 3 o

KRT3: 12q13  Meesman

o

KRT12: 17q12  Stocker Holt



Keratoconus: VSX1, SOD1



Glaucoma Genes nosology: o

GLC is name given to primary gene loci by HUGO: Human Genome Organisation, Geneva

o

GLC1: open angle (only 10% pt): AD 

Only 3 genes are known till now



GLC1A: JOAG 36%, POAG 4%  1q23-25  MYOC/TIGR



GLC1B: POAG  2q  nI IOP



GLC1C: POAG 3q  high IOP



GLC1D: POAG  8q23  high IOP



GLC1E: POAG/NTG 16%  10p14  Optineurin (OPTIc NEURopathy INducing), nI IOP



GLC1F: POAG  7q



GLC1G: POAG 5%  5q  WDR36 (WD Region 36)

o

GLC2: close angle

o

GLC3: congenital (>25%): AR

o



GLC3A: 2p21  CYP1B1, cyrochrome P450 gene



GLC3B: 1p36



GLC3C: 14q24



MYOC is responsible for 5.5% PCG

Pigment Dispersion Genes: AD, 7q35 31

Ophthalmology Explorer o

Pseudoexfoliation syndrome: LOXL1, 15q24-25

o

Genes associated with MMP

o

o



Dhaval Patel MD



MMP9 downregulated during acute PACG



SNP rs17576 of MMP9 at chromosome 20q11 is strongly associated with acure PACG.

Genes Causing Early-Onset or Familial Glaucoma 

CYP1B1, Cytochrome p450  Congenital glaucoma



LTBP2, Latent transforming growth factor beta binding protein 2  Congenital glaucoma



PITX2, Paired-like homeodomain 2  Axenfeld-Riegers



FOXC1, Forkhead box C1  Anterior segment dysgenesis



PAX6, Paired box 6  Aniridia



MYOC, Myocilin  Primary open-angle glaucoma (juvenile and familial)



OPTN, Optineurin Familial normal-tension glaucoma



TBK1, TANK-binding kinase 1  Familial normal-tension glaucoma



LMX1B (9q34, glaucoma associated with nail-patella syndrome)

Glaucoma Gene Testing 

Congenital glaucoma  CYP1B1, LTBP2



Anterior segment dysgenesis  FOXC1, PITX2, PAX6



Primary open-angle glaucoma  MYOC



Normal-tension glaucoma  OPTN, TBK1, OPA1

Eyelid Tumors genes o

o

BCC: 

Sonic hedgehog pathway



PTCH1 (patched 1): in BCNS or Gorlin syndrome

SeCA: 32

Ophthalmology Explorer 

o

Muir Torre Syndrome 

MMR- Mismatch Repair genes (MSH-2, MSH-6, MLH-1)



MSI- high frequency of Micro Satelite Imbalance

Merkel Cell Carcinoma 

MCPyV: Merkel Cell Polyoma Virus  70% cases 

o





Dhaval Patel MD

LTA: Large T Antigen binds to host proteins, forces cell into Sphase

Cutaneous Malignant Melanoma 

C-KIT activating mutations  chronic sun damage MM (Acral MM, Mucosal MM)



BRAF activating mutations V600E (90%)  Non chronic sun damage MM  Nevi



P16INK4a-Rb pathway: loss of function mutation of CDKN2A  Familial melanoma (dysplastic nevus syndrome)



Melanocortin receptor (MC1R) varients  increased risk of MM and BCC independent of cutaneous pigmentation

ARMD o

Complement factor H gene (CFH): 1q32

o

Apolipoprotein E: 19q13.2

o

Many others..BIG BIG list!!

Retinal/Macular Dystrophies o

Best macular dystrophy

o

Stargardt disease ABCA4, Chr 1

o

Stargardt-like dominant macular dystrophy

o

Pattern dystrophy PRPH2

o

Sorsby fundus dystrophy TIMP3 Chr 22 AD

BEST1,

Chr11 AD/AR AR ELOVL4 Chr 6 AD

Chr 6 AD

33

Ophthalmology Explorer



Dhaval Patel MD

o

Autosomal dominant radial drusen

EFEMP1

Chr 2 AD

o

North Carolina macular dystrophy

Unknown

Chr 5 and 6

o

Spotted cystic dystrophy Unknown

Unknown

AD

o

Dominant cystoid macular edema

Unknown

Chr 7 AD

o

Fenestrated sheen macular dystrophy

Unknown

Unknown

o

Glomerulonephritis type II CFH

AD

AD

Chr 1 AR

Mutations of LHON o

11778: 98% patients, VA < 20/200, worst prognosis

o

14484: 10-15% patients, high incidence of spontaneous VA recovery, best prognosis

o

3460: 8-15% of patients, high incidence of visual recovery, family history positive



Gene therapy: for LCA, RPE 65 gene, NEJM 2008 study, Lancet 2009



Ocular development genes: o

Sonic hedgehog

o

Paired box

o



PAX2: (during optic vescicle, causes ocular-renal coloboma syndrome)



PAX6 (eye development)

Other downstream genes  CHX10, FKHL7 (6p15, forkhead transcription factor, ? neural crest), PITX2



Genes causing Diabetes: ALR2, RHGE, TGF beta1



Uveal melanoma gene: DDEF1 gene, chromosome 8q



The ATP-binding cassette o

Subfamily A:ABCA 

Adrenoleukodystrophy 34

Ophthalmology Explorer

o



Zellweger syndrome



Stargardt disease (ABCA4)



Autosomal recessive retinitis pigmentosa



Cone-rod dystrophy

Dhaval Patel MD

Subfamily G: ABCG 

ABCG2: limbal stem cells



Giant Cells 

Langhans giant cells: peripheral ring of nuclei, associated with tuberculosis, sarcoidosis



Touton giant cells: midperipheral ring of nuclei surrounded by a peripheral ring of lipid, associated with xanthogranulomatous disease



Foreign body giant cells: randomly dispersed nuclei, associated with foreign material and fungi

Growth Factors 

INF-Y: decreases angiogenesis



PEGF: decreases neovascularisation



Angiopoeitin: decreases leakage o

Angiopoietins-1–4 (Ang1–4) form a family of growth factors involved in angiogenesis

o

only Ang1 and Ang2 currently are known to have roles in ocular neovascular disease

o

Endothelial cells are a primary source of Ang2 production where it is stored in Weibel–Palade bodies (WPB) from which it can be released by a variety of stimuli



Myofibroblasts are derived from keratocytes under influence of TGF beta1.



HGF and KGF are predictor of corneal epithelial healing.



Keratocytes apoptosis is mediated by IL-1. 35

Ophthalmology Explorer

Dhaval Patel MD



PKC beta is most important in DR pathogenesis. It increases basement membrane permeability.



Angiogenesis is regulated by a balance between VEGF and PEDF (pigment endothelium derived factor), as evidence is emerging that PEDF may inhibit new blood vessel growth.



PDGF-B is a growth factor structurally related to VEGF. The contributions of PDGF-B to angiogenesis are mediated largely through its effects on mural cells such as pericytes and vascular smooth muscle cells.



Half Life









IVTA o

Normal eye: 41 days

o

Vitrectomised eye: 16 days

o

Aphakic eye: 6.5 days

PST o

Aqueous: 11 days

o

Vitreous: 17 days

o

Plasma: 25 days

Intravitreal Bevacizumab 1.25mg o

4.32 days rabbit

o

5 days in humans

Intravitreal Ranibizumab 0.5 mg o



3 days in monkeys

Strontium-90: 28 years

36

Ophthalmology Explorer

Dhaval Patel MD

HLA HLA wise Diseases 

A2: JIA



A11: Sympathetic ophthalmia



A29: birdshot chorioretinopathy (90-100% association)



B5, B12: behcet's dz



B7: toxoplasmosis, POHS, serpiginous choroidopathy, ankylosing spondylitis, APMPPE



B8: Sjögren‘s syndrome, sarcoidosis



B12: Ocular cicatricial pemphigoid



B13: sarcoidosis



B27: PAIR  Ankylosing spondylitis (88%), Reiter‘s syndrome (85–95%), inflammatory bowel disease (60%), psoriatic arthritis (also B17).



B51: behcet‘s disease, eales



Bw54: Posner-Schlossman syndrome, VKH?



DR2: POHS, intermediate uveitis, APMPPE



DR4: VKH, SO, OCP.



DR2/15: pars planitis and Multiple Sclerosis

Disease wise HLAs 

Keratoconus: A9/10/12, B5/21



PXF: A1/33, B8



OHT progression to Glaucoma: B7/12



AMD: A3, CW02/07



Diabetic Retinopathy (DR) development: DR1/7



Diabetic Retinopathy (DR) proliferation: DR4, DQ8 37

Ophthalmology Explorer

Dhaval Patel MD



Retinal vasculitis: B44



Eales: B51, DR1/4



IU: B8/51, DR2



Pars Planitis: DR15/17/51



VKH: HLA-DR4 and HLA-Dw53 are more common in Chinese patients, HLA-DR1 and HLA DR4 more common in Hispanic patients, and HLA DRB1 in Indian patients



SJS: significantly increased incidence of HLA-B12, HLA-Aw33, and DRw53



HSV EM: HLA-DQw3



TEN: HLA-B12



ocular lesions of SJS: HLA-B44



Birdshot choroidopathy: White, HLA-A29, 96%



Ankylosing spondylitis: White and asians, HLA-B27, 89%



Behçet's disease: Japanese, HLA-B5, 68%



Reiter's syndrome: White, HLA-B27, 80%



POHS: White, HLA-B7-77%, HLA-DR2-81%

Host Cell Receptors 

Adenovirus type 37: CD46



Epstein–Barr virus: CD21



Herpes simplex virus: Heparan sulfate



Human cytomegalovirus: Heparan sulfate



Human papillomavirus: Integrin a6



Influenza virus: Sialic acid



Rhinovirus: ICAM-1



Vaccinia virus: EGF receptor 38

Ophthalmology Explorer

Dhaval Patel MD

Host for Parasites







Definitive: o

Toxoplasma gondii: domestic and wild cats

o

Echinococcus granulosus: dog

o

Taenia solium: human

Intermediate host o

Taenia solium: pig

o

Toxoplasma gondii: animals including humans

o

Echinococcus granulosus: sheep, cattles, pigs

o

Francisella tularensis: rabbit, squirrels, cats, foxes, raccoons

o

Brucellosis: veterinarians and abattoir workers

o

Oncocerca volvulus: many species of black fly simulium

Both definitive and intermediate: o

Taenia solium: human

Hypersensitivity in Eye Gell, Coombs, and Lackmann‘s classification of Hypersensitivity Reactions o

Type 1: VKC, AKC, SAC, GPC

o

Type 2: OCP, PV, DH

o

Type 3: SJS, RA, SLE, PAN, RP

o

Type 4: TB, WG, Contact dermatitis, herpes disciform keratitis, sarcoidosis, transplant rejection

39

Ophthalmology Explorer

Dhaval Patel MD

IHC Markers 

Melanoma markers: HMB45, melan A, tyrosinase, S-100 , MITF



Epithelial markers: Cytokeratins (CAM 5.2, AE1, AE3, CK7, CK20, involucrin, etc.)



Endothelial markers: Factor VIII, CD34



Muscle markers: Muscle specific actin (MSA), smooth muscle action (SMA), desmin, myogenin



Neuroendocrine tumors: Chromogranin



Melanoma: HMB45, S100



Neural tumor: S100, Leu7



Fibrous histiocytoma: CD68



Spindle cell carcinoma: Cytokeratin



Rhabdomyosarcoma: Desmin, Vimentin, Muscle specific actin, Myoglobin, Myogenin, MyoD1, Caveolin-3



lymphoid tumors o

CD3: T cells

o

CD5: T cells, mantle cells, SLL/CLL

o

CD10: follicular lymphoma

o

CD20: B cells

o

CD23: follicular dendritic cells

o

Bcl-2: follicular, anti-apoptosis

o

Bcl-1: cyclin D1, mantle cell



Retinoblastoma is positive for neuron-specific enolase (also found in aqueous of RB), class III tubulin isotype (h4), microtubuleassociated protein 2 (MAP2), and synaptophysin; they are negative for glial fibrillary acidic protein and S-100 protein



Retinal stem cell marker: nestin, CD 34



Mitosis specific marker in cornea: Ki67

40

Ophthalmology Explorer

Dhaval Patel MD



Limbus Stem Cells: CK 5/14+ve, CK 19+ve, P63+ve, Vimentin+ve, ABCG2, alpha-enolase (5+14 =19)



Central Corneal Cells: CK 3/12+ve, Connexin 43+ve (3 x 4 = 12, 4.3)

 

Inheritence



All vitreoretinopathy are AD except o

Norrie  XL

o

XLRS  XL

o

Glodman favre  AR

o

Stickler  AD but rarely AR

o

FEVR  AD AR XR



All MPSs are transmitted by the AR mode, except MPS II (Hunter syndrome) which is XR.



albinism inheritance



o

All OCA are AR except ADOCA

o

OA are XR.

All corneal dystrophies are AD except o

Macular  AR

o

Gelatinous droplike  AR

o

LCD type 3  AR 41

Ophthalmology Explorer o



Dhaval Patel MD

CHED type 2  AR

Microcornea: AD Megalocornea: XR



Familial ectopia lentis is AD Ectopia lentis et pupillae is AR.



Simple myopia and simple hypermetropia: AD

Inside Retinal Layers 

The nuclei of the Müller cells lie in the inner nuclear layer, whereas the nuclei of the photoreceptors lie in the outer nuclear layer.



The nerve fiber layer contains the axons of the ganglion cells.



The inner plexiform layer has axons of the bipolar and amacrine cells and the synapses of the ganglion cells.



The outer plexiform layer has connections between the photoreceptors, horizontal cells, and bipolar cells.



The footplates of the Müller cells form the internal limiting membrane.



cell bodies whose processes project into the lateral geniculate and pretectal nuclei ganglion cell layer



Müller's cell nuclei  inner nuclear layer



Photoreceptors nuclei  Outer nuclear layer



horizontal and bipolar synapses  outer plexiform layer



amacrine and bipolar cell synapses  inner plexiform layer



storage of dietary vitamin A  retinal pigment epithelium (RPE)



cell bodies whose processes form spherules and pedicles  outer nuclear layer 42

Ophthalmology Explorer

Dhaval Patel MD



high baseline cyclic guanosine monophosphate (cGMP) levels and membrane depolarization  photoreceptor layer



flame-shaped retinal hemorrhages  nerve fiber layer



dot hemorrhages  inner nuclear layer



Hard exudates  OPL



Soft exudates/ CWS  NFL

Interferons Therapy & Eye



Alpha 2a: capillary hemangioma



Alpha 2b: papilloma



Beta 1a:



o

Avonex: for MS, intramuscular, once weekly

o

Rebif: for MS, subcutaneous, thrice weekly, EVIDENCE Trial

Beta 1b: o



Betaseron and Extavia: for MS, subcutaneous

Gamma o

chronic granulomatous disease, kidney tumors and leishmania and other parasites.

43

Ophthalmology Explorer

Dhaval Patel MD

Intraocular Gases Physical characteristics

Gases

Mol wt.

Purity (mole%)

Expansion

Longevity (days)

Nonexpansile conc. (%)

Air

29

99.99

0

5-7

----

SF6

146

99.9

1.9-2.0 times

10-14

18

C3F8

188

99.7

4 times

55-65

14

Intracameral Dosages 

Vancomycin: 1 mg/ml



Cefazolin: 1 mg/0.1 ml



Cefuroxime: 1 mg/0.1 ml (ESCRS Study)



Gatifloxacin: 100 mcg/0.1 ml



Moxifloxacin: 100 mcg/ 0.1 ml



Amphotericin B: 5-10 mcg/0.1 ml



Irrigating fluid o

Vancomycin: 25-50 mcg/ml

o

Gentamycin: 0.008 mg/ml



Adrenaline tartarate: 1:10,000 (0.1 ml of 1:1000 is diluted with 0.9ml)



Pilocarpine: 0.1 ml of the drug (25 mg/ml) is diluted in 0.1 ml ringer lactate

44

Ophthalmology Explorer

Dhaval Patel MD

Intrastromal Dosages 

Voriconazole: 50 microgram/ 0.1 ml



Amphotericin B: 5-7.5 microgram/0.1 ml



Ciprofloxacin: 0.3 mg/0.1 ml



MMC: 0.02-0.04% for 15-30 sec to reduce post-operative interphase haze

Intravitreal Dosages 









Antibiotics o

Vancomycin: 1mg/0.1ml

o

Ceftazidime: 2.25mg/0.1ml

o

Amikacin: 400 migrogram/0.1 ml

o

Gentamycin: 200 migrogram/0.1 ml

Antifungals o

Voriconazole: 50-100micrgram/0.1ml

o

Amphotericin B: 5 migrogram/0.1 ml

Antivirals o

Ganciclovir (Cytovene): 200–400 mg/0.1 mL

o

Foscarnet (Foscavir): 1200 mg/0.05 mL

o

Cidofovir (Vistide): 20 mg/0.1 mL

Steroids o

Dexamethasone: 400 mcg/0.1 ml

o

Triamcinolone acetonide: 1-4 mg/ 0.1 ml

Anti VEGFs o

Pegaptinib MACUGEN: 0.3 mg in 0.09 ml pre-filled syringe 45

Ophthalmology Explorer o

Dhaval Patel MD

Bevacizumab AVASTIN: 1.25 mg in 0.05 ml 

1 ampoule: 0.2 ml



1 vial: 4 ml or 16 ml of 25 mg/ml

o

Ranibizumab LUCENTIS: 0.5 mg in 0.05 ml

o

VEGF Trap EYELEA: 0.05, 2, 4 mg in 0.05 ml

o

SiRNA: 70-300 mcg

Intravitreal Implants 





Dexamethasone intravitreal implant (DEX implant; Ozurdex, Allergan, Irvine, CA) o

delivers the steroid intravitreally for 6 months

o

consists of poly (lactic-co-glycolic acid), a DEgradable polyester and dexamethasone

o

single-use applicator through a 22-gauge

o

uveitis and macular edema caused by retinal vein occlusion

o

350 µg and 700 µg version

o

Uses NOVADUR Delivery system

o

GENEVA (dexamethasone implant) study: Global Evaluation of implantable dexamethasone in retinal Vein occlusion with macular edema (GENEVA) study

Vitrasert ganciclovir implant o

poly(vinyl alcohol) and poly(ethylene vinyl acetate)

o

delivers the medication for approximately 32 weeks (8 months) and has been shown to halt the progression of CMV

o

nondegradable

o

5/4.5 mg implant

o

Releases 1 mcg/ hour

o

Approaches concentration of 4 ug/ml intravitreal

Retisert fluocinolone implant 46

Ophthalmology Explorer









Dhaval Patel MD

o

blend of the drug with poly(vinyl alcohol) and methylcellulose

o

0.59 mg pellet embedded in a nonbiodegradable scaffold designed to be implanted in the vitreous cavity via a sclerotomy and anchored by a suture to the eye wall

o

releases drug at steady state between 0.3 and 0.4µg/day for approximately 30 months

o

used most commonly for treatment of chronic non-infectious posterior uveitis.

o

Studied for DME also

Iluvien fluocinolone implant o

narrow cylinder 3.5 × 0.37 mm

o

25-gauge

o

lowest dose format (0.2 µg/day)

o

higher-dose (0.5 µg/day) system

o

FAVOR (iluvien) study

I-vation triamcinolone implant o

helical screw coated with triamcinolone acetonide that delivers the drug intravitreally for 36 months

o

25-gauge

o

drug is entirely within the coating on the helical structure and not within the bulk of the device

ECT CNTF Implant o

which allows the intravitreal implantation of a chamber containing live cells programmed to release CNTF

o

1.5 ng/day

o

possible efficacy for age-related macular degeneration (AMD) involving geographic atrophy and for RP

o

2 years or more

ECT technology anti-VEGF implant o

NT-503 47

Ophthalmology Explorer o 

Dhaval Patel MD

For ARMD

Brimonidine Intravitreal Implant o

Patients With Geographic Atrophy Due to Age-related Macular Degeneration (AMD)

o

This is a randomized, double-masked, dose-response, sham-controlled evaluation of the safety and efficacy of brimonidine tartarate intravitreal implant in patients with geographic atrophy from age-related macular degeneration. It is hypothesized that the implant may promote the release of neuroprotective factors that may slow the progression of retinal degenerative disease.

Iris Nodules & Pathology



Lisch nodule, neural crest hamartoma: NF 1



JXG nodules are composed of histiocytes and Touton giant cells: JXG



Koeppe nodules are collections of inflammatory cells, near pupillary margin: granulomatous and non-granulomatous uvetis



Bassaca Nodules are seen at base: only in granulomatous uveitis (sarcoid, Tb, syphilis, VKH); often look gelatinous



Brushfield spots are stromal hyperplasia: Downs syndrome



Berlin nodules are seen in angle: granulomatous uveitis

Laser Facts Brief History 

1917 - A. Einstein: Laser possible.



1958 - C.H. Townes, A.L. Schawlow: Theoretical basis for lasers.



1960 - T. Maiman: Built first laser. 48

Ophthalmology Explorer 

1963 - C. Zweng: First medical laser trial (retinal coagulation).



1965 - W.Z. Yarn: First clinical laser surgery.

Dhaval Patel MD

Instrument Wavelengths (Chronological order in nm) 

SWAP: 440, blue light



Retinal Thickness Analyser RTA: green, 540-nm HeNe laser



Hertmann Shack‘s Aberrometer: 575 nm



HRT- CSLO: 670 diode



GDX-SLO: 780 diode



IOL Master: 780 diode



Lenstar: 820, SLD



Macular OCT (Posterior Segment OCT): 830



RNFL OCT: 810/850, SLD



AS-OCT: 1310, SLD



Swept Source OCT: 1050

Therapeutic Wavelengths (nm) 

Excimer laser: 193, Argon Fluoride (ultraviolet)



Excimer laser: 308, Xenon Cloride (ultraviolet)



Excimer laser trabeculostomy ELT: 308, Xenon Cloride



Argon blue-green: 488



Df Nd YAG: 512 (green)



ND YLF laser: 527 (in the treatment of diabetic macular edema) 49

Ophthalmology Explorer 

Argon green: 514



Yellow dye laser: 577 for DME



Krypton red or Dye red: 620-630



He Ne Gas laser: 632, for Laser interferometry



Rostaporphin PDT: 664 nm



Diode: 689, PDT (its verteporphin‘s peak absorption)



Ruby laser: 694, red



Infrared diode laser: 780, IOL Master



Transpupilary thermotherapy, DLCP: 810



subthreshold micropulse STMP diode 810nm: for DME



Intralase: Nd: YLF, wavelength is 1053 nm



Nd YAG: 1064



Ho YAG: 2100, used for laser thermokeratoplasty



Erbium YAG: 2940, for laser phacoemulsification



CO2 laser: 10600

Dhaval Patel MD

Laser settings for glaucoma 

ND YAG PI: 500u, 5-15mJ, 12ns pulse, 1-3 pulse/sec



Argon PI: 50u, 1000mW, 0.1-0.2s,



Laser pupilloplasty: 200u, 0.2s, 400mW



Laser sphincterotomy: 50u, 0.01-0.05s, 1.5W



ALT: 50u, 100ms, 1000mW



SLT: 400u, 0.5-1.2mJ



DLCP: 810 nm, 2 mm from limbus, 8 spots per quadrent, 2000 ms, 1200-2000 mW 50

Ophthalmology Explorer

Dhaval Patel MD

Laser settings in Retina 



PRP: df NdYAG o

200-500 micron spot size

o

200-500 ms

o

200-500 mW

Macular Grid Laser: df NdYAG o

50-100 micron spot size

o

50-100 ms

o

50-100 mW

Laser Parameters for PTK 

Fluence: 160 ± 10 mJ/cm2



Repetition rate: 5 Hz



Ablation rate: 0.20-0.35 mm per pulse



Ablation diameter: 5.5–6 mm including a 0.5 mm transition zone



Ablation depths: o

Epithelium 40 mm (default value) or as determined by pachymetry

o

Stroma: Depth of scar or opacity (postoperative corneal thickness should be at least 250 mm)

Modes of Laser There are three modes of laser: continuous, Q-switched and mode-locked. o

Laser from continuous mode has a constant power and is measured in watts.

o

Q-switched and mode-locked increases the energy by compressing the energy in time and the energy is best measured in joules.

51

Ophthalmology Explorer o

Dhaval Patel MD

Mode-locked laser compresses the laser more than Q-switched laser and therefore produces more energy.

Laser Mediums 

Solid state lasers have lasing material distributed in a solid matrix, e.g., the ruby or neodymium-YAG (yttrium aluminum garnet) lasers. The neodymium-YAG laser emits infrared light at 1.064 micrometers.



Gas lasers (helium and helium-neon, HeNe, are the most common gas lasers) have a primary output of a visible red light. CO2 lasers emit energy in the far-infrared, 10.6 micrometers, and are used for cutting hard materials.



Excimer lasers (the name is derived from the terms excited and dimers) use reactive gases such as chlorine and fluorine mixed with inert gases such as argon, krypton, or xenon. When electrically stimulated, a pseudomolecule or dimer is produced and when lased, produces light in the ultraviolet range.



Dye lasers use complex organic dyes like rhodamine 6G in liquid solution or suspension as lasing media. They are tunable over a broad range of wavelengths.



Semiconductor lasers, sometimes called diode lasers, are not solid-state lasers. These electronic devices are generally very small and use low power. They may be built into larger arrays, e.g., the writing source in some laser printers or compact disk players.

Laser Safety Classification The International Safety Classification of Lasers divides the lasers into 4 groups. Group 3 is subdivided into 3a and 3b. Class 3b and above is damaging to the eye and their powers are 5MW and above. All lasers used in ophthalmology are classed as 3b and above. Safety goggles should always be worn by people in the vicinity. Class I: Do not emit hazardous levels. Class II: Visible light lasers that are safe for momentary viewing but should not be stared into continuously; an example is the aiming beam of ophthalmic lasers, or laser pointers. Class III: Unsafe for even momentary viewing, requiring procedural controls and safety equipment. 52

Ophthalmology Explorer

Dhaval Patel MD

Class IV: Also pose a significant fire and skin hazard; most therapeutic laser beams used in ocular surgery are in this class

Latest Drugs



Lampalizumab: new monoclonal antibody that inhibits complement factor D, which is a ratelimiting enzyme of the alternative complement pathway, first positive treatment result for patients with dry age-related macular degeneration and geographic atrophy.



Pazopanib is a small molecule lipophilic potent and selective multitargeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/β, and c-kit that inhibits angiogenesis.







o

Pazopanib eye drops

o

5-10 mg/ml TID

o

failed to reduce as-needed ranibizumab injections by ≥ 50%

AGN-150998: o

Designed Ankyrin Repeat Proteins (DARPins)

o

Concept Study

o

Selectively binds to vascular endothelial growth factor-A with high binding affinity.

ROCK inhibitors:

o

Rho-kinase inhibitors (ROCK)  novel drug in glaucoma

o

human trabecular meshwork and Schlemm‘s canal cells to produce reversible changes in cell shape, focal adhesions and decreases in stress of the actin fibers. This resulted in an increase in permeability of the Schlemm cells‘ monolayer by 80%

o

decrease intraocular pressure by 25% to 32% and have a duration of action of 10 to 12 hours

o

ATS907, ATS8535, AR-12286, AR-13324, AMA0076

nitric oxide-donating prostaglandin F2-alpha analog  BOL-303259-X o

comparable to latanoprost 53

Ophthalmology Explorer



Dhaval Patel MD

Aganocides: novel class of compounds that mimic the body‘s natural defense against infection o

NVC-422  Phase IIb clinical trial to treat adenoviral conjunctivitis.



Voclosporin (Luveniq): novel immunomodulatory drug that inhibits the calcineurin enzyme, was originally developed to prevent organ graft rejection and to treat autoimmune diseases. The chemical structure of voclosporin is similar to that of cyclosporine A, but with a difference in one amino acid, leading to superior calcineurin inhibition and less variability in plasma concentration.



Mapracorat:



o

selective glucocorticoid receptor agonist (SEGRA)

o

similar anti-inflammatory and immunosuppressive effects as the glucocorticoids but with a decreased potential of the steroid side effects

o

Phase II study is evaluating its effectiveness in preventing the signs and symptoms of allergic conjunctivitis. In addition, a Phase III study is underway for the treatment of ocular inflammation after cataract surgery.

CF101: adenosine A3 receptor agonist o

Adenosine has been shown to inhibit leukotriene B4 (LTB4), which is part of the arachidonic acid cascade for the synthesis of prostaglandins and leukotrienes

o

For patients with moderate to severe dry eye



Lifitegrast: lifitegrast is a potent and selective small molecule drug being investigated for the treatment of dry eye and ocular allergy. It inhibits T-cell inflammation by blocking the binding of two key cellular surface proteins that mediate the chronic inflammatory cascade.



SMO Inhibitors (Smoothin): for advanced BCC o

Cyclopamine (SMO Inhibitors): 54

Ophthalmology Explorer

o





naturally occurring sterol alkaloid, topical drug is in clinical trials



it is obtained from Veratum calnifornicum (rocky mountain corn lily) ingestion of which causes serious malformation known as cyclopia and hence the name given cyclopamine

Vismodegib (GDC-0449): 

Synthetic small molecule



Orally active

o

Statins

o

Vitamin D3

Downstream SHH pathway inhibitors o

o

Rapamycin (sirolimus) 

Macrolide antibiotic



Inhibits MTOR in GLI1-transforme cells



No human stdies for BCC

MYCN anti-sence oligonucleotides 





No human studies for BCC

BRAF inhibitors: for Malignant Melanoma o

Sorafinib (pan BRAF)

o

PLX4032 (V600E-BRAF)

C-KIT inhibiors o



Dhaval Patel MD

Imatinib

Sutent: Sunitimab o

orally available multi-kinase inhibitor

o

Inhibits c-Kit, VEGFR, PDGFR etc

o

Activity against c-kit mutations that render OMs resistant to Gleevec 55

Ophthalmology Explorer o

Synergistic effects with radiation and chemotherapy

o

Combination of Sutent, tamoxifan, cisplatin



Tegretin (Bexarotene): for CTCL (Mycosis Fungoides)



FOVISTA: Binds PDGF-B, phase 3 trials going on for wet AMD and CNVM.



Natalizumab: alpha 4 integrin



NT- 501

Dhaval Patel MD

o intra-vitreal implant is a Ciliary Neurotrophic Factor (CNTF) secreting encapsulated cell device

o CNTF is a cytokine, which is a survival factor for various neuronal cells and seems to prevent neurodegeneration. o

CNTF may act through the IL-6 receptor.

o A semi-permeable membrane encapsulates genetically engineered human RPE cells that secrete CNTF. It prevents host antibodies and immune cells from entering the device but allows nutrients to diffuse in, to nourish the cells within and CNTF to diffuse out. This holds promise for retinitis pigmentosa and dry age related macular degeneration



Bevasiranib (CAND5) is a siRNA which switches off VEGF production, but clinical effect is not seen till the preexisting VEGF is cleared. It has a potentially longer duration of effect than currently available anti-VEGF agents. It is well tolerated at multiple doses.



Vatalanib is a VEGF receptor tyrosine kinase inhibitor given orally.



Fenofibrate is drug of the fibrate class used to treat dyslipidemia. Raises HDL and lowers LDL and triglycerides and typically is used in combination with a statin. It lowers lipid levels by activating peroxisome proliferator-activated receptor alpha (PPARα). PPARα activates lipoprotein lipase and reduces apoprotein CIII, which increases lipolysis and elimination of triglyceride-rich particles from plasma.



Fenretinide in Dry AMD: This drug is an oral vitamin A binding protein antagonist and is being studied in patients with geographic atrophy (GA).It halts the accumulation of retinol (vitamin A) toxins through affinity for retinol-binding protein. One of the hallmarks of dry macular degeneration is the accumulation of lipofuscin that is responsible for drusen formation and geographic atrophy. One year interim data showed that fenretinide slowed the growth of geographic atrophy lesions by 45% in the 300 mg dose. 56

Ophthalmology Explorer

Dhaval Patel MD



Copaxone (glatiramer acetate): weekly vaccination, Macular degeneration, Alzheimer‘s disease and Multiple sclerosis



Citicholine (Cytidin-5-diphposphocholine): It is similar in action to levodopa. When administered in adult patients with strabismic amblyopia (1gm\day i.m for 15 days), it has showed improvement lasting over 6 months including improvement in contrast sensitivity and VEP.

Mechanism of Action 

Local anesthetics block the generation and conduction of nerve impulses



General Anesthetics: multiple



Fluoroquinolones: bactericidal agents that act by inhibiting DNA replication. They have dual targets, topoisomerase II (DNA gyrase) and topoisomerase IV



Tetracyclines: broad-spectrum antibiotics that inhibit bacterial protein synthesis by binding to the 30-S ribosomal subunit of the bacteria



Aminoglycosides: inhibit bacterial protein synthesis by binding irreversibly to the bacterial 30S ribosomal subunit.



Glycopeptides (Vancomycin and teicoplanin): inhibit peptidoglycan synthesis in the bacterial cell wall by complexing with cell wall precursors



Macrolides: bacteriostatic agents that inhibit bacterial RNA-dependent protein synthesis by binding reversibly to the 23S tRNA of the 50S ribosomal subunits



Chloramphenicol: bacteriostatic agent that inhibits protein synthesis by binding reversibly to the peptidyltransferase component of the 50S ribosomal subunit and prevents the transpeptidation process of peptide chain elongation



SMX-TMP: competitively inhibit the bacterial modification of p-aminobenzoic acid into dihydrofolate, and trimethoprim inhibits bacterial dihydrofolate reductase



Bacitracin and gramidicin: Bacitracin disrupts bacterial cell-wall synthesis by inhibiting the dephosphorylation of a lipid pyrophosphate, while gramicidin interferes more with cell membrane permeability



Polymyxins: interact with the phospholipids of the bacterial cell membrane, which increases the cell permeability and disrupts osmotic integrity. This process results in leakage of intracellular constituents, leading to cell death 57

Ophthalmology Explorer

Dhaval Patel MD



Trifluridine: potent inhibitor of thymidylate synthetase and therefore inhibits DNA synthesis



Vidarabine: interfere with the early steps of viral DNA synthesis and arrests the growth of the viral deoxynucleotide chain



Acyclovir: inhibits viral dependant TK (thymidine kinase)



Ganciclovir: competition with deoxyguanosine for incorporation into viral DNA



Polyenes: binds esterols in the fungal cell wall, forming ‗blisters‘ and causing lysis of the cell



Imidazoles: affect the formation of ergosterol needed by the cell membranes by inhibiting the enzyme lanosterol 14 α-demethylase



Caspofungin: inhibits synthesis of B(1,3)-D glucan,a component of fungal cell wall

MIP 

major intrinsic membrane protein



The most abundant membrane protein of the lens is intrinsic membrane protein 26 (MP26, MIP). It is a lens-specific single polypeptide with a molecular mass of 28,200 kDa (263 residues) that makes up about 50% of the lens membrane protein.



MIP26 is a member of the aquaporin (AQP) family, members of which transport small molecules such as water and glycerol.



MIP26 is termed aquaporin O



A locus for autosomal dominant cataracts has been mapped to chromosome 12q12-14.1 near the MIP gene

MMPs 

MMP 1: collagen 1,2,3



MMP 2,9: collagen 4,5,7 and laminin



MMP 3: GAGs and Fibronectin



Only MMP 2 is found in normal cornea.

58

Ophthalmology Explorer

Dhaval Patel MD

Molecular Weights 

Sodium fluorescein: 376.27 daltons



Indocyanine green: 775 daltons



VEGF: 45kDa



Bevacizumab: 149 kDa



Ranibizumab: 48 kDa



Sodium Hyaluronate: 2–5 million d



Chondroitin Sulfate: 50,000 d



Silicone oil: 28,000 (1,000 centistokes)



Air: 29



Sulfur hexafluoride (SF6): 146



Perfluoroethane (C2F6): 138



Perfluoropropane (C3F8): 188



PMMA IOLs: 2.5 to 3 million Da



Acylic IOLs: 80 000 to 140 000 Da



Botulinum toxin: 900 000 Da

MUCins 

Mucins are classified by the nomenclature MUC1–21 and are divided into secreted and membrane-spanning categories o

Membrane-spanning mucins consist of a short intracellular tail, membranespanning domain, and large, extended extracellular domain that forms the glycocalyx.

o

Secreted mucins are either gel-forming or small soluble. 

Gel-forming mucins are large molecules (20–40 million Da) secreted by exocytosis from Goblet cells.



Small soluble mucins are secreted by the lacrimal gland. 59

Ophthalmology Explorer

Dhaval Patel MD



MUC 1, MUC 4, and MUC 16: apical surface of the corneal epithelium



MUC 5AC and MUC 2: aqueous layer of the tear film (membrane-spanning, gel-forming mucins)



MUC16 protein levels decreased in conjunctival epithelium and increased in tears of patients with Sjogren's syndrome



MUC1 splice variants also play a role in dry eye



MUC5AC is the gel-forming mucin forming mucous layer backbone

NV %

BRVO NVI: 1 NVD: 10 NVE: 30

Ischemic BRVO 40% of patients with an ischemic BRVO develop NVE or NVD. 60% of the patients with NVE-NVD develop VH/PRH.

Ich CRVO NVI: 50 NVD: 30-35 NVE: 20-25 NVG: 45

CRAO 60

Ophthalmology Explorer

Dhaval Patel MD

NVI: 20 NVD: 2

OIS NVI: 67 NVD: 35 NVE: 8

EALES‘ DISEASE NVI: 0.5-0.8 % NVD: 10-18 % NVE: 50 % Sec RRD: 8-11 %

OCT Review 





Time Domain OCT (TD-OCT) o

Light echoes from each time delay measured sequentially

o

Slow acquisition speeds, high signal-to-noise ratio, poor view of the choroid

o

400 A-scans per minute, 6 B-scans per macula, 10-μm resolution

Spectral Domain OCT (SD-OCT) o

Light echoes from each time delay, all measured simultaneously (high-speed spectrometer)

o

Fast acquisition speeds, low signal-to-noise ratio, view to the choroid possible

o

52,000 A-scans per minute, 20-40 B-scans per macula (up to 100), 5-μm resolution

Enhanced Depth Imaging OCT (EDI-OCT) 61

Ophthalmology Explorer





Dhaval Patel MD

o

Zero delay line (ZDL) positioned at the inner retina

o

The further from the zero-delay line (ZDL), the lower the signal resolution.

o

EDI moves the ZDL closer to the choroid; negative images when the ZDL is crossed.

o

Thinner layers permit deeper tissues to be closer to the ZDL.

Full Depth or Combined Depth Imaging OCT (CDI-OCT) o

100 B-scans averaged for a single line scan.

o

50 in standard SD-OCT mode and 50 in EDI mode

o

Maximizes resolution of vitreoretinal and choroidal structures in a single scan

Swept Source OCT o

Topcon DRI OCT-1 Atlantis

o

Longer wavelength light source (1050 nm)

o

Fast (100,000 A scans per second)

o

Uniform sensitivity, allowing excellent visualization of structures from vitreous to sclera in one scan

o

Automated segmentation (7 layers)

o

100,000 A-scans per second, 1-μm resolution

o

12-μm wide scans (vs. 9- and 6-μm scans)

o

Image depth of 2.6 mm vs. 1.9 mm for EDI—even more ideal for choroidal tumors

Optic Nerve Segments

Longest segment  intraorbital Shortest segment  intraocular Segment with the most variable length  intracranial Divided into three subsegments  intraocular Most vulnerable to indirect trauma  intracanalicular 62

Ophthalmology Explorer

Dhaval Patel MD

Most redundant segment  intraorbital The only segment not bathed in cerebrospinal fluid  intraocular

Orders of Abberations

0. Piston 1. Vertical and horizontal prisms 2. Myopia (positive defocus), hyperopia (negative defocus), Regular (cylindrical) astigmatism 3. Coma, trefoil 4. Spherical astigmatism 5. rosette 6. pentacle, axial coma

Percentages % Primer



50% of patients with scleritis have systemic disease



Steroid-induced increases in intraocular pressure occur in about 6% of patients on topical dexamethasone



30–50% of individuals with glaucomatous optic nerve damage and visual field loss have an initial intraocular pressure measurement less than 22 mmHg.



sporadic inheritance of aniridia need to be evaluated for Wilms‘ tumor, which is associated with 25% of cases.



BCC 3% mortality rate



83% of macular holes are idiopathic, and 15% are due to some sort of trauma



Deuteranomaly is present in approximately 5% of the population; deuteranopia, protanopia, and protanomaly in 1% each; and tritanopia or tritanomaly in only 0.002%. 63

Ophthalmology Explorer

Dhaval Patel MD



ACUTE ACG: 40–80% chance of an acute attack in the fellow eye over the next 5–10 years.



PPMD: Glaucoma is associated in 15%.



Axenfeld‘s syndrome is the anomaly with coincident glaucoma in 50% of cases.



Glaucoma in hyphema: Secondary glaucoma occurred in o

13.5% of those eyes in which blood filled half of the anterior chamber,

o

in 27% of those eyes in which blood filled greater than half of the anterior chamber, and

o

in 52% of those eyes in which there was a total hyphema.



Angle recession is found in 60–90% of patients with a traumatic hyphema



Up to 10% of patients with greater than 180 degrees of angle recession will eventually develop a chronic traumatic glaucoma



Expulsive choroidal hemorrhage after cataract surgery: 0.2%



Retinal detachment after cataract surgery: 1–2%



PCO: 8-50%



HLA-B27–associated conditions account for approximately 45% of acute NGAU.



The incidence of HLA-B27 in the general population is 8%.



HLA B27 is present in 90% of patients with AS and 80% of those with Reiter‘s disease.



16% of patients of intermediate uveitis may develop multiple sclerosis



Sympathetic ophthalmia incidence: o

perforating ocular injury (0.2%)

o

ocular surgery (0.01%)

o

80% of cases develop within 3 months of injury, and 90% develop within 1 year.



Among patients whose CD4+ count is less than 50 cells/mL, 20% per year develop CMV retinitis.



A daily dose of >8 mg/kg/day of hydroxychloroquine produces retinopathy in 40% of cases.



Posttraumatic endophthalmitis incidence after penetrating ocular trauma: 7% of cases 64

Ophthalmology Explorer

Dhaval Patel MD



complement factor H gene is a single nuclear polymorphism responsible for nearly 50% of ARMD risk.



90% of infants who develop acute ROP undergo spontaneous regression



The risk of bilaterality in retinal arterial obstruction is approximately 10%.



Approximately 10% of patients with a BRVO will develop a retinal vein occlusion in the fellow eye.



The prevalence of endophthalmitis is 1.4% after intravitreal triamcinolone injection. However, this also includes cases of pseudoendophthalmitis. Excluding pseudoendophthalmitis, the prevalence is approximately 0.6%.



The cilioretinal artery is present in up to 20% of individuals.



In uveal melanoma, if no epithelioid cells are present, the expected survival at 15 years is 72%. If epithelioid cells are present (mixed, epithelioid, or necrotic cell type), the survival at 15 years drops to 37%.



Liver metastases occur in 93% of patients who develop metastatic uveal melanoma. Other sites include the lungs (24%) and bone (16%).



15% of eyes with symptomatic PVD develops retinal tear.



Untreated symptomatic retinal tear causes RD in 35-50% cases.



Pharyngoconjunctival fever: 30% keratitis Epidemic keratoconjunctivitis: 80% keratitis

Phacomatosis The 9 Phacomatosis: (there are total 9 phacomatosis which are numbered as follow)

1. neurofibromatosis type I - autosomal dominant - chromosome 17 2. NF type II - autosomal dominant - chromosome 22 3. tuberous sclerosis – autosomal dominant - chromosome 9 4. Sturge-Weber's syndrome – sporadic 65

Ophthalmology Explorer

Dhaval Patel MD

5. von Hippei-Lindau's syndrome - autosomal dominant - chromosome 3 6. Louis-Bar syndrome-autosomal recessive - chromosome 11 7. Wyburn-Mason syndrome - sporadic 8. Klippel-Trenaunay-Weber syndrome – autosomal dominant – chromosome unknown 9. cutis marmarata telangiectasia congenita - sporadic.

Phakomatosis is an outdated term and concept and term. Neither the AAO‘s monograph on Inherited Diseases and the Eye (Traboulsi) nor the WHO‘s text on CNS Tumors includes the term in the index. The WHO lists the disorders as familial cancer syndromes

Principles



CSLO: light projected toward the plane of interest through a conjugated set of pinholes allows the light to reach the detector only from the desired plane, while light coming from all other locations is blocked.



4 Δ prism test: Hering law and convergence, this test differentiates bifoveal fixation (normal BSV) from a central suppression scotoma (CSS) in microtropia.



Faden procedure: suture the muscle belly to the sclera posteriorly so as to decrease the pull of the muscle in its field of action without affecting the eye in the primary position.



VEP: recording of electrical activity of the visual cortex created by stimulation of the retina.



Laser: Stimulated emission of a photon of electromagnetic radiation



Nd-YAG: photodisruption.



Pinhole: It decreases size of blur circle. A narrower pupillary aperture decreases the angle of the cone of light that produces the blur circle. Ultimately the blur circle, albeit dimmer, is the size of the limiting cluster of photoreceptors (i.e., pixel-size or grain-size equivalent). A stenopeic slit may be considered as a line of pinholes.



Jackson Cross-Cylinder (JCC) test: placing the circle of least confusion on the retina



Keratometer: The cornea (with its overlying tear film) acts as a convex mirror to produce a virtual, erect image of the ring. The size and position of the virtual image are measured 66

Ophthalmology Explorer

Dhaval Patel MD



Scheiner‘s disc: Light enters the two pinholes and produces two images on the retina until the light is brought to a focus.



OPD-Scan optical path difference scanning system: dynamic SkiaScopy and involves acquisition of 1440 data points to produce a map of the optics of the whole eye



Allegretto wave analyzer: Tscherning principle of wavefront sensing.



Hartman-Shack devices: direction of propagation of light rays will be perpendicular to the wavefront.



Non-contact pachymeters: optical low – coherence reflectometry

Radiation and Eye 

The most sensitive ocular structure is the lens. (The minimum cataractogenic dose was 5.5 Gy and the maximum noncataractogenic dose was 11 Gy)



The sclera is the most resistant: easily tolerating >1000 Gy. Even up to 5000 Gy has been given to the sclera without causing perforation



lacrimal gland, cornea, and conjunctiva: can tolerate up to 50 Gy (5000 rad) of radiation



retina tolerates: >55 Gy o

The retinal pigment epithelial (RPE) cells were more radioresistant than photoreceptors and RPE cell loss was only observed at doses of more than 1500 cGy

o

Most radioresistant in retina: Ganglion cell layer (?)

Rates 

Aqueous humor production: 2 to 2.5 µL/min o



Approximately 1% of the anterior chamber and 1.5% of the posterior chamber volume of aqueous humor are replaced each minute

Outflow facility of fetal eyes: o

0.09 µl/min/mmHg before 7 month 67

Ophthalmology Explorer



o

0.3 µl/min/mmHg at 8 months

o

Average human value for C: 0.28 µl/min/mmHg.

Dhaval Patel MD

Pseudofacility: o

0.06 µl/min/mmHg

o

20% of the normal human C value



Uveoscleral pathway: 0.5 µL/min



Tear fluid production: 1.2 µL/minute



Choroidal blood flow: 800 to 2000 mL/min/100 g of tissue



blood flow for the entire retina: 80 ± 12 µL/min



Tear Evaporation: o

Normally: 0.14 µL/min

o

In dry eye: 0.43 µL/min

Recurrence % 

Weiss procedure (transverse tarsotomy) alone for entropion: 11%



Pterygium Surgeries o

Bare sclera type procedure for pterygium: 8% to 94%

o

Sliding Flaps for pterygium: 5%

o

Free flaps: 5%

o

Thiotepa: 11%

o

beta radiation:0% to 16%



surgical excision of CNV in pterygium: 38%



secondary membrane after Nd:YAG capsulotomy: 34-57%



meningioma: 22% 68

Ophthalmology Explorer 

idiopathic facial nerve palsy: 12%



Epithelioid sarcoma: 66%



IOID: 21% to 52%



orbital hemangiopericytomas: 30% upto 7 years



epithelioid hemangioma after surgical excision: 33%

Dhaval Patel MD

Refractive Indices 

Water: 1.33



Cornea: 1.375 (for power calculation it is fudged to 1.337 to take into account negative posterior curvature)



Aqueous 1.336



Lens cortex 1.386



Lens core 1.406



Vitreous 1.336



silicone oil: 1.400 and 1.405



PFCL: 1.27-1.33



IOLs o

Silicon IOLs: 1.33 

1st generation  Polydimethylsiloxane: 1.41



2nd generation  Polydimethyl diphenyl siloxane: 1.46



3rd generation  Biosil: 1.43 (Crystalens)

o

PMMA IOLs: 1.49

o

Acrylic IOLs: 1.55 69

Ophthalmology Explorer



o

STAAR Surgical Collamer IOL, ICL: 1.45

o

CeeOn: 1.46

o

Array lens by AMO: 1.46

o

Akkommodative 1CU: 1.46

o

ThinLens (ThinOptX): 1.47 (acrylic)

o

Crystalens: 1.43

o

SmartIOL: 1.47

o

Light-Adjustable Lens: 1.43 (silicone)

o

Medennium Phakic Refractive Lens: 1.46

Dhaval Patel MD

Glasses o

Crown glass: 1.52

o

CR-39: 1.49

o

Polycarbonate: 1.58

o

Flint glass: 1.66

Resolutions 

Slit Lamp: 20 μm (Transverse)



Specular microscope: 2-5 μm (Lateral and Axial)



Confocal microscope: 1-2 μm (lateral), 5-10 μm (axial)



ASOCR: 18 um (axial), 60 um (transverse)



Stratus TD OCT: 8-10 um (axial), 20 um (transverse)



Cirrus FD/SD OCT: 5 um (axial), 16 um (transverse)



HR-OCT: 3 um (axial), 10 um (transverse)



SL-OCT: 15 um abnormal Elevation on posterior float: 17-20 um suspicious, >20 um abnormal



After placing INTACS, cornea becomes more prolate.

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Keratitis with lid lesions: zoster, chickenpox, molluscum contagiosum, and ulcerative blepharitis with keratitis caused by staphylococcal infection. Keratitis without lid lesions: vaccinia, adenoviral infections (types 3, 7, and 8 and 19), chlamydial infections, herpes zoster and Epstein-Barr keratitis.



Papillae in lower fornix are generally not found in vernal conjunctivitis.



Common causes of DLK are: Meibomitis, bacterial endotoxin, marker ink, microkeratome blade debris, preservatives in drops, interface hemoglobin.



Important complication of trachoma is dry eye due to fibrosis of the upper fornix affecting accessory lacrimal glands.



In angular conjunctivitis caused by Moraxella axenfield diplo bacillus, maceration of skin is due to proteolytic enzymes secreted by the bacillus.



The cornea magnifies the image of iris by 10%.



Hirschberg‘s sign: Pale round spots (Koplik spots) on conjunctiva and caruncle in measles



Basal tear secretion = 2 μL/min



Keratinization of the caruncle is a common early sign of mucous membrane pemphigoid.



In GPC, In contrast to VKC, keratopathy is rare due to less secretion of toxic cytokines. 162

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In SJS, contrast to ocular pemphigoid, immunosuppression is not required prior to conjunctival or lid surgery.



In PUK, Unlike Mooren ulcer the process may also extend to involve the sclera.



Rizutti‘s sign: Triangle of light on iris from oblique penlight beam focused by cone in keratoconus



In Thygeson superficial punctate keratitis, conjunctiva is uninvolved and vascularization is not a feature. The most common differential diagnosis is staphylococcal hypersensitivity, punctate epitheliopathy or adenoviral keratitis.



Central cloudy dystrophy of François is similar to crocodile shagreen but is differentiated by its posterior location and AD inheritance.



Kayes‘ dots: Subepithelial infiltrates in corneal allograft rejection



Khodadoust line: Corneal graft endothelial rejection line composed of inflammatory cells



Deficiency of the mucin layer may be a feature of both aqueous deficiency and evaporative states. Goblet cell loss is associated with cicatrizing conjunctivitis, vitamin A deficiency, chemical burns and toxicity to medications.



Follicles are usually seen in viral and chlamydial Conjunctivitis. F-VC Trachoma Acute follicular conjunctivitis 163

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Dhaval Patel MD

Chronic follicular conjunctivitis Benign (School) folliculosis

Papillae are usually seen in allergic and bacterial conjunctivitis. P-AB Trachoma Spring catarrh Allergic conjunctivitis Giant papillary conjunctivitis



Epithelial downgrowth has been reported most commonly as a complication of cataract surgery, but it can occur after penetrating keratoplasty, glaucoma surgery, penetrating trauma, and partial removal of epithelial cysts of the anterior segment. Irradiation and photocoagulation have been abandoned as ineffective. Excision of involved iris tissue with cryotherapy to remaining corneal membranes is currently the best technique, although good vision is maintained in only a few cases. Prevention is much more effective than the treatment of established disease.



Keratoconus is rare in diabetes. Diabetes, Aging and Smoking increases corneal collagen cross linking just like C3R.



Membrane on conjunctiva: o

o

True membrane: 

Greyish white dense membrane covering both the bulbar and palpebral conjunctiva



Densely adherent, bleeds on attempting to remove



Corynebacterium Diphtheria

Pseudo membrane:

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Whitish membrane, not as dense, irregularly covering bulbar and palpebral conjuoctiva.



Not as densely adherent, comes off comparatively easily



Streptococcus pyogenes



Infectious Crystalline Keratopathy ICK is most commonly seen after  post keratoplasty.



MCC of ICK is streptococcus viridans.



The corneal endothelium and stroma are derived from the neural crest, but the epithelium is derived from surface ectoderm.



Keratoconus is typically associated with Marfan's syndrome. Keratoglobus is typically associated with Ehlers-Danlos syndrome.



In congenital hereditary stromal dystrophy, the cloudy stroma is of normal thickness, and the epithelium is normal. In congenital heriditary endothelial dystrophy (CHED), there is epithelial edema and a thickened stroma. In both conditions, intraocular pressure (IOP) is usually normal.



Arcus senilis shows deposition of lipid in all layers of cornea.



The limbal lesions in vernal keratoconjunctivitis are more papilliform because they have a central vascular core. When a central pit full of degenerated eosinophils forms, the term Horner-Trantas dot is applied.



Horner-Trantas dots are clumps of degenerated eosinophils, whereas Herbert's pits are depressed, necrotic follicles at the limbus. 165

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Small changes in corneal shape do occur throughout life: o

In infancy, the cornea is fairly spherical

o

In childhood and adolescence, probably due to eyelid pressure on a young tissue, cornea becomes slightly astigmatic with the-rule (WTR)

o

In the middle age, cornea tends to recover its sphericity

o

Late in life, against-the-rule (ATR) astigmatism tends to develop.



Unlike Scheimpflug based topographers, Placido-based topographers measure angle kappa.



The cornea transmits radiation from approximately 310 nm in the ultraviolet to 2500 nm in the infrared region. The cornea is extremely sensitive to UV radiation at 270 nm and corneal absorption of this radiation results in photo keratitis after exposure to welding arcs.



Conjunctival papillae form whenever there is conjunctival swelling of any cause in certain areas. The tarsal and limbal conjunctiva is unique because their subepithelial substantia propria contains fibrous tissue septa that interconnect to form polygonal lobules with a central vascular bundle. Any inflammation in these regions will result in papillae. Papillae 1 mm in diameter (giant papillae), they are more specific. Most young people with healthy eyes will have small conjunctival papillae along the superior margin of the upper tarsus



Conjunctival follicles represent focal lymphoid aggregates in the substantia propria.



In GPC, the inferior fornix is generally the least involved, whereas in viral conjunctivitis, it tends to be the most severely involved.

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Follicular conjunctivitides are typically more severe inferiorly than superiorly except for trachoma. This is in stark contrast to inclusion conjunctivitis, another chlamydial disease, which is more severe inferiorly.



Neonatal inclusion conjunctivitis may be pseudomembranous or membranous, but this is rare in adults.



Typical microcystic corneal epithelial edema is in the intercellular space and results from an imbalance between corneal turgescence (swelling due to intraocular pressure [IOP]) and deturgescence (drying due to endothelial pumping). Intracellular epithelial edema does occur, as a result of epithelial hypoxia, but this appears different clinically— as a fine, frosted-glass appearance (Sattler's veil), generally associated with contact lens use.



Sattler‘s veil: Superficial corneal edema (bedewing) caused by hypoxia (contact lens)



Development of corneal epithelial filaments—increased mucus production along with increased, deranged epithelial turnover. The filaments themselves are composed of mucus and desquamated epithelial cells.



KPs: Lymphocytes & PMNs Mutton-fat KPs: Macrophages, greasy look



Endophthalmitis rates are higher with laser-assisted in situ keratomileusis (LASIK) than with photorefractive keratectomy (PRK). LASIK does offer a reduced incidence of stromal haze and more rapid epithelial healing. Photorefractive keratectomy (PRK) can have significant postoperative pain. PRK offers a reduced incidence of endophthalmitis and corneal perforation.

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fluorescent treponemal antibody-absorption (FTA-ABS) and microhemagglutination of Treponema pallidum (MHA-TP), are the closest to a ―gold standard‖ for syphilis testing. The Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR) tests reflect treponemal infection and revert to normal when treated. The value of these tests is primarily to monitor response to treatment because they are less sensitive and specific. The fluorescent treponemal antibody (FTA) and microhemagglutination of Treponema pallidum (MHA-TP) offer greater sensitivity and specificity and do not normalize with treatment. They are lifelong markers of previous or active treponemal infection.



Fusarium has septate hyphae, whereas Mucor has nonseptate hyphae.



Intranuclear inclusion bodies of herpes simplex virus (HSV) epithelial infection: Lipschütz bodies (Papanicolaou (Pap) smear)



multinucleated giant cells seen in epithelial herpes simplex virus (HSV) infection: Tzanck prep (Giemsa stain)



A granulomatous reaction to Descemet's membrane (including multinucleated giant cells) is most frequently seen with disciform keratitis with a history of herpes simplex or herpes zoster keratitis. This peculiar reaction to Descemet's membrane may be related to an altered antigenicity of the membrane and subsequent development of an autosensitivity reaction. This reaction is very uncommon with other etiologic agents.



There are five anti-Epstein-Barr virus (EBV) antibodies: 1. viral capsid antigen (VCA)-IgG 2. VCA-IgM 3. early antigen-diffuse (EA-D) 4. EA-R (early antigen-restricted) 5. Epstein-Barr nuclear antigen (EBNA) Only EBNA does not peak in the first 6 to 8 weeks of infection. 168

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Viral capsid antigen (VCA)-IgG and Epstein-Barr nuclear antigen (EBNA) provide lifelong evidence of Epstein-Barr virus (EBV) infection.



Like bacteria (and unlike viruses), chlamydiae have both DNA and RNA, replicate by binary fission, have lipopolysaccharide cell walls, and respond to certain antibiotics. Unlike bacteria, chlamydiae do not possess all organelles and require a host cell for replication.



Difficult to culture: lyme dz, chlamydia, acanthameba



Double walled cyst appearance: acanthameaba



In neonatal inclusion conjunctivitis, the likelihood of finding cytoplasmic or intranuclear inclusions is higher than adult one.



Acyclovir is activated by viral thymidine kinase and is relatively nontoxic to mammalian cells. Trifluridine (Viroptic) inhibits another virus-specific enzyme, thymidylate synthetase.



Acyclovir is not effective against CMV.



presumed filamentous keratomycosis: topical natamycin TOC



Amphotericin has less predictable activity against filamentous species than natamycin.



polyene class: renal toxicity (POLY-uria) imidazole: hepatic (ICTerus)



Suspensions must be shaken to be effective. Acetate preparations (suspensions) are more potent than phosphate preparations. 169

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Local steroids do not reactivate latent virus, but caution should be exercised because intermittent shedding of the virus from the trigeminal ganglion (unrelated to steroid use) may coincide with steroid use and exacerbate subsequent disease.



Pedunculated conjunctival papillomas are generally associated with human papilloma virus (HPV) types 6 and 8. sessile conjunctival papillomas are associated with HPV-16 and HPV-18.



Blephroconjunctivits: Collarettes indicate Staphylococcus. Scurf indicates seborrhea. Sleeving of the lashes is a sign of Demodex infestation.



The most common cause of phlyctenulosis is Staphylococcus, followed by active or latent tuberculosis.



Neisseria gonorrhoeae is the only bacterial conjunctivitis that causes preauricular adenopathy.



Gonococcal conjunctivitis: ceftriaxone 1 g intramuscularly daily for 5 days and doxycycline orally twice daily for 3 weeks. Doxycycline (or tetracycline) is added to treat potential chlamydial infection (sexually transmitted diseases tend to run together).



Although neonatal inclusion conjunctivitis usually responds to topical therapy, systemic erythromycin is recommended because of associated chlamydial infections, such as otitis media and pneumonitis.



Topical antihistamines do not work well in atopic keratoconjunctivitis; systemic antihistamines are critical for its control. 170

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SAC & VKC: SAC response to topical antihistamines & has giant papillae



Type 2 herpes usually resides latently in spinal ganglia.

Dhaval Patel MD

Type 1 herpes: The gasserian (or trigeminal) ganglion, located in Meckel's cave, contains the cell bodies of the trigeminal nerve.



Wessely's ring: circular, superficial distribution of neutrophils around an area of corneal edema or inflammation. It is identical to the immunoprecipitate formed in the Ouchterlony gel.



Topical steroids in disciform keratitis: 1. the visual axis must be involved 2. neovascularization must be progressing



Reactivation and not Reinfection has been reported to lead to typical herpes zoster ophthalmicus (HZO).



Postherpetic neuralgia: oral TCA & Steroids (7 to 10 days after eruption of active dermatitis)



Herpes zoster ―dendrites‖ (pseudodendrites) are typically smaller and less branching than their simplex counterparts.



Cogan's syndrome is frequently associated with polyarteritis nodosa.



About one half of patients with superior limbic keratoconjunctivitis (SLK) have some form of thyroid disease. 171

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Treatment of the thyroid disorder, however, has little effect on the SLK. A recent study suggests that orbital decompression for thyroid optic neuropathy is required more frequently in patients with thyroidassociated SLK. steroids are not effective therapy for superior limbic keratoconjunctivitis (SLK). Surgical resection of the superior bulbar conjunctiva is definitive.



Episcleritis rarely progresses to scleritis; however, episcleritis nearly always accompanies scleritis. o

Generally, episcleritis causes minimal pain, whereas scleritis is moderately to severely painful.

o

Episcleritis is usually of rapid onset as opposed to scleritis, which is usually gradual, over days.

o

In scleritis, the scleral (deep episcleral) plexus is immobile and bluish-red in color; episcleritis appears salmon pink.

o

Scleral vessels do not blanch with phenylephrine, as do those in episcleritis.

o

Lastly, scleritis is frequently seen with systemic connective tissue disorders; this is not true of episcleritis.



Posterior uveitis occurs in virtually all patients with posterior scleritis and is not uncommon in patients with anterior scleritis. Anterior uveitis occurs in about one third of all patients with scleritis.



Chronic dacryoadenitis is sometimes accompanied by inflammation and swelling of the salivary glands, which is referred to as ―Mikulicz's syndrome.‖



Silent dacryocystitis is usually produced by Streptococcus pneumoniae and may present with no clinical symptoms other than occasional epiphora.



Eyes without any astigmatism will not have any wavefront aberration. Wavefront analysis is used to analyze irregular astigmatism. 172

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Dhaval Patel MD

Munnerlyn's formula: The ablation depth (in microns) is equal to the diopters of myopia divided by 3 and multiplied by the square of the optical zone (in millimeters). It is most useful with low amounts of correction ( macular > granular > lattice



Corneal dystrophy associated with glaucoma: PPCD



TC- 199 = tissue culture medium 199



Riboflavin is hydrophilic solution so during C3R, ideally epithelium should be removed.



The Athens Protocol: The management of keratoconus and post-LASIK ectasia by means of combined, same-day, topography-guided partial PRK and collagen cross-linking.



The excimer laser was originally applied to the cornea to produce more accurate RK incisions, not for surface ablation or laser in situ keratomileusis (LASIK), for which the excimer laser is now used. 177

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Dhaval Patel MD



Arcuate keratotomy differs from LRIs by its midperipheral location and its greater relative depth.



Studies have demonstrated that up to 15° of cyclotorsion can occur when patients move from an upright to a supine position.



Ligneous conjunctivitis is actually a genetic disease. It results from homozygous mutations in the PLG gene (6q26) that codes for plasminogen and therefore is inherited in an autosomal recessive pattern. Tears contain plasminogen activators that convert plasminogen into the fibrinolytic enzyme plasmin which normally clears conjunctival and corneal fibrin deposits. The lack of normal plasminogen allows fibrin to accumulate on all mucosal surfaces.



Pingecula are histologically ACTINIC ELASTOSIS.



Concretions are collection of inspissated protein within the pseudoglands of henle.



Most accurate method for RSBT measurement: intraoperative measurement after creating flap by UBM.



Corneal infection with bloody looking perfotation  Moraxella



McCoy cell culture is highly specific for TRIC.



Tobramycin is better than gentamycin only in pseudomonas, but as pseudomonas is one of the infections we should worry about, we start generally tobramycin instead gentamycin. If you are sure that it‘s not going to be pseudomonas, you can start gentamycin also.

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Dhaval Patel MD

Tsukamurella keratitis o

gram-positive bacilli

o

severe eye pain, typical of bacterial keratitis

o

infiltrates in the peripheral parts of the cornea near the limbus, resembling that of marginal keratitis.

o

relatively less virulent nature

o

microtrauma to the epithelial surface of the cornea

Corneal Nerves o

o

Prominent corneal nerves: 

Keratoconus.



Ichthyosis



Fuchs corneal (Reis-Buckler's ) dystrophy



Corneal edema



Congenital glaucoma



Acanthamoeba Keratitis



corneal graft failure.



Trauma.



Idiopathic.

Enlarged Corneal Nerves: 

MEN IIb



Phytanic acid storage dis (Refsum syndrome).



Hansen dis (leprosy,beading of nerves



Familial dysautonomia(Riley- Day)



Neurofibromatosis.



Acanthamoeba perineuritis. 179

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Dhaval Patel MD

primary amyloidosis



sequential sector conjunctival epitheliectomy (SSCE): for partial LSCD involving the visual axis



Corneal Hysteresis: measure of viscous damping of cornea



Corneal resistance Factor: measure of resistance/rigidity of cornea



Boston scleral lens= PROSE: Prosthetic Replacement of the Ocular Surface Ecosystem, sed for irregular corneas



Concentration of riboflavin for C3R: 0.1%, in 20% dextran, 30 min, 370 nm, 3 mW/cm2



In corneal blood staining, hemoglobin products accumulate in corneal stroma. (not RBCs)



Progression of bacterial corneal ulcers: Proteases released by bacteria



Most stable flap in femtosecond laser: zig-zag



Flat cornea: 50D, Buttonhole, thin flap



Q value: Corneal asphericity o

By applying certain mathematical equations, eccentricity can be calculated and given a value from which Q-value can be derived. 180

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Dhaval Patel MD

o

Positive: center of the cornea is flatter than the periphery, oblate cornea

o

Zero: center equals the periphery, sphere cornea

o

Negative: center is steeper than the periphery, prolate cornea

o

Q-value is considered normal when it falls between 0 and -1 [-1, 0].



PPMD: AD, incomplete penetrance, variable expression, 20q11



Macular dystrophy: hypo/non-sulfated keratin



Bacterial ulcer simulating fungal ulcer: Hyphate edges, satellite lesion o

Nocardia: calcerous bodies

o

Actinomyces

o

Streptomyces



Corneal sensations are normal in adenoviral keratitis.



Goblet cells are most dense in inferonasal quadrent.



Acanthameba transport media: page‘s medium Virus transport medium: Hank‘s medium Chlamydia transport medium: 0.2M sucrose phosphate medium



w3 fatty acid  anti inflammatory products like PGE3, LBT5 w6 fatty acid  pro inflammatory prodcts like PGE1, PGE2, LBT4



HBID: Hereditary benign intraepithelial dyskeratosis 181

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o

Also called Witkop von Sallman syndrome, red eye disease

o

Acanthotic and dyskeratotic epithelium of conjunctiva and oral mucosa

o

Rare, autosomal dominant disease with incomplete penetrance, which usually appears in first decade of life

o

Originally described in Haliwa Indians in North Carolina (USA), also elsewhere in US and Europe

o

Gray-white, inflamed, horseshoe shaped elevated lesions of conjunctiva and oral mucosa; bilateral corneal involvement



ProClear Contact Lens: biocompatible omafilcon, a material with phosphorylcholine integrated into lens polymer. PC molecule attach to H2O allowing the lens to resist deposits and thus function better.



Acid injuries causes less damage than alkalies in general except Hydrofluoric acid used in glass etching and cleaning also tends to rapidly penetrate the eye, whilst sulphuric acid may be complicated by thermal effects and high velocity impact after car battery explosions.



Unlike CHQ-HCHQ retinopathy, vortex keratopathy caused by them bears no relationship to dosage or duration of treatment. The changes are usually reversible on cessation of therapy, although they may clear despite continued administration.



Phenol red thread test uses a thread impregnated with a pH sensitive dye. The end of the thread is placed over the lower lid and the length wetted (the dye changes from yellow to red in tears) is measured after 15 seconds. A value of 6 mm is abnormal. It is comparable to Schirmer test but takes less time.



Zidovudine, an anti-retroviral agent, may be beneficial in primary Sjögren syndrome.



The adenoid superficial layer of the conjunctiva does not develop until about 3 months after birth, hence the inability of the newborn to produce a follicular conjunctival reaction. 182

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Dhaval Patel MD

In hyperacute conjunctivitis caused by Neisseria, drug of choice is o

Ceftriaxone 1 gm IM + azithromycin 1 gm PO

o

Azithromycin is given to treat concurrent chlamydia infection.

o

Even if concurrent chlamydia is not suspected, treat with both drugs as azithromycin covers ceftriaxone resistance.



Hertoghe sign is characterized by absence of the lateral portion of the eyebrows. It is seen in Atopic Keratoconjunctivitis.



Mucus fishing syndrome: in a variety of underlying anterior segment disorders, patients develop or exacerbate a chronic papillary reaction due to repetitive manual removal of mucus which results into GPC like state.



Ocular Protection Index (OPI): OPI = BUT/IBI. Values below 1 are characteristic of tear film instability and dry eye disease. Blink rate, which is calculated by dividing 60 by the number of observed blinks per second. (IBI: InterBlink Interval)



Meibography is a technique that uses transillumination biomicroscopy of the everted eyelid with infrared photography Meibometry is used to measure the amount of lipid on the lid margin by determining the degree of translucency induced on plastic tape applied to the lid margin.



Tetracycline reduces lipase production in S. epidermidis, S. aureus, and P. acnes. It also decreases serum cholesterol in mice, has antichemotactic effects on neutrophils, and has activity against collagenase and other metalloproteinases. Any of these properties may produce a marked therapeutic effect in many patients with meibomian gland dysfunction and rosacea.

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The currently accepted WHO guidelines include community-wide antibiotic treatment if there is >10% active trachoma in children aged 1–9 years. This treatment should be reinstituted annually for 3 years, with reassessment at that time.



In contrast to VKC, the papillary hypertrophy of AKC is more prominent in the inferior conjunctival fornix.



keratotorus = Schlappi’s pellucid marginal degeneration



Cause of the foamy appearance of the Bitot's spot: due to gas production by Corynebacterium xerosis in the horny epithelium



Types of xerosis: o

Xerosis epitheliasis - Due to vitamin A deficiency and associated with protein energy malnutrition.

o

Xerosis parenchymatas - Sequale of ocular inflammation  Trachoma, Chemical injury, Diphtheria, Ocular pemphigoid



Anterior stromal cautery: Application of light burns to Bowman's layer using a thermal cautery (Salleras procedure)



Unlike meibomian gland secretion, sebum contains more triglycerides and free fatty acids and considerably less sterol esters. Squalene is present in sebum and absent in meibomian gland secretion. The wax ester proportion is similar in both secretions. Overall, sebum is much more polar and will contaminate the tear film when mixed with it.



Large-diameter lamellar grafts: Malbran procedure  advanced keratoconus Malbran‘s ―peeling off‖ technique is the safest lamellar keratoplasty procedure and yields postoperative visual results equal to the more risky deep lamellar techniques.

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Follicular reactions are not seen in the neonate because of the immaturity of the immune system and adenoid layer of conjunctiva is not matured till 3 months.



Corneal Collagen Cross-linking C3R: 1. Biomechanical stabilization: 

primary and secondary keratectasia



4-fold increase of stiffness of the anterior cornea

2. Biochemical stabilization: 

crosslinked collagen is more resistant against digesting enzymes



crosslinks are produced in the outer surface of the collagen molecule, blocking the docking stations for enzymes, and therefore the enzymatic activity is blocked



melting can be stopped

3. Cytotoxic effect:





killing keratocytes up to 350 μm deep in the cornea



also used to kill germs

Enhancers for Epi-On C3R o

Trometamol (Tris-[hydroxymethyl]aminometane)

o

Sodium ethylenediaminetetraacetic acid (EDTA)

o

Benzalkonium chloride BAC



Contact lens cornea is seen in rheumatoid arthritis.



Keratoconus indices o

Keratoconus Severity Index KSI >0.15

o

Keratoconus Predicctability Index KPI >0.23 185

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Dhaval Patel MD

Keratometry Inferior Superior Asmmetry KISA >100%



Posterior elevation >40um on orbscan precludes LASIK.



INTACS o

150 degrees

o

PMMA segments

o

7.5 to 8.1 mm

o

68% depth

o

250-400 microns thick



CALAK: Corneal Augmentation Lamellar Keratoplasty, combination of LASIK and keratophakia



Post PRK stromal Haze increases after UV-B exposure.



DLK can induce hyperopia.



Most common cause of acute conjunctivitis: streptococcus pneumonia Most common cause of chronic conjunctivitis: staphylococcus aureus Most common cause of blephroconjunctivitis: staphylococcus aureus Most common cause of chalazion: staphylococcus aureus



Conjunctival SCRAPPING is done for chlamydia and viruses as they are intracellular, conjunctival SWAB is taken for bacteria.

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Newer therapy to prevent graft rejection: o

FK 506

o

Rapamycin

o

15-deoxypergualin

o

Anti CD-154 antibody

o

antiVEGFs

o

leflomide



The ring-shaped stromal infiltrate seen in herpes simplex keratitis is thought to be similar to the line of precipitation in the Ouchterlony test. Antigens diffuse from one area of the gel and antibodies diffuse from another. The line forms at the meeting point of the diffusing antigen and antibodies.



All hyperlipoproteinemias except TYPE I are associated with arcus.



Conjunctival Sickle Sign: Abnormalities of the bulbar conjunctival blood vessels provide direct evidence of the vaso-occlusive process and were one of the earliest reported ocular changes.



Acanthameba Stains:



o

The trichrome-eosin and iron-hematoxylin stains showed good color contrast for detecting all three stages, the trophozoite, cyst and flagellate

o

Giemsa and Gram stained the trophozoite and flagellate stages;

o

Modified Field‘s and modified AFB stains stained only the trophozoite stage.

o

Depending on the purpose, all these stains (except the AFB stain) can be used.

In pterygium, IL-7 is decreased.

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LASIK Interface Fluid Syndrome o

first described by Lyle and Jin in 1999

o

accumulation of fluid in the LASIK flap interface due to steroid induced IOP spike, uveitis, and vitreoretinal and cataract surgery, as well as endothelial decompensation

Corneal Inlays o

o

o



Dhaval Patel MD

Pinhole Corneal Inlays 

small-aperture corneal inlay (Kamra, AcuFocus; Irvine,Calif., USA)



for the correction of presbyopia is based on the principle of changing the depth of focus



ACI 7000

Refractive Corneal Inlays 

intracorneal inlay Flexivue Microlens



Presbia



Hydrophilic acrylic

Nonrefractive Inlays 

Raindrop (Vue+; Revision Optics)



Hydrogel

Corneal Laser Surgery in Presbyopia o

o

Multifocal ablations 

Supracor (Bausch + Lomb Technolas; Munich, Germany),



PresbyMAX (Schwind Eye-Tech-Solutions GmbH and Kleinostheim, Germany)



Pseudoaccommodative cornea (PAC; Nidek Co. Ltd.; Gamagori, Aichi, Japan)

Monofocal ablations 188

Ophthalmology Explorer 

classic monovision LASIK



laser blended vision (Carl Zeiss; Germany)

Dhaval Patel MD



A rare clinical syndrome consisting of a fixed dilated pupil, iris atrophy, and glaucoma, known as Uretts-Zavalia syndrome, has been observed following penetrating keratoplasty and deep lamellar keratoplasty for keratoconus.



Photochemical keratodesmos o

method of producing sutureless adhesion by applying a photosensitizer to wound surfaces followed by low energy laser irradiation.

o

The laser promotes crosslinking between collagen molecules on opposing surface to produce a tight seal without inducing thermal damage to adjacent tissue.

o

It uses rosebengal dye, which activated by low energy argon ion laser at a wavelengtyh of 514 nm.

o

This Photochemical keratodesmos system may be useful adjunct to sutures in immediate postoperative period



A randomized, masked clinical trial of 18 participants allergic to grass pollen found that signs of allergic conjunctivitis were reversed most effectively by CCs plus ATs or EH drops; however, hyperemia was reduced more by ATs combined with CC than other treatments.



Prospective Review of Early Cataract Outcomes and Grading (PRECOG) study



o

designed to test new approaches for the measurement of cataract surgical quality in settings with poor rates of follow-up.

o

The study, conducted at 40 centers in 11 countries in Asia, Africa, and Latin America, shows that visual outcome measured at 3 days after cataract surgery correlates well with long-term outcome and can be used as a measure of surgical quality in regions of the world in which longer-term follow-up is rare.

Brown-McLean Syndrome: 189

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Dhaval Patel MD

o

rarest and most benign form of corneal edema

o

peripheral corneal stromal and epithelial edema that spares the central and superior cornea with pigment deposits are present on the underlying endothelium

o

A central zone of 5–7 mm remains clear and compact indefinitely despite the peripheral edema.

o

The peripheral iris may show transillumination, but the trabecular meshwork is not necessarily hyperpigmented.

o

If the patient is bilaterally aphakic, the syndrome is usually present in both eyes.

o

There is no clinical inflammation, and the cause is unknown.

o

Although the classic presentation follows intracapsular cataract extraction, it may occur after extracapsular cataract extraction



The adenovirus test, which detects the most common cause of viral conjunctivitis, requires only 10 minutes to develop after sample collection. It uses direct sampling microfiltration, similar to a home pregnancy test, to produce visual results, with a blue control line and, if positive, a red test line. Compared with cell culture, the traditional definitive test for adenovirus infection, this rapid test has a 90% sensitivity and a 96% specificity.



The ‗pump-leak‘ hypothesis: When the rate of fluid leakage into the stroma is balanced by the rate of fluid pumped out of the stroma, normal corneal architecture and thickness are maintained.



Indications for Simultaneous Keratoplasty in Cataract Surgery



o

Frank epithelial edema, or

o

Blurry vision in the morning, or

o

Corneal thickness above 0.70 mm, or

o

Endothelial cell density less than 500 cells/mm2

Location of corneal epithelial stem cells (SC): basal layer of the limbus

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Thoft and Friends‘ X, Y, and Z hypothesis of corneal epithelial maintenance o





X+Y = Z 

X= proliferation of basal cells



Y= centripetal movement of cells



Z=cell loss from the surface

Specular Microscopy Finding in Posterior Corneal Disorders o

Fuchs‘: decreased ECD, polymegathism, pleomorphism, disruption from guttae

o

PPMD: Pleomorphism, irregular large cells with scalloped edges as dark rings around lighter center, vescicles/pits in DM, Disrupted by crater-like focal lesions

o

ICE: enlarged ICE cells, white reflections in center of dark cells ‗dark-light reversal‘, no disruption from craters or guttae

TYROSINEMIA o

o



Dhaval Patel MD

type 1 

most common



hepatorenal tyrosinemia



deficiency of fumarylacetoacetate hydrolase



no corneal involvement

type 2 

oculocutaneous tyrosinemia or Richner–Hanhart syndrome



deficiency of hepatic tyrosine aminotransferase, the gene for which is located on chromosome 16q22



can develop superficial punctate crystalline lesions, often in a dendritiform pattern, that may mimic HSV keratitis

Left eyes seem to be affected more commonly than right eyes because neonates usually present in the left-occiput-anterior position 191

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Peters‘-plus syndrome: Peters‘ anomaly + short stature, brachymorphy, mental retardation, abnormal ears, and, in some patients, cleft lip and palate Krause-Kivlin syndrome: Peters‘ anomaly + facial abnormalities, disproportionate short stature, retarded skeletal maturation and developmental delay (probably inherited in an autosomal recessive manner)



Unlike meibomian gland secretion, sebum contains more triglycerides and free fatty acids and considerably less sterol esters. Squalene is present in sebum and absent in meibomian gland secretion. The wax ester proportion is similar in both secretions. Overall, sebum is much more polar and will contaminate the tear film when mixed with it.



Lens 

Juvenile xanthogranuloma (JXG) can cause spontaneous hyphemas. However, in any infant that presents with ―spontaneous hyphema,‖ an ophthalmologist must consider child abuse. Other causes of spontaneous hyphema include bleeding diatheses, leukemia, and retinoblastoma.



Lens does not contain hydroxyProlene, Cysteine and Tryptophan. (PCT)



Predominant cation in lens is K+ and anion is PO4-.

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Cataracts may occur both in galactosemia (galactose-1-phosphate uridyltransferase deficiency: GAL1PUT) and galactokinase deficiency. Galactosemia, however, also can feature hepatosplenomegaly, mental retardation, and other systemic manifestations.



Neurofibromatosis type 2, not type 1, may be associated with posterior subcapsular cataracts (and acoustic neuromas as well).



Posterior capsule opacification, glaucoma (angle closure caused by excessive inflammation), and retinal detachment (caused by vitreous loss) are more common postoperative complications in children undergoing cataract extraction. The incidence of cystoid macular edema (CME) is lower in children than in adults.



Polyopia, pupillary block, and corneal-lenticular touch are indications for medical or surgical intervention in lens subluxation (which can be accomplished with the implantation of a Morcher endocapsular tension ring). Decreased vision often can be corrected solely with an aphakic refraction.



Pyramidal cataracts are a distinct and more severe form of anterior polar opacity, named because the shape of the anterior opacity resembles a pyramid. A more accurate and modern description is a likeness to the shape of the chocolate candy called the Hershey's Kiss. The tips of these opacities extend into the anterior chamber and rarely have even been known to be fused with the cornea. They are fibrous and may be associated with an anterior subcapsular cataract that, when present, often progresses to become visually significant. At surgery, the fibrous ―Hershey's Kiss” is not easily removed with the vitreous cutter. After it is detached from the anterior capsule, it usually spins around the anterior chamber and has to be delivered through the incision using forceps. These pyramidal cataracts are almost always bilaterally symmetric and may be dominantly inherited.



Homocystinuria o

It is AR with the gene locus on chromosome 21q.22.3.

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o

Affected patients are generally tall with osteoporosis, scoliosis, and chest deformities.

o

About 50% of the time there is associated mental retardation.

o

These patients are at increased risk of thrombotic vascular occlusions, and this should be taken into consideration if general anesthesia is planned.

o

Lens dislocation occurs in 90% of patients and is generally inferior and bilateral.

o

Homocystinuria may lead to angle closure glaucoma if the lens dislocates into the anterior chamber.

o

In homocystinuria, serum levels of homocystine and methionine are elevated. Patients are normal at birth but develop seizures, osteoporosis, and mental retardation. Classic lens dislocation is bilateral, symmetric, usually inferonasal.

o

Decreased hepatic activity of cystathionine beta-synthase results in systemic accumulation of homocysteine and methionine.

o

Normal lens zonules have a high concentration of cysteine, and deficiency results in abnormal, brittle zonules.

o

A diet low in methionine and high in cysteine can reduce lens dislocation.

o

Vitamin B6 supplementation have shown promise in treating these patients and in reducing ectopia lentis.



The Malyugin ring is a device to enlarge a small pupil and/or stabilize an atonic iris. This may be necessary in patients with pilocarpine treatment, pseudoexfoliation, and IFIS. Pupillary dilation is usually not an issue in ectopia lentis.



Z-syndrome refers to a complication of the Crystalens in which the plate haptics are bent asymmetrically so the lens has a ―Z‖ configuration. Z phenomenon: earliest models of foldable IOLs were too long, so that when they were well fixated within the capsular bag they caused wrinkling of capsule centrally because of capsule contraction.



Coloboma of the lens is not a true coloboma. Instead the notch in the equator resulted from an absence of zonular fibers from an underlying colobomatous ciliary body. This absence results in a lack of tension on the lens capsule in that region. The lens tissue is not missing. 194

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Ectopia lentis associated with mental retardation: o

Hyperlysinemia

o

Weill-Marchesani syndrome

o

Homocystinuria



Young, myopic males may be predisposed to pigmentary dispersion syndrome.



Amiodarone and phenothiazine cause stellate cataracts in the anterior lens capsule. All forms of steroids have been associated with cataract formation.



Persistent hyperplastic primary vitreous (PHPV) is a congenital, nonhereditary ocular malformation. Associated findings include elongation of ciliary processes, prominent radial iris vessels, persistent hyaloid artery, microphthalmia, and ectopia lentis.



Monocular visual deprivation, most likely with nuclear cataract, is the most ―amblyogenic.‖



Vitamin B6  homocystinuria Coenzyme Q  Leber's hereditary optic neuropathy Vitamin A  retinitis pigmentosa



20% of patients with cataract have significant preexisting astigmatism.



Three kinds of aspiration systems exist in phacoemulsification machines. o

The peristaltic pump has rollers that move along tubing and create a relatively rapid rise in vacuum.

o

The diaphragm pump has valves over both the inlet and outlet of a fluid chamber covered by a diaphragm. This system allows a slower build of vacuum. 195

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The Venturi pump produces the most rapid increase in vacuum. This, however, can be the most dangerous because it allows almost instantaneous engagement of unwanted tissues such as capsule or iris.



PMMA lenses, when packaged, may pick up static charges that attract dust and debris when opened. Therefore, the lens may be rinsed with balanced salt solution before insertion. Silicone lenses do not require this and, in fact, may be more difficult to handle once they have gotten wet. Application of a viscoelastic, such as sodium hyaluronate, may facilitate insertion of a lens, especially a foldable one, through a small incision.



IOL implantation is contraindicated in patients with juvenile rheumatoid arthritis-associated iridocyclitis. Development of cyclitic membranes and subsequent ciliary body detachment following extracapsular cataract extraction suggest the need for complete capsular removal. Therefore, combined lensectomy and subtotal vitrectomy is recommended either through the limbus or pars plana. But recent data suggests that IOL can be implanted in JIA associated uveitis without significantly affecting post operative uveitis incidence. (Foster’s Uveitis Book)



Lane and colleagues evaluated IOP elevation associated with three commonly used viscoelastic agents (sodium hyaluronate, chondroitin sulfate, and hydroxymethylcellulose) and all produced significant pressure elevations at 4 ± 1 hours postoperatively. Removing the viscoelastic did not eliminate significant postoperative IOP elevation, although when chondroitin sulfate was removed, the pressure elevation was slightly less.



The ciliary sulcus is only 0.83-mm posterior to the limbus vertically and 0.46-mm posterior horizontally



The incidence of clinical cystoid macular edema is less than 1% following uncomplicated cataract extraction. The incidence of angiographic evidence of cystoid macular edema is approximately 10 times this.



Congential epicapsular pigment stars: its can be seen normally on anterior lens capsule. They are remnants of the anterior tunica vasculosa. 196

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Systemic Investigations for subluxated lens: o

Echocardiogram may show enlarged aortic roots or mitral valve prolapse in Marian's syndrome.

o

High serum methionine is seen in homocystinuria.

o

Serum FTA-ABS for Syphilis as it is a known cause of ectopia lentis.

o

Urine thiosulphate is seen in sulphite oxidase deficiency, in which the disulphide bond is disrupted and can cause ectopia lentis



Myotonic dystrophy: These patients have polychromatic cataract which is classically described as "Christmas tree" cataract.



youngster with bilateral cataracts and epilepsy Check Serum calcium. The disease is hypoparathyroidism or psuedohypoparathyroidism. Both these conditions are associated with epilepsy and bilateral cataracts and the blood test shows a low serum calcium and a high serum phosphate. In the former condition the parathyroid glands do not produce parathyroid hormone while in the latter, parathyroid hormone is produced but the tissues especially the kidneys are resistant to its actions. The two conditions can usually be differentiated by measuring the parathyroid hormone concentration in the serum. They are both treated with calcium supplements and vitamin D supplements.



What clinical condition leads to phimotic anterior capsule opening? Pseudoexfoliation, because zonules can get stretched and your rhexis is made smaller than you intended.



Singh signs for PPCD o

A deep anterior chamber

o

White to chalky-white spots are produced, which are seen in front of and around the posterior capsular defect. 197

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o

The capsule behind the opaque lens may show a partial or a complete white ringshaped opacity. This opacity is contained within the posterior cortex, while the posterior capsule shows a hole with chalky-white spots on and around the defect.

o

Rarely, an opening in the posterior capsule shows pigment along the margins. Fine dustlike pigment along with fine dense white opacities may be seen in the Berger space. The presence of pigment suggests widespread movement of the fluid beyond the posterior capsular defect.



Argentina flag sign: complication when performing capsulorrhexis in intumescent cataracts stained with trypan blue



In diabetic cataract, hyperglycaemia results in myopia and vice versa.



Steroid induced cataract: 10 mg prednisolone/day for > 2 years can cause cataract. 100% incidence with 20 mg prednisolone/day > 4 year



Wrinkling of capsule at the start of capsulorrhexis is pathognomonic sign of inadequate capsular support.



Membranous cataract is rare and may be associated with Hallermann–Streiff–François syndrome. It occurs when the lenticular material partially or completely reabsorbs leaving behind residual chalky-white lens matter sandwiched between the anterior and posterior capsules.



Advantages of capsulorrhexis: o

Traps the lens inside bag

o

Better control of surgery

o

ELP better

o

Resists tearing 198

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PCO is decreased when overlap of IOL

Disadvantage of capsulorrhexis: o

Phimosis

o

Sphincter effect leading to bag-IOL dislocation in PXF



Bryan Little‘s manouevre: capsule tear out and rescue manouere.



CRYSTALENS does not have UV bocking property.



The predominant yellow chromophores in the young human lens are metabolites of tryptophan, especially N-formyl kynurenine glucoside.



Calib chop: preoperatively calculated the calibrated tip not only marks the entry point on lens surface, it also measures as it reaches the desired depth when a vertical chop can be effectively and safely executed called a calibchop.



The IDEM lens or the ―IDeal EMmetropia lens‖, was that IOL power which when implanted within the eye restored emmetropic status after cataract surgery. The power of this lens was mathematically deduced to be +17.0 D for an AC lens, +19.0D for an iris fixated lens and +21.0D for a posterior chamber lens.



The Third and fourth generation IOL power calculation formulae incorporate a bit of both theoretical and regression types which was called the ―Fudge factor‖ by duke elder.



The Haigis formula o

4th generation formula which was an adaptation of the formula first suggested by Gernet, Ostholt and Werner as early as 1970

o

also called the GOW 70 formula

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o

The versatility of the formula lies in the three individualized A constants namely a0, a1 and a2.

o

The a0 is linked to the manufacturers lens constant.

o

The a1 is linked to the pre operative ultrasonically measured ACD (this has a default value of 0.4).

o

a2 which is linked to the axial length measurements and which has a default value of 0.1



Desmosomes of lens epithelial cells contain VIMENTIN whereas most epithelial cells in the body contain cytokeratin.



Prechopping techniques:



o

Akahoshi technique: using special prechopper created by akahoshi

o

Preslice technique

o

Ultrachopper technique: Luis Escaf, ultrasonic knife that cuts the nuclear substance

CDI = cohesion- dispersion index (%aspirated/mm Hg): o

Cohesive OVDs: CDI >30

o

Dispersive OVDs: CDI IL6 (10>6  which should not confuse you now)



ibopamine: increases aqueous production (Italy) 266

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drug which may worsen MS: infliximab



drug-induced lupus caused by: infliximab



Jenson‘s Juxtapapillary Choroiditis: histoplasmosis should be considered, differentiate it from papilledema.



'Cracked mud appearance' of Progressive outer retinal necrosis (PORN), choroideremia??



Uveitis and poliosis: 1. sympathetic ophthalmia 2. VKH



Arlt‘s triangle: (Ehrlich–Türck line) base-down triangle of central keratic precipitates in uveitis



Kunkmann–Wolffian bodies: Small white peripheral iris spots that resemble Brushfield spots but occur in normal individuals. They are more peripheral than brushfield‘s apots which are around midperiphery.



Kyreileis‘ plaques: White–yellow vascular plaques in toxoplasmosis



Lander‘s sign: Inferior preretinal nodules in sarcoidosis



Patient with uveitis undergoing cataract surgery, Prophylactic systemic steroid treatment is only recommended in patients with previous macular oedema caused by the uveitis. 267

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JIA is not the same as juvenile rheumatoid arthritis (JRA); the former is negative for rheumatoid factor whereas the latter is positive. JRA is the same disease as rheumatoid arthritis except that it occurs before the age of 16 years.



In Fuchs‘ heterochromic iridocyclitis, the fine ‗‗stellate‘‘ KP are found scattered diffusely on the entire posterior surface of the cornea, unlike most KP, which are located in the inferior cornea.



In Uveitis, Low intraocular pressure (IOP) may occur as a result of reduced secretion of aqueous by the ciliary epithelium. Occasionally the intraocular pressure may be elevated (hypertensive uveitis) as in herpetic uveitis and Posner–Schlossman syndrome.



In CAU, Aqueous flare may be more marked than cells in eyes with prolonged activity and its severity may act as an indicator of disease activity (contrary to previous teaching). The classical teaching that only cellular reaction in the anterior chamber represents active inflammation has been challenged. Flare is caused by chronic break-down of the blood– aqueous barrier, but the intensity of the flare can also indicate an active process, which may respond to therapy.



Iris atrophy that is sectoral occurs characteristically in herpes simplex and herpes zoster. Diffuse iris atrophy occurs in Fuchs uveitis syndrome.



Large KPs in granulomatous disease have a greasy (‗mutton-fat‘) appearance. They are often more numerous inferiorly and may form in a triangular pattern with the apex pointing up = Arlt triangle



DUSN is thought to be caused by migration of a nematode under the retina.



Onchocerciasis: Also known as river blindness, this is caused by infection with the filaria parasite Onchocerca volvulus, which is transmitted by the bite of species of Simulium flies (so-called buffalo gnats). Clinically there are skin changes, nodules and eye changes that can lead to blindness. The nodules develop in subcutaneous tissue especially near bony 268

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structures and contain living or dead adult worms. Fundus of oncocerciasis is known as Ridley‘s fundus.



MAGIC Syndrome: Mouth and genital ulcers with inflamed cartilage syndrome is a cutaneous condition with features of both Behçet's disease and relapsing polychondritis



Dadizumab (Zenapax): A completely humanised IL- 2 receptor antibody used in kidneytransplant recipients, has shown encouraging clinical results in uveitis patients. In a phase 2 trial, subcutaneous daclizumab was injected at the dose of 2 mg/kg separated by 2 weeks and then 1 mg/kg subcutaneous(SC) every 2 weeks for 26 weeks. The objective of the trial was to reduce the load of the other immunosuppressive agents by half. Immunosuppressive therapy was tapered off in a staggered fashion to SO% or less in 8 to 12 weeks. At 12 weeks, 10 of the lS patients (67%) receiving SC daclizumab successfully achieved the primary end point of reducing concomitant immunosuppression load by SO%.



Anakinra: Anakinra is a recombinant, human, nonglycosylated IL-1 receptor antagonist (IL-1RA). It inhibits IL-1 activity, downregulating the proinflammato1y functions of IL-1 including chemotaxis, activation of antigen-presenting cells, and the upregulation of cell surface adhesion molecules involved in leucocyte trafficking. The use of Anakinra has so far been reported in few cases of scleritis associated with rheumatoid arthritis and few cases of posterior uveitis. It has been used in the dose of 100 mg/ day and the main side effects have been the injection site reactions.



taches de bougie is a French of candle-wax drippings.



Phacoanaphylactic uveitis is an immune complex disease that develops when normal tolerance to lens protein is lost, not a cell-mediated rejection of "foreign tissue" (Contrary to prior teachings lens proteins are not totally sequestered or organ specific. They are normally found in aqueous and expressed in other extraocular tissues. Anti-lens antibodies are found in some normal individuals).



AC flare: Tyndal effect  focused beam of light illuminating the anterior chamber becomes visible, just as a projector beam is visible in a smoky room. This phenomenon, which is termed aqueous ―flare‖ or ―ray,‖ is caused by the Tyndall effect. 269

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AC cells: The cells normally move with the convection currents in the aqueous. (They sink anteriorly where the aqueous is cooled by the cornea and rise posteriorly where the aqueous is heated by the iris.) Absence of cellular convection currents may indicate clotting of fibrin-rich aqueous in a case with severe vascular permeability.



Blood level of cyclosporine: 100-150 ug/ml



Nozik technique: a 25-gauge, 1/2-inch needle is used. If the injection is given in the superote m poral quadrant (the preferred location), the upper eyelid is retracted and t he patient is instr u cted to look down and nasally. After anesthesia is applied with a cotton swab soaked in propa racaine or tetracaine, the needle is placed bevel-down against the sclera and advanced through the conjunctiva and Tenon capsule using a side-to- side movement, which allows the physician to deter mine whether the needle has entered the sclera or not. As long as the globe does not torq ue with the side-to-side movement of the needle, the physician can be reasonably sure t hat the needle has not penet rated t he sclera. Once the needle has been advanced to the hub, t he corticosteroid is injected into the sub-Tenon space. Complications of the superotem poral approach include upper lid ptosis, periorbital hemorrhage, and globe perforation.



The Goldmann-Witmer (GW) coefficient is a test that compares the levels of intraocular antibody production to that of serum, as measured by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay. The coefficient is defined as GW = X/Y; where GW = Goldmann-Witmer coefficient; X = specific antibody in aqueous or vitreous divided by total IgG in aqueous or vitreous; and Y = specific antibody in serum divided by total IgG in serum. A GW ratio > 4 is diagnostic of local antibody production to a specific microbial pathogen. It‘s especially useful for ARN.



7 g of protein/100 mL of blood, but only 11 mg of protein/100 mL of aqueous.



pink hypopyon: Serratia marcescens endophthalmitis. Cytologic examination reveales no erythrocytes, and the pink color is due to the bacteria.



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Types of KPs 

Fine/coarse (lymphocytes and plasma cells) – found in allergic or acute iridocyclitis.



Mutton fat (Macrophage and epitheloid cells) – found in granulomatous uveitis – e.g. TB, sarcoidosis.

fresh KPs/Old KPs 

Fresh KPs – Solid, round, white, fluffy



Old KPs – Faded, shrunken, pigmented, crenated edge



The absence of CME distinguishes Fuchs‘ heterochromatic iridocyclitis from other uveitis syndrome with chronic vitritis.



Aspirin is the treatment of choice for patients with Kawasaki syndrome. Systemic corticosteroid therapy use is associated with an increased rate of coronary artery aneurysm formation and is therefore contraindicated.



Serpiginous choroidopathy (geographic helicoid peripapillary choroidopathy GHPC) is a chronic, recurrent, indolent disease of unknown etiology. It usually affects adults with painless loss of vision. Lesions are peripapillary or perimacular and, in the active phase, have inflammation along the edges. Centrifugal spread in a snake-like pattern occurs over months to years. Treatment with steroids or immunosuppressive agents has had variable success.



Inflammation in Behçet's disease o

affects the anterior and posterior segments and is generally a bilateral process.

o

Recurrent explosive inflammatory episodes are typical with active episodes that range from 2 to 4 weeks.

o

A chronic, lingering inflammatory stage typically does not develop.

o

A nongranulomatous anterior uveitis with formation of a transient hypopyon is common.

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o

Posterior inflammation is characterized by recurrent vascular occlusive episodes with retinal hemorrhage and vitreous inflammation. The inflammation is typically confined to the retina and retinal vasculature. Choroidal involvement is rarely seen.

o

The retinitis of Behçet's disease is very suggestive of a viral retinitis and must be considered in the differential.

Toxoplasmosis drugs o

Pyrimethamine actually inhibits dihydrofolate reductase.

o

Sulfadiazine blocks the production of dihydrofolate from para-aminobenzoic acid.

o

Clindamycin is an antibiotic that can effectively kill Toxoplasma organisms.

o

Systemic and periocular steroids can be used in the treatment of ocular toxoplasmosis in immunocompetent patients.

Fuchs' heterochromic iridocyclitis o

an insidious, chronic intraocular inflammation that may not respond well to topical corticosteroids.

o

Characteristic findings include diffusely distributed stellate keratitis precipitates and mild anterior segment cell and flare with loss of iris crypts and detail.

o

Blue irides become more blue, and brown irides become less brown in cases of Fuchs' heterochromic iridocyclitis.

o

Gonioscopy will reveal evidence of abnormal bridging vessels in the angle, although neovascular glaucoma with angle closure does not develop.

o

A paracentesis of the anterior chamber may result in a small, splinter-shaped filiform hemorrhage in the angle.

o

Fifty percent of patients with Fuchs' heterochromic iridocyclitis develop cataracts; 60% develop glaucoma.

o

Cataract surgery is not associated with any higher rate of vitreous loss or posterior capsular rupture compared to normal eyes.

o

No posterior synechia, no increased risk of CME after cataract surgery

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Iris mammilations are seen in o

Nevus of ota

o

NF-1

o

Peter‘s

o

Axenfield Reiger‘s



Gordon‘s dictum for systemic steroids in uveitis – ―Use enough, soon enough, taper and discontinue‖



Although syphilitic uveitis may mimic any other form of uveitis, intermediate uveitis is a distinctly uncommon presentation.



Rod dysfunction seen in birdshot retinochoroidopathy leading to electroretinogram reveals diminished scotopic responses.



Cystoid macular edema is not typically seen in patients with Vogt-Koyanagi-Harada syndrome.



Diffuse unilateral subacute neuroretinitis DUSN is thought to be caused by numerous different types of roundworms. Baylisascaris species have been implicated most consistently.



Polymyalgia rheumatica is an inflammatory condition but it does not manifest as scleritis.



Primary intraocular lymphoma: leopard skin pattern of yellowish retinal pigment epithelium and subretinal infiltration of lymphomatous cells are typically seen in patients over the age of 70 years

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Onchocerca volvulus infection results in widespread dissemination of the microfilarial larvae. These microfilaria can be seen swimming in the anterior chamber. The live organisms may cause a mild uveitis and obstruct the trabecular meshwork; however, dead organisms incite a vigorous inflammatory reaction, which causes much more ocular damage.



An eosinophilic granuloma occurs with Toxocara intraocular infection. On histopathology, the reaction may be so vigorous that the Toxocara organism may not be visible.



Retinal antigens to induce EAU (Experimental Anterior Uveitis)



o

retinal S-antigen, also known as ―arrestin,‖ found in the photoreceptor outer segments and in the pineal gland of some species; it competes with transducin for rhodopsin in its photoexcited and phosphorylated state

o

interphotoreceptor retinoid-binding protein (IRBP), a major soluble protein in the interphotoreceptor matrix

o

rhodopsin, a well-defined transmembrane protein of rod outer segments, participating in visual transduction

o

recoverin, a calcium-binding protein that selectively localizes to the retina and pineal gland, associated with cancer-associated retinopathy

Combination therapy with cyclosporine A, azathioprine and prednisolone was first described by Hooper and Kaplan to control inflammation rapidly and promote visual recovery in five patients with bilateral serpiginous choroiditis.



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Strabismus 

The Bruckner test is a bilateral red reflex test, and if strabismus is present the brighter reflex is in the deviated eye. This is because the light reflects from peripheral retina in the deviated eye. Because there is less pigment in the peripheral retina than the macula, there is more reflection of light from the peripheral retina of the deviated eye.



Alexander‘s law: Jerk nystagmus, usually increases in amplitude with gaze in direction of the fast phase



Enthesiotomy: tenotomy and reattachment of muscle. It is done as nystagmus surgery.



The inferior and superior obliques are abductors of the eye in synergy with the lateral rectus. The superior, inferior, and medial recti are all adductors.



A very important thing to understand about Moebius is that many other characteristics have been found in patients who have the signal features of lack of abduction (or in some cases, gaze palsy) and weakness of the facial muscles. These include: deafness, webbed fingers or toes, supernumerary digits, defects in the muscles of the chest (Poland syndrome), neck and tongue, missing fingers or toes and more. Because of the wide list of associated features some would prefer to call this the Moebius sequence.



The parieto-occipital lobe controls the slow pursuit component, whereas the frontal lobes control the saccadic component.

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Exception to Sherrington‘s law: DRS, Retraction nystagmus Exception to Hering‘s law: DVD



Several ocular and systemic anomalies have been associated with DRS: cataracts, iris anomalies, Marcus Gunn jaw winking, microphthalmos, crocodile tears, Goldenhar's syndrome, maternal thalidomide use, and Klippel-Feil syndrome.



There are three and possibly 4 classes of CFEOM that are genetically defined and have different characteristics. Class 1 has aligned eyes in down gaze which become esotropic on attempted up gaze. Class 2 characterized by limited up gaze, ptosis and exotropia. Class 3 is a milder form that can be a mixture of class 1 and 2 and may be unilateral. A new classification of CFEOM called Turkel has an added finding of missing fingers. CFEOM is a rare genetic disorder that results in varying degrees of inability to look up along with ptosis and a chin up head posture. Treatment of any of the classes of CFEOM presents a significant challenge and is usually done in stages.



Large vertical fusional amplitudes (>5 prism diopters) and facial asymmetry from childhood headtilting suggest a decompensated congenital lesion.



In case of Restrictive Myopathy, A rectus muscle should never be resected but only recessed.



Positive forced ductions indicate a restrictive process that may be caused by thyroid eye disease, blow-out fractures, fat adherence syndrome, and Brown's syndrome, among others.



Amblyopic eye functions better in mesopic condition.



A strabismic deviation can be neutralized by orienting an appropriate power prism with the apex in the same direction as the deviation. 276

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A prism diopter is defined as the amount of deviation of a light by the prism measured at 100 cm.



Prism power can be represented by vectors and added as this mathematical entity.



All rays parallel to the lens axis will converge on the secondary focal point whose location can be calculated as 100 cm/Power = distance cm.



extraocular muscle is commonly involved in a dog bite: The superior oblique muscle: This result from direct trauma (from the lower teeth of the dog) to the trochlear causing paralysis of the superior oblique muscle and a Brown's syndrome due to scarring. This condition is also called dog-bite syndrome or canine tooth syndrome.



The normal range of fusion as measured from 0° on the major amblyoscope is that of 30-35 convergence, 5° of divergence and 3-4 of vertical vergence.



Incidence of amblyopia in myopia is much less almost unknown for the reason that myopia at least sees the near objects more clearly than in hypermetropia where all accommodation reserve is up for distance and he neither sees dist/ance nor see near objects clearly. Therefore, near vision stimulus is not deprived in myopia.



4-PD base-in prism test  differentiates convergence insufficiency [near vision improves] from accommodative insufficiency [near vision worsens]



Faden: The lever arm of the muscle is weakened thus decreasing its action. Best for MR and not for LR. (as MR has 6.0 mm arc of contact, LR has 15 mm arc of contact.) o

Non accomodative convergence excess esotropia

o

Nystagmus blockade syndrome

o

Paralytic strabismus 277

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o

Duane retraction syndrome

o

Dissociated vertical deviation

Dhaval Patel MD

Hummelsheim‘s procedure: For LR palsy Lateral halves of sup and inf recti are dissected and reinserted near LR insertion



Jensen‘s procedure: For LR palsy Lateral halves of sup and inf recti and upper and lower halves of LR dissected free



In the presence of microtropia "with identity," the cover test result is negative but the 4 prism diopter base-out test reveals a foveal suppression scotoma in one eye that generally is also amblyopic.



The limbal incision for squint surgery may be done at the limbus for MR-LR-IR - but allow a 1.5 to 2.0 mm "cuff" for SR to avoid increasing pannus at superior limbus.



A compensatory head posture with the chin elevated and pointing toward the opposite shoulder permits fusion in Brown syndrome.



Pleoptoscope: Opthalmoscope fitted with a projected fixation target.



o

Used for Small-angle strabismus , with fixation anomaly and amblyopia.

o

It can also be treated by Occlusion of the amblyopic eye, followed by foveal stimulation. Rotating blue polarised light, light ablation of the fixation zone followed by repetitive foveal stimulation. Treatment unlikely to be successful if the other eye has normal vision.

Bielschowsky phenomenon: Downdrift of occluded eye as increasing neutral density filters are placed over fixating eye in dissociated vertical deviation (DVD)

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Dhaval Patel MD

DVD o

present in 60% to 80% of patients with congenital esotropia.

o

DVD is usually bilateral and asymmetric.

o

The etiology is unknown but appears to be associated with an early disruption of binocular development. Thus, high-grade stereopsis and bifoveal fixation are not seen.

o

During times of visual inattention, the nonfixating eye slowly drifts up, extorts, and abducts without a corresponding hypotropia of the fellow eye on alternate cover testing. This is the hallmark of this disorder—it does not obey Hering's law.

o

DVD can simulate Inferior Oblique Overaction (IOOA) in side gaze when the nose acts as an occluder. The hyperdeviation in DVD is of the same amount in adduction, abduction, and primary position. This is in contrast to IOOA, in which the hyperdeviation is greatest in its field of action.

Duane Retraction Syndrome (DRS) can be associated with Anisometropia, coloboma, microphthalmos and heterochromia. o

Two syndromes associated with this are: Goldenhar and Wildervanck syndrome. The child can have a hearing or a speech disorder as well

o

The phenomenon commonly seen is the leash phenomenon and a severe leash is treated with Y splitting of the lateral rectus muscle with posterior fixation sutures of the lateral rectus muscle.



A right superior oblique palsy can result in vertical or torsional diplopia. Vertical diplopia may be treated with either ipsilateral inferior oblique myectomy or anterior transposition, contralateral inferior rectus recession or ipsilateral superior oblique tuck (sometimes in combination}. Torsional diplopia can be treated with anterior transposition of the superior oblique muscle.



Differentiation of unilateral from bilateral fourth nerve palsy is essential for successful surgical management. o

Features of unilateral fourth nerve palsy include: head tilt to the affected side, unilateral hypertropia on lateral gaze, less than 5 of exocyclotorsion.

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Dhaval Patel MD

Features of bilateral fourth nerve palsy Include: chin down posture with eyes looking up, alternating hypertropia on right and left gaze respectively, large exocyclotorsion of more than 10



Infantile esotropia has large angle esotropia. Binocular single vision is usually poor despite early treatment. The temporal-to-nasal movement is usually better than nasal-totemporal movement on optokinetic testing. Dissociated vertical deviation and inferior oblique overaction are common and have been reported in about 90% of patients. Post-surgical esotropia may be caused by an accommodative component.



Optokinetic response tests the pursuit and saccadic movements. When the drum is rotated to the right, the pursuit movement is mediated by the right parietal lobe and the saccadic movement by the right frontal lobe, i.e. the optokinetic response tests the pursuit and saccadic movement on the side towards which the drum is moving. Parinaud's syndrome causes up-gaze palsy and vertical rotation of the drum will elicit convergence retraction nystagmus. In a patient with a frontal lobe lesion, there may be deviation of his or her eyes to the side of the lesion. However, provided the contralateral frontal lobe is intact, rotating an optokinetic drum away from the side of the frontal lobe will elicit a response.





How to dissociate two eyes? o

Septum so that one half of the field is seen by one eye exclusively and the other by the other eye.

o

Two tubes one in front of each eye.

o

Red-green glasses, which are complementary in the sense that with red filter sees only red light other with green filter sees only green.

o

Polaroid dissociation, each eye views through polaroid filters each one at 90 degrees to each other.

o

Bagolini's striations, a spot light scattered striations, the two glasses set at 90° to other.

Mary Maddox: English Strabismologist o

Maddox tangent scale 280

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Maddox rod

o

Maddox hand frame: uniocular and binocular

o

Maddox Wing

Dhaval Patel MD



The torsional eye movements occur around the anteroposterior or Fick's Y axis. This does not pass through the centre of cornea but at a point on the lateral limbus as shown by Linwong.



Magician Forceps Phenomenon: On passive adduction of the dominant eye, the other eye's exodeviation gets corrected. This reflex is present even in the dark. This reflex is abolished by deep retrobulbar anesthaesia.



Phospoline iodide: medicine that affects accommodative convergence and used as a therapy sometimes.



Isolated agonist model was described by Duane for eye movements. However, it is important to remember that during eye movements, all six extraocular muscles are in some state of contraction or relaxation, and it is strictly hypothetical to discuss the movement of the eye as if only one muscle contracts.



Paired Antagonist Model was described by Boeder.



Aging chages in EOM



o

Both horizontal rectus muscles are displaced inferiorly with age (MR >> LR)

o

The superior rectus and inferior rectus muscles do not change locations

o

greater variety in fiber sizes, increased connective tissue in the muscle, increased adipose tissue in the bundles, deposits of lipofuscin, and degenerative changes.

amblyopia ex anopsia: amblyopia due to media opacity 281

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Antepodean Strabismus: It is present when the patient has esotropia while fixing with one eye and exotropia when fixing with the other eye. This occurs with anisometropia and an improperly corrected refractive error. Some cases are believed to be due to unequal accomodation.



Principle of Faden: Point of posterior fixation is new insertion for action. As antagonist entire muscle acts. Therefore limits muscle action only in field of its action.



Adherence syndrome: The orbital fat is separated from the globe by Tenon‘s capsule. If an accidental opening is made in the portion of Tenon‘s capsule that separates the orbital fat from sclera, orbital fat may be pressed through the opening and adhere to the globe. This adherence often results in limited eye moments. It is best treated by prevention. The orbital fat comes forward around the equator of the globe to within 10 mm of the limbus. Care should be taken not to cut Tenon‘s capsule more than 10 mm from the limbus.



Only fusional convergence (i.e. overcoming exophoria) dampens nystagmus. Accommodative convergence does not dampen nystagmus and even works against the patient by increasing accommodative demands and may cause the near point to recede with reduced visual acuity at near. So minus glasses does not improve nystagmus.



Centre for voluntary convergence: Frontal oculogyric area (area 8) Centre for reflex convergence: peristriate area of occipital cortex Lower convergence centre: nucleus of Perlia



NPC is usually 11 cm or inability to maintain 30 degree convergence on synaptophore.

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In class 7 SO palsy, traumatic paresis plus restriction of relaxation of the superior oblique, also known as the canine tooth syndrome because it is most frequently caused by a dogbite injury to the trochlear area, requires surgery to correct the Brown syndrome first, with a subsequent attempt at correcting paresis of the superior oblique if possible.



Cooper's Dictum: Stretched scar may have been the mechanism behind Cooper's report of failure of advancing previously recessed medial recti for consecutive exotropia. He advocated instead recessing the antagonist lateral recti. This principle is known as Cooper's Dictum.



Liquid crystal glasses have recently been developed as a new treatment for amblyopia. They provide an electronic, controlled, intermittent occlusion of the sound eye allowing for visual stimuli input to the amblyopic fellow eye. A liquid crystal glass in the sound eye is used as an intermittent flickering shutter switched between ―on‖, or occlusion and ―off‖ or light transmission. The flickering sequence can be adapted to the depth of amblyopia, the length of treatment, and the patient‘s age.



CAM Vision Stimulator - Amblyopic eye is stimulated by slowly rotating, high contrast, square wave gratings of different spatial frequencies for 7 minutes but the results are not much promising.



Hertle Dell‘ Osso proceduce: tenotomy and re attachment (rectus muscle) surgery done for nystagmus.



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Neurophthalmology 

Location of Lesion: o

WEBINO (wall-eyed bilateral internuclear ophthalmoplegia): riMLF and 3rd CNN (Involvement of the paired medial rectus subnuclei)

o

Internuclear ophthalmoplegia: Ipsilateral MLF, i.e. the same side as the eye that has adduction restriction.

o

Down-gaze palsy: riMLF

o

The lesion for skew deviation is in the brain stem but the exact location is unknown.

o

One and a half syndrome - ipsilateral MLF and 6th CNN



Aberrant regeneration of the oculomotor nerve occurs in ‗surgical‘ third nerve palsy and not in 'medical' third nerve palsy such as diabetes mellitus or hypertension. Retraction of the upper lid on down-gaze is called pseudo von Graefe's sign and miosis of the pupil on adduction is termed pseudo Argyll-Robertson pupil.



Kollner‘s Rule: o

Retinal Disease causes Blue-yellow defects 

o

Optic nerve disorders causes Red Green defects 



Exceptions: Stargardt‘s and Cone dystrophy

Exceptions: Glaucoma and autosomal dominant optic atrophy

The Pulfrich phenomenon probably reflects delayed conduction in the demyelinated nerve. Oscillating objects perceived by the affected eye appear to be behind the image seen with the healthy eye, simulating three-dimensional movement where there is only movement within one plane.

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Cogan's lid twitch - overshoot on moving from depression to primary position in myasthenia.



Heidenhain variant of Alzheimer disease of CJD causes visual hallucinations.



lce test- reduced ptosis after ice pack applied for 2 minutes.



Alternating Anisocoria:





o

Aka See-saw anisocoria

o

One pupil larger in light and other is larger in dark  3rd nerve palsy and horner‘s syndrome

Benign alternating anisocoria: o

discreet entity not found in normal subjects but which may be present in more than one member of a family

o

some patients in whom apparently physiological anisocoria appears to change from side to side with the larger pupil appearing on occasion in one eye and on occasion in the fellow eye

Alternating Horner‘s syndrome: o

Cervical cord lesions, syringomyelia, radiation myelopathy, shy-daeger syndrome



Horner syndrome with 6th nerve palsy together: cavernous sinus lesion



Reasons for Light near dissociation  o

30 times more fibres serve miosis through accommodation than through light.

o

Aberrant innervation of iris sphincter by accommodative neurons 285

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Causes: Unilateral Afferent conduction defect Adie pupil Herpes zoster ophthalmicus Aberrant regeneration of the 3rd nerve Bilateral Neurosyphilis- Argyll Robertson pupils Type 1 diabetes Myotonic dystrophy Parinaud (dorsal midbrain) syndrome Familial amyloidosis Encephalitis Chronic alcoholism



There is no clinical condition in which the light reflex is present but the near response absent but vice versa is not true.



The midbrain centre for the near reflex is probably located more ventrally than the pretectal nucleus and this is why compressive lesions such as pinealomas, preferentially involving the dorsal internuncial neurones involved in the light reflex, spare the near reflex fibres until later.



Pupillary sphincter has atlease 20 segments each of this innervated by different branches of short ciliary nerve.



Wernicke‘s hemianopic pupil occurs in  optic tract lesion

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In afferent (sensory) lesions, the pupils are equal in size. Anisocoria (inequality of pupillary size) implies disease of the efferent (motor) nerve, iris or muscles of the pupil.



blurring of vision worse on waking: Impending central retinal vein occlusion Papillophlebitis NAION



Reverse RAPD: When the pupil of the involved eye is nonreactive or nonfunctional, observe the fellow, normal eye for a ―reverse‖ RAPD (dilation when light is on nonreactive eye, constriction when light is shined on reactive eye).



Morning glory disc is a congenital coloboma of the disc or glial tissue of the disc head. o

It may be associated with congenital forebrain anomalies including basal encephalocele, frontonasal dysplasia and NF-2.

o

May be associated with the papillorenal syndrome, a PAX2 gene mutation.

o

Approximately 30% patients can have subsequent serous RD.

o

PHACE syndrome characterized by posterior fossa brain malformations, large facial haemangiomas and cardiovascular anomalies. It almost exclusively affects females. It is also associated with morning glory disc.



Ophthalmic artery obstruction usually does not produce a cherry-red spot due to underlying choroidal ischemia.



Approximately half of the fibers of the optic nerve decussate in the optic chiasm, and the input to each of the parasympathetic nuclei in the brain stem remains equal. Therefore, relative afferent pupillary defects do not cause anisocoria because any changes in light input are distributed equally to both pupils.

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Retinal migraine: ―Ocular‖ migraine, rare; monocular scotoma or visual loss for minutes to an hour due to retinal or optic nerve ischemia.



Willebrandt‘s knee: Inferonasal optic nerve fibers that decussate in chiasm and loop into contralateral optic nerve before traveling back to optic tract



Inadvertent ocular exposure to anticholinergic agents also has been reported. Patients using scopolamine patches have been noted to have self-limited mydriasis, which has been dubbed ―cruise ship anisocoria‖. Anticholinesterases- flea collar anisocoria



Oculodigital sign of Franceschetti is seen in Leber congenital amaurosis. They also have severe visual impairment from birth. Vision remains stable or worsens slowly over time. These individuals tend to be hyperopic and have photophobia. They also are likely to engage in eye poking or oculo-digital massage, presumably to create light flashes. This behavior is called blindism.



Collier‘s sign: Bilateral eyelid retraction associated with midbrain lesions



Clonazepam and suboccipital craniotomy have been used in the treatment of downbeat nystagmus in patients with Arnold-Chiari malformation.



The differential diagnosis for posterior ischemic optic neuropathy (PION) should include radiation optic neuropathy, status post-coronary artery bypass graft, anemia, acute systemic hypotension, giant cell arteritis (GCA), and syphilis. Well-controlled essential hypertension is associated with anterior ischemic optic neuropathy (AION) but not PION.



In Giant cell arteritis: CRP > 2.45 mg%, ESR >47 mm/hour

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Optic disc drusen may be associated with retinitis pigmentosa, pseudoxanthoma elasticum, angioid streaks and allagile syndrome.



In general, optic nerve compression >1 cm posterior to the globe does not cause disc edema.



A skew deviation is a motility disturbance with a vertical component that does not have a pattern consistent with a discrete muscle underaction or nerve palsy. They are generally due to supranuclear or vestibuloocular dysfunction and generally reflect brainstem disease. They are typically comitant but not always.



Although transient changes in vertical eye movements and slowing of vertical saccades can result from lesions of the paramedian pontine reticular formation, nuclei crucial for the initiation of vertical eye movements are the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (INC).



Isolated sixth nerve palsy in children is most commonly attributable to postviral inflammation occurring 1 to 3 weeks following a nonspecific viral illness of the upper respiratory tract. Recovery is generally complete and occurs within 10 to 12 weeks.



Czarnecki‘s sign: Segmental pupillary constriction with eye movements due to aberrant regeneration of cranial nerve III



Medial rectus contracture is distinctly uncommon in Duane's syndrome. In congenital sixth nerve palsy, it is quite common and results in esotropia in primary position.



Exotropia in primary position can occasionally occur in association with a bilateral INO (A lesion that involves both medial longitudinal fasciculi near their junctions with the third nerve nuclei) resulting in a syndrome called wall-eyed bilateral INO - WEBINO.

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Sixth nerve palsy caused by an intracavernous lesion may present as abduction palsy plus miosis because within the cavernous sinus, sympathetic branches of the paracarotid plexus join the sixth nerve briefly.



In the cavernous sinus, cranial nerves III, IV, and V are relatively protected within the walls of the sinus, but cranial nerve VI runs in the middle of the sinus and is more prone to injury.



Horizontal saccades originate in the contralateral frontal lobe, but either hemisphere can produce ipsilateral saccades if the other hemisphere is damaged.



Oculomotor apraxia is an inability to initiate voluntary horizontal saccades. Congenital oculomotor apraxia is characterized by striking compensatory head movements, and acquired lesions (e.g., resulting from bilateral frontal lobe strokes) usually produce defects in initiation of bidirectional saccades—patients may blink to break fixation and then turn their head to fixate on something else. Pursuits remain relatively unaffected.



Opsoclonus consists of nonstop, random, directionally unpredictable saccades. Ocular flutter consists of spontaneous groups of back-and-forth horizontal saccades that may occur during fixation or at the end of a normal horizontal saccade. Both ocular flutter and opsoclonus may be associated with malignancy, such as metastatic neuroblastoma in children or small cell cancer of the lung in adults. These eye movements may be the first presenting sign of cancer. Multiple sclerosis (MS) also can cause ocular flutter. Square-wave jerks are a microsaccadic fixation disturbance associated with cerebellar diseases of various kinds. Ocular motor dysmetria is a back-and-forth saccadic motion about the point of fixation that occurs following an otherwise normal saccade. It is felt to represent ―overshooting‖ of the intended fixation point. Ocular bobbing is most commonly seen in comatose or quadriplegic patients with large infarcts or brainstem hemorrhages.

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In progressive supranuclear palsy (PSP), downward gaze is generally affected, becoming smaller and slower. Saccades are affected more than pursuits. This is in distinction to the dorsal midbrain syndrome, in which upward saccades are generally affected.



The period between detection of movement and the beginning of smooth pursuit (for tracking) is between 125 and 135 milliseconds. Initiation of saccadic movement requires from 150 to 200 milliseconds from the first perception of a target. The latency in generating a pursuit movement is shorter than that for a saccade movement.



Skew deviation is, by definition, a vertical misalignment of gaze that cannot be assigned to a single nerve or muscle weakness. In the presence of an internuclear opthalmoplegia (INO), the hypertropic eye is often on the same side as the adduction deficit (medial rectus dysfunction).



Upward gaze paresis, light-near dissociation, lid retraction, accommodative abnormalities, and convergence-retraction nystagmus, fixation instability, small-amplitude skew deviation, and papilledema (if ventricular outflow has been compromised) are all features of the dorsal midbrain (Parinaud's) syndrome. Furthermore, skew deviation and papilledema may be seen, depending on the etiology. Lid retraction—the Collier sign—may worsen with attempted upgaze. Convergence-retraction nystagmus is also a response to an effort at upgaze that triggers medial rectus contractions. Hence, this form of ―nystagmus‖ is worsened by upward optokinetic nystagmus (OKN) testing.



Monocular nystagmus has been associated with chiasmal and hypothalamic gliomas. It is also seen in blind eyes, multiple sclerosis (MS), and spasmus nutans—a transient, fastbeating, but low-amplitude nystagmus found during the first 5 years of life.



The classic triad of spasmus nutans includes monocular or dissociated small-amplitude nystagmus, head bobbing, and torticollis. The differential diagnosis for this disorder includes patients with chiasmatic gliomas and subacute necrotizing encephalomyopathy. Features of these two disorders may include optic atrophy, irritability, vomiting, and increased intracranial pressure. Spasmus nutans should be considered only after these two disorders are excluded. Spasmus nutans usually disappears within 2 years of onset.

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Alexander's law describes the increased frequency and amplitude of nystagmus movements accompanying gaze in the direction of the fast-beating component. Of the various forms of nystagmus, downbeat nystagmus most frequently violates Alexander's law.



Upbeat nystagmus can be caused by lesions of the anterior vermis and lower brainstem, as well as drugs and Wernicke's encephalopathy. Downbeat nystagmus may be localized to anatomic structures at the craniocervical junction (e.g., Arnold-Chiari malformation) and may be seen in certain intoxications (alcohol, lithium). Vestibular nystagmus has its etiology within the vestibular system. Periodic alternating nystagmus also can localize to the craniocervical junction but may be seen in other forms of posterior fossa disease. Seesaw nystagmus results from third ventricle tumors or diencephalic lesions involving the connections to the interstitial nucleus of Cajal (INC) and is therefore the most localizing.



Vergence eye movements are felt to have a pathway of their own for stimulating the brainstem motor nuclei. Saccades originate in the contralateral frontal lobe, whereas pursuits arise in the ipsilateral parietal lobe.



Marcus Gunn's ―jaw-wink‖ reflex is an example of synkinesis (abnormal innervation connecting two groups of normally unrelated muscles, such that they contract together), but it is not synkinesis because of aberrant regeneration, which usually follows a peripheral neuropathy or trauma to the nerve. The ―jaw-wink‖ is a congenital/neurogenic phenomenon.



three most common causes of facial nerve overactivity: 1. only essential blepharospasm is believed to be related to basal ganglia dysfunction. 2. Compression of the facial nerve in the cerebellopontine angle by anomalous vessels has been demonstrated in 90% of cases of hemifacial spasm. Tumors in the cerebellopontine angle also can cause hemifacial spasm. 3. Facial myokymia is caused by disease in the pons involving the facial nucleus or fascicle. The most common causes include multiple sclerosis (MS) in adults and pontine glioma in children. 292

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The afferent pupillomotor fibers exit the optic tracts just before the lateral geniculate body (LGB); they do not pass through the LGB. Although postganglionic pupillomotor fibers in the sympathetic pathway do arise from the superior cervical ganglion, the sympathetic pathway leading to these fibers is thought to originate in the posterior hypothalamus. In addition, postganglionic sympathetic fibers enter the orbit with the ophthalmic division of the trigeminal nerve through the superior orbital fissure. The consensual pupillary response is seen because of decussation at the pretectal nuclei. Were the chiasm split in half, consensual responses would be preserved.



In uncal herniation and basilar meningitis, pupil dilation may be the only sign of third nerve palsy. In the case of a cerebral aneurysm, the pupil is usually involved, along with other functions of the third nerve. If the pupil is not involved, it is less likely that an aneurysm is the cause of the palsy. Total oculomotor palsy with a spared pupil in elderly patients usually suggests a microvascular etiology.



Horner's syndrome is defined as ipsilateral ptosis and miosis. Ptosis is secondary to lack of Müller's muscle function. Anhidrosis may or may not be present. Localization of the lesion in Horner's syndrome is part of the clinical workup and sometimes guided by the extent of anhidrosis. First-order lesions (central nervous system) cause ipsilateral anhidrosis of the entire body. Second-order lesions (Pancoast's tumor, neck trauma) cause ipsilateral facial anhidrosis. Third-order lesions (carotid dissection) cause anhidrosis only around the affected eye or none at all. 1. In response to 4% cocaine, a normal pupil will dilate, but a Horner's pupil will dilate poorly. 2. Hydroxyamphetamine (Paredrine) will cause a similar response in preganglionic Horner's syndrome only. Painful Horner's syndrome may be caused by many disorders (neck trauma, migraine, cluster headaches), but spontaneous dissection of the common carotid artery must be ruled out with angiography or magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA)

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It is important to examine the optic disc carefully in all patients with suspected central serous retinopathy. (a/w Optic Disc Pit)



The temporal 30 degrees of a binocular visual field is perceived by the nasalmost retina of the ipsilateral eye only. These ―temporal crescents‖ are represented in the anterior-most occipital lobe. Therefore, a lesion in this area will produce a monocular visual field defect in the far temporal periphery of the contralateral eye, the so-called temporal crescent syndrome. For example, a right anterior occipital lobe lesion would produce a far temporal field defect in the left eye. Similarly, a right posterior occipital lobe lesion may spare the far temporal field in the left eye.



Inferior nerve fibers from the superior retina course anteriorly in Meyer's loop; therefore, lesions affecting Meyer's loop will result in pie-in-the-sky defects contralateral to the lesion.



Although loss of spontaneous venous pulsations is an early sign of papilledema, approximately 20% of normal patients lack venous pulsations.



Pseudotumor cerebri is characterized by (i) increased intracranial pressure on lumbar puncture, (ii) normal neuroimaging studies (although the ventricles may be small), and (iii) normal cerebrospinal fluid (CSF). Papilledema need not be present for the diagnosis.



The various ways to differentiate the NAION from optic neuritis include (i) the absence of pain with eye movement, (ii) the age group affected, and (iii) delayed optic disc filling present in 75% of NAION cases (whereas filling should be normal in optic neuritis).



Collateral vessels (optociliary shunt vessels) at the disc connecting the retinal and choroidal vascular systems may be seen in association with optic nerve meningioma, central retinal vein occlusion (CRVO), sphenoid wing meningioma, long-standing primary openangle glaucoma (POAG), optic gliomas, or chronic papilledema.



Patients with ―papillophlebitis‖ have normal or near normal visual acuity. It may be a form of incomplete central retinal vein occlusion (CRVO) and usually resolves spontaneously within 12 months. 294

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Optic nerve hypoplasia is seen with greater incidence in children of diabetic mothers and following fetal exposure to antiepileptic medications, quinine, or lysergic acid diethylamide (LSD). Optic nerve hypoplasia, particularly bilateral involvement, has been associated with other midline developmental anomalies—that is, absence of the septum pellucidum and hypothalamic-pituitary abnormalities. Endocrine dysfunction is manifested as hypoglycemic seizures and growth retardation. This combination of clinical findings is known as DeMorsier's syndrome in 10% (septo-optic dysplasia).



Babies of IDDM mothers more likely to have superior segment hypoplasia giving rise to inferior field defects.



Nonsecreting pitutary tumors often present with visual field loss, whereas secreting tumors present with endocrine dysfunction. An exception is prolactin-secreting tumor in male patients because the decreased libido and impotence are often not reported early in their course.



Bitemporal macular hemianopia can only arise from compression of the posterior chiasm. Although most lesions responsible for this compression are parasellar, a lesion distant from this site (e.g., a tumor at the base of the brainstem) also may lead to chiasmal compression. This occurs if the lesion causes obstructive hydrocephalus, which enlarges the third ventricle, compressing the chiasm.



The most common location for a cerebral aneurysm with third nerve palsy is the junction of posterior communicating artery and internal carotid artery. PCA-ICA



Third nerve aberrant regeneration never occurs with diabetic oculomotor neuropathy. Aberrant regeneration of the third nerve implies another etiology, such as aneurysm, tumor, inflammation, or trauma. Other classic findings of aberrant regeneration include persistent vertical gaze limitation secondary to simultaneous contraction of superior and inferior recti, and pupillary miosis with elevation, adduction, or depression.



The earliest loss of visual field in chronic papilledema is typically in the inferior nasal quadrant. 295

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Retinal and optic nerve lesions produce field defects that do not generally respect the vertical midline. The presence of a field defect that respects the vertical midline should always arouse suspicion of a neurologic lesion (e.g., cerebrovascular accident, tumor), especially when the disc and field changes do not correspond.



The only location at which oculomotor superior division nerve palsy could occur without affecting additional cranial nerves or the inferior division of cranial nerve III is in the orbital apex.



The location of a lesion affecting the oculomotor nerve can be determined by the associated neurologic deficits. An oculomotor nuclear lesion also involving the ipsilateral cerebral peduncle causes contralateral hemiparesis (Weber's syndrome). Cranial nerve III palsy with contralateral decreased sensation and contralateral tremor (red nucleus affected) is Benedikt's syndrome.



The parasympathetic pupillomotor fibers controlling the pupil are found on the outside of the oculomotor nerve and are the first to be injured with external pressure. Diabetic microvascular insults affect the central fibers of the nerve to a greater degree than the outer fibers, and as a result, pupil involvement is less common ( 50 cells

o

Ask patients about urinary retention

o

Nausea, vomiting and hiccups 307

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Dhaval Patel MD

Interferon-beta makes NMO worse in contrast to MS

Blind spot of mariotte o

physiological blind spot, "blind point", or punctum caecum

o

The first documented observation of the phenomenon was in the 1660s by Edme Mariotte in France. At the time it was generally thought that the point at which the optic nerve entered the eye should actually be the most sensitive portion of the retina; however, Mariotte's discovery disproved this theory.

o

It is not present in octopus eye.



Kestenbaum's number: Kestenbaum proposed a test that is loosely based on the Gunn phenomenon, in which the patient fixes in the distance with one eye, while the other eye is occluded by the palm of the hand. The examiner holds a handlight with fresh batteries 1 inch from the uncovered eye for 5 seconds to allow the pupils to stabilize. The size of the uncovered pupil is then measured with a pupil gauge to the nearest 0.25 mm. The size of the opposite pupil is then measured in the same fashion, and the difference between the two eyes is determined after correcting for any initial anisocoria. This result is called ―Kestenbaum's number.‖



Supranuclear Imbalance: o

Nystagmus: always has slow phase

o

Saccadic ossilation: they are rapid.



PCA: Posterior cortical atrophy is visual variant of Alzheimer disease.



Saccadic eye movements in neurological lesions are reduced in velocity, while restrictive defects manifest normal saccadic velocity with sudden halting of ocular movement.



Patients with tonic pupil may also sweat excessively, sometimes only on one side of the body. The combination of these 3 symptoms – abnormal pupil size, loss of deep tendon 308

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reflexes, and excessive sweating – is usually called Ross‘s syndrome. Mx: Thoracic sympathectomy



Any lesion anterior to the lateral geniculate body would cause the ganglion axon cells to degenerate leading to optic atrophy.



A junctional scotoma is a unilateral central scotoma associated with a contralateral superior temporal field defect. In a patient that comes in with poor vision in one eye, it is very important to check the contralateral visual field for superior temporal field loss. Inferonasal retina fibers cross in the chiasm, passing into the contralateral optic nerve (Willebrand‘s knee). The contralateral optic nerve is compressed near the chiasm. These patients have decreased visual acuity and a relative afferent visual defect.



Monocular defects are prechiasmal except that the far temporal visual field is seen only by one eye. Watch this in an anterior occipital infarct, which can produce a monocular temporal defect.



Patients with postchiasmal defects typically have normal visual acuity, normal pupils, and a normal exam of the ocular fundus. Papilledema, however, may be seen in patients with space-occupying lesions.



Optic nerve sheath decompression does not relieve the orbital congestion and would not be effective in thyroid eye disease.



Alexia and agraphia can occur in dominant angular gyrus involvement.



D15 testing can help distinguish the usual red-green color blindness from tritan axis defects, which are commonly found in dominant optic atrophy.



The inability to initiate voluntary saccades is known as ocular motor apraxia. The patient with the congenital onset of this disorder is unable to initiate voluntary horizontal saccades, 309

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but can make normal vertical saccades. Acquired ocular motor apraxia usually occurs with bilateral cerebral hemisphere disease. Patients with Parkinson's disease show difficulty in initiating multiple repetitive saccades.



Oculoplasty 



Valves in Lacrimal System o

The valve of Rosenmüller is located between the common canaliculus (sinus of Maier) and the lacrimal sac and prevents reflux back into the canalicular system.

o

The valve of Bochdalek is at proximal end of common canaliculus.

o

The valve of Krause (and sinus of Arlt) is located at the junction of the nasolacrimal sac and duct.

o

The spiral valve of Hyrtle and the valve of Taillefer are located within the nasolacrimal duct.

o

Valve of Hasner is at the end of NLD at opening in inferior meatus.

Enophthalmos o

Metastatic schirrous breast carcinoma

o

Malignant syringomas (rare forms of sweat gland carcinoma of eyelid) 310

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Blow-out fracture



A rare variant of dermoid cyst, which has been termed a ―conjunctivoid‖ occasionally, is found in the nasal orbit. These unusual dermoids are lined by conjunctival epithelium and has goblet cells which are PAS positive.



Festoons: malar bags, seen in patients with thyroid orbitopathy



Kimura‘s disease is a rare inflammatory disorder of unknown cause, primarily seen in young Asian males. The disease is characterized by a triad of painless subcutaneous masses in the head or neck region, blood and tissue eosinophilia, and markedly elevated serum immunoglobulin E levels.



Rosai-Dorfman disease: Sinus histiocytosis with massive lymphadenopathy. Large histiocytes in orbital infiltrate have phagocytized lymphocytes, a process called emperipolesis. The histiocytes are S-100 positive.



Algernon Reese 50-50 Rule of Lacrimal Gland Pathology



o

~50% of the lesions originate from epithelial elements of the lacrimal gland and 50% are of nonepithelial origin.

o

Of nonepithelial lesions, 50% are lymphoid tumors and 50% are comprised of various infections and inflammatory pseudotumors. (though now inflammatory are more common 60-80%)

o

Among the epithelial tumors of the lacrimal gland, ~50% are pleomorphic adenomas (benign mixed tumors) and 25% adenoid cystic carcinoma, while the remaining tumors are composed of other types of carcinoma.

Rundle Curve: According to the Rundle's curve, Graves' ophthalmopathy (GO) worsens during an initial phase up to a peak of maximum severity, to then improve and reach a static plateau, with the activity curve preceding the severity curve by a few months.

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Detection of mild pulsatile proptosis: Mild pulsation is best detected on the slit-lamp, particularly during applanation tonometry.



The Zimmerman-McLean-Foster hypothesis: o

In 1979, Zimmerman and colleagues proposed that enucleation of a globe with choroidal melanoma may actually decrease survival, noting the rise in the mortality rate in the years following enucleation from a baseline of 1% per year to a peak of 8% per year during the second year following enucleation.

o

The rate subsequently returned to its baseline level of 1% per year over the next 3 to 5 years.

o

The authors suggested two possible explanations:

o







overwhelming tumor dissemination during surgery



lowering of the host‘s immunologic defense.

data from the COMS published in 1998 demonstrated that no survival advantage was gained by pre-enucleation radiation in more than 1,000 patients with large choroidal melanomas. This result suggests that metastasis occurs prior to enucleation.

Choroidal melanoma o

Mixed type is most common

o

Spindle A has best prognosis

o

Epithelioid has worst prognosis

Pseudoretraction is ruled out by elevating the other side eyelid (appearing ptotic) and making that eye to fixate. In case of pseudoretraction the retracted appearing eyelid assumes normal position once the contralateral eye is made to take up fixation. Causes of pseudoretraction are: ptosis of the other eye, namely acquired apponeurotic type, facial palsy of the same side causing unopposed action of the levator and hemifacial spasm on the opposite side.

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Floppy eyelid syndrome would have a papillary conjunctival reaction. Filaments are not associated with this condition.



Although Marfan's disease is a disorder of collagen synthesis, blue sclera is not seen in this condition? (This is controversial! some reference says it is a cause of blue sclera and some says it is not. I also found one MCQ which answers marfans as an exception of cause of blue sclera. Oh Dear GOD!)



Dermoids are choristomas containing ectodermal elements (skin, hair, fat, and sebaceous glands). Muscle tissue is not expected to be found in such a lesion.



Fraser Syndrome (cryptophthalmos-syndactyly syndrome): cryptophthalmos, renal agenesis, laryngeal stenosis, syndactyly, aural and genital anomalies



Parry‘s sign: Exophthalmos in thyroid disease



Pseudo–von Graefe sign: Lid elevation on adduction or downgaze due to aberrant regeneration of cranial nerve III.



von Graefe's sign: slow or restricted descent of the lid on attempted down gaze seen in thyroid ophthalmopathy.



Limbal dermoids are usually an isolated abnormality but may on occasion be part of Goldenhar's syndrome, Treacher Collins' syndrome or the naevus sebaceous syndrome of Jadassohn.



Very rarely, capillary haemangioma is part of a wider syndrome Maffucci's (multiple systemic haemangiomata and bone lesions) or Kasabach-Merritt (haematological abnormalities).

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JACOB‘s ulcer: BCC or rodent ulcer of an eyelid.



Multiple endocrine neoplasia, type IIb (Sipple-Gorlin syndrome), is associated with enlarged corneal nerves, not type 1.



Phthirus pubis (crab louse) infests pubic hair and eyelashes and is transmitted by sexual contact. Treatment is by mechanical removal or with bland ointments applied to the lids to suffocate adult lice. Physostigmine is effective as a respiratory poison against the lice but has many ocular side effects, limiting its effectiveness. Demodex is a normal commensal in adults living in meibomian glands. Classically, ―sleeves‖ are found at the base of lashes, indicating Demodex infestation. Treatment is through lid scrubs. Collarettes are found more commonly with staphylococcal blepharitis.



Conjunctival lymphoma: painless, salmon-colored lesion on the bulbar conjunctiva.



Mucoepidermoid carcinoma: aggressive variant of squamous cell carcinoma. It should be suspected in cases involving recurrence after primary excision or in which no invasion into the globe occurs. It typically occurs in patients over age 60 and involves cells that are able to produce malignant mucussecreting cells (goblet cells).



Basal cell carcinoma is the most common malignant tumor of the eyelid skin, but squamous cell carcinoma is the most frequently occurring malignancy of the conjunctiva. Squamous papillomas are benign lesions that can, on rare occasions, undergo malignant transformation.



Conjunctival malignant melanoma: pigmented elevated lesion, enlarges progressively with time. It occurs most commonly on the bulbar conjunctiva. These tumors are very vascular, and dilated vessels may be seen feeding the tumor. The prognosis is generally better than cutaneous melanomas. A systemic metastatic work-up is necessary to direct treatment. Conjunctival melanomas can arise de novo (30%), from nevi (40%), or from primary acquired melanosis (30%). A conjunctival nevus: flat or slightly elevated pigmented lesion of the bulbar conjunctiva. It may have epithelial inclusion cysts within its substance. These lesions can grow or 314

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enlarge during adolescence or with pregnancy. Suspicious lesions should be biopsied to rule out melanoma. Primary acquired melanosis (PAM): unilateral condition found in middle-aged white people. These multiple, superficial, flat patches of pigmentation develop into malignant melanoma in 20% to 30% of these patients. Excisional biopsy should be performed on any suspicious nodular lesions. Racial or ocular melanosis: most commonly in pigmented individuals and represents benign collections of melanin in the conjunctiva. It appears as a perilimbal dusting of light brown pigment. No malignant potential exists.



Congenital NLDO: o

It is estimated that congenital nasolacrimal duct obstruction occurs in 73% of newborns but only 6% are symptomatic.

o

The most common site of obstruction is at the valve of Hasner.

o

In a dacryocystocele, there is concurrent obstruction in the common canaliculus - therefore, compression of the sac does not show reflux.

o

A mucocele increases the risk of orbital cellulitis and early probing is recommended. The success of first probing in congenital nasolacrimal duct obstruction approaches 90%.

o

Probing for congenital NLDO should not be done before 9 months??

o

In dacryocystocele, early NLD probing is required.



Synophrys is extension of the eyebrows to the midline. It can occur in naturally hairy individuals who are otherwise normal. It also occurs in Cornelia de Lange syndrome which is characterized by mental retardation, limb reduction, flared nostrils, and hirsutism.



Involutional ptosis should not be confused with myasthenic ptosis because it frequently worsens towards the end of the day. This is because of fatigue of Müller muscle, which has to work harder to keep the lid elevated.



After permanent punctal occlusion with cautery, 20-30% rate of recanalization is expected. 315

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potential ocular complications associated with nevus of Ito & nevus of Ota: a. Open-angle glaucoma. b. Malignant melanoma.



Squamous cell carcinoma is the most common malignant tumour of the conjunctiva and typically affects the limbus. It typically occurs in people over the age of 50. Because of its limbal location, it may sometimes be misdiagnosed as pterygium or pingueculae.



SCC is rare amongst healthy young people, its occurrence in patients under the age of 50 should raise the possibilities of AIDS. In African countries where AIDS is endemic, SCC conjunctiva is now recognized as an AIDS defining disease.



Basal cell carcinoma that involves the medial canthus is the most likely to invade the deep orbital structure.



Recently, intralesional injection of OK-432 (group A Streptococcus pyogenes of human origin which is used as an anticancer agent) has been reported to shrink orbital lymphangioma.



Axis of optic canal make 36 degree angle with the midline.



Melanoma with best prognosis: Iris. (can be excised completely) If isolated to the iris, malignant melanoma behaves in a more benign fashion than does melanoma of the choroid. Involvement of the ciliary body or choroid portends a poorer prognosis. Metastases are rare, and localized iridectomy may remove the tumor entirely. These lesions may be pigmented or amelanotic. Ipsilateral hyperchromia may be present. Iris melanoma has spindle B cells(?)



Epiphora is watering due to lacrimal outflow abormality. 316

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Complications of chronic dacryocystitis are all except entropion.



Everbusch operation for Ptosis: Skin side

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Blascovisc operation for Ptosis: Conjunctiva Side



ROPLAS: Regurgitaion over pressure on lacrimal sac



Entropion does not have any subtype like paralytic entropion.??



Congenital acquired fistula: probe test positive, both opening probe touch…why to differentiate?  as it does not close its own.. whereas acquired one closes once u treat the cause.



Sac dilatation: atonicity, long term



Quikert suture: entropion and ectropion: place knot where u want lid to be.If entropion, at margin and vice versa.



RB patients will least likely to have low IOP, microphthalmos, Cataract.



Iris Nevus and Melanoma: o

An iris nevus can be distinguished from a melanoma by: size (1, phosphoglucose to isomerase ratio should be >2.



Molluscum contagiosum: large poxvirus o

Syndrome associated are weskott-aldrich syndrome and AIDS



PIEZOMETRY: orbitometry



Hypotelorism is seen in patau syndrome.



Iliff's sign: This involves everting the eyelid and asking the patient to look up. Failure of the eyelid return to its normal position when the patient looks up indicates poor LPS muscle function.



The ETA as described by Baylis is an accurate technique for ptosis correction in patients with poor EPMs. o

External Tarsal Aponeurectomy ETA

o

millimeter for millimeter correction of ptosis 330

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not only elevates the upper eyelid but also provides a spacer or graft for the lower eyelid

dictyoma o

A benign tumor of the ciliary epithelium with a netlike structure resembling embryonic retina.

o

aka medulloepithelioma

o

Nonteratoid and teratoid varieties (presence of heteroplastic elements) are known. Both can be benign or malignant.

o

The teratoid type may contain cartilage and/or rhabdomyoblasts.



Cicatricial entropion is seen in  trachoma, due to cicatritial contraction of conjunctiva.



Removal of the palpebral part of lacrimal gland leads to the gland becoming non-secreting.



The Neosynephrine test is an evaluation of the effect of Muller‘s muscle contraction on the degree of ptosis. One drop of 2.5% phenylephrine is placed in the eye. After 5 minutes, the degree of ptosis is reevaluated. The phenylephrine causes contraction of the sympathetic Horner‘s muscle, sometimes causing dramatic improvement in the degree of ptosis. If phenylephrine corrects the ptosis completely, many surgeons elect to perform a Muller‘s muscle resection as opposed to a levator resection.



Whitnall's orbital tubercle is located entirely on the zygomatic bone approximately 2 mm inferior to the frontozygomatic suture line.



Rosengren-Doane‘s Lacrimal Pump Mechanism: o

Contraction of the orbicularis muscle provides a positive pressure in the tear sac, forcing tears into the nose through the valve of Hasner.

o

Once the eyelids open and move laterally, a negative pressure is produced in the tear sac, which is maintained by the valve of Hasner. 331

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The lacrimal sac fossa is bordered by the anterior lacrimal crest of the maxillary bone and the posterior lacrimal crest of the lacrimal bone. In a dacryocystorhinostomy (DCR), the ostomy is created at the maxillolacrimal suture line located in the lacrimal sac fossa.



Pseudostratified columnar epithelium lines the nasolacrimal sac, duct, and canaliculi.



The slight indentation or groove in the central aspect of the eyelid margin is the sulcus intermarginalis of Graefe or the gray line which corresponds to the lid's orbicularis muscle layer, the muscle of Riolan. It is not the mucocutaneous junction of the eyelid margin. The mucocutaneous junction occurs posterior to the eyelashes near the opening of the meibomian glands.



The Reese-Ellsworth classification was developed in the 1950s as a guide for predicting visual prognosis in eyes treated by methods other than enucleation. It has been used erroneously to predict patient prognosis for life.



The capillary hemangiomas are characteristically high flow lesions, in contrast to cavernous hemangiomas, which are hemodynamically low flow.



Erdheim-Chester disease is a multisystem disease with lipogranuloma formation in the liver, heart, kidneys, and bones. Histologically, these lipogranulomas contain histiocytes, Touton giant cells, lymphocytes, and plasma cells. Ophthalmic manifestations of this disease can include proptosis and xanthelasma-like skin lesions



Euryblepharon is a horizontal widening of the palpebral fissure. Epiblepharon is commonly seen in Asian children and is caused by altered lower eyelid retractor (aponeurosis) attachments, which allow overriding of the pretarsal orbicularis above the eyelid margin. The result is posterior misdirection of the lower eyelashes and potential keratopathy.

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Blepharochalasis is a rare inherited condition that occurs more commonly in young females than in males and consists of repeated bouts of eyelid inflammation and edema. Recurrent idiopathic eyelid swelling eventually leads to blepharoptosis secondary to dehiscence or attenuation of the levator aponeurosis. Anterior bulging of the lacrimal gland or orbital fat may also occur. Dermatochalasis refers to the excess eyelid skin that occurs with aging. Steatoblepharon refers to the bulging of orbital fat that also commonly occurs with aging or attenuation of the orbital septum. Blepharospasm may be associated with blepharoptosis and entropion caused by aponeurotic dehiscence. Dermatochalasis, steatoblepharon, and blepharospasm typically are not associated with repeated bouts of eyelid edema and inflammation.



A retroblepharoplasty (transconjunctival blepharoplasty) or blepharoplasty via the transconjunctival approach is used in lower eyelid blepharoplasty, NOT upper eyelid blepharoplasty.



The two most common causes of DCR failure are obstruction at the common canaliculus and obstruction at the bony ostomy site.



Studies have demonstrated that in up to 50% of patients tested, creation of a monocanalicular state resulted in symptomatic epiphora. So upper or lower, canalicular repair should be done leaving open the possibility of future trauma and disease to the remaining canaliculus, and considering present surgical techniques with a high success rate of repair, many recommend attempted repair of all recent canalicular lacerations.



Pneumococci are the most common organism causing acute dacryocystitis. Other organisms include streptococci, diphtheroids, Klebsiella pneumonia, Haemophilus influenzae, Pseudomonas aeruginosa, and mixed organisms. Actinomyces and fungi, such as Candida, are also frequently seen.



Although Actinomyces israelii is associated most frequently with acute canaliculitis, multiple organisms have been shown to cause this disorder. Streptomyces, Arachnia 333

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propionica (previously Streptothrix), Nocardia, and fungi, such as Candida albicans and Aspergillus niger, have been documented to cause canaliculitis.



Chronic dacryoadenitis: nocardia



Nocardia is acid fast, actinomyces is non acid fast.



Of patients with mucormycosis, 70% have diabetes mellitus, 5% have renal disease, 18% have other immunosuppressed states, 3% have leukemia, and only 4% have no systemic illness.



The clinical signs of thyroid-related orbitopathy can be generally grouped into two independent manifestations: type 1 and type 2 orbitopathy. Type 1 orbitopathy comprises symmetric proptosis with symmetric eyelid retraction, minimal orbital inflammation, and minimal extraocular muscle inflammation or restrictive myopathy. Type 2 orbitopathy comprises extraocular muscle myositis, restrictive myopathy, orbital inflammation, and chemosis. Compressive optic neuropathy is more commonly a feature of type 2 orbitopathy.



Fuchs' adenoma: o

Fuchs' reactive hyperplasia, coronal adenoma, Fuchs' epithelioma, benign ciliary epithelioma

o

proliferative rather than neoplastic

o

The lesion is composed of basement membrane material (type IV collagen and laminin), acid mucopolysaccharides, glycoproteins, and proliferating cells of the nonpigmented ciliary body epithelium.

o

It rarely may cause localized occlusion of the chamber angle.

o

A metastatic lesion from a malignant melanoma would display mostly pleomorphic, pigmented cells with malignant features (high nuclear-cytoplasmic ratio, nucleoli, and mitotic figures). 334

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Homer-Wright rosettes are characterized by cells that line up around an area containing cobweb-like material, but no acid mucopolysaccharides are present. These rosettes are not specific for retinoblastoma and are found also in neuroblastoma and medulloepithelioma. Rhabdomyosarcoma displays no rosette formation. In contrast, Flexner-Wintersteiner rosettes are the characteristic rosettes of retinoblastoma but are not always present. The presence of Flexner Wintersteiner rosettes makes the diagnosis of a well-differentiated retinoblastoma. In Flexner-Wintersteiner rosettes, the cells line up around an apparently empty central lumen. However, special stains show hyaluronidase-resistant acid mucopolysaccharides in the lumen.





Malignant Melanoma Eyelid Skin o

all are rare representing less than 1% of eyelid tumors.

o

Superficial spreading melanoma accounts for 80% of cases. Superficial spreading melanoma occurs both in sun-exposed and in nonexposed areas.

o

lentigo maligna and nodular melanoma each occur in 10% of cases. Lentigo maligna, also known as melanotic freckle of Hutchinson, is sun induced.

o

Both have a long horizontal growth phase before invading the deeper tissues.

o

Nodular melanoma is more aggressive with earlier vertical invasion and has worst prognosis.

Fibrous histiocytoma o

slightly more common in men

o

Most are benign (>90%), and have a storiform, or matlike, pattern on histopathology.

o

Most common mesenchymal tumor of orbit in adults

o

It is usually very firm and can displace other orbital structures.

o

Ten percent have metastatic potential. Another 16% are termed ―locally aggressive‖ but not frankly malignant.

o

CD 34 positive on IHC, vimentin +, S100 -

o

Most common site is superonasal orbit 335

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Pagetoid spread: Sebaceous cell carcinoma and PAM



Papilloma is treated with interferon alpha 2b. in recurrent cases oral cimetidine can be used.



Capillary hemangioma in PHACE syndrome:



o

Caution while using Propanolol

o

Due to Increased stroke risk

IgG4-Associated Orbital Inflammatory Disease o

first recognized by the Japanese in 2001 in autoimmune pancreatitis (AIP)

o

number of diseases have now been recognized as part of the spectrum of IgG4-RD, and these include sclerosing cholangitis, Mickulicz disease, Küttner tumor (sclerosing sialadenitis), Riedel thyroiditis, multifocal fibrosis, Ormond disease (idiopathic retroperitoneal fibrosis), and others

o

evidence of a role for Helicobacter pylori

o

Several recognizable patterns of orbital disease may occur with IgG4-ROD

o



Dacryoadenitis,



Dacryoadenitis (bilateral) with enlarged parotid and submandibular glands (previously called Mickulicz disease



Orbital myositis



Sclerosing orbital disease

Treatment 

empirical use of corticosteroids



methotrexate, mycophenolate, and cyclophosphamide.



rituximab.

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Community Ophthalmology 



WHO declared the year 1976 as "The Year of Prevention of Blindness" and stated that the 6 main causes of blindness were: o

Cataract

o

Trachoma

o

Xerophthahnia

o

Onchocerciasis

o

Glaucoma and

o

Trauma

Severe visual loss is defined as a vision of 20/200 or worse. Profound visual loss is defined as visual acuity worse than 20/400. The World Health Organization (WHO) defines blindness as vision worse than 20/400. The World Health Organization (WHO) defines low vision as vision worse than 20/60. Eyes with severe visual loss (20/200 or worse) are considered legally blind in the United States.



In 1948, the first randomized clinical trial (RCT) was published on the use of streptomycin in pulmonary tuberculosis.



The Consolidated Standards of Reporting Trials (CONSORT) statement, which is ascribed to by leading peer-reviewed journals, sets a high standard of quality in the 337

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reporting of randomized clinical trials (RCTs) in order to allow the reader to adequately judge the quality of the study.



Average visual acuity is significantly better than 20/20 in individuals younger than 60 years.



Worldwide, more adults than children are blind.



Pediatric blindness most commonly occurs from corneal scarring and retinal diseases.



Studies have shown that ethnicity does not affect the incidence of ophthalmia neonatorum, but socioeconomic status certainly does.



Ophthalmia neonatorum treatment: o

Chlamydiae trachomatis: Oral erythromycin 50 mg/kg in four divided dose for 14 days

o

Gram-positive bacteria: Erythromycin 0.5% e/o QID

o

Gram-negative bacteria: gonococcal 

Systemic: Inj. ceftriaxone 25–50 mg/kg IV or IM single dose X 7 days



Inj. cefotaxime 100 mg/kg IV or IM single dose X 7 days



Topical: saline lavage hourly, bacitracin eye ointment qid, or penicillin drops 5000-10,000 IU/ml



Worldwide, 135 million people have vision
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