Retina & Vitreous - Postgraduate MD Ophthalmology Notes- Dr. Prabhat Devkota,MD

PG Notes: Vitreous & Retina Dr. Prabhat Devkota, MD
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drprabhatdevkota@gmail.com
Postgraduate Ophthalmology Exam Notes
© First Edition, 2026
Author
Dr. Prabhat Kiran Devkota, MBBS(TU), MD(NAMS)
MBBS – Chitwan Medical College Teaching Hospital, Institute of
Medicine, Tribhuvan University (TU), Nepal
MD (Ophthalmology) – Lumbini Eye Institute & Research Center,
National Academy of Medical Sciences (NAMS), Nepal
Email: drprabhatdevkota@gmail.com
All rights reserved.
No part of this publication may be reproduced, stored in a retrieval system,
transmitted, or distributed in any form or by any means, whether electronic,
mechanical, photocopying, recording, or otherwise, without prior written permission
of the author, except for brief quotations used for academic, educational, or review
purposes.
Disclaimer
This book is intended solely as an educational and revision resource for postgraduate
ophthalmology trainees and practitioners. While every effort has been made to ensure
the accuracy and reliability of the information presented, the author does not
guarantee that all content is free from errors or omissions. Readers are encouraged to
consult standard textbooks, peer-reviewed literature, institutional guidelines, and
current evidence-based recommendations before making clinical decisions.
The author shall not be held responsible for any consequences arising from the use of
information contained in this book.

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Preface
This book is a compilation of notes gathered during my preparation for the Final MD
Examination in Ophthalmology. The material has been collected from standard
textbooks, lecture notes, journals, online resources, and personal study notes.
Topics have been organized in a chapter-wise format to facilitate quick revision and
easy reference. Although there are many excellent ophthalmology resources available,
I felt it worthwhile to compile and share these notes with future ophthalmology
trainees and colleagues.
This work represents a continuous learning process rather than a definitive textbook.
Suggestions, corrections, contributions, and constructive feedback are greatly
appreciated and will help improve future editions.
I sincerely hope this book serves as a useful companion in your postgraduate
ophthalmology journey.
Good Luck and Best Wishes!
For comments, suggestions, or contributions, please contact:
Dr. Prabhat Devkota, MD

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TABLE OF CONTENT
Topics
1. RETINAL VASCULAR DISORDERS
2. ANGIOGENESIS & ANTI-VEGF THERAPY
3. CENTRAL SEROUS CHORIORETINOPATHY
4. RETINOPATHY OF PREMATURITY
5. HYPERTENSIVE RETINOPATHY
6. DIABETIC RETINOPATHY
7. AGE-RELATED MACULAR DEGENERATION
8. RETINAL DETACHMENT & PERIPHERAL RETINAL DISORDERS
9. MACULAR DISORDERS
10.INHERITED RETINAL DISORDERS
11.RETINAL & CHOROIDAL TUMORS
12.RETINAL TOXICITY
13.OCULAR IMAGING
14.RETINAL LASERS & PHARMACOTHERAPY
15.VITREORETINAL SURGERY

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RETINAL VEIN OCCLUSION (RVO)
1. INTRODUCTION
Retinal vein occlusion (RVO) is a common retinal vascular disorder characterized by
obstruction of venous outflow from the retina, leading to venous congestion,
hemorrhage, retinal ischemia, and vision loss. It is the second most common retinal
vascular disease after diabetic retinopathy.
Visual impairment in RVO results from:
• Macular edema
• Macular ischemia
• Retinal and vitreous hemorrhage
• Neovascular complications → neovascular glaucoma (NVG)
2. CLASSIFICATION
A. Anatomical Classification
1. Branch Retinal Vein Occlusion (BRVO)
2. Central Retinal Vein Occlusion (CRVO)
3. Hemicentral / Hemiretinal Vein Occlusion (HCRVO / HRVO)
B. Clinical Classification (CRVO)
1. Non-ischemic CRVO (Venous stasis type)
2. Ischemic CRVO (Hemorrhagic type)
3. Impending CRVO
3. EPIDEMIOLOGY
• Incidence increases with advancing age
• Majority occur after 60–65 years
• BRVO is 3 times more common than CRVO
• Usually unilateral
• Risk of second RVO:
o Same eye: ~2.5%
o Fellow eye: ~11–12% over 4 years
4. PATHOGENESIS
A. Virchow’s Triad
1. Altered blood flow – venous stasis
2. Vessel wall abnormality – arteriosclerosis
3. Hypercoagulability

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B. VEGF-Mediated Mechanism
Venous obstruction →
↑ Venous pressure →
Capillary dilatation and leakage →
Retinal hypoxia →
↑ VEGF production →
• Macular edema
• Retinal & iris neovascularization
• Breakdown of blood-retinal barrier
5. RISK FACTORS
A. Systemic Risk Factors
Modifiable:
• Hypertension (m/c)
• Diabetes mellitus
• Hyperlipidemia
• Smoking
• Obesity
• Oral contraceptive pills / HRT
• Dehydration
• Hyperviscosity states:
o Polycythemia
o Leukemia
o Multiple myeloma
• Thrombophilic disorders:
o Hyperhomocysteinemia
o Antiphospholipid antibody syndrome
o Protein C/S deficiency
o Factor V Leiden mutation
Non-modifiable:
• Age
• Genetic predisposition
• Structural abnormality of retinal vessels
B. Ocular Risk Factors
Modifiable:
• Primary open-angle glaucoma / ocular hypertension
• Thyroid eye disease
Non-modifiable / Structural:
• Optic disc drusen
• Tilted optic disc
• Short posterior ciliary arteries compromise

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6. SYSTEMIC EVALUATION
Routine Investigations (All Patients)
• Blood pressure
• Fasting blood sugar / HbA1c
• Lipid profile
• Complete blood count
• ESR / CRP
• Renal function tests
• ECG
Selective Investigations
(Young patients <50 years, bilateral RVO, recurrent RVO, no risk factors)
• Plasma homocysteine
• Thrombophilia profile
• ANA, APLA
• Serum ACE
• Chest X-ray
• Carotid Doppler (rule out ocular ischemic syndrome)

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BRANCH RETINAL VEIN OCCLUSION (BRVO)
7.1 Pathogenesis
• Occurs at arteriovenous crossings
• Artery and vein share a common adventitial sheath
• Thickened atherosclerotic artery compresses underlying vein
• Turbulent flow → endothelial damage → thrombosis
• BRVO is always ischemic
7.2 Types
1. Major BRVO
2. Macular BRVO
7.3 Clinical Features (Major BRVO)
• Sudden, painless visual loss (if macula involved)
• Most common site: superotemporal quadrant
• Fundus findings:
o Sectoral flame-shaped and dot-blot hemorrhages
o Dilated, tortuous vein
o Cotton wool spots
o Retinal edema
o Macular edema
7.4 Complications
• Chronic cystoid macular edema (most common)
• Neovascularization:
o NVE more common than NVD
• Vitreous hemorrhage
• Epiretinal membrane
7.5 Investigations
• OCT – gold standard for macular edema
• FFA (around 6 to 8 weeks)
o Capillary non-perfusion
o Leakage from incompetent capillaries
o 5 disc areas of non-perfusion → high NV risk
7.6 Management of BRVO
A. Observation
• Good vision (≥6/9)
• Improving macular edema

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B. Macular Edema (First-Line)
• Anti-VEGF therapy
o Ranibizumab (BRAVO trial)
o Aflibercept (VIBRANT trial)
o Bevacizumab
C. Second-Line / Adjunct
• Dexamethasone intravitreal implant (Ozurdex)
• Grid laser photocoagulation (rarely used now)
D. Neovascularization
• Sectoral panretinal photocoagulation
• Anti-VEGF as adjunct
7.7 Follow-Up (BRVO)
• Monthly follow-up
• At each visit:
o Visual acuity
o IOP
o Dilated fundus examination
• OCT to monitor macular edema
• Baseline FFA after ~4 weeks
• Repeat FFA if suspected CNP/NVE
• After laser: monthly follow-up × minimum 6 months
• Control systemic risk factors with internist
7.8 Prognosis (BRVO)
• Overall prognosis is good
• ~50% develop collaterals within 6 months
• VA improves to ≥6/12 in majority
• Poor prognostic factors:
o Persistent CME
o Macular ischemia
o Enlarged FAZ
• NVD: ~10%
• NVE: ~25%
• Timely laser prevents vitreous hemorrhage

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MACULAR BRVO
Definition
Occlusion of a tributary vein draining the macula, usually from superior or inferior
temporal vein.
Clinical Features
• Sudden painless central vision loss
• Normal anterior segment
• Localized macular hemorrhages
• Few cotton wool spots
• Foveal edema
FFA
• Capillary non-perfusion
• Incomplete petalloid hyperfluorescence
• Neovascularization does not occur
Differential Diagnosis
• Exudative ARMD
Treatment
• Anti-VEGF injections
• Grid laser avoided in anti-VEGF era

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CENTRAL RETINAL VEIN OCCLUSION
Site of Occlusion
• Ischemic CRVO: At or just posterior to lamina cribrosa → few collaterals
• NonIschemic CRVO: 6mm behind lamina cribrosa → more collaterals
• Central retinal artery and vein share a common sheath
Pathogenesis:
Arteriosclerosis of adjacent Central Retinal Artery (CRA)
↓
Compression of Central Retinal Vein (CRV) at lamina cribrosa
↓
Turbulence of blood flow in CRV
↓
Damage to venous endothelium
↓
Thrombus formation → Venous occlusion
↓
Elevated venous and capillary pressure
↓
Stagnation of blood flow
↓
Retinal hypoxia / ischemia
↓
Capillary endothelial damage & breakdown of blood-retinal barrier
↓
Extravasation of blood constituents → retinal hemorrhages & edema
1 Non-Ischemic CRVO
• VA usually >6/60
• Mild hemorrhages
• No RAPD
• Minimal capillary non-perfusion
• 30% may convert to ischemic
2 Ischemic CRVO
• VA <6/60
• Relative afferent pupillary defect
• “Tomato ketchup” fundus
• Extensive hemorrhages and cotton wool spots

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• FFA: >10 disc areas of non-perfusion
(Indication of FFA in CRVO: to look for macular ischemia, CNP areas, conversion to
ischemic)
• High risk of NVI and NVG (critical period of neovascularization 7 months to 2
years)
• 100-day glaucoma
Feature Ischemic CRVO Non-Ischemic CRVO
Age Old Age Young Age
Frequency ~20–25% ~75–80%
VA Poor, often ≤6/60 Mildly reduced / near normal (>6/60)
RAPD Usually present Rare
VFD Severe, generalized Mild / sectoral
Fundus
Marked retinal hemorrhages, CWS
common, disc edema
Mild hemorrhages, few/no CWS, mild
disc swelling
ME Often severe Mild–moderate
NV
High → neovascular glaucoma
common
Low
OCTA
Extensive capillary non-perfusion,
reduced FAZ flow
Minimal capillary non-perfusion,
preserved FAZ flow
FFA
Increased AV transit time
Large areas (>10 DA) of capillary
non-perfusion
Delayed AV transit time
Minimal / patchy (<10 DA) non-
perfusion
ERG
Markedly reduced b-wave
amplitude & reduced b:a ratio
Near normal b-wave
Prognosis Poor; high risk of complications Better
Complications
NVG, vitreous hemorrhage, macular
ischemia
Mild ME, fewer complications
Impending CRVO
• Younger patients
• Mild venous dilatation
• Few hemorrhages
• May resolve or progress
Indeterminate CRVO
• Intraretinal hemorrhage obscures the angiographic determination of perfusion
status.

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Hemicentral Retinal Vein Occlusion
• Occlusion of one trunk of CRV
• Sectoral hemorrhages + disc edema
• Prognosis better than CRVO
10. Management of CRVO
Systemic
• Control hypertension, diabetes, lipids
• No proven role of anticoagulants
Macular Edema
• Anti-VEGF (CRUISE, COPERNICUS trials)
• Dexamethasone implant
• Intravitreal triamcinolone (SCORE)
Neovascularization
• PRP only after NV develops
• Anti-VEGF adjunct
Surgery:
• PPV; Indications: Persistent VH, Persistent ME, ERM with ME, TRD
• Radial Optic Neurotomy
11. Follow-Up (CRVO)
Initial VA Follow-up
≥6/12 Every 1–2 months
6/18–6/60 Monthly × 6 months
<6/60 Monthly × 6–12 months
• Gonioscopy at every visit
12. PROGNOSIS (CRVO)
• Best predictor: initial visual acuity
• Non-ischemic → favorable
• Ischemic → poor
• Presence of disc collaterals → better outcome
13. IMPORTANT CLINICAL TRIALS
• BRAVO / CRUISE – Ranibizumab
• VIBRANT / COPERNICUS – Aflibercept
• GENEVA – Ozurdex
• SCORE – Triamcinolone
• CRVO Study – PRP only after NV

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Q. How Glaucoma predisposes CRVO?
Glaucoma
↓
↑ Intraocular Pressure (IOP)
↓
Compression of Central Retinal Vein
(at the Lamina Cribrosa)
↓
Venous Obstruction
↓
Venous Stasis
↓
Endothelial Damage
↓
Thrombus Formation
↓
Central Retinal Vein Occlusion (CRVO)
CRVO High-Yield
• VFD: Central scotoma
• Commonest NV site: Iris (NVI → NVG)
• Ischemic Index: CNP/Total retinal area
• ERG:
o a-wave: Photoreceptors
o b-wave: Bipolar + Müller cells
o c-wave: RPE
o d-wave: OFF bipolar cells

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CLINICAL TRIALS IN RVO
I. BRANCH RETINAL VEIN OCCLUSION (BRVO) STUDIES
1. BVOS (Branch Vein Occlusion Study, 1984)
• Purpose: Evaluate scatter argon photocoagulation for preventing NV and vitreous
hemorrhage; improve VA in ME.
• Inclusion: Major BRVO ± NV, ME with reduced VA.
• Outcome: VA, development of NV or vitreous hemorrhage.
• Results/Conclusion:
o Scatter laser prevents NV and VH if applied after NV develops.
o Argon laser improves VA in eyes with ME.
• Clinical Implication: Laser still has historical relevance; now largely replaced by
anti-VEGF therapy.
2. BRAVO (Ranibizumab for BRVO, 2007/2010)
• Purpose: Evaluate intravitreal ranibizumab (RBZ) vs sham in ME due to BRVO.
• Inclusion: ME involving fovea, CFT ≥250 μm, BCVA 20/40–20/400.
• Outcome: Mean change in BCVA at 6 months.
• Results:
o Rapid, effective VA improvement.
o Low ocular and systemic adverse events.
• Clinical Implication: Gold standard for BRVO ME.
• Exam Pearl: BRAVO = Ranibizumab in BRVO
3. SCORE-BRVO (2009)
• Purpose: Compare intravitreal triamcinolone vs grid laser.
• Outcome: Similar VA gain; steroids ↑ risk of cataract & IOP rise.
• Clinical Implication: Steroids reserved for selected cases; laser historical
comparator.

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4. VIBRANT (Aflibercept for BRVO, 2016)
• Purpose: 2 mg intravitreal aflibercept vs grid laser.
• Outcome: ≥15-letter gain at weeks 24 and 52.
• Results: Anti-VEGF maintained control of ME and VA.
5. MARVEL (2015)
• Purpose: Compare intravitreal bevacizumab (BVZ) vs ranibizumab (RBZ).
• Outcome: Mean BCVA change at 6 months; CRT; NV development.
• Result: Both BVZ and RBZ significantly improve VA.
Summary – BRVO
Therapy Trial Key Point
Anti-VEGF BRAVO, VIBRANT, MARVEL First-line therapy for ME
Steroids SCORE-BRVO Second-line; risk of cataract/IOP rise
Laser BVOS Historical; now largely replaced
II. CENTRAL RETINAL VEIN OCCLUSION (CRVO) STUDIES
1. CVOS (Central Vein Occlusion Study, 1988)
• Purpose: Assess early PRP for preventing INV in ischemic CRVO; grid laser for ME.
• Inclusion: CRVO, age ≥21, VA ≥ light perception, IOP <30 mmHg.
• Results:
o Prophylactic PRP does NOT prevent INV.
o Grid laser reduces angiographic ME but does not improve VA.
o Frequent follow-up (monthly for 6 months) recommended.
• Clinical Implication: PRP only after NV develops.
• Exam Pearl: CVOS → PRP only after NV

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2. CRUISE (Ranibizumab in CRVO, 2007/2010)
• Purpose: RBZ vs sham for ME in CRVO.
• Outcome: Mean BCVA improvement at 6 months.
• Results:
o ~45% gained ≥15 ETDRS letters.
o Significant CMT reduction.
• Clinical Implication: First-line therapy for CRVO ME.
• Exam Pearl: CRUISE = Ranibizumab in CRVO
3. COPERNICUS (Aflibercept in CRVO, 2012)
• Purpose: Intravitreal aflibercept (2 mg) for ME secondary to CRVO.
• Outcome: Proportion gaining ≥15 letters at 24 weeks.
• Results: Significant VA improvement, reduced CMT and NV progression.
• Clinical Implication: Strong evidence for aflibercept.
4. GENEVA (Ozurdex/Dexamethasone implant, 2004/2011)
• Purpose: Dexamethasone implant vs sham for ME in CRVO & BRVO.
• Outcome: ≥15-letter BCVA improvement, speed of visual improvement.
• Results: VA improved in ~30%; effect lasts ~5–6 months; ↑IOP (12–15%), cataract
risk.
• Clinical Implication: Steroids effective but require monitoring.
• Exam Pearl: Ozurdex → IOP rise & cataract
5. SCORE-CRVO (2004/2009)
• Purpose: Triamcinolone (1 mg vs 4 mg) vs observation for CRVO ME.
• Results:
o 1 mg safer; 4 mg ↑ complications.
o ~26–27% gained ≥15 letters.

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• Clinical Implication: 1 mg preferred; steroid therapy reserved for selected cases.
6. COPERNICUS & GALILEO (VEGF Trap/Eye, 2012–2013)
• Purpose: Evaluate efficacy and safety of VEGF Trap-eye (aflibercept) in CRVO ME.
• Outcome: ≥15-letter BCVA gain at 24 weeks.
• Result: Significant VA improvement with acceptable safety profile.
7. SCORE-2 (2017)
• Purpose: Compare bevacizumab (BVZ) vs aflibercept for ME in CR or hemiretinal
vein occlusion.
• Outcome: Mean BCVA change at 6 months.
• Result: BVZ noninferior to aflibercept.
Summary – CRVO
Therapy Trial Key Point
Anti-
VEGF
CRUISE (RBZ), COPERNICUS/GALILEO (Aflibercept),
SCORE-2 (BVZ vs aflibercept)
First-line therapy for ME
Steroids SCORE-CRVO, GENEVA (Ozurdex)
Second-line; monitor IOP
& cataract
PRP CVOS Only after NV develops
Surgical CRVO Bypass/L-CRA
Investigational; rarely
used

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ANGIOGENESIS
Definition: Formation of new blood vessels from pre-existing vessels; essential in
development, wound healing, and pathological conditions like retinal
neovascularization and tumors.
A. Angiogenic Factors:
• Vasculo-endothelial Growth Factor (VEGF) -m/c
• Fibroblast growth factor (FGF)
• Platelet Derived Growth Factor (PDGF)
• Placental Growth Factor
• Hypoxia Induced Growth Factor
• Integrins
• Angiopoietins
• Protein kinase C (PKC)
B. Antiangiogenic Factors:
• Pigment epithelial-derived factor (PEDF)
• Matrix metalloproteinases (MMPs)
• Angiostatin
• Endostatin
• Thrombospondin
VEGF Family
Types of VEGF: VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E
VEGF-A Isoforms: VEGF-206, VEGF-189, VEGF-165 (main isoform), VEGF-145, VEGF-
121
Roles of VEGFs:
• VEGF-A → developmental & pathological angiogenesis
• VEGF-B/C/D → tumor angiogenesis, lymphangiogenesis
• VEGF-E → similar to VEGF-A
VEGF Receptors (VEGFR):
• VEGFR-1, VEGFR-2 on endothelial cells, retinal epithelium, bone marrow–
derived precursors
• Activation → angiogenesis + vascular permeability
VEGF Regulation:
• Upregulated by hypoxia, hypoglycemia, β-estradiol, EGF, IGF, FGF
• Sources in retina: Müller cells, retinal endothelial cells
Properties of VEGF:
• Stimulates angiogenesis
• Increases vascular permeability
• Proinflammatory

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• Endothelial survival & fenestration
• Neuroprotective
G. Pathological Roles:
• Retinal: Neovascular AMD, diabetic retinopathy, RVO, ROP, corneal & iris
neovascularization
• Systemic: cancer, psoriasis, rheumatoid arthritis
Anti-VEGF
Intravitreal Injection
• Preferred site: Inferotemporal quadrant (Parsplana wide & adv of bells phenomena)
• Avoid: 3 & 9 o'clock meridians (long posterior ciliary nerves & arteries)
• Pars plana entry:
o Phakic: 4 mm
o Pseudophakic: 3.5 mm
o Aphakic: 3 mm (from limbus)
Strategies:
1. Monthly Dosing
• Best visual outcomes
• High treatment burden
2. Pro ReNata (PRN)
• 3initial loading doses
• Monthly monitoring/ follow-up
• Inject when needed (wet)
3. Treat & Extend (TREX)
• 3initial loading doses f/b monthly injection till stability
• Gradually extend interval by 1-2 weeks based on CST &BCVA
(max: 12 wk, min: 4wk)
• Inject when come
10% Central Subfield Thickness (CST) & 5 letter rule
Worsening:
• ↑ CST > 10%
• ↓ BCVA >5 ETDRS letter (ie. 1 Snellen line)
Improving:
• ↓ CST > 10%
• ↑ BCVA >5 ETDRS letter (ie. 1 Snellen line)

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Indications:
• Wet AMD/CNV, DME, PDR, RVO with CME, ROP, Myopic CNV
• Corneal neovascularization, Pterygium
• NVI, NVG
Advantages:
• Targeted inhibition of pathological angiogenesis
• Reduces macular edema, neovascularization, leakage
• Prolonged effect with newer agents (Brolucizumab, Faricimab)
Complications:
• Ocular: Endophthalmitis, ↑IOP, uveitis, retinal detachment, VH, Cataract, SCH
(injection related)
• Systemic (rare): Stroke, MI, thromboembolic events
Contraindications:
• Pregnancy,
• Active ocular infection/inflammation,
• Hypersensitivity,
• Recent CVA/MI (relative caution)
Mechanism of Action
• Pegaptanib: Selectively binds VEGF-165 → blocks VEGFR-1/2 → inhibits
angiogenesis and vascular leakage.
• Bevacizumab: Binds all VEGF-A isoforms → prevents VEGFR activation → inhibits
endothelial proliferation, neovascularization, and leakage.
• Ranibizumab: High-affinity VEGF-A binding → blocks VEGFR-mediated
angiogenesis and vascular permeability; small Fab fragment → better retinal
penetration and low systemic exposure.
Newer Anti-VEGF:
• Aflibercept: Soluble VEGF trap (VEGFR-1/2 fused to IgG Fc) → binds VEGF-A,
VEGF-B, PlGF → inhibits VEGFR signaling and vascular leakage.
• Brolucizumab: Small Single Chain Fragent(scFv) binds VEGF-A → high molar dose
in small volume → long-lasting intravitreal VEGF inhibition.
• Faricimab: Bispecific antibody →
1. VEGF-A inhibition → reduces angiogenesis & leakage,
2. Ang-2 inhibition → stabilizes vessels, reduces vascular inflammation →
prolonged durability.

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Drug Class / Target MOA
MW
(kDa)
t½
(Vitreous)
IVT Dose FDA
Pegaptanib
(Macugen)
Pegylated RNA
aptamer / VEGF-
165
Selectively binds
VEGF-165 → ↓
angiogenesis &
leakage
50 ~10 d
0.3 mg q6
wk
2004
Bevacizumab
(Avastin)
Full length
monoclonal Ab /
VEGF-A
Binds all VEGF-A →
inhibits
angiogenesis &
leakage
149 ~ 21 d
1.25 mg
q4–6 wk
Off-
label
Ranibizumab
(Lucentis)
Fab fragment /
VEGF-A
High-affinity VEGF-A
inhibition
48 ~ 9 d
0.5 mg q4
wk
2006
Aflibercept
(Eylea)
Fusion protein /
VEGF-A, VEGF-B,
PlGF
Decoy receptor
binds VEGF-A/B &
PlGF
115 ~7–9 d
2 mg q8
wk (after
loading)
2011
Brolucizumab
(Beovu)
Single Chain
Fragent(scFv) /
VEGF-A
Small scFv → high
molar dose,
prolonged VEGF
suppression
26 ~3–4 d
6 mg q8–
12 wk
2019
Faricimab
(Vabysmo)
Bispecific mAb /
VEGF-A + Ang-2
Dual inhibition →
anti-VEGF + vessel
stabilization
150 ~7.5 d
6 mg q8–
16 wk
2022
PEGAPTANIB (Macugen)
Class: Pegylated RNA aptamer (not antibody)
MOA
Selectively binds VEGF-165 isoform
Blocks VEGFR-1 and VEGFR-2 activation
↓ Angiogenesis and vascular leakage
Indications
Neovascular AMD (historical use)
Dose
0.3mg intravitreal every 6 weeks
ADR
Injection-related complications
Less effective than newer agents

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BEVACIZUMAB (Avastin)
Class: Full-length humanized monoclonal antibody (149 kDa)
MOA:
Binds all VEGF-A isoforms
Prevents VEGFR activation
Inhibits endothelial proliferation &leakage
Indications
• Wet AMD (off-label)
• DME
• BRVO /CRVO macular edema
• ROP
• NVG /iris neovascularization
• Oncology (systemic)- RCC, Ca Cervix/Ovary, Breast mets, SCC (lungs)
Dose
1.25mg /0.05 mL intravitreal
Monthly or OCT-guided (PRN/T&E)
Most cost-effective; off-label use
ADR
Ocular:
Endophthalmitis
IOP spike
Vitreous hemorrhage
Systemic(rare):
↑ BP
Thromboembolic events
GI bleeding/perforation
RANIBIZUMAB (Lucentis)
Class: Monoclonal antibody fragment (Fab) – 48kDa
MOA
High-affinity binding to all VEGF-A isoforms
Small size → better retinal penetration
Minimal systemic exposure
Indications
• Wet AMD (FDA approved 2006)
• DME
• RVO macular edema
• Myopic CNV
Dose
0.5mg /0.05 mL intravitreal
Monthly OR PRN OR Treat-and-Extend

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ADR
Similar to other intravitreal agents
Lower systemic risk compared to bevacizumab
NEWER ANTI-VEGFs: AFLIBERCEPT (Eylea), BROLUCIZUMAB, FARICIMAB
AFLIBERCEPT (Eylea)
Class: Receptor-antibody fusion protein (VEGF Trap) – 115 kDa
MOA
Decoy receptor (VEGFR-1 + VEGFR-2 fused to IgG Fc)
Binds:
VEGF-A
VEGF-B
Placental Growth Factor (PlGF)
Strong binding affinity
Indications
• Wet AMD
• DME
• RVO macular edema
• Myopic CNV
Dose
2mg /0.05 mL
3monthly loading doses
Then every 8weeks
ADR
Similar injection risks
Rare intraocular inflammation
BROLUCIZUMAB (Beovu)
Class: Single-chain antibody fragment (scFv) – 26 kDa
MOA
Binds VEGF-A
Very small size → high molar dose
Prolonged VEGFsuppression
Indications
Wet AMD
Dose
6mg intravitreal
q8–12 weeks after loading
ADR

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Intraocular inflammation
Retinal vasculitis
Occlusive retinal vasculitis (rare but serious)
FARICIMAB (Vabysmo)
Class: Bispecific monoclonal antibody (150 kDa)
MOA
Dual mechanism:
• VEGF-A inhibition →↓ angiogenesis & leakage
• Angiopoietin-2 inhibition →vessel stabilization, ↓ inflammation
Indications
Wet AMD
DME
Dose
6mg intravitreal
Can extend to 12–16 weeks
ADR
Similar to other anti-VEGF
Inflammation possible

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RETINAL ARTERY OCCLUSIVE DISEASE
Retinal artery occlusive disease comprises a spectrum of conditions resulting from
obstruction of the retinal arterial circulation, leading to acute retinal ischaemia and sudden
visual loss. Based on the site of occlusion, RAOD is classified into:
• Central retinal artery occlusion (CRAO) – ~57%
• Branch retinal artery occlusion (BRAO) – ~38%
• Cilioretinal artery occlusion (CLRAO) – ~5%
CRAO carries the worst visual prognosis, while BRAO and cilioretinal artery occlusion
generally have better outcomes depending on foveal involvement and associated pathology.
ANATOMY & VASCULAR SUPPLY
• Inner retina: Supplied by the central retinal artery (CRA)
• Outer retina: Supplied by posterior ciliary arteries via the choriocapillaris
• The ophthalmic artery, first branch of the internal carotid artery (ICA), gives rise to:
o Central retinal artery
o Posterior ciliary arteries (also supplying anterior segment via muscular
branches)
Because the ophthalmic artery is the first ICA branch, emboli from carotid plaques have a
direct route to the eye.
INCIDENCE & DEMOGRAPHY
• CRAO incidence (Western data): ~1 per 10,000 outpatient visits
• Commonest in 7th decade
• Male predominance
• No racial predilection
• Bilateral involvement: 1–2%
ETIOPATHOGENESIS
Multiple mechanisms may coexist in the same patient.
1. Embolic (Most common)
• Accounts for majority, especially in elderly
• Sources:
o Carotid atherosclerosis (~80%)
o Cardiac: atrial fibrillation, valvular disease, infective endocarditis, atrial
myxoma

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• Types of emboli:
o Cholesterol (Hollenhorst plaques): yellow, refractile
o Platelet–fibrin: grey, elongated
o Calcific: white, non-scintillating (cardiac valves)
o Rare: fat, tumour fragments, bacterial vegetations
• Lodges at:
o Lamina cribrosa (CRAO)
o Arterial bifurcations (BRAO)
2. Thrombotic
• More relevant in younger patients
• Related to:
o Vessel wall abnormalities (e.g. prepapillary arterial loop)
o Hypercoagulable states: pregnancy, OCPs, malignancy, smoking
• Thrombophilic disorders:
o Hyperhomocysteinaemia
o Antiphospholipid antibody syndrome
o Protein C, Protein S, antithrombin III deficiency
o Factor V Leiden, activated protein C resistance
3. Vasculitic
• Giant cell arteritis (GCA) – classical cause
• Other systemic vasculitides: SLE, rheumatoid arthritis, Behçet disease, granulomatosis
with polyangiitis, PAN
• Combined vasculitis + thrombosis mechanism
4. Vasospastic / Hemodynamic
• Migraine-associated vasospasm
• Systemic hypotension, shock
5. Rare associations
• Sickle cell disease
• Susac syndrome (retinocochleocerebral vasculopathy): BRAO + sensorineural
deafness + encephalopathy
AMAUROSIS FUGAX
• Transient, painless monocular visual loss ("curtain coming down")
• Usually embolic
• Lasts minutes; recovery gradual
• May be associated with ipsilateral cerebral TIA

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• High short-term stroke risk
• Systemic evaluation same as RAO → urgent stroke work-up mandatory

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CENTRAL RETINAL ARTERY OCCLUSION
CLINICAL FEATURES
m/c site: Lamina Cribrosa
Symptoms
• Sudden, profound, painless loss of vision
• VA <3/60 in >90%
• Preceded by amaurosis fugax in embolic cases
• Absence of light perception suggests:
o GCA
o Ophthalmic artery occlusion
Signs
• Profound RAPD (amaurotic pupil)
• Fundus:
o Diffuse retinal whitening (inner retinal oedema)
o Cherry-red spot at fovea
o Markedly attenuated arteries
o Segmentation/box-carring of blood column
o Emboli visible in ~20–40%
o Small retinal haemorrhages may occur
• With cilioretinal artery: part of macula retains normal colour
Investigations
• FFA: delayed/absent retinal arterial filling; intact choroidal flush
• OCT: inner retinal hyperreflectivity; embolic plaque at ONH
• ERG: reduced/absent b-wave (a-wave preserved)
Course & Complications
• Retinal whitening resolves in 4–6 weeks
• Late: optic atrophy, vessel attenuation, inner retinal atrophy
• Neovascularization:
o Retina/disc ~2%
o Rubeosis iridis up to ~20% (earlier than CRVO)
a-wave → Photoreceptors (rods & cones) → Outer retina → Choroidal circulation
b-wave → ON bipolar cells + Müller cells → Inner retina → Central retinal artery (CRA)

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BRANCH RETINAL ARTERY OCCLUSION
Symptoms
• Sudden painless sectoral/altitudinal visual field defect
• May be asymptomatic if macula spared
Signs
• Variable VA
• RAPD often present
• Fundus:
o Localized retinal whitening along artery distribution
o Attenuated vessel
o Embolus often at bifurcation (~30%)
Investigations
• Visual fields: permanent defect
• FFA: delayed filling of affected branch; retrograde filling late
Prognosis
• Good if fovea spared
• ~80% achieve ≥6/12
• Field defect usually permanent
CILIORETINAL ARTERY OCCLUSION
• Present in ~30% of eyes
• Origin: short posterior ciliary arteries
• Fills with choroidal circulation on FFA
Types
1. Isolated (rare, often young, vasculitis)
2. With CRVO (common, transient, good prognosis)
3. With AION (often GCA, very poor prognosis)
Features
• Paracentral scotoma
• RAPD usually absent
• Localized retinal whitening
Prognosis
• Isolated or with CRVO: excellent (70–90% ≥6/12)
• With AION: poor

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OPHTHALMIC ARTERY OCCLUSION
Pathogenesis
• Similar to CRAO but proximal to both CRA and PCAs
Clinical Features
• Profound visual loss
• RAPD present
• Fundus:
o Diffuse retinal whitening
o No cherry-red spot (choroidal circulation compromised)
Investigations
• FFA: absent/delayed choroidal and retinal filling
• ERG: absent a- and b-waves
Prognosis
• Extremely poor
SYSTEMIC ASSESSMENT (ESSENTIAL)
All Patients
• Smoking history
• Symptoms of GCA (age >55): headache, jaw claudication, scalp tenderness, PMR
• BP measurement
• Pulse (atrial fibrillation)
• Cardiac and carotid auscultation
• ECG
• Blood tests:
o ESR / CRP
o CBC (platelets)
o Glucose, lipid profile
o Renal function
• Carotid duplex ultrasound
Selected Patients (Young / Atypical)
• Echocardiography
• 24-hour Holter
• MRI/CT brain
• Thrombophilia screen

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• Homocysteine
• Autoimmune profile
• Syphilis serology
• Blood cultures
TIP: Retinal artery occlusion is a stroke equivalent → urgent stroke-team referral
mandatory.
MANAGEMENT OF ACUTE RETINAL ARTERY OCCLUSION
Principle: Emergency – irreversible retinal infarction occurs within hours.
Time window
• Experimental recovery possible <4 hours
• Benefit uncertain beyond 6 hours
Acute Measures (within 24 hours; limited evidence)
• Ocular massage
• IOP reduction:
o AC paracentesis
o Topical beta-blocker/apraclonidine
o IV acetazolamide
o Hyperosmotic agents
• Vasodilatation:
o Carbogen (95% O2 + 5%CO2)
o Rebreathing into paper bag
o Sublingual nitrates
Interventional
• Nd:YAG laser embolysis/embolectomy (visible embolus)
• Thrombolysis (IA/IV rtPA): no proven benefit in trials
GCA
• Immediate high-dose systemic steroids
MANAGEMENT OF SEQUELAE
• Monitor for neovascularization (3–4 weeks, then monthly)
• PRP for neovascularization
• Anti-VEGF for rubeosis/NVG
• Manage NVG medically/surgically

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SYSTEMIC MANAGEMENT & STROKE PREVENTION
• Urgent stroke clinic referral
• Risk factor control (HTN, DM, lipids, smoking)
• Antiplatelet therapy (aspirin ± clopidogrel/dipyridamole)
• Anticoagulation for AF
• Carotid endarterectomy for symptomatic stenosis >70%
ASYMPTOMATIC RETINAL EMBOLUS
• Marker of high cardiovascular risk
• Full systemic evaluation mandatory
• Higher threshold for carotid surgery
OCULAR ISCHAEMIC SYNDROME (OIS)
Definition
Chronic ocular hypoperfusion due to severe (>90%) ipsilateral carotid stenosis.
Features
• Gradual visual loss, pain, bright-light amaurosis
• Anterior segment ischaemia, rubeosis, NVG
• Fundus: venous dilatation, arteriolar narrowing, haemorrhages, CWS, NVD/NVE
• FFA: delayed choroidal filling, prolonged AV transit
Management
• Treat inflammation
• PRP / anti-VEGF
• NVG management
• Carotid endarterectomy or stenting
• Aggressive cardiovascular risk control
KEY EXAM PEARLS
• CRAO = stroke of the eye
• Cherry-red spot → intact choroid
• No cherry-red spot → ophthalmic artery occlusion
• Early rubeosis after CRAO suggests ophthalmic artery occlusion
• Always exclude GCA in elderly

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Causes Of Cherry-Red Spot-on Macula
• Vascular causes
Central Retinal Artery Occlusion (m/c), Cilioretinal Artery Occlusion
• Metabolic (lysosomal storage) diseases
o Tay–Sachs disease
o Sandhoff disease
o Niemann–Pick disease
o GM1 gangliosidosis
o Sialidosis
o Farber disease
o Metachromatic leukodystrophy
o Galactosialidosis
o Mucolipidosis
• Trauma
Berlin’s edema (commotio retinae)
• Toxic
Quinine toxicity
• Others
Macular Hole
Differential Diagnosis of Bull’s-eye Maculopathy
• Drug toxicity
o Hydroxychloroquine toxicity
o Chloroquine toxicity
o Tamoxifen toxicity
• Benign Concentric Annular Macular Dystrophy (BCAMD)
• Stargardt disease
• Cone-rod dystrophy
• Batten disease (neuronal ceroid lipofuscinosis)
• Macular telangiectasia Type 2
• Advanced dry ARMD (central geographic atrophy)
• Chronic CSCR

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Hydroxychloroquine Retinopathy
Risk Factors
• Daily dose >5 mg/kg/day (actual body weight)
• Duration >5 years (or cumulative dose >1000 g)
• Renal disease
• Tamoxifen use
• Pre-existing retinal disease
Clinical Features
• Early: Often asymptomatic
• ↓ Color vision, paracentral blur, difficulty reading
• Bull's-eye maculopathy (late)
• RPE atrophy, photoreceptor loss (advanced)
Visual Field Defect (VFD)
• 10-2 HVF: Paracentral scotoma (classic)
Investigations
• SD-OCT: Parafoveal outer retinal/ellipsoid zone loss ("flying saucer sign")
• Fundus Autofluorescence (FAF): Parafoveal hyper-/hypo-autofluorescence
• mfERG: ↓ Parafoveal responses (most sensitive functional test)
• ERG: Full-field ERG usually normal
• OCT-A: Reduced parafoveal capillary density (adjunct)
Management
• Stop HCQ immediately (after discussion with prescribing physician)
• No proven treatment
• Regular follow-up (toxicity may progress after cessation)
• Low-vision rehabilitation if advanced
Screening
• Baseline: Within 1 year of starting HCQ
• Annual screening: After 5 years (earlier if high risk)
• Preferred tests: 10-2 HVF + SD-OCT (± FAF/mfERG)

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CENTRAL SEROUS CHORIORETINOPATHY
INTRODUCTION - sporadic disorder of outer BRB
CSCR also termed central serous retinopathy or idiopathic central serous
choroidopathy, is an idiopathic chorioretinal disorder characterized by serous
detachment of the neurosensory retina and/or retinal pigment epithelium (RPE) at the
posterior pole due to leakage from the choriocapillaris through hyperpermeable or
dysfunctional RPE.
CSCR is now considered part of the pachychoroid disease spectrum, characterized by
choroidal thickening and hyperpermeability.
EPIDEMIOLOGY
• Predominantly affects young to middle-aged adults (25–55 years)
• Male predominance: M:F = 3–6 : 1
• Females are usually older and more prone to chronic disease
• Peak incidence around 40–45 years
• More severe disease reported in Asians and Hispanics; relatively rare in African-
Americans
• Bilateral involvement in up to 40% (often sequential)
RISK FACTORS & ASSOCIATIONS
• Steroids (oral, inhaled, topical, intra-articular)
• Stress, Type A personality
• Insomnia
• Smoking
• Endogenous hypercortisolism (Cushing syndrome)
• Systemic hypertension
• Pregnancy, oral contraceptive use
• Psychotropic medications
• Sleep apnoea syndrome
• Renal dialysis
• Helicobacter pylori infection
• Refractive status: emmetropia or mild hyperopia
• Genetic association: CFH gene SNP (chromosome 1) → chronic CSCR
PATHOPHYSIOLOGY
CSCR is multifactorial. Proposed mechanisms include:
1. RPE Barrier Defect Theory
o Focal RPE defects allow leakage of fluid into the subretinal space
o Explains focal FA leaks

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2. RPE Dysfunction Theory
o Diffusion of dye through dysfunctional RPE rather than true breaks
3. Altered RPE Polarity Theory
o Loss of normal RPE pump polarity → reverse fluid transport into subretinal
space
4. Choroidal Vascular Hyperpermeability (Most Accepted)
o Demonstrated on ICGA
o Corticosteroids and sympathomimetics impair choroidal autoregulation
o Increased choroidal hydrostatic pressure → PED → RPE disruption → subretinal
fluid

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CLASSIFICATION
❖ Typical CSCR: Acute, unilateral with single focal leak (ink-blot/smoke-stack); self-
resolves in 3–4 months.
❖ Atypical CSCR: Chronic/recurrent, often bilateral, with diffuse RPE
decompensation, persistent SRF (>4–6 months), and poor visual prognosis.
CLINICAL CLASSIFICATION
1. Acute (Classic) CSCR
• Localized neurosensory detachment
• One or few focal leaks on FA
• Self-limiting (3–6 months)
2. Chronic CSCR / Diffuse Retinal Pigment Epitheliopathy (DRPE)
• Persistent subretinal fluid >3–6 months
• Widespread RPE decompensation
• Often steroid-related
3. Bullous CSCR
• Large inferior serous retinal ± RPE detachments
• Shifting fluid
• Seen in Asians, post-organ transplantation
Disease Activity
• Active CSCR: SRF present
• Inactive CSCR: SRF resolved with residual RPE changes
HISTOLOGICAL CLASSIFICATION
❖ Type 1: NS detachment
❖ Type 2: RPE detachment
❖ Type 3: NS & RPE detachment
SYMPTOMS
• Painless blurring of central vision
• Metamorphopsia
• Micropsia
• Mild dyschromatopsia
• Central scotoma or dim spot (grey/purple hue)
• VA typically 6/9–6/18, improves with low plus lens
• Severe/recurrent cases: VA may fall to 6/60–6/200

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OCULAR SIGNS
Acute CSCR
• Solitary, round/oval neurosensory detachment at macula
• Clear or mildly turbid subretinal fluid
• Light reflex ring at margin of detachment
• Small RPE defects or serous PEDs at leak site
Chronic CSCR
• Patchy RPE atrophy and hyperplasia
• Descending gravitational tracts (best seen on FAF)
• Cystoid degeneration of retina
Bullous CSCR
• Large inferior bullous retinal detachments
INVESTIGATIONS
Amsler Grid
• Central metamorphopsia corresponding to SRF
Optical Coherence Tomography (OCT)
• Optically empty neurosensory detachment
• Serous PEDs
• Hyperreflective precipitates on posterior retina
• Thickened choroid (pachychoroid)
• Photoreceptor/RPE degeneration in chronic disease
Fundus Fluorescein Angiography (FFA)
• Ink-blot leak (most common)
• Smokestack pattern (less common)
• Multiple leaks or diffuse leakage in chronic CSCR
• Demonstrates associated PEDs
Fundus Autofluorescence (FAF)
• Hypoautofluorescence at active leak
• Mixed hypo/hyperautofluorescence in chronic disease
• Gravitational tracts
Indocyanine Green Angiography (ICGA)
• Dilated choroidal vessels (early phase)

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• Mid-phase choroidal hyperpermeability
• Reveals subclinical disease
DIFFERENTIAL DIAGNOSIS
• Choroidal neovascular membrane (CNV)
• Optic disc pit maculopathy
• Vogt–Koyanagi–Harada disease
• Posterior scleritis
• Uveal effusion syndrome
• Inflammatory serous detachments
NATURAL COURSE & PROGNOSIS
• ~80% acute CSCR resolves spontaneously within 3–6 months
• Mild permanent symptoms (contrast, color, distortion) may persist
• Recurrence rate: 40–50%
• ~15% progress to chronic CSCR
• Poor prognosis associated with:
o Chronic disease
o Bullous CSCR
o Recurrent attacks
o Photoreceptor/RPE atrophy
• Complications:
o Secondary CNV
o Cystoid macular edema
o RPE tears (spontaneous or treatment-related)
MANAGEMENT

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1. Observation
• First-line for acute classic CSCR
• Counsel stress reduction & smoking cessation
• Stop corticosteroids if possible
2. Medical Therapy
• Mineralocorticoid receptor antagonists:
o Spironolactone 40 mg BD
o Eplerenone (alternative)
• Acetazolamide – hastens SRF absorption (limited evidence)
• Anti-VEGF: limited role (mainly if CNV suspected)
Corticosteroids are contraindicated
3. Focal Laser Photocoagulation (Conventional)
Indications
• Persistent SRF >4 months
• Leak >375 µm from foveal center (Extrafoveal)
• Recurrent CSCR with poor fellow eye
• Occupational need for early recovery
Settings
• Spot size: 200 µm
• Power: ~100 mW
• Duration: 100 ms
Limitations
• Does not improve final VA
• Does not reduce recurrence
• Risk of CNV
4. Subthreshold / Micropulse Laser
• Targets RPE without retinal damage
• Effective for focal and diffuse leaks (Juxtafoveal)
• Preferred over conventional laser
5. Photodynamic Therapy (PDT – Verteporphin)
Indications
• Chronic CSCR / DRPE
• Diffuse leakage
• Subfoveal leaks
• Recurrent disease
Protocol
• Half-dose or half-fluence PDT
• Spot guided by ICGA hyperpermeability

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Advantages
• High SRF resolution rates
• Less choroidal ischemia
EXAM PEARLS
• CSCR = young stressed male + serous macular detachment
• VA improves with plus lens
• Ink-blot leak is classic FA sign
• ICGA shows choroidal hyperpermeability
• Steroids worsen CSCR
• PDT is treatment of choice for chronic CSCR

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RETINOPATHY OF PREMATURITY
Retinopathy of Prematurity (ROP) is a potentially blinding vasoproliferative retinal
disorder affecting premature, low birth weight infants. It results from disordered
retinal vascular development following premature birth. Terry first described the
condition in 1942 as retrolental fibroplasia, which corresponds to Stage 5 ROP.
With advances in neonatal care, survival of extremely premature infants has increased,
leading to a rising incidence of ROP, especially in middle-income countries, described
as the “third epidemic” of ROP.
EPIDEMIOLOGY & INCIDENCE
• Incidence inversely related to gestational age (GA) and birth weight (BW)
• ROP incidence by GA:
o 28–29 weeks: ~83%
o 30–31 weeks: ~60%
o 32–33 weeks: ~50%
• For every 100 g increase in BW, risk of threshold ROP decreases by ~27%
• In India and similar settings:
o Incidence ranges from 11–47.7%
o Accounts for ~0.2% of childhood blindness
o ~15% of affected infants require treatment
NORMAL RETINAL VASCULAR DEVELOPMENT
• Begins at 16 weeks gestation
• Originates from hyaloid artery spindle cells near optic disc
• Progresses centrifugally via angiogenesis
• Nasal retina vascularized by 7–8 months gestation
• Temporal retina vascularized by ~9 months gestation / 1 month post-term
Premature birth interrupts this process, leaving peripheral avascular retina.
PATHOGENESIS (TWO-PHASE THEORY)
Phase I – Hyperoxic Phase (Birth to ~32–34 weeks PMA)
• Premature exposure to relatively hyperoxic extrauterine environment
• ↓ VEGF and IGF-1
• Arrested vascular growth, capillary obliteration
• Retinal ischemia develops
Phase II – Hypoxic Vasoproliferative Phase (>34 weeks PMA)
• Increasing metabolic demand → retinal hypoxia
• ↑ VEGF and other angiogenic factors
• Abnormal neovascularization with fibrovascular proliferation
• Vessels develop contractile properties, leading to traction

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RISK FACTORS (CRYO-ROP STUDY)
Major
• Low birth weight (LBW) -- (west: <1.5kg, india:<2kg)
• Low gestational age -- (west: <28-30wog, india:<34-35wog)
• Oxygen supplementation
Other Factors
• Sepsis, anemia, apnea
• Respiratory distress syndrome (RDS)
• Acidosis, shock, asphyxia
• Patent ductus arteriosus (PDA)
• Blood transfusions / exchange transfusion
• Intraventricular hemorrhage (IVH)
• Bronchopulmonary dysplasia (BPD)
• Vitamin E deficiency
• Multiple births, out-of-hospital birth
Risk factors associated with poor outcome:
• Zone I disease
• Plus disease
• Stage 3 with >6 clock hours
• Iris vessel dilatation
CLASSIFICATION – ICROP (2005)
ROP is classified by Zone, Stage, Extent, and Plus disease.
ZONES OF ROP
• Zone I: Circle with radius = 2× disc–macula distance
• Zone II: Extends from zone I to nasal ora serrata
• Zone III: Residual temporal crescent
Posterior involvement = worse prognosis.

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STAGES OF ROP
Stage 1 – Demarcation Line
• Thin, flat gray-white line
• Abnormal vascular branching posteriorly
Stage 2 – Ridge
• Elevated ridge with height and width
• Vessels enter ridge; small neovascular tufts
Stage 3 – Extraretinal Fibrovascular Proliferation
• Neovascular tissue extending into vitreous
• Subdivided into mild / moderate / severe
• Peak incidence ~35 weeks PMA
Stage 4 – Partial Retinal Detachment
• 4A: Macula sparing
• 4B: Macula involved
Stage 5 – Total Retinal Detachment
• Funnel-shaped, retrolental fibroplasia
EXTENT OF ROP
• Recorded in clock hours of the highest stage present
PLUS & PRE-PLUS DISEASE
Plus Disease
• Dilated, tortuous posterior pole vessels (≥2 quadrants)
• Poor pupillary dilation
• Vitreous haze
• Indicates active, progressive disease
Pre-Plus
• Vascular changes less severe than plus disease

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AGGRESSIVE POSTERIOR ROP (AP-ROP)
• Rapidly progressive, severe form
• Located in Zone I or posterior Zone II
• Flat neovascular fronds without ridge
• Severe AV shunting, marked plus disease
• Progresses within days to Stage 5 if untreated
THRESHOLD DISEASE (CRYO-ROP)
• Defined as:
o Stage 3 ROP
o Zones I or II
o ≥5 contiguous or ≥8 cumulative clock hours
o With plus disease
• Carries ~50% risk of unfavorable outcome
Limitations: underestimated severity of Zone I disease.
ETROP CLASSIFICATION
TYPE 1 ROP – Treat within 72 hours
• Any stage in Zone I with plus
• Stage 3 in Zone I (± plus)
• Stage 2 or 3 in Zone II with plus
TYPE 2 ROP – Observe
• Zone I Stage 1–2 without plus
• Zone II Stage 3 without plus
Early treatment reduces unfavorable visual and structural outcomes.
SCREENING FOR ROP
General Principles
• Indirect ophthalmoscopy (28D / wide-field camera)
• Scleral depression essential
• Begin at 4 weeks postnatal or 31–33 weeks PMA
Western Guidelines
• BW ≤1500 g or GA ≤28–30 weeks
• Larger infants with unstable course
Indian / Developing Country Guidelines
• BW ≤2000 g or GA ≤34–35 weeks
• Earlier screening (32 weeks PMA or 4 weeks after birth)
• <28 weeks or <1200 g: screen at 2–3 weeks
Follow-Up
• Every 1–3 weeks depending on severity
• Continue until vascularization reaches Zone III

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EXAMINATION PRECAUTIONS
• Dilatation: 0.5% cyclopentolate + 2.5% phenylephrine
• Topical anesthetic
• Neonatal speculum
• Monitor for apnea, bradycardia
ROLE OF TELEMEDICINE & OCT
• Digital fundus imaging for remote screening
• OCT reveals subclinical macular edema, retinoschisis
• Useful for prognostication
TREATMENT OF ROP
LASER PHOTOCOAGULATION (LIO) -- (Gold Standard)
• Ablation of avascular peripheral retina
• Nearly confluent burns
• Superior to cryotherapy
Complications: cataract, anterior segment ischemia, corneal/iris burns
CRYOTHERAPY
• Reserved when laser not possible
• Requires general anesthesia
• Inferior outcomes compared to laser
ANTI-VEGF THERAPY
• Bevacizumab (BEAT-ROP study)
• Effective especially in Zone I Stage 3+ ROP
Advantages:
• Preserves peripheral retina
Concerns:
• Systemic VEGF suppression
• Late recurrence → prolonged follow-up mandatory
SURGICAL MANAGEMENT
Stage 4A
• Lens-sparing vitrectomy
• ~90% anatomical success
Stage 4B
• Lower visual outcomes (~60%)
Stage 5
• Lensectomy + vitrectomy
• Limited functional success (~20%)
• Goal: anatomical reattachment, central fixation

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SEQUELAE OF ROP
After Regression
• Foveal pigment changes
• Abnormal vascular arcades
• Vitreoretinal membranes
After Treatment
• Macular heterotopia
• Narrowed temporal arcade
• Vessel tortuosity
LONG-TERM COMPLICATIONS
• Myopia (up to 70%; high myopia ~25%)
• Strabismus
• Amblyopia
• Cataract
• Glaucoma
• Rhegmatogenous retinal detachment in adulthood
Lifelong ophthalmic follow-up is essential.
MAJOR CLINICAL TRIALS IN ROP
• CRYO-ROP
• ETROP
• BEAT-ROP
• LIGHT-ROP
• STOP-ROP
• HOPE-ROP
KEY EXAM PEARLS
• Zone I disease = worst prognosis
• Plus disease = treat early
• ETROP supersedes threshold concept
• Anti-VEGF requires long-term surveillance
• Screening timing differs in developing countries

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HYPERTENSIVE RETINOPATHY
Systemic arterial hypertension is a common chronic systemic disorder and a major
cause of cardiovascular, cerebrovascular, and renal morbidity and mortality. The eye is
a unique target organ where vascular changes can be directly visualized. Hypertensive
eye disease encompasses hypertensive retinopathy, hypertensive choroidopathy, and
hypertensive optic neuropathy, reflecting damage to the retinal, choroidal, and optic
nerve head circulations respectively.
Hypertensive retinopathy refers to the spectrum of structural and functional retinal
vascular changes resulting from acute or chronic elevation of systemic blood pressure.
These ocular changes provide important information regarding the severity, duration,
and systemic impact of hypertension and have significant prognostic implications.
EPIDEMIOLOGY
• Prevalence of hypertensive retinopathy varies widely depending on age, population
studied, and associated systemic diseases.
• In large population-based studies (e.g., Beaver Dam Eye Study), the prevalence is
approximately 10–15% in individuals aged ≥50 years without coexisting diabetes.
• In developing countries, including India and South Asia, the prevalence of systemic
hypertension has increased markedly over recent decades.
• Hypertension is more prevalent in males until menopause, after which gender
differences narrow.
• Ophthalmoscopic findings alone have limited sensitivity for diagnosing systemic
hypertension; blood pressure measurement remains the gold standard.
ANATOMY AND PHYSIOLOGY
Retinal Vasculature
• Retinal arteries are end-arteries supplying the inner retinal layers.
• Major retinal arteries measure approximately 110 μm at the optic disc margin; veins
are approximately 150 μm.
• Retinal arterioles lack elastic tissue and have minimal autonomic innervation.
• Retinal circulation depends on local metabolic autoregulation rather than neural
control.
Blood–Retinal Barrier
• Inner blood–retinal barrier: tight junctions of retinal vascular endothelium.
• Outer blood–retinal barrier: retinal pigment epithelium (RPE).
• Acute severe hypertension disrupts these barriers, causing edema, hemorrhages, and
exudation.

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Choroidal Circulation
• Supplied by posterior ciliary arteries.(PCA)
• Profuse sympathetic nerve supply
• No BOB, No Autoregulation
• Rich autonomic innervation; lacks autoregulation.
• Highly susceptible to acute blood pressure elevations, especially in young patients.
Optic Nerve Head Circulation
• Supplied mainly by the peripapillary choroid.
• Exhibits partial autoregulation with an incompetent blood–ocular barrier.
PATHOPHYSIOLOGY
The ocular effects of hypertension arise from its impact on the microvasculature:
1. Vasoconstriction – initial functional response to raised blood pressure.
2. Arteriolosclerosis – chronic structural thickening and rigidity of arteriolar walls
due to medial hyperplasia and hyalinization.
3. Breakdown of autoregulation – especially in acute severe hypertension.
4. Increased vascular permeability – disruption of blood–retinal barrier.
5. Ischemia and infarction – occlusion of terminal arterioles and capillaries.
The severity of retinal damage depends on:
• Level of blood pressure
• Duration of hypertension
• Rapidity of rise in blood pressure
• Patient age and vascular resilience

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CLINICAL TYPES OF HYPERTENSIVE RETINOPATHY
(retinopathy, choroidopathy & optic neuropathy)
CHRONIC HYPERTENSIVE RETINOPATHY
Occurs due to long-standing essential hypertension.
Fundus Changes
1. Arteriolar narrowing
o Generalized narrowing: due to diffuse vasospasm.
o Focal narrowing: due to localized arteriolar spasm.
2. Arteriovenous (AV) crossing changes
o Common adventitial sheath causes venous compression.
o Gunn sign: tapering of vein on either side of crossing.
o Salus sign: deflection of vein at crossing.
o Bonnet sign: banking of vein distal to crossing.
3. Altered arteriolar light reflex – d/t arteriosclerosis
o Copper wiring: reddish-brown reflex due to wall thickening.
o Silver wiring: opaque white reflex due to severe sclerosis.
4. Retinal hemorrhages
o Flame-shaped hemorrhages in nerve fiber layer. (NFL)
o Resolve in 3–5 weeks with BP control.
5. Hard exudates
o Lipid deposition in outer plexiform layer. (OPL)
o May form macular star or macular fan.
6. Cotton-wool spots (soft exudates)
o Microinfarcts of nerve fiber layer.
o Represent axoplasmic flow stasis.
o Heal with residual RNFL defects.
7. Late changes
o Microaneurysms, shunt vessels, collaterals

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ACUTE (MALIGNANT) HYPERTENSIVE RETINOPATHY
Results from a sudden, severe rise in blood pressure and represents a medical
emergency.
Retinal Changes
• Marked generalized arteriolar narrowing with straightened vessels
• Numerous flame-shaped hemorrhages, sometimes confluent
• Extensive cotton-wool spots
• Hard exudates
• Focal intraretinal periarteriolar transudates (FIPTs) – small white oval lesions
along arterioles, hyperfluorescent on FFA
HYPERTENSIVE CHOROIDOPATHY
Occurs mainly in young patients with acute hypertensive crisis.
R/F:
o Toxemia of pregnancy
o Renal disease
o Malignant Hypertension
o Pheochromocytoma
Features
• Choroidal vasoconstriction → choriocapillaris ischemia
• Elschnig spots: focal RPE infarcts with later pigmentation and atrophy
• Siegrist streaks: linear hyperpigmented lesions along choroidal vessels—
fibrinoid necrosis
• Serous (exudative) retinal detachment, often involving the macula
HYPERTENSIVE OPTIC NEUROPATHY
• Optic disc edema due to ischemia of peripapillary choroid
• Hemorrhages on and around the disc
• Late optic disc pallor
• May result in anterior ischemic optic neuropathy (AION)
STAGING AND CLASSIFICATION
KEITH–WAGENER–BARKER CLASSIFICATION (1939)
• Grade 1: Mild generalized arteriolar narrowing
• Grade 2: Grade 1 + focal narrowing and AV nicking
• Grade 3: Grade 2 + hemorrhages, exudates, cotton-wool spots
• Grade 4: Grade 3 + optic disc edema (malignant hypertension)
SCHEIE CLASSIFICATION
Retinopathy Changes
• Stage 0: No changes
• Stage 1: Diffuse arteriolar narrowing

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• Stage 2: Focal narrowing
• Stage 3: Hemorrhages and exudates
• Stage 4: Retinal and optic disc edema
Arteriolosclerosis Grading
• Grade 0: Normal
• Grade 1: Broad light reflex
• Grade 2: Prominent light reflex and AV changes
• Grade 3: Copper wiring
• Grade 4: Silver wiring
WONG AND McINTOSH CLASSIFICATION (2005)
Retinopathy Description Systemic associations
Mild
Generalized/focal arteriolar
narrowing, AV nicking, arteriolar wall
opacity
Weak association with stroke
and coronary heart disease
Moderate
Mild changes + hemorrhages,
microaneurysms, cotton-wool spots,
hard exudates
Strong association with
stroke, CHF, renal
dysfunction, CV mortality
Accelerated Moderate changes + optic disc edema
High mortality and renal
failure
DIFFERENTIAL DIAGNOSIS
• Diabetic retinopathy
• Central retinal vein occlusion
• Hyperviscosity syndromes
• Radiation retinopathy
• Neuroretinitis
MANAGEMENT
• Primary treatment is systemic blood pressure control
• Identification and treatment of secondary causes of hypertension
• Caution: rapid BP reduction may worsen optic nerve ischemia
• No specific ocular treatment except in complications
COMPLICATIONS OF HR
• RVO
• Macular Edema
• VH
• ERM
• Macroaneurysm
• Retinal Neovascularization

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PROGNOSIS
• Retinal changes often regress with adequate BP control
• Grade 4 disease may result in permanent optic nerve or macular damage
• Severe hypertensive retinopathy indicates high risk of stroke, heart failure, and renal
disease
KEY EXAM POINTS
• Hypertensive retinopathy reflects both severity and duration of hypertension
• Choroidopathy is more common in young patients with acute hypertension
• Optic disc edema signifies malignant hypertension
• Wong and McIntosh classification is most useful for systemic risk stratification
• Malignant Hypertension (HTN): BP ≥180/120 mmHg with acute target-organ damage,
characterized by fibrinoid necrosis of arterioles
D/D of macular star:
• Hypertensive retinopathy
• Neuroretinitis
• Branch retinal vein occlusion
• Central retinal vein occlusion
• Papilledema

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DIABETIC RETINOPATHY
Introduction
• Diabetic retinopathy is a microvascular complication of diabetes mellitus and a
leading cause of preventable blindness in adults aged 20–64 years.
• Nearly 40–50% of diabetics develop DR over time.
• Diabetic macular oedema (DMO) is the commonest cause of visual loss, while
proliferative diabetic retinopathy (PDR) is the most vision-threatening stage.
• Ocular involvement reflects severity, duration, and systemic control of diabetes, with
important prognostic implications.
Definition of Diabetes Mellitus (WHO)
• Fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dL)
• HbA1c ≥ 6.5% (on two occasions)
Epidemiology & Burden
• Global diabetics: 171 million (2000) → >350 million (2030).
• India: 31 million (2000) → ~79 million (2030) (“diabetes capital”).
• Prevalence of DR: ~40%; sight-threatening DR: ~10%.
• PDR: 5–10% of diabetics.
• Type 1 DM:
o DR after 20–30 years: 90–99%
• Type 2 DM:
o DR at diagnosis: 3–5%
o DR after 20 years: ~60%
• CSME (10-year incidence):
o Type 1 DM: 20%
o Type 2 DM (on insulin): 25%
o Type 2 DM (not on insulin): 14%
Risk Factors
Major
1. Duration of diabetes (strongest predictor)
2. Poor glycaemic control
o DCCT & UKPDS: Tight control ↓ DR progression
o ↓ HbA1c by 1% → ↓ microvascular complications by ~33%
3. Hypertension (especially type 2 DM)
4. Pregnancy
o Risk higher with pre-existing DR
o Rapid tightening of control → early worsening
5. Nephropathy
o Renal transplant may improve DR

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Other
• Hyperlipidaemia
• Smoking
• Anaemia
• Obesity
• Cataract surgery
Q. Causes of Decreased Vision in Diabetic Retinopathy:
• Retinal causes: Diabetic macular edema (DME),Macular ischemia, Tractional retinal
detachment (TRD), Epiretinal membrane (ERM), Combined tractional–
rhegmatogenous retinal detachment (TRD + RRD)
• Non-retinal causes: Vitreous hemorrhage (VH), Preretinal/Subhyaloid hemorrhage
(PRH/SHH), Neovascular glaucoma (NVG), Diabetic papillopathy, Cataract, Ghost
cell glaucoma, RPE atrophy / Subretinal fibrosis
Q. Ocular Condition with decreased progression to DR:
Chorioretinal Scarring, RP, High myopia, Optic Atrophy

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Pathogenesis of Diabetic Retinopathy:
Chronic Hyperglycaemia
→ Retinal microangiopathy involving: • Pre-capillary arterioles • Capillaries • Venules
I. Hyperglycaemia-Induced Biochemical & Cellular Damage
Chronic hyperglycaemia activates multiple inter-related pathways:
1. Polyol (Aldose reductase) pathway
Glucose → Sorbitol accumulation → Osmotic stress → Cellular injury
2. Oxidative stress
↑ Free radicals + ↓ Antioxidant defense
3. Advanced Glycation End Products (AGEs) accumulation
Non-enzymatic protein glycation → Basement membrane thickening +
Endothelial dysfunction
4. Protein Kinase C (PKC-β) activation
Altered retinal blood flow → ↑ Vascular permeability → ↑ VEGF expression
5. Ion channel dysfunction
Endothelial and neuronal injury
II. Hematological & Biochemical Abnormalities
• ↑ Platelet adhesiveness
• ↑ Serum lipids
• ↑ Blood/plasma viscosity
• ↓ Fibrinolysis
• RBC deformation & rouleaux formation
• Leukostasis (ICAM-1 upregulation, CD18-mediated leukocyte adhesion)
➡ Capillary plugging & closure
III. Retinal Capillaropathy / Microangiopathy
• Pericyte loss (capillary wall weakening)
• Endothelial cell damage
• Capillary acellularity
• Thickened basement membrane
• Breakdown of blood–retinal barrier (BRB)
• Microvascular occlusion
IV. Pathophysiological Consequences
A. Retinal Ischaemia
• Capillary non-perfusion
• Retinal hypoxia
B. Breakdown of Blood–Retinal Barrier
• Increased vascular permeability
• Retinal vascular leakage → Macular oedema

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C. Capillary Leakage (Clinical Manifestations)
• Microaneurysms
• Dot & blot haemorrhages
• Retinal oedema
• Hard exudates
D. Vascular Remodeling
• Arteriovenous shunts
• IRMA (Intraretinal Microvascular Abnormalities)
V. Angiogenesis (Neovascularisation)
↑ Pro-angiogenic factors
• VEGF (central mediator)
• PDGF, IGF-1, HGF
• EPO, Ang-2, TNF-α
↓ Anti-angiogenic factors
• PEDF (Pigment epithelium-derived factor)
• Endostatin
• Angiostatin
• Platelet factor-4
Final Outcome
Neovascularisation + Fibrovascular proliferation ➡ Proliferative Diabetic Retinopathy
(PDR)
Polyol Pathway

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Pathophysiology of DME:
Diabetes
↓
Chronic Hyperglycemia
(± Hypertension, Dyslipidemia)
↓
Biochemical & Molecular Changes
(Polyol pathway, AGE, PKC activation, Oxidative stress)
↓
Hypoxia + Inflammation + ROS
↓
Release of Cytokines & Growth Factors
(↑ VEGF, inflammatory mediators)
↓
Microvascular Damage
• Endothelial junction breakdown
• Pericyte loss
• Basement membrane thickening
• Leukostasis
↓
Breakdown of Blood–Retinal Barrier
↓
Increased Vascular Permeability
↓
Diabetic Macular Edema

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Ophthalmic Complications of Diabetes
Common
• Diabetic retinopathy
• Diabetic macular oedema
• Unstable refraction
• Minor iris changes
Uncommon
• Accelerated cataract
• Neovascular glaucoma
• Cranial nerve palsies
• Reduced corneal sensitivity
Rare
• Diabetic papillopathy
• Acute cataract
• Wolfram syndrome
• Rhino-orbital mucormycosis
Descriptive Clinical Classification
1. Background Diabetic Retinopathy (BDR)
• Microaneurysms
• Dot and blot haemorrhages
• Hard exudates
Earliest stage; lesions persist as disease progresses
2. Diabetic Maculopathy:
Retinopathy involving the macula, leading to visual impairment. It includes Clinically
Significant Macular Oedema (CSME) and macular ischaemia.
Clinically Significant Macular Oedema (CSME) – ETDRS Criteria
Diagnosed on slit-lamp biomicroscopy (90D lens) if any one is present:
• Retinal thickening at or within 500 µm of the foveal centre
• Hard exudates at or within 500 µm of the foveal centre with adjacent
thickening
• Zone of retinal thickening ≥ 1 disc diameter (DD), any part within 1 DD of the
foveal centre
Clinico–Angiographic Classification of Diabetic Maculopathy
o Exudative Maculopathy
▪ Focal: Microaneurysms, dot/blot haemorrhages, localized macular
oedema, circinate hard exudates

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▪ Diffuse: Diffuse retinal oedema and thickening, involves posterior pole,
fewer hard exudates
o Ischaemic Maculopathy
▪ Severe visual loss disproportionate to fundus findings
▪ Microaneurysms and haemorrhages
▪ Mild/absent oedema, few hard exudates
▪ Enlarged/irregular foveal avascular zone on FFA
o Mixed Maculopathy
▪ Combined features of exudative and ischaemic maculopathy
3. Preproliferative Diabetic Retinopathy (PPDR)
• Cotton-wool spots
• Venous abnormalities (beading, looping)
• Intraretinal microvascular abnormalities (IRMA)
• Deep retinal haemorrhages
Indicates progressive retinal ischaemia and high risk of PDR
4. Proliferative Diabetic Retinopathy (PDR)
• Neovascularisation at disc (NVD)
• Neovascularisation elsewhere (NVE)
5. Advanced Diabetic Eye Disease (ADED)
End-stage of uncontrolled proliferative diabetic retinopathy (PDR) with severe vision-
threatening complications.
Clinical Features / Complications:
▪ Persistent or recurrent vitreous haemorrhage (VH)
▪ Tractional retinal detachment (TRD)
▪ Neovascular glaucoma (NVG) – also called 90-day glaucoma
▪ Severe visual loss or blindness

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ETDRS Classification of Diabetic Retinopathy
1. Non-Proliferative Diabetic Retinopathy (NPDR)
Mild NPDR
• Few microaneurysms only
Moderate NPDR
• Microaneurysms
• Dot/blot haemorrhages
• Cotton-wool spots
• Mild venous changes
Severe NPDR (4-2-1 rule)
• ≥4 quadrants haemorrhages
• ≥2 quadrants venous beading
• ≥1 quadrant IRMA
Very Severe NPDR
• Any two or more of the above
2. Proliferative Diabetic Retinopathy (PDR)
Defined by neovascularisation
• NVD (on/within 1 DD of disc)
• NVE (elsewhere)
High-risk PDR (DRS)
• NVD ≥ ¼–⅓ disc area
• NVD with vitreous/preretinal haemorrhage
• NVE ≥ ½ disc area with haemorrhage
ETDRS Follow-up Schedule
• No DR: Review in 12 months
• Very mild NPDR: Review in 12 months
• Mild NPDR: Review in 6–12 months
• Moderate NPDR: Review in ~6 months
• Severe NPDR: Review in 4 months
• Very severe NPDR: Review in 2–3 months
• Mild–moderate PDR (untreated): Review within 2 months
• High-risk PDR: Immediate treatment (no routine follow-up delay)
• Advanced diabetic eye disease: Follow-up as per detailed management plan

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Clinical Signs
Microaneurysms
• Earliest sign
• 30-120micron
• Buldging from weak point d/t pericyte loss
• Inner capillary plexus (INL)
• FA: early hyperfluorescence + late leakage
Haemorrhages
• Flame-shaped (NFL)—follows the architecture of NFL
• Dot/blot (INL/OPL)—inner retinal strs are perpendicular to the retinal surface &
compact
• Deep round haemorrhages → severe ischaemia
Hard Exudates
• Lipoprotein deposits in OPL
• Yellow, waxy, circinate
• Associated with chronic leakage
Cotton-Wool Spots
• NFL infarcts (axoplasmic stasis)—ischemic necrosis of NFL
• FA: hypofluorescence
Venous Changes
• Dilatation, beading, looping
• Marker of severe ischaemia
IRMA
• Intraretinal shunts
• Do not leak on FA
Feature IRMA NVE
Location Within retina, near capillary closure
On retinal surface, grows
into vitreous
Origin
Pre-existing retinal vessels (arteriovenous
shunts)
New vessels from ischemic
retina
Appearance
Cockscrew shaped, Fine, flat, slightly
tortuous; may mimic shunts
Fragile, lacy/tufted, rises
above retina
Leakage on
FA
Minimal or none Marked leakage
DR Stage Severe NPDR / pre-proliferative Proliferative DR
Complications Usually stable; indicates capillary closure
Vitreous haemorrhage,
tractional RD
Flow Rapid arteriovenous shunt flow Fragile, leaky vessels
FFA Do not leaks leaks

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Diabetic Macular Oedema (DMO)
DME is part of diabetic maculopathy, the most common cause of visual impairment in
diabetic patients (type 2). It results from capillary leakage, leading to retinal thickening and
oedema.
Pathophysiology:
• Diffuse oedema: Extensive capillary leakage
• Focal oedema: Localized leakage from microaneurysms and dilated capillary
segments
• Fluid accumulation:
o Initially between outer plexiform layer (OPL) and inner nuclear layer (INL)
o Later involves inner plexiform layer (IPL) and nerve fibre layer (NFL)
o Severe cases: full-thickness retinal oedema
• Cystoid macular oedema (CMO): Central fluid accumulation forming cystoid spaces
detectable on OCT; shows flower-petal pattern on FA
I. Clinical /FFA based Types of DME
1. Focal Maculopathy
o Well-circumscribed retinal thickening with complete/incomplete rings of
hard exudates
o FA: Late focal hyperfluorescence due to leakage
o Typically good macular perfusion
2. Diffuse Maculopathy
o Diffuse retinal thickening, often with cystoid changes
o Scattered microaneurysms and small haemorrhages
o Oedema may obscure landmarks, sometimes fovea localization difficult
o FA: Mid- and late-phase diffuse hyperfluorescence; demonstrates CMO if
present
3. Ischaemic Maculopathy
o Variable signs; macula may appear normal despite reduced vision
o FA: Capillary non-perfusion at fovea (enlarged FAZ), multiple CWS,
Attenuated arterioles
o May coexist with pre-proliferative DR (PPDR)
II. Central Subfield (CST) Classification of DME
1. Center-Involving (CI-DME)
• Edema involves foveal center (central 1 mm).
• OCT: Foveal thickening, cysts or subretinal fluid, possible outer retinal
disruption.
• Significance: Usually reduces vision; needs prompt anti-VEGF/steroid
treatment.
2. Non–Center-Involving (NCI-DME)
• Edema spares foveal center.

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• OCT: Thickening/cysts outside central 1 mm; fovea normal.
• Significance: Vision often preserved; observation or focal laser may suffice.
Tip: Central subfield thickness (CST) on OCT differentiates CI- vs NCI-DME.
III. OCT-Based Classification of DME
1. Sponge-like diffuse oedema
2. Cystoid macular oedema
3. Serous retinal detachment
4. Tractional macular oedema
OCT Biomarkers in Diabetic Retinopathy (DR)
A. Fluid Biomarkers:
• Intraretinal Fluid (IRF)
• Subretinal Fluid (SRF)
B. Structural Biomarkers:
1. Vitreoretinal Interface
• Epiretinal Membrane (ERM)
• Vitreomacular Traction (VMT) / Vitreoschisis
• NVD / NVE
• Venous Loops
2. Retinal Changes
• Disorganization of Retinal Inner Layers (DRIL)
• Bridging Retinal Processes (BRP)
• Ellipsoid Zone (EZ) & External Limiting Membrane (ELM) Disruption
• Hard Exudates (HE)
• Hyperreflective Dots / Hyperreflective Foci (HRF)
• Intracystic Hyperreflective Material (ICHRM)
• Microaneurysms (MAs) / Cotton Wool Spots (CWS)
3. Choroidal Biomarkers
• Choroidal Vascularity Index (CVI)
• Choroidal Thickness (CT)
• Hyperreflective Foci (HRF) in Choroid
Investigations
• Fundus fluorescein angiography (FFA):
o Leakage sites
o Neovascularisation

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• Optical coherence tomography (OCT):
o Quantifies oedema
o Guides treatment
Management
General Measures
• Tight glycaemic control (HbA1c 6–7%)
• BP control (<140/80 mmHg)
• Lipid control (Fenofibrate beneficial)
• Treat anaemia, nephropathy
• Smoking cessation
• Regular retinal screening
Treatment of Diabetic Macular Oedema
First-line: Anti-VEGF
• Ranibizumab, Aflibercept, Bevacizumab
• DRCR.net:
o Anti-VEGF superior to laser for centre-involving DMO
o Aflibercept better if VA ≤6/15
Laser Photocoagulation
• Focal/grid (modified ETDRS)
• Off-centre CSMO
Steroids
• Intravitreal triamcinolone
• Dexamethasone / Fluocinolone implants
• Useful in pseudophakia, pregnancy
Vitrectomy
• Tractional DMO
• Persistent vitreous haemorrhage

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Treatment of PDR
Panretinal Photocoagulation (PRP)
• Gold standard
• Reduces severe visual loss by >50%
Anti-VEGF for PDR
• Protocol S & CLARITY:
o Anti-VEGF ≈ PRP at 5 years
o Requires strict follow-up
Advanced Diabetic Eye Disease
• Vitreous haemorrhage
• Tractional RD
• Combined tractional + rhegmatogenous RD
• Rubeosis iridis → NVG
Indications for Pars Plana Vitrectomy
• Persistent vitreous haemorrhage
• Macula-threatening tractional RD
• Combined RD
• Dense premacular haemorrhage
• Media opacity with active PDR
Key Exam Pearls
• Duration is the strongest risk factor
• DMO = commonest cause of visual loss
• PRP = mainstay of PDR
• Anti-VEGF = first-line for centre-involving DMO
• NVD bleeds more than NVE d/t absence of ILM
• MA of 20 micron can be seen by DO
• Collaterals (bypass): within existing vascular network, A-A, V-V, slow flow, no leak on
FFA
• Shunts (shortcut): direct A-V connection, rapid flow, no leak on FFA
• Inner Capillary Plexus lies in GCL, Outer Capillary Plexus lies in INL
Q. Why Does Edema Occur in the Macula?
High density of retinal cells High metabolic activity
Absence of inner retinal layers at the fovea (FAZ region)
Henle’s fiber layer – radial arrangement of fibers with loose tissue architecture,
facilitating fluid accumulation.
Q. Causes of Cotton-Wool Spots
Diabetic retinopathy (DR) Hypertensive retinopathy (HR) Retinal vein occlusion (CRVO,
BRVO) HIV retinopathy Toxoplasmosis Leukemia Severe anemia Hypercoagulable
states Radiation retinopathy Interferon therapy Purtscher retinopathy

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Feature Drusen Hard Exudates (HE)
Appearance Round/oval, yellow-white, indistinct Irregular/waxy, bright yellow, sharp
Location Beneath RPE Outer plexiform layer (OPL)
Cause RPE/Bruch's membrane deposits Lipid leakage from retinal vessels
Association AMD DR, HR, RVO
DRCR.net Protocol:
• Protocol T:
o Compared Aflibercept vs Bevacizumab vs Ranibizumab for center-involved
DME.
o Aflibercept showed better visual outcomes in eyes with worse baseline vision
(20/50 or worse).
• Protocol S:
o PRP vs Ranibizumab for PDR.
o Ranibizumab was non-inferior to PRP for visual acuity.
o Less visual field loss and lower incidence of DME with Ranibizumab.
• Protocol I:
o Ranibizumab + deferred laser for DME.
o Ranibizumab + deferred laser produced the best long-term visual outcomes
compared with prompt laser.
Diabetic Retinopathy Study (DRS)
• PRP ↓ severe vision loss by >50% in high-risk PDR.
Early Treatment Diabetic Retinopathy Study (ETDRS)
• Aspirin: No effect on DR progression or vision loss; does not ↑
vitreous/preretinal hemorrhage.
• Scatter PRP: For severe NPDR/early PDR → small ↓ risk of severe vision loss
(defer until high-risk PDR if follow-up is good).
• Focal/Grid laser (DME): ↓ moderate vision loss by ~50% ↓ retinal
thickening ↑ visual improvement

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AGE-RELATED MACULAR DEGENERATION
Definition
Age-related macular degeneration (AMD), also called age-related maculopathy (ARM),
is a degenerative disorder of the macula characterized by drusen formation and
retinal pigment epithelium (RPE) abnormalities, in the absence of other retinal
disease, leading to progressive, irreversible central vision loss, particularly in the
elderly.
Pathology primarily involves the RPE–Bruch’s membrane–choriocapillaris–
photoreceptor complex.
Epidemiology
• Leading cause of irreversible blindness in industrialized / Western countries
• Most common cause of central vision loss in whites >50 years
• Rare below 50 years; prevalence increases steeply with age
• USA:
o ~8 million affected
o Advanced AMD in >1.75 million
o ~50% of irreversible visual loss in whites
• UK:
o ≥75 years: ~4% have VA ≤6/18
o ≥90 years: ~14% affected
• Blue Mountains Eye Study:
o Early AMD: 1.3% (49–54 yrs) → 28% (>80 yrs)
o Late AMD: 0.1% (49–54 yrs) → 7.1% (75–86 yrs)
• Dry AMD: 80–90% of cases
• Wet AMD: 10–20% but causes ~90% of severe vision loss
• Fellow-eye risk: ~50% risk of advanced AMD within 5 years if one eye is affected
• Rising prevalence due to aging population
Classification
A. Conventional Classification
1. Non-exudative (Dry / Non-neovascular) AMD
• Drusen
• RPE pigmentary abnormalities
• Geographic atrophy (GA) – advanced stage
(Strictly, the term “dry AMD” should be reserved for GA)
2. Exudative (Wet / Neovascular) AMD
• Choroidal neovascularization (CNV)
• Pigment epithelial detachment (PED)
• Subretinal / intraretinal fluid or hemorrhage
• Disciform scar
• Special entities:

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o Retinal angiomatous proliferation (RAP / Type 3)
o Polypoidal choroidal vasculopathy (PCV)
Feature Dry ARMD (Non-exudative) Wet ARMD (Exudative)
Frequency Most common (≈85–90%) Less common (≈10–15%)
Pathology
RPE atrophy ± hypertrophy with
drusen
Choroidal neovascular
membrane (CNVM)
Mechanism Degenerative changes
Leakage of blood and fluid from
CNVM
Progression Slow; may progress to wet ARMD Rapid progression
Vision loss
Gradual; geographic atrophy →
central scotoma
Sudden, severe central vision loss
Characteristic
lesion
Geographic atrophy Disciform scar
Risk Factors
Non-modifiable
• Age (strongest risk factor)
• Race: Whites > Asians > Blacks
• Genetics:
o CFH (1q31) – complement dysregulation
o ARMS2 / HTRA1 (10q26)
o 50 genes implicated
• Female sex (late AMD)
Modifiable
• Smoking (strongest modifiable factor; ~2× risk)
• Hypertension, cardiovascular disease
• Hyperlipidemia, obesity
• High-fat diet
• Low antioxidant intake
• Excess sunlight exposure
• Cataract surgery (possible association)
• Aspirin (possible ↑ risk of neovascular AMD)
• Light iris color
• Hyperopia
• Low lutein/zeaxanthin levels
Pathophysiology (Core Concept)
AMD primarily affects:
• Outer retina

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• RPE
• Bruch’s membrane
• Choriocapillaris
Early Lesions
• Basal laminar deposits (BlamD)
Between RPE plasma membrane & basement membrane
• Basal linear deposits (BlinD)
Between RPE basement membrane & inner collagenous layer of Bruch’s membrane
→ Strongest predictor of progression to late AMD
• Drusen: focal extracellular deposits between RPE & Bruch’s membrane
Advanced Disease
• Dry AMD → RPE atrophy → photoreceptor loss → geographic atrophy
• Wet AMD → CNV → fibrosis → disciform scar
Pathological Changes in Dry AMD
Bruch’s Membrane
• Thickening, lipid & calcium deposition
• Focal thinning and breaks
• Suggests inflammatory and complement-mediated damage
RPE
• Lipofuscin accumulation
• Hypo-/hyper-pigmentation
• Non-geographic and geographic atrophy
Choriocapillaris
• Thinning and sclerosis
• Reduced perfusion
Neurosensory Retina
• Rod loss early
• Cone loss later (blue cones first)
• Maximal photoreceptor loss in parafovea
• Complete loss in GA or disciform scar
Basal Deposits
Basal Laminar Deposit (BlamD)
• Location: Between RPE plasma membrane & basement membrane
• Composition: Type IV collagen, laminin, glycoproteins, GAGs, cholesterol, Apo-B &
Apo-E
• Associated with RPE atrophy and photoreceptor degeneration
Basal Linear Deposit (BlinD)
• Location: Inner collagenous zone of Bruch’s membrane
• Lipid-rich vesicular material
• More specific for AMD and strongest predictor of late disease

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Drusen
Histopathology
• Hyaline material accumulation
• Extracellular deposits between RPE & Bruch’s membrane
• Contain lipids, apolipoproteins, complement components
• Closely related to disease progression
Clinical Types
1. Hard (Small) drusen
o ≤63 µm, discrete, hyaline
o Common with aging
o Usually benign
2. Intermediate drusen
o 63–125 µm
o Progression risk ↑ with pigment changes
3. Soft (Large) drusen
o ≥125 µm, ill-defined, confluent
o High risk for GA & CNV
o May form drusenoid PED
4. Crystalline (Calcified) drusen
o Dehydrated soft drusen
o Strong association with GA
5. Cuticular (Basal laminar) drusen
o Younger patients
o FA: “starry-sky” appearance
o Usually good vision
o Weak association with progression
Key Exam Rule:
Risk of advanced AMD ∝ drusen size + pigmentary abnormalities
Geographic Atrophy (GA)
• End-stage dry AMD
• Well-demarcated RPE loss
• Associated photoreceptor and choriocapillaris atrophy
• Slowly progressive
• Fovea spared until late
• Drusen may disappear
Exudative (Wet) AMD
Choroidal Neovascularization (CNV)
• Abnormal fragile new blood vessels sprout from choriocapillaris d/t defect in Bruch’s
membrane

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• Hallmark of wet AMD
• Origin mainly from choroid
• Due to:
o Breaks in Bruch’s membrane
o Increased VEGF expression
CNV Types
• Type 1 (Occult) – sub-RPE
• Type 2 (Classic) – subretinal
• Type 3 – RAP (retinal origin)
• Combined CNV
Disciform Scar
• End-stage wet AMD
• Fibrovascular tissue replaces retina
• Severe, irreversible vision loss
• Blood supply: Choroid (96%), Retina (2.5%)
Role of VEGF
• Central mediator of CNV
• Promotes angiogenesis & vascular permeability
• Anti-VEGF therapy is the treatment cornerstone
Immune Mechanisms
• Activation of innate and adaptive immunity
• Complement cascade dysregulation
• Involvement of macrophages, dendritic cells, mast cells & lymphocytes
Clinical Features
• ↓ Color & contrast sensitivity
• Night vision difficulty (delayed dark adaptation)
• Slow visual recovery after bright light exposure
Dry AMD
• Soft drusen
• RPE pigmentary changes
• Gradual, bilateral (asymmetric) central vision loss
• GA → absolute central scotoma
Wet AMD
• Sudden painless vision loss
• Metamorphopsia
• Central scotoma
• Subretinal fluid/hemorrhage
• PED
• Grayish subretinal membrane

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Investigations
• Fundus examination
• OCT (most important)
• Fluorescein angiography (FA)
• Indocyanine green angiography (ICG) – essential for PCV & RAP
• Preferential hyperacuity perimetry (PHP)
AREDS & AREDS-2
Indications for Supplements
• Extensive intermediate drusen
• ≥1 large drusen
• Geographic atrophy
• Late AMD in one eye
AREDS-2 Formula
• Vitamin C 500 mg
• Vitamin E 400 IU
• Lutein 10 mg
• Zeaxanthin 2 mg
• Zinc 25–80 mg
• Copper 2 mg
Key AREDS-2 Findings
• β-carotene ↑ lung cancer risk → removed
• Omega-3 fatty acids → no benefit
• Lutein/zeaxanthin safer & possibly superior
• ~25–30% reduction in progression to advanced AMD
Management of Dry AMD
• AREDS-2 supplementation
• Smoking cessation
• Amsler grid self-monitoring
• Regular follow-up
• Low-vision rehabilitation
Emerging / Investigational Therapies
• Fenretinide – reduces lipofuscin (45% GA reduction in trials)
• CNTF (NT-501 implant) – neuroprotection
• Copaxone (glatiramer acetate) – immune modulation
• Stem cell therapy
• Nanosecond laser (experimental)

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Pigment Epithelial Detachment (PED)
Types
• Serous
• Fibrovascular (occult CNV)
• Drusenoid
• Hemorrhagic
Exam Pearl:
Large PED + anti-VEGF → ↑ risk of RPE tear
Retinal Pigment Epithelial Tear
• Occurs at junction of attached & detached RPE
• Risk factors: large PED, advanced age, RPE folds on OCT
• Poor prognosis if fovea involved
Treatment of Wet AMD
Location of CNVM Treatment
Subfoveal
Anti-VEGF ± Thermal laser
photocoagulation ±
Photodynamic therapy (PDT)
Juxtafoveal
Anti-VEGF ± Photodynamic
therapy (PDT)
Extrafoveal Anti-VEGF
Anti-VEGF Therapy (Gold Standard)
• Ranibizumab
• Bevacizumab
• Aflibercept
• Brolucizumab
Landmark Trials: MARINA, ANCHOR, PIER, CATT, IVAN, VIEW 1/2, HAWK & HARRIER
Principle:Better baseline VA → better final VA
Photodynamic Therapy (Verteporfin)
• Limited role now
• IV Verteporfin → Wait 15 min → 689 nm laser (90 sec) → Verteporfin activation →
Photochemical reaction → CNVM endothelial damage → Thrombosis & vascular
occlusion → CNVM regression
• Useful in:
o PCV
o Combination therapy
o Patients refusing injections

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Special Forms of Neovascular AMD
Polypoidal Choroidal Vasculopathy (PCV)
• Pachychoroid disease
• More common in Asians & Africans
• ICG diagnostic
• Anti-VEGF + PDT superior to anti-VEGF alone (EVEREST-II)
Retinal Angiomatous Proliferation (RAP / Type 3)
• Retinal origin
• Often bilateral
• Poor prognosis
• Anti-VEGF ± PDT
Peripheral Exudative Hemorrhagic Chorioretinopathy (PEHCR)
• Peripheral hemorrhage & PED
• Often benign
• Treat if macula threatened
Idiopathic CNV
• <50 years
• Diagnosis of exclusion
• Better prognosis than AMD-CNV
• Anti-VEGF effective
Recent Advances in Management of ARMD
1. VEGF Trap
• Aflibercept (VEGF Trap / Regeneron) – Recombinant soluble VEGF receptor fusion
protein that binds VEGF-A, VEGF-B, and PlGF.
2. Anecortave Acetate
• Posterior juxtascleral injection (every 6 months).
• Anti-angiogenic agent (limited current clinical use).
3. siRNA Therapy
• Inhibits the VEGF pathway.
• Cand5 (Bevasiranib) – Suppresses VEGF production.
• Sirna-027 – Targets VEGFR-1.
4. Surgical Approaches
• Macular translocation – Moves the fovea onto healthy RPE.
• RPE transplantation – Fetal, macular, or autologous RPE graft.
• Surgical CNV removal.
• Retinal rotation – Repositions the fovea over healthy RPE.
• Autologous RPE–choroid patch graft.
Advanced Imaging in ARMD
• OCTA – Non-invasive detection of CNV.
• SS-OCT – Better choroidal imaging.
• EDI-OCT – Measures choroidal thickness.

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• FAF – Maps RPE damage & monitors geographic atrophy.
• OCT biomarkers – IRF, SRF, PED, SHRM, HRF, EZ disruption → prognosis &
treatment response.
• AI-assisted retinal imaging – Early detection & progression prediction.
Q. Differential Diagnosis of CNVM: PCV, Pathologic myopia, Angioid streaks, Presumed
Ocular Histoplasmosis Syndrome (POHS).
Q. Signs of Conversion of Dry → Wet ARMD
o Sudden ↓ central vision
o Metamorphopsia (Amsler grid +)
o Subretinal hemorrhage
o Subretinal/Intraretinal fluid (OCT)
o PED
Differential Diagnosis of Angioid Streaks (Mnemonic: PEPSI)
• P – Pseudoxanthoma elasticum
• E – Ehlers–Danlos syndrome
• P – Paget disease of bone
• S – Sickle cell disease
• I – Idiopathic
Differential Diagnosis of Roth Spots
• Bacterial endocarditis (classical association)
• Leukemia
• Severe anemia
• Sickle cell disease
• Collagen vascular diseases (e.g., SLE)
• Multiple myeloma
• HIV infection
High-Yield Exam Pearls
• Dry AMD common; wet AMD causes most blindness
• Drusen size + pigment changes predict progression
• Basal linear deposits are strongest histologic predictor
• VEGF is central to CNV pathogenesis
• OCT is the most important monitoring tool
• Anti-VEGF is current gold standard
• Suspect PCV in Asian patients with hemorrhage & minimal drusen

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RETINAL DETACHMENT
Retinal detachment (RD) is the separation of the neurosensory retina (NSR) from the
retinal pigment epithelium (RPE) with accumulation of fluid in the potential
subretinal space.
It is a misnomer, as the retina does not detach from the choroid directly but separates
at an embryologically determined cleavage plane between NSR and RPE.
This separation disrupts metabolic support from the RPE to photoreceptors, resulting
in visual dysfunction and, if untreated, permanent vision loss.
2. FACTORS MAINTAINING NORMAL RETINAL ADHESION
The retina remains attached due to a combination of mechanical, biochemical, and
physiological forces:
1. Interphotoreceptor Matrix & RPE Microvilli – Acts as a biological “glue,”
maintaining apposition of photoreceptors to the RPE.
2. Active RPE Pump – Na⁺/K⁺-ATPase–mediated transport removes fluid from the
subretinal space into the choroid, creating a suction effect.
3. Hydrostatic & Osmotic Forces – IOP and osmotic gradients drive fluid from the
vitreous toward the choroid.
4. Vitreous Support – The formed vitreous acts as an internal tamponade, stabilizing
the retina and plugging minor breaks.
5. Integrity of the Neurosensory Retina – Absence of full-thickness retinal breaks is
essential for maintaining adhesion.
Retinal detachment occurs when these adhesive forces are overwhelmed.
3. CLASSIFICATION OF RETINAL DETACHMENT
A. Based on Pathogenesis
1. Rhegmatogenous RD (RRD)
• Most common (~90%)
• Requires a full-thickness retinal break
• Liquefied vitreous enters subretinal space
o Primary Rhegmatogenous RD (RRD): Spontaneous retinal detachment
following PVD without pre-existing retinal disease.
o Secondary Rhegmatogenous RD (RRD): Retinal detachment secondary to
pre-existing retinal pathology (e.g., lattice degeneration, trauma, retinal
degenerations).
2. Tractional RD (TRD)
• Retina pulled off by contracting vitreoretinal membranes
• No break initially

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3. Exudative (Serous/Secondary) RD
• Fluid accumulation without break or traction
• Due to breakdown of blood–retinal barrier
4. Combined Tractional–Rhegmatogenous RD
• Traction causes a secondary retinal break
5. Subclinical RD
• Asymptomatic retinal break with SRF extending
1 DD but <2 DD posterior to equator
• No subjective field defect
4. RHEGMATOGENOUS RETINAL DETACHMENT (RRD)
4.1 Pathogenesis (Triad)
All three are essential:
1. Liquefied vitreous (synchysis)
2. Vitreoretinal traction
3. Full-thickness retinal break
Explains why 5–10% of people with retinal breaks never develop RD.
4.2 Vitreous Changes and Posterior Vitreous Detachment (PVD)
• Aging → collagen fragmentation + hyaluronic acid dissociation
• Leads to vitreous liquefaction (synchysis) and collapse (syneresis)
• PVD prevalence:
– 27% (60–69 yrs)
– 63% (>70 yrs)
Early PVD: myopia, trauma, inflammation, post-cataract surgery
Clinical sign: Weiss ring
Complication: abnormal vitreoretinal adhesion → horseshoe tear ± vitreous
hemorrhage
Q. Causes of Vitreous Liquefaction (Synchysis): Aging, High myopia, Uveitis, Coloboma,
Genetic disorders: Stickler syndrome Marfan syndrome
4.3 Peripheral Retinal Degenerations Predisposing to RD
A. Lattice Degeneration
• Seen in 7–8% population
• Present in 30–40% of RDs
• Bilateral ~45%, common in myopes
• Temporal > nasal, superior > inferior
Features:
– Cigar-shaped circumferential lesions
– White arborizing vessels
– Thinned retina with yellow flecks

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– Overlying vitreous liquefaction
– Strong vitreoretinal adhesion at margins
Complications:
– Horseshoe tears (posterior margin)
– Atrophic round holes (16–18%)
B. Snail Track Degeneration
• Variant of lattice
• Shiny frost-like appearance
• Longer lesions
• Atrophic holes common
C. Degenerative Retinoschisis
• Splitting of NSR
• Typical: outer plexiform layer
• Reticular: nerve fiber layer
Typical retinoschisis:
– Seen in 4–22% >40 yrs
– Inferotemporal most common
– Smooth, immobile dome-shaped elevation
– Snowflake dots (Müller cell remnants)
Key point: Breaks in both layers → rhegmatogenous RD
D. White Without Pressure (WWP)
• Peripheral retinal whitening without indentation
• Seen in ~30%, bilateral in 20%
• Usually benign
• Significant in fellow eye of giant retinal tear → prophylactic 360° laser
4.4 Developmental Lesions Predisposing to RD
• Enclosed oral bays
• Meridional folds and complexes
• Cystic retinal tufts
• Zonular traction tufts (aphakic RD)
4.5 Risk Factors for RRD
• High myopia (lifetime risk 0.7–6%)
• Aphakia / pseudophakia (esp. post-YAG capsulotomy)
• Trauma (retinal dialysis)
• Family history (Stickler, Marfan)
• Fellow eye RD (8–10%)
• Acute symptomatic PVD

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5. RETINAL BREAKS
Tears (tractional):
• Horseshoe tear (most common)
• Operculated tear
• Giant retinal tear (≥90°)
Holes (atrophic): • Round/oval (lattice, snail track)
Dialysis: • Circumferential disinsertion at ora serrata • Usually traumatic
Distribution of breaks:
• Superotemporal – ~60%
• Superonasal – ~15%
• Inferotemporal – ~15%
• Inferonasal – ~10%
• Multiple breaks in ~50%
6. CLINICAL FEATURES OF RRD
Symptoms – “4 F’s”
• Flashes (photopsia)—VRT—prod. of phosphanes
• Floaters – microbleeding from tears
• Field defect (curtain/veil) – d/t SRF
• Failing vision (macular involvement)
Note: Site of photopsia does NOT localize the break.
Signs
Anterior segment
• IOP ~5 mmHg lower – (Early: inflamm & decreased IOP prod, Late: posterior flow
through RPE break)
• RAPD in extensive RD
• Tobacco dust (Shafer’s sign)—macrophage containing RPE in ant. vitreous
• Mild secondary iritis
• Raised IOP in Schwartz–Matsuo syndrome
Posterior segment
• Grey-white elevated retina
• Corrugations (fresh RD)
• Loss of choroidal pattern
• Dark, reflexless vessels
7. MORPHOLOGY OF RRD
Fresh RD
• Convex, mobile, corrugated retina
• Opaque appearance

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• SRF reaches ora serrata
• Macular pseudohole
• B-scan: mobile membrane
Long-standing RD
• Retinal thinning and atrophy
• PVR changes
• Pigmentation
• Intraretinal cysts (>1 year)
• Subretinal demarcation lines (high-water marks)—d/t RPE proliferation &
migration
Complications of Long-standing RD: Uveitis, Complicated cataract, Rubeosis Iridis,
Glaucoma, BSK, Phthisis
8. MODIFIED LINCOFF’S RULES
Principle: The configuration of rhegmatogenous retinal detachment (RRD) predicts
the location of the primary retinal break.
RD Configuration Likely Primary Break
1. Superior temporal/nasal RD
Within 1.5 clock hours of the highest border of
RD
2. Superior RD crossing 12 o'clock At 12 o'clock (±1.5 clock hours)
3. Total RD Superiorly, usually at 12 o'clock
4. Inferior RD with unequal SRF
levels
On the side with the higher SRF level
5. Inferior RD with equal SRF levels At 6 o'clock
6. Bullous inferior RD
Small superior break (within the superior
detached wedge)

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9. PROLIFERATIVE VITREORETINOPATHY (PVR)
Pathological wound-healing response with epiretinal and subretinal membrane
proliferation causing traction, retinal folds, and recurrent RD.
Classification (Retina Society)
• Grade A – Vitreous haze, pigment clumps
• Grade B – Retinal wrinkling, vessel tortuosity
• Grade C – Fixed full-thickness folds (clock hours)
• Advanced – Funnel-shaped shortened retina
Risk Factors
• Large/giant tears
• Chronic RD
• Excessive cryotherapy
• Choroidal detachment
10. DIFFERENTIAL DIAGNOSIS
Degenerative Retinoschisis
• Smooth, immobile
• Absolute scotoma
Choroidal Detachment
• Brown, smooth, convex, immobile
• Four lobes, do not reach posterior pole
• Causes: hypotony, uveitis, drugs, tumors
Uveal Effusion Syndrome
• Hypermetropic middle-aged men
• Exudative RD
• Leopard-spot RPE changes after resolution
11. MANAGEMENT OF RHEGMATOGENOUS RD
Indications for Urgent Surgery
• Acute progressive macula-ON RD
• Superior or large breaks
• RD with dense vitreous hemorrhage
12. SURGICAL OPTIONS
A. Pneumatic Retinopexy
• Intravitreal gas + laser/cryotherapy
• Small superior breaks (<2 clock hours)

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• Success ~80%
• Requires strict positioning
B. Scleral Buckling (SB)
Indications
• Retinal Dialysis
• Inferior Retinal Break
• Single break
• Young patient
• Phakic patient
Principles
• Indents sclera to oppose RPE to retina
• Reduces vitreoretinal traction
Explants
• Silicone sponges/bands
• Radial, segmental, circumferential, encircling (240 band)
D-ACE Technique
• Drainage
• Air
• Cryotherapy
• Explant
Complications
• PVR (commonest cause of failure)
• Missed/new breaks
• Diplopia
• Anterior segment ischemia
• Buckle extrusion/infection
• Raised IOP, choroidal detachment
C. Pars Plana Vitrectomy (PPV)
Instrumentation
• 20G, 23G, 25G, 27G
• Wide-angle viewing systems
Tamponades
• Gases: SF6, C2F6, C3F8
• Silicone oil: 1000cs, 5000cs
• Heavy liquids: PFCL
Indications
• PVR-associated RD
• Giant/posterior/multiple breaks
• Pseudophakic/aphakic RD

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• TRD and combined RD
• Failed buckle
13. TRACTIONAL RETINAL DETACHMENT
Retinal detachment caused by contraction of fibrovascular/vitreoretinal membranes,
causing retinal elevation without a retinal break.
Etiology (Mnemonic: "DROP PET")
• D – Diabetic retinopathy (PDR) (Most common)
• R – ROP (Retinopathy of Prematurity)
• O – Ocular trauma (penetrating/perforating injury)
• P – PFV/PHPV (Persistent fetal vasculature)
• P – Pars planitis (Intermediate uveitis)
• E – Eales disease
• T – Toxoplasmosis (post-inflammatory vitreoretinal fibrosis)
Others
• Cataract surgery with vitreous incarceration
• Retrolental fibroplasia
Features
• Concave, immobile retina
• No shifting fluid
• SRF shallow, does not reach ora
Surgery
• Segmentation
• Delamination
• En-bloc dissection
14. EXUDATIVE (SEROUS) RETINAL DETACHMENT
Retinal detachment due to breakdown of the outer blood–retinal barrier
(RPE/choroid) → subretinal fluid accumulation without retinal break or vitreoretinal
traction.
Etiology (Mnemonic: "ISRCT")
I – Inflammatory
• Posterior scleritis
• VKH / Posterior uveitis
• Peripheral choroidal effusion
• Excessive PRP / Cryotherapy
S – Systemic
• Malignant hypertension
• Renal failure
• Hyperviscosity / Dysproteinemia (e.g., Waldenström macroglobulinemia)
R – RPE Defects

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• CSCR
• Pigment epithelial detachment (PED)
C – Choroidal Neovascularization (CNV)
• AMD
• Choroidal rupture
• Angioid streaks
• POHS
T – Tumors
• Choroidal melanoma
• Choroidal metastasis
• Retinoblastoma
Key Feature: Shifting subretinal fluid
Treatment
• Treat underlying cause
• Steroids for inflammation
• Laser for focal leaks
15. COMPLICATIONS OF VITRECTOMY
Intraoperative
• Iatrogenic breaks
• Choroidal hemorrhage
Postoperative
• Re-detachment
• Raised IOP
• Cataract
• CME
• Band keratopathy
16. PROGNOSIS
• Anatomical success: up to 90%
• Visual outcome depends on:
– Macular status
– Duration of detachment
– Presence of PVR

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Differences between Rhegmatogenous RD and Choroidal Detachment
Feature Rhegmatogenous RD Choroidal Detachment (CD)
Symptoms
Flashes and floaters
present
Usually asymptomatic (no
vitreoretinal traction)
Visual field defect Develops rapidly
Absent unless very extensive (e.g.,
kissing choroidals)
Appearance / Color
Grey-white, convex,
undulating, corrugated;
lighter in color
Brownish, darker; convex, smooth,
bullous
Mobility
Mobile with eye
movements
Relatively immobile
Retinal break Present Absent
Extent From disc to ora serrata
Usually anterior to equator; rarely
reaches disc
Macular involvement May be involved
Elevations do not extend to
posterior pole
Anterior chamber Normal depth Shallow
Intraocular pressure (IOP) Normal or low Very low
Peripheral examination
Scleral indentation
required
Peripheral retina & ora seen
without indentation
Associated traction
Vitreoretinal traction
present
No vitreoretinal traction
Treatment Surgical repair
Often spontaneous resolution;
treat underlying cause

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Differences between Retinal Detachment and Degenerative Retinoschisis
Feature Rhegmatogenous RD Retinoschisis
Symptoms
Photopsia and floaters
present
Usually asymptomatic; photopsia/floaters
absent (no vitreoretinal traction)
Clinical
appearance
Convex, undulating retinal
folds
Convex, smooth, dome-shaped elevation
Mobility Mobile Fixed / immobile
Transparency Translucent Transparent
Extent From ora serrata to disc Usually from ora to equator
Visual field defect
Relative scotoma with
sloping margin
Absolute scotoma with sharp border
Retinal break Must be present May or may not be present
Associated signs
Tobacco dusting,
demarcation line,
intraretinal cysts
Absent
Reaction to laser
photocoagulation
No burn (SRF under retina) Whitening / burn seen
USG with scleral
depression
Detachment becomes
shallow
No change
Vitreoretinal
traction
Present Absent
Nature of
detachment
True neurosensory retinal
separation
Splitting of retinal layers (schisis cavity)

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Differences between Rhegmatogenous, Tractional, and Exudative Retinal Detachment
Feature Rhegmatogenous RD Tractional RD Exudative (Serous) RD
History / Risk
factors
Photopsia, floaters;
PVD, myopia, lattice,
trauma
Diabetes, sickle
cell, ROP,
penetrating
trauma
Systemic/inflammatory: HTN,
pre-eclampsia, renal failure,
uveitis, tumors
Symptoms
Flashes & floaters
common
Usually absent Usually absent
Visual field defect Rapid progression
Slow, may
remain static
Rapid
Laterality
Usually unilateral
(fellow eye later)
Usually unilateral Often bilateral, simultaneous
Association with
PVD
Usually follows
complete PVD
Not associated
(incomplete PVD)
Not associated
Retinal break Always present
Absent initially
(secondary break
may occur)
Absent
RPE pump
function
Intact Not affected Impaired (primary pathology)
Configuration /
Shape
Convex, bullous,
corrugated folds
Concave, tented
at traction points
Convex but smooth, no
corrugations
Retinal mobility
Mobile (↓ in chronic
cases)
Restricted /
immobile
Mobile
Extent of
detachment
Extends to ora serrata
Seldom extends
to ora
Extends to ora serrata
Elevation Low–moderate
Focal elevation at
traction
Moderate–very high
Signs of
chronicity
Demarcation lines,
intraretinal cysts
Demarcation
lines
Usually none
Pigment in
vitreous
Present (~70%)
Present in
trauma
Absent
Vitreous changes
Syneresis, PVD,
flap/tear
Vitreoretinal
traction
Usually clear (± uveitis)
Subretinal fluid
(SRF)
Clear, no shifting
Shallow, no
shifting
Turbid, shifts with posture
Choroidal mass None None May be present
Intraocular
pressure
Often low Usually normal Variable

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Feature Rhegmatogenous RD Tractional RD Exudative (Serous) RD
Transillumination Normal Normal
Blocked if pigmented choroidal
mass
PVR
Develops with
duration
Absent Absent
Treatment Surgical Surgical Medical – treat cause
Common causes
PVD, lattice, CMVR,
Stickler, Marfan
PDR, ROP, sickle
retinopathy,
trauma
Uveitis, metastasis, melanoma,
Coats, VKH, scleritis,
retinoblastoma
Exam Pearls
• PVD: Separation of the posterior vitreous cortex from the retina (ILM).
• Weiss ring: Detached annular vitreous opacity from the optic disc margin (sign of
PVD).
• Causes of Floaters: PVD, vitreous degeneration (synchysis), vitreous hemorrhage
(VH), Weiss ring, high myopia, retinal tear/RD, uveitis, diabetic retinopathy, retinitis,
endophthalmitis, trauma, intraocular foreign body (IOFB), asteroid hyalosis.
• Causes of Flashes (Photopsia): PVD, vitreoretinal traction (VRT), retinal tear, retinal
detachment (RD), retinal migraine, retinitis, trauma.
• Tessellated/Tigroid fundus = ↓ RPE pigmentation + ↓ choroidal pigmentation →
prominent choroidal vessels.
• Retinal Dialysis: Circumferential disinsertion of the neurosensory retina (NSR) from
the non-pigmented epithelium (NPE) at the ora serrata, most commonly due to blunt
ocular trauma (usually inferotemporal).

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RETINAL DETACHMENT SURGERY
Goals of RD Surgery
Goals of RRD surgery:
• Identify the retinal break, relieve traction, seal the break, reattach the retina (with or
without SRF drainage), and maintain attachment with tamponade until chorioretinal
adhesion develops.
• Once the breaks are sealed, residual SRF is actively absorbed by the RPE pump,
leading to anatomical reattachment.
2. TYPES OF RETINAL REATTACHMENT SURGERY
A. Scleral Buckling (SB)
• Extraocular procedure
• Produces inward indentation of sclera
B. Pars Plana Vitrectomy (PPV)
• Intraocular procedure
• Removes vitreous traction directly
C. Pneumatic Retinopexy (PR)
• Intravitreal gas injection
• Minimally invasive
Choice of Surgery Depends On
• Number, size, and location of breaks
• Extent and height of RD
• Presence and grade of PVR
• Lens status (phakic / pseudophakic / aphakic)
• Vitreous clarity
• Macular status
• Patient’s ability to posture
• Surgeon’s expertise
3. HISTORICAL EVOLUTION OF RD SURGERY
• 1918 – Jules Gonin: Retinal break theory; ignipuncture
• 1947 – Schepens: Indirect ophthalmoscope
• 1950s – Meyer-Schwickerath: Photocoagulation
• 1960s – Lincoff: Cryopexy

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• 1950s–60s: Scleral buckling (Schepens, Custodis)
• 1971 – Machemer: First pars plana vitrectomy
• 1972 – O’Malley & Heinz: Three-port vitrectomy
• Modern era: Endolaser, PFCLs, long-acting gases, silicone oil, MIVS (23/25/27G),
chandelier illumination
4. PATHOGENESIS OF RHEGMATOGENOUS RD
Forces Maintaining Retinal Attachment
• Hydrostatic pressure (IOP > choroidal pressure)
• Oncotic pressure (choroid > vitreous)
• Active RPE pump
Forces Causing Detachment
• Vitreoretinal traction (most important)
• Gravity
• Eye movements
Role of Retinal Breaks
Liquefied vitreous enters the subretinal space → RD occurs when detaching forces
exceed attaching forces.
Common Causes of Surgical Failure
• Missed retinal breaks
• Persistent vitreoretinal traction

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❖ SCLERAL BUCKLING SURGERY (custodis)
Indication: young, phakic, localized break, inferior retinal dialysis
Principle
Indentation of sclera, choroid, and RPE to:
• Relieve vitreoretinal traction
• Support retinal breaks
• Promote NSR–RPE apposition
• Facilitate chorioretinal adhesion
Mechanism
• Indirect relief of radial vitreous traction
• Displacement of SRF away from breaks
• Supports unidentified breaks (major advantage)
6. TYPES OF SCLERAL BUCKLING
A. Based on Extent
• Segmental buckle: Localized breaks, less morbidity
• Encircling buckle (cerclage): 360° support
o Indications: Aphakia, PVR, multiple breaks
B. Based on Orientation
• Circumferential buckle
• Radial buckle – ideal for large posterior horseshoe tears
7. DRAINAGE OF SUBRETINAL FLUID (SRF)
Indications
• Long-standing RD
• Bullous RD
• Inferior breaks
• PVR
• Elderly patients
• Unknown break
Complications
• Choroidal/subretinal hemorrhage
• Retinal/vitreous incarceration
• Hypotony

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• Endophthalmitis
⚠ Note: Drainage is an intraocular step in an extraocular surgery.
8. PREOPERATIVE EVALUATION
History
• Floaters, photopsia, field defects
• Duration of symptoms
• Trauma, myopia, cataract surgery
• Previous RD
Examination
• Visual acuity, RAPD, IOP
• Shafer’s sign
• Lens status, vitreous clarity
Fundus Examination
• Indirect ophthalmoscopy with scleral depression
• Amsler–Dubois chart
Identify:
• All breaks
• Extent of RD
• Lattice degeneration
• PVR
• Macular status
9. LINCOFF’S RULES
• Shape of RD predicts break location in ~96%
• Superior RD → break near highest point
• Inferior RD → break on higher side
• Bullous inferior RD → break above horizontal meridian
10. TIMING OF SURGERY
• Macula-on RD: Emergency (within 24–48 h)
• Recent macula-off (<5 days): Early surgery
• Chronic macula-off: Elective

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❖ PARS PLANA VITRECTOMY (PPV) -Machemer
Definition
PPV is an intraocular procedure involving removal of vitreous gel to:
• Relieve anteroposterior and tangential traction
• Permit direct visualization and treatment of breaks
• Allow internal SRF drainage
• Enable endolaser photocoagulation
• Facilitate internal tamponade
Indications
• PVR
• Pseudophakic/aphakic RD
• Giant retinal tears
• Posterior breaks
• Combined TRD + RRD
Advantages
• Direct traction relief
• Clears media opacity
• Immediate retinal reattachment
• Superior outcomes in pseudophakic RD
12. EVOLUTION OF VITRECTOMY INSTRUMENTATION
Gauge Systems
Gauge Diameter Characteristics
20G 0.9 mm Conventional, sutured
23G 0.64 mm MIVS, versatile
25G 0.51 mm Less trauma
27G 0.4 mm Ultra-MIVS
Advantages of MIVS
• Transconjunctival, sutureless
• Less inflammation
• Faster rehabilitation
• Less surgically induced astigmatism

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13. CORE COMPONENTS OF PPV SYSTEM
Vitreous Cutter
• Ultra-high cut rates (5000–7500 cpm)
• Smaller vitreous bites → ↓ traction
• Safer vitreous base shaving
Illumination
• Xenon / mercury vapour light sources
• Chandelier illumination → true bimanual surgery
Infusion Cannula
• Maintains IOP and globe volume
• Must be confirmed intravitreal before activation
Viewing Systems
• Non-contact wide-angle: BIOM, EIBOS (preferred)
• Contact lenses: higher magnification, limited field
14. BASIC SURGICAL STEPS OF PPV
1. Port placement
2. Core vitrectomy
3. Induction of posterior vitreous detachment
4. Vitreous base shaving
5. Membrane dissection (if present)
6. Internal SRF drainage
7. Endolaser photocoagulation
8. Internal tamponade
15. VITREOUS SUBSTITUTES (TAMPONADES)
A. Intraocular Gases
Gas Expansion Duration
Air None 5–7 days
SF₆ 2× 10–15 days
C₃F₈ 3–4× 1-2month
(SF6: Sulfur Hexafluoride, C3F8: Perfluoropropane)
Mechanism: Surface tension at gas–fluid interface
⚠ Contraindications: Air travel, nitrous oxide anesthesia

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B. Silicone Oil (Polydimethyl siloxane, Trifluoromethyl siloxane)
• Long-term tamponade
• Viscosities: 1000–5000 cSt
• Patient can see better through SO
Indications
• PVR
• GRT
• Trauma
• Recurrent RD
• Patients unable to posture
Complications
• Cataract
• Glaucoma
• Emulsification
• Keratopathy
16. PERFLUOROCARBON LIQUIDS (PFCLs)
Fully fluorinated synthetic analogs of hydrocarbons containing C-F bond
Properties
• High specific gravity (~1.9)
• Optical clarity
• Immiscible with saline
Indications
• Giant retinal tears
• PVR
• Traumatic RD
• Subretinal hemorrhage
• Dislocated lens/IOL
⚠ Not for long-term tamponade
17. GIANT RETINAL TEARS (GRT)
Definition
Full-thickness retinal break ≥90° with detached posterior vitreous.
Surgical Principles
• Complete vitrectomy

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• PFCL-assisted flap unfolding
• Extensive endolaser
• Long-term tamponade
• ± encircling buckle
18. ROLE OF SCLERAL BUCKLE IN GRT
• Strongly recommended in PVR
• Reduces peripheral traction
• Prevents redetachment

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❖ PNEUMATIC RETINOPEXY
Indications
• Single superior break
• Minimal traction
• Cooperative patient
Principle
• Mechanical closure – RPE pump removes SRF
• Surface tension
• Buoyancy
Limitations
• No traction relief
• Poor for inferior breaks
• Lower success rate
20. COMPARISON OF TECHNIQUES
Feature Buckle PPV Pneumatic
Traction relief Indirect Direct No
Vitreous removal No Yes No
Immediate reattachment No Yes No
Inferior breaks Yes Yes No
21. POSTOPERATIVE CARE
• Antibiotic–steroid drops
• Cycloplegics
• IOP monitoring
• Posturing
Monitor for: PVR, Raised IOP, Redetachment, Buckle-related complications

Retina & Vitreous - Postgraduate MD Ophthalmology Notes- Dr. Prabhat Devkota,MD

Retina & Vitreous - Postgraduate MD Ophthalmology Notes- Dr. Prabhat Devkota,MD

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