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Diabetic Retinopathy — Complete Detailed Notes (RGUHS Exam Format)

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INTRODUCTION

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OPHTHALMIC COMPLICATIONS OF DIABETES

Common

• Diabetic maculopathy (oedema + ischaemia)
• Retinopathy (neovascularisation of disc/retina, vitreous haemorrhage)
• Unstable refraction (osmotic lens changes)

Uncommon

• Recurrent styes; xanthelasma
• Accelerated age-related cataract
• Tractional retinal detachment
• Neovascularization of iris and angle → Neovascular glaucoma (NVG)
• Ocular motor nerve palsies (3rd, 4th, 6th)
• Reduced corneal sensitivity

Rare

• Diabetic papillopathy
• Acute-onset cataract
• Wolfram syndrome (optic atrophy + neurological abnormalities)
• Rhino-orbital mucormycosis

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PREVALENCE

• DR occurs in approximately 40% of all diabetics
• Type 2 diabetes: 67% prevalence at 10 years after diagnosis; 10% will have proliferative disease
• More common in Type 1 than Type 2 diabetes

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RISK FACTORS (AK Khurana Mnemonic: DOGS-HP)

⚠️ A sudden improvement in diabetic control may paradoxically cause progression of retinopathy.

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PATHOGENESIS

Key Mechanisms:

• Polyol pathway activation → sorbitol accumulation → osmotic damage
• Advanced Glycation End-products (AGEs) → basement membrane thickening
• Protein Kinase C (PKC) activation → increased vascular permeability
• Hexosamine pathway → endothelial dysfunction
• Oxidative stress → free radical damage

• Pericyte loss → earliest histological change; pericytes maintain capillary integrity and autoregulation
• Basement membrane thickening → barrier dysfunction
• Endothelial cell loss → breakdown of blood-retinal barrier
• Formation of acellular capillaries → capillary occlusion

• Capillary occlusion → retinal ischaemia
• Ischaemia → upregulation of Vascular Endothelial Growth Factor (VEGF) (most important angiogenic mediator)
• VEGF → neovascularization (new vessel formation — abnormal, fragile, leaky)

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CLASSIFICATION

ETDRS Classification (Modified Airlie House Classification — most widely used internationally):

Simplified Clinical Classification (AK Khurana):

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SIGNS — DETAILED

1. Background Diabetic Retinopathy

• Earliest clinically detectable sign
• Small, round, red dots (~15–60 µm); lie in inner nuclear layer
• FA: early bright hyperfluorescence (leakage)

• Dot haemorrhages: in inner nuclear layer (may look like microaneurysms)
• Blot haemorrhages: in inner nuclear/outer plexiform layer; larger, darker

• Yellow-white deposits with sharp margins at outer plexiform layer
• Lipid/protein leakage from abnormal vessels
• Often arranged in rings (circinate pattern) around leaking microaneurysms
• FA: hypofluorescent (block fluorescence)

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2. Diabetic Maculopathy (Clinically Significant Macular Oedema — CSMO)

1. Retinal thickening within 500 µm of centre of fovea
2. Hard exudates within 500 µm of centre with adjacent retinal thickening
3. Retinal thickening ≥1 disc area within 1 disc diameter of fovea

• Focal maculopathy: Ring of exudates temporal to macula; FA shows focal leakage at centre of ring
• Diffuse maculopathy: Diffuse retinal thickening, dot/blot haemorrhages throughout posterior pole; FA shows extensive hyperfluorescence
• Ischaemic maculopathy: Good fundal appearance but poor VA; FA shows enlarged foveal avascular zone (FAZ) with capillary dropout — worst prognosis
• Mixed maculopathy: Combination of oedematous + ischaemic

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3. Preproliferative DR (PPDR)

• Fluffy white superficial lesions; nerve fibre layer infarcts
• Axoplasmic flow obstruction at capillary occlusions

• Generalised dilatation and tortuosity
• Venous beading (focal narrowing and dilatation — most specific sign of PPDR)
• Looping and sausage-like segmentation

• Arteriolar-venular shunts bypassing capillary bed
• Fine, irregular red intraretinal lines running from arterioles to venules
• FA: hypofluorescence (capillary dropout) — no leakage (unlike NV)
• OCT: IRMA do not breach the internal limiting membrane (ILM) — distinguishes from NV

• Severe haemorrhages in 4 quadrants
• Venous beading in 2 quadrants
• IRMA in 1 quadrant
• (Any one = severe NPDR; two or more = very severe NPDR)

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4. Proliferative DR (PDR)

• On or within 1 disc diameter of optic disc
• Arise from disc or peripapillary vessels
• FA: early, profuse, irregular fluorescein leakage from disc

• Beyond 1 disc diameter of disc
• Arise from venules, often adjacent to areas of capillary non-perfusion

1. Presence of vitreous haemorrhage or preretinal haemorrhage
2. Presence of any active neovascularization
3. NV at or within 1 disc diameter of optic disc
4. NVD > 1/3 disc area OR NVE > 1/2 disc area

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5. Advanced Diabetic Eye Disease

• Vitreous haemorrhage: Preretinal (retrohyaloid) or intragel; can form "ochre membrane"
• Tractional retinal detachment: Contraction of fibrovascular membranes; incomplete PVD due to strong adhesions
• Rubeosis iridis (NVI): Iris neovascularization → angle closure → Neovascular glaucoma (NVG)
• Diabetic papillopathy: Disc oedema without significant haemorrhage or exudate; usually self-limiting

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INVESTIGATIONS

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TREATMENT

A. Systemic Control (Medical Management)

• Glycaemic control: Target HbA1c < 7% (DCCT/UKPDS evidence); reduces onset and progression
• BP control: Target < 130/80 mmHg; ACE inhibitors preferred (Ramipril — EURODIAB study)
• Lipid control: Fenofibrate reduces hard exudate formation (FIELD study)
• Anaemia correction

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B. Laser Photocoagulation

• Focal laser: Treat specific leaking microaneurysms within 500–3000 µm of fovea
• Grid laser: For diffuse maculopathy; grid pattern over thickened retina
• Burns: 50–100 µm, 0.05–0.1 sec, 50–100 mW
• Traditional gold standard (now largely replaced by anti-VEGF)

• 1200–1800 burns applied beyond major vascular arcades
• Destroys ischaemic retina → reduces VEGF production → regression of NV
• Burns: 500 µm, 0.1–0.2 sec, white-grey burns
• Indications: High-risk PDR, any PDR with poor follow-up, severe NPDR progressing
• Pattern: Start inferior fundus first (haemorrhage gravitates inferiorly)
• Avoid areas of vitreoretinal traction
• Side effects: Peripheral field constriction, reduced night vision, macular oedema, choroidal detachment

• Wide-field FA delineates peripheral non-perfusion
• Selective treatment of these areas — preserves more field than PRP

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C. Anti-VEGF Therapy

• First-line treatment (superior to laser for CSMO)
• Protocol T (DRCR.net): Aflibercept superior to ranibizumab/bevacizumab at 1 year for worse VA; equivalent at 2 years
• Intravitreal injection every 4 weeks × 5 loading doses, then PRN/treat-and-extend

• DRCR.net Protocol S: Intravitreal ranibizumab as effective as PRP at 5 years for high-risk PDR
• Macular oedema rate reduced with anti-VEGF
• PRP preferred if follow-up is unreliable or cost is an issue

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D. Intravitreal Steroids (for DME)

• Triamcinolone acetonide (off-label)
• Dexamethasone implant (Ozurdex) — 6-month biodegradable implant
• Fluocinolone acetonide implant (ILUVIEN) — 36-month sustained release
• Used in: Pseudophakic eyes, steroid-responder evaluation, non-responders to anti-VEGF

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E. Vitreoretinal Surgery (Pars Plana Vitrectomy — PPV)

1. Dense, non-clearing vitreous haemorrhage (>3 months in Type 2; >1 month in Type 1)
2. Tractional retinal detachment (TRD) involving/threatening macula
3. Combined TRD + rhegmatogenous RD
4. Macular traction with significant oedema
5. Epiretinal membrane formation

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SCREENING PROTOCOL (AK Khurana / National Guidelines)

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DIABETIC PAPILLOPATHY

• Rare complication; disc oedema without significant disc pallor or haemorrhage
• Occurs in both Type 1 and Type 2 DM
• Usually unilateral; mild visual disturbance
• FA: disc hyperfluorescence
• Typically self-limiting over months; prognosis generally good
• Must be distinguished from AION and papilloedema

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IMPORTANT CLINICAL TRIALS (RGUHS Exam High-Yield)

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FUNDUS IMAGES

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QUICK REVISION — EXAM MNEMONICS

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