Diabetic Retinopathy

🔬 Pathophysiology of Diabetic Retinopathy

  1. Chronic Hyperglycemia (High Blood Sugar)

    • Leads to biochemical changes in retinal blood vessels:

      • Polyol pathway activation → sorbitol accumulation → oxidative stress.

      • Advanced Glycation End Products (AGEs) → thicken basement membrane.

      • Protein Kinase C activation → abnormal blood flow, vascular leakage.

      • Inflammatory mediators increase.


Microvascular Damage

  • Capillary basement membrane thickens.

  • Pericytes (supporting cells) are lost → vessel walls weaken.

  • Endothelial cell dysfunction → poor barrier function.

Microaneurysms & Leakage

  • Weak capillaries bulge (microaneurysms).

  • Leakage of plasma, lipids, and blood → retinal edema & hard exudates.

Capillary Occlusion

  • Damaged vessels close → ischemia (lack of oxygen to retina).

  • Ischemia causes cotton wool spots (nerve fiber infarcts).

Neovascularization

  • Retina releases VEGF (Vascular Endothelial Growth Factor) in response to ischemia.

  • New abnormal vessels form (fragile & leaky).

  • Leads to vitreous hemorrhage (bleeding into the eye).

Fibrosis & Retinal Detachment

  • Scar tissue forms around new vessels.

  • Contraction of scar tissue pulls the retina → tractional retinal 


 Non-Proliferative DR (NPDR)

🔴 Microaneurysms



  • Definition:
    Small, round outpouchings (balloon-like swellings) of capillary walls in the retina.

  • Cause:

    • Loss of pericytes (cells that support capillaries) due to chronic high blood sugar.

    • Weakening of the retinal capillary wall.

  • Appearance (on fundus exam):

    • Tiny red dots (first visible clinical sign of diabetic retinopathy).

    • Usually seen in the posterior pole (central retina

  • Significance:

    • They are the earliest clinical sign of non-proliferative diabetic retinopathy (NPDR).

    • Can rupture → causing dot and blot hemorrhages.

    • Can leak plasma → leading to retinal edema and hard exudates.


Microaneurysms = earliest visible change in diabetic retinopathy → tiny balloon-like dilations of weakened capillaries → cause leakage and hemorrhages in the retina.


🔴 Retinal Hemorrhages

Bleeding inside the retina due to rupture of weakened or damaged retinal blood vessels.

🧾 Types of Retinal Hemorrhages

Dot and Blot Hemorrhages
  • Found in inner nuclear and outer plexiform layers.
  • Look like small red spots or blots (deeper in retina).
  • Common in Diabetic Retinopathy.

Flame-Shaped Hemorrhages

  • Found in the nerve fiber layer.

  • Blood spreads along nerve fibers → looks like a flame or brushstroke.

  • Seen in Hypertensive Retinopathy and sometimes in diabetes

Preretinal (Boat-Shaped) Hemorrhages

  • Blood collects between retina and vitreous.

  • Looks like a boat or D-shaped hemorrhage (flat upper border).

  • Often seen in Proliferative Diabetic Retinopathy.

Vitreous Hemorrhage

  • Bleeding into the vitreous cavity (gel-like part of the eye).

  • Causes sudden loss of vision / floaters.

  • Often due to rupture of neovascular vessels in proliferative DR.

🟡 Retinal Exudates


1. Hard Exudates

  • Definition: Yellow-white, sharp-edged lipid deposits in the retina.

  • Cause: Leakage of lipids and proteins from damaged retinal capillaries or microaneurysms.

  • Appearance:

    • Small, bright yellow spots with well-defined borders.

    • Often arranged in a circinate (ring-like) pattern around leaking microaneurysms.

  • Significance: Common in diabetic retinopathy and hypertensive retinopathy.

  • Complication: If they involve the macula, they cause macular edema → blurred vision.

2. Soft Exudates (Cotton Wool Spots)

  • Definition: Fluffy, white patches on the retina.

  • Cause: Micro-infarction of nerve fiber layer → axoplasmic flow stasis.

  • Appearance:

    • Pale, fuzzy/“cotton-like” patches with indistinct edges.

  • Significance: Indicates ischemia (poor blood supply) of the retina.

  • Seen in: Diabetic retinopathy, hypertensive retinopathy, anemia, AIDS retinopathy.


🌟 Macular Edema

🔹 Definition

Swelling or thickening of the macula (the central part of the retina responsible for sharp vision) due to fluid leakage from retinal blood vessels.

🔹 Cause

  • In Diabetic Retinopathy, high blood sugar damages capillaries → microaneurysms and leaky vessels.

  • Plasma and fluid leak into the macula, disrupting its function.

🔹 Pathophysiology (Stepwise)

  1. Microaneurysms & damaged capillaries → become leaky.

  2. Plasma & fluid seep into macula → thickening of retinal tissue.

  3. Lipid leakage → hard exudates deposited in/around the macula.

  4. Persistent edema → photoreceptor dysfunction → blurred or distorted central vision.

🔹 Clinical Features

  • Blurred or distorted central vision (difficulty reading, recognizing faces).

  • Straight lines may appear wavy (metamorphopsia).

  • Colors may look faded.

  • Fundus exam: retinal thickening, hard exudates in circinate pattern around macula.

🔹 Types of Diabetic Macular Edema (DME)

  1. Focal – localized leakage from microaneurysms.

  2. Diffuse – widespread capillary leakage.

  3. Ischemic – macular capillary closure → poor prognosis.


🔹 Complications

  • Major cause of vision loss in diabetic patients.

  • Can progress to irreversible central vision loss if untreated.


🔹 Treatment

  • Control of diabetes (sugar, BP, lipids).

  • Anti-VEGF injections (Ranibizumab, Aflibercept, Bevacizumab) – reduce leakage.

  • Laser photocoagulation – seal leaking vessels.

  • Steroid injections/implants – reduce inflammation.





🌱 Neovascularization

🔹 Definition

The abnormal growth of new, fragile blood vessels from the retina or optic disc in response to ischemia (lack of oxygen).

🔹 Cause (Pathophysiology)

  1. In diabetic retinopathy, many capillaries get blocked (ischemia).

  2. Retina senses low oxygen → releases VEGF (Vascular Endothelial Growth Factor).

  3. VEGF stimulates growth of new vessels.

  4. These new vessels are:

    • Fragile & leaky → cause hemorrhages (into retina or vitreous).

    • Grow along vitreous → form fibrous tissue → can pull retina → tractional retinal detachment.

🔹 Sites of Neovascularization

  • Neovascularization of the Disc (NVD): On the optic disc.

  • Neovascularization Elsewhere (NVE): On the retina outside the disc.

  • Neovascularization of the Iris (Rubeosis Iridis): On iris → can lead to neovascular glaucoma.

🔹 Complications

  • Vitreous hemorrhage.

  • Tractional retinal detachment.

  • Neovascular glaucoma (if iris vessels grow and block angle).

🔹 Treatment

  • Panretinal photocoagulation (PRP) laser – destroys ischemic retina → reduces VEGF production.

  • Anti-VEGF injections (Ranibizumab, Bevacizumab, Aflibercept).

  • Vitrectomy if non-resolving vitreous hemorrhage or tractional retinal detachment.



Neovascularization = new vessel growth due to ischemia → fragile vessels → bleeding, fibrosis, retinal detachment, glaucoma.


🔴 Vitreous Hemorrhage

🔹 Definition

Bleeding into the vitreous cavity (the gel-like space filling the back of the eye between the lens and retina).

🔹 Causes

Most common: Proliferative Diabetic Retinopathy (due to fragile new vessels).
Other causes:

  • Retinal vein occlusion.

  • Retinal tear or detachment.

  • Trauma.

  • Age-related macular degeneration (wet type).

  • Posterior vitreous detachment with vessel rupture.


🔹 Pathophysiology

  1. Fragile vessels (from neovascularization or trauma) rupture.

  2. Blood leaks into vitreous gel.

  3. Blood blocks light from reaching the retina → sudden vision loss.

  4. If not cleared, can cause fibrosis, retinal traction, or detachment


🔹 Symptoms

  • Sudden, painless vision loss (can be partial or complete).

  • Floaters (black spots, cobwebs, or red haze in vision).

  • Severe hemorrhage → vision may reduce to just light perception.


🔹 Clinical Signs

  • Fundus view may be obscured by blood.

  • Fresh blood looks red, old hemorrhage looks yellow-brown.

  • Ultrasound (B-scan) is used if fundus is not visible.


🔹 Management

  • Treat underlying cause (e.g., diabetic retinopathy, retinal tear).

  • Small VH: Bed rest, head elevation, avoid strenuous activity (blood may settle).

  • Persistent / severe VH:

    • Pars plana vitrectomy (surgery to remove vitreous gel & blood).

    • Laser photocoagulation (after clearing blood or during vitrectomy).

    • Anti-VEGF injections (if neovascularization is present).


Vitreous hemorrhage = sudden painless vision loss due to bleeding in vitreous cavity → most often from fragile new vessels in proliferative diabetic retinopathy.

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