Sickle Cell Retinopathy

Pathophysiology

⚠️ Carbonic anhydrase inhibitors (CAIs) are contraindicated in all sickling disorders — they precipitate sickling and vascular occlusion. This applies to IOP management in hyphaema as well.

Anterior Segment Findings

• Conjunctiva: Dark red corkscrew- or comma-shaped vessels (typically transient)
• Iris: Patches of ischaemic atrophy from pupillary edge to collarette; occasional rubeosis
• Hyphaema: May be spontaneous or post-traumatic; requires careful IOP control (avoid CAIs)

Non-Proliferative Retinopathy

Proliferative Retinopathy — Goldberg Staging

Fundus Images

Differential Diagnosis of Peripheral Retinal Neovascularization

• Sarcoidosis — sea fan NV with uveitis; common in young patients of African descent
• Diabetic retinopathy — posterior pathology predominates; dot-blot haemorrhages
• Eales disease — peripheral vascular occlusion of unknown aetiology (diagnosis of exclusion)
• ROP, FEVR, pars planitis, radiation retinopathy, OIS, collagen vascular disease
• Talc retinopathy — IV drug use history; refractile particles in macular arterioles

Workup

1. Full medical and family history (sickle cell disease, diabetes, IV drug use)
2. Dilated fundus examination with indirect ophthalmoscopy
3. Sickledex, sickle cell preparation, hemoglobin electrophoresis
   • Note: HbSC and HbC disease may give a negative Sickledex — electrophoresis is needed
4. Widefield IVFA — aids diagnosis and guides treatment planning
5. OCT-A — emerging role in monitoring (see recent evidence below)

Treatment

Follow-Up

Recent Evidence

Central Retinal Vein Occlusion (CRVO)

1) What CRVO is and why it matters

• Non-ischemic CRVO (more common, better prognosis)
• Ischemic CRVO (less common, vision-threatening, high neovascular glaucoma risk)

2) Impending CRVO (partial CRVO)

• May be asymptomatic or have mild/transient blur, often worse on waking
• Mild venous dilatation/tortuosity
• Few scattered dot-blot hemorrhages
• Possible mild macular edema

• Often good prognosis
• Some cases progress to ischemic CRVO
• Boundary between impending CRVO and mild non-ischemic CRVO is not always clear

• Evidence base is limited
• Address systemic risk factors, avoid dehydration, optimize ocular perfusion/IOP
• Antiplatelets/anticoagulants/hemodilution have no proven benefit in routine use

3) Non-ischemic CRVO

Symptoms and signs

• Sudden, painless, unilateral vision drop
• VA impairment is variable
• RAPD absent or mild
• Fundus: diffuse venous tortuosity/dilatation in all quadrants, mild-moderate dot/blot/flame hemorrhages, mild cotton-wool spots, disc and macular edema possible

Natural history

• About one-third may convert to ischemic CRVO, often within months
• If not becoming ischemic, about half can recover to near-normal vision
• Initial VA gives prognostic clues:
  • Better starting VA -> better outcomes
  • Mid-range VA is less predictive
  • Very poor baseline VA suggests significant ischemia

4) Ischemic CRVO

Typical presentation

• Sudden severe painless monocular vision loss
• VA often counting fingers or worse
• RAPD present
• Marked widespread hemorrhages, cotton-wool spots, disc edema/hyperemia
• FA: delayed AV transit, extensive capillary non-perfusion, leakage/staining

Major complications

• Iris/angle neovascularization and neovascular glaucoma (NVG)
• Rubeosis can develop in about half, classically around 2-4 months ("100-day glaucoma")
• Gonioscopy is important because angle NV can occur even without visible pupillary margin NV
• Macular ischemia drives poor visual outcome

Important quantitative risk marker

• More than 10 disc areas of retinal capillary non-perfusion is associated with higher neovascularization risk.

5) Imaging and investigations in CRVO

• OCT: quantifies central macular edema, monitors treatment response
• FA (fluorescein angiography): defines perfusion status, ischemic burden, leakage
• ERG: can reflect ischemia severity in some settings
• Serial anterior-segment exam (pupil margin + gonioscopy) is critical in ischemic disease surveillance

6) Treatment of CRVO complications (Kanski approach)

A) Macular edema (main treatable visual morbidity)

• Intravitreal anti-VEGF
• Intravitreal dexamethasone implant

• CRUISE: ranibizumab improves VA versus sham
• COPERNICUS: aflibercept effective
• GENEVA: dexamethasone implant gives anatomic/visual gains, may need repeat treatment
• COMRADE: ranibizumab showed better VA than dexamethasone at 6 months
• SCORE: intravitreal triamcinolone can improve vision in a subset but with steroid-related risks

• Benefit is less likely in very poor baseline VA (for example, profound ischemic damage)

B) Neovascularization/NVG prevention and treatment

• Close follow-up in ischemic CRVO
• Prompt PRP when indicated for anterior/posterior segment NV
• Manage IOP/NVG per glaucoma protocols

7) Follow-up strategy

• Non-ischemic CRVO: less aggressive than ischemic CRVO; monitor for conversion to ischemia and new NV
• Patients should urgently report:
  • New vision decline
  • Ocular pain/redness (possible NVG)
• Follow-up intensity depends on severity and response to therapy; many cases are followed over many months to up to 18-24 months

8) Prognosis

• Persistent/chronic macular edema
• In ischemic CRVO, additionally macular ischemia + NVG lead to very poor outcomes

• Good initial VA -> often remains good
• Intermediate VA -> variable
• Very poor initial VA -> recovery less likely

9) Systemic management in all RVO (including CRVO)

• Control cardiovascular risk factors (BP, diabetes, lipids, smoking)
• These measures benefit systemic health and may lower recurrence risk
• Aspirin/antiplatelets are not routinely prescribed solely for RVO unless systemic indication exists
• Review estrogen-containing HRT risk individually

10) Recent evidence update (last 2 years, systematic reviews)

• Intravitreal dexamethasone implant long-term efficacy/safety in RVO (PMID: 39678032)
• Anti-VEGF effects on choroidal thickness in RVO (PMID: 41451105)

Key exam-style differentiation: non-ischemic vs ischemic CRVO

1. a one-page viva answer for CRVO,
2. a management flowchart (diagnosis -> classify -> treat -> follow-up), or
3. a comparison table of CRVO vs BRVO vs ocular ischemic syndrome.

Central Retinal Vein Occlusion (CRVO)

Long answer for a 20-mark ophthalmology question

Introduction

Classification

1. Impending (partial) CRVO
2. Non-ischemic CRVO (venous stasis type, more common)
3. Ischemic CRVO (severe form with extensive capillary non-perfusion)

Etiopathogenesis and risk factors

Ocular risk factors

• Primary open-angle glaucoma or ocular hypertension
• Increased IOP and reduced retinal perfusion pressure

Systemic risk factors

• Hypertension
• Diabetes mellitus
• Dyslipidemia
• Smoking
• Hyperviscosity/thrombophilic states (selected cases, especially younger patients)

Clinical features

Symptoms

• Sudden, painless, unilateral blurring/loss of vision
• Severity varies:
  • mild in non-ischemic CRVO
  • marked in ischemic CRVO
• Some impending CRVO patients may have transient blur, often worse on waking

Signs

• Dilated tortuous retinal veins in all quadrants
• Retinal hemorrhages (dot, blot, flame-shaped)
• Cotton-wool spots
• Optic disc edema/hyperemia
• Macular edema
• Relative afferent pupillary defect (RAPD):
  • absent/mild in non-ischemic
  • present in ischemic

Types in detail

1) Impending CRVO

• Mild venous dilatation and tortuosity with few scattered hemorrhages
• Mild or no visual symptoms
• Prognosis often good, but some progress to ischemic CRVO
• Management is largely empirical with correction of risk factors and careful follow-up

2) Non-ischemic CRVO

• More common form
• Variable visual reduction
• Fundus changes present but less severe than ischemic type
• Around one-third may convert to ischemic CRVO, often within first few months
• Better overall visual prognosis compared with ischemic CRVO

3) Ischemic CRVO

• Severe retinal non-perfusion and hypoxia
• Marked visual loss (often counting fingers or worse)
• Extensive hemorrhages, cotton-wool spots, disc edema
• High risk of anterior segment neovascularization and neovascular glaucoma
• Worst visual prognosis due to macular ischemia and NVG

Investigations

1. Visual acuity and pupillary reactions (look for RAPD)
2. Slit-lamp and IOP measurement
3. Dilated fundus examination
4. Gonioscopy in ischemic/suspected ischemic cases (angle NV may precede obvious iris NV)
5. OCT macula
   • Quantifies and monitors macular edema
6. Fundus fluorescein angiography (FFA)
   • Demonstrates delayed venous transit, leakage, and capillary non-perfusion

   • 10 disc areas of non-perfusion suggests high NV risk

7. Systemic workup
   • BP, blood sugar, lipid profile, CBC
   • Selected thrombophilia/hyperviscosity tests in young/atypical patients

Complications

• Chronic cystoid macular edema
• Macular ischemia
• Retinal neovascularization
• Iris neovascularization (NVI) and angle neovascularization
• Neovascular glaucoma (classically around 2-4 months in ischemic CRVO)
• Vitreous hemorrhage (less common than BRVO but can occur)
• Epiretinal membrane, RPE changes, opticociliary shunts

Management

A) Ocular management

1. Macular edema (main treatable cause of visual loss)

• Intravitreal anti-VEGF agents (ranibizumab/aflibercept/bevacizumab)
• Intravitreal dexamethasone implant in selected cases

• IOP rise
• Cataract progression

2. Neovascularization

• Careful serial review for NVI/NVA, especially in ischemic CRVO
• Panretinal photocoagulation (PRP) when neovascularization develops
• Early treatment to prevent/treat neovascular glaucoma

3. Neovascular glaucoma

• Aggressive IOP control
• PRP and anti-VEGF as indicated
• Glaucoma procedures when needed

B) Systemic management

• Control hypertension, diabetes, and dyslipidemia
• Smoking cessation
• Correct dehydration and vascular risk profile
• Antiplatelet/anticoagulant therapy is not routine solely for CRVO unless systemic indication exists

Follow-up

Non-ischemic CRVO

• Initial follow-up in weeks to months depending on severity and edema treatment
• Watch for conversion to ischemic type

Ischemic CRVO

• Frequent follow-up during first 6 months
• Mandatory repeated iris and angle evaluation for neovascularization

Prognosis

• Initial VA 6/18 or better: likely to remain good
• 6/24 to 6/60: variable course
• Worse than 6/60: poorer visual recovery

1. Chronic macular edema
2. Macular ischemia
3. Neovascular glaucoma

Conclusion

Central Retinal Artery Occlusion (CRAO)

20-mark long answer format

Introduction

Etiology and risk factors

Major causes

1. Embolic
   • Carotid atherosclerotic plaque (cholesterol emboli)
   • Cardiac emboli (valvular disease, atrial fibrillation)
2. Thrombotic
   • Local atherosclerotic disease
3. Inflammatory arteritic occlusion
   • Giant cell arteritis (GCA), especially in elderly
4. Less common
   • Hypercoagulable states
   • Vasculitis, trauma, iatrogenic causes

Risk factors

• Hypertension
• Diabetes mellitus
• Dyslipidemia
• Smoking
• Carotid/cardiac vascular disease
• Advanced age

Pathophysiology

Clinical features

Symptoms

• Sudden, profound, painless unilateral visual loss
• May have history of transient monocular visual loss (amaurosis fugax)

Signs

• Very poor visual acuity (often counting fingers/hand movements or worse)
• Relative afferent pupillary defect (RAPD)
• Fundus:
  • Retinal whitening/opacification (ischemic edema)
  • Cherry-red spot at fovea
  • Attenuated retinal arteries, "box-carring"/segmentation of blood column
  • Visible embolus may be seen in some cases

Variants

1. Non-arteritic CRAO
2. Arteritic CRAO (GCA-related; urgent steroids required)
3. CRAO with cilioretinal artery sparing (better central vision possible)
4. Transient CRAO

Investigations

Ocular

• Visual acuity, pupil exam (RAPD), slit lamp, IOP
• Dilated fundus examination
• OCT: inner retinal hyperreflectivity/thickening in acute phase
• FFA: delayed/absent arterial filling

Systemic and stroke workup (urgent)

• Blood pressure, glucose, lipid profile, CBC
• ESR, CRP, platelet count (especially to exclude GCA)
• Carotid Doppler/vascular imaging
• Cardiac evaluation (ECG, echocardiography as indicated)
• Neuroimaging and stroke-team referral

Management

Immediate measures (time-critical, variable benefit)

• Urgent referral to ophthalmology + stroke services
• Ocular massage (historically used)
• Reduction of IOP (topical/oral/IV agents, anterior chamber paracentesis in selected settings)
• Carbogen/hyperventilation or rebreathing approaches historically described
• Hyperbaric oxygen may help in selected early presenters where available

Thrombolysis

• Intravenous or intra-arterial thrombolysis remains center-dependent and controversial
• May be considered in selected patients presenting very early within protocolized stroke pathways

Arteritic CRAO (suspected GCA)

• Immediate high-dose systemic corticosteroids (do not delay for biopsy)
• Protects fellow eye and systemic ischemic complications

Secondary prevention

• Treat vascular risk factors aggressively
• Antiplatelet/statin as per stroke physician/cardiology guidance
• Smoking cessation and lifestyle modification
• Manage carotid/cardiac source where identified

Complications

• Permanent severe visual loss/optic atrophy
• Ocular neovascularization (less common than ischemic CRVO but possible)
• Cerebral stroke and other systemic vascular events

Prognosis

• Generally poor visual prognosis in complete CRAO
• Better outcomes in:
  • Very early reperfusion
  • Incomplete/transient occlusion
  • CRAO with cilioretinal sparing
• Final vision depends on duration of ischemia and underlying cause

Differential diagnosis

• Ophthalmic artery occlusion
• Ischemic optic neuropathy
• Severe retinal vasospasm
• CRAO mimics causing sudden vision loss (vitreous hemorrhage, retinal detachment, optic neuritis)

Conclusion

1. a CRAO vs CRVO 20-mark comparison table, or
2. a short note format (5 marks), or
3. a recent guideline-based management algorithm.