Central Retinal Artery Occlusion (CRAO)

Pathophysiology

Fundus Appearance

Symptoms

• Sudden, profound, painless, monocular vision loss (over seconds)
• VA is severely reduced — counting fingers to light perception in ~94% of eyes
• Often preceded by episodes of amaurosis fugax
• Pain suggests giant cell arteritis (GCA)
• Absence of light perception → suspect GCA or ophthalmic artery occlusion (not just CRAO)

Signs

Etiology

Workup

1. ESR, CRP, platelets — rule out GCA in patients ≥55 years (if no visible embolus)
2. Blood pressure check
3. Labs: Fasting glucose, HbA1c, CBC with differential, PT/PTT. In patients <50 years or with atypical features: lipid panel, ANA, RF, syphilis serology (RPR/VDRL + FTA-ABS), SPEP, hypercoagulable workup
4. Carotid duplex Doppler US
5. Cardiac workup: ECG, echocardiography, Holter or bubble study
6. OCT (confirms diagnosis; highly reflective embolic plaque in superficial nerve head on OCT); consider IVFA or ERG if diagnosis uncertain

Treatment

No treatment has been proven effective in RCTs. All ocular measures are anecdotal.

Systemic / Stroke pathway

• Immediate transfer to stroke centre
• IV tPA within 4.5 hours of onset has some supporting evidence (multiple observational studies)
• If GCA suspected: high-dose systemic corticosteroids immediately
• Cardiology and neurology consultation

Ocular measures (attempted within 90–120 min, limited evidence)

Differential Diagnosis of Cherry-Red Spot

Follow-Up

• Repeat eye exam 1–4 weeks post-event
• Monitor for neovascularization of iris (NVI), disc (NVD), angle (NVA), or retina (NVE) — occurs in up to 20% at ~4 weeks
• If neovascularization develops: panretinal photocoagulation (PRP) and/or intravitreal anti-VEGF
• Long-term systemic cardiovascular risk factor management

Prognosis

Recent evidence (PMID 41006752): A 2025 systematic review and meta-analysis confirmed that retinal artery occlusion patients carry a significantly elevated risk of concurrent and subsequent ischemic cerebrovascular disease — reinforcing the importance of the acute stroke workup.

Retinitis Pigmentosa (RP)

Definition

Epidemiology

• Most common hereditary retinal degeneration
• Prevalence: 1 in 3,000 to 1 in 5,000
• No sex predilection; affects all races
• Onset, rate of progression, and severity are related to the mode of inheritance

Genetics & Inheritance

• Phototransduction cascade — most AD cases: rhodopsin gene mutations
• Retinoid cycle — RPE65 mutations (target of gene therapy)
• Photoreceptor structure — peripherin (PRPH2) mutations
• Connecting cilium — RPGR gene mutations (90% of X-linked cases)

Pathophysiology

1. Primary degeneration of rod photoreceptors → night blindness and peripheral field loss
2. Secondary degeneration of cones → central vision loss (late)
3. Degeneration of RPE → accumulation of lipofuscin, migration of RPE cells into the retina forming bone-spicule deposits around perivascular spaces
4. Inner retina remains relatively intact initially, preserving the ERG b-wave only transiently

Clinical Features

Symptoms (in order of progression)

1. Nyctalopia (night blindness) — often the presenting symptom; earliest manifestation of rod dysfunction
2. Peripheral visual field loss — gradual constriction; "tunnel vision"
3. Ring scotoma — characteristic progressive visual field defect (mid-peripheral ring that expands inward and outward)
4. Photopsia — flickering/flashing lights
5. Loss of central vision — late feature (unless early cataract develops)
6. Colour vision loss — variable; later in disease

Signs — Classic Triad

• Vitreous cells — most consistent sign (Wills Eye)
• Posterior subcapsular cataract (PSC) — common in all forms
• Cystoid macular oedema (CME) — in ~15% on OCT
• Epiretinal membrane (ERM)
• Optic disc drusen — more frequent than in general population
• Tessellated fundus (unmasking of choroidal vessels due to RPE atrophy)

Natural History & Progression

• Perimetry initially shows small mid-peripheral scotomas → coalesce into ring scotoma → tunnel vision → extinction
• XLR: central VA reduced to ≤6/60 by the 5th decade
• AD: best prognosis; AR: intermediate severity

Investigations

Differential Diagnosis — Conditions Mimicking RP

Complications

1. Posterior subcapsular cataract (most common)
2. Cystoid macular oedema (CME) — reversible with carbonic anhydrase inhibitors
3. Epiretinal membrane
4. Open-angle glaucoma (~3%)
5. Posterior vitreous detachment
6. Neovascularization (rare)

Associated Systemic Syndromes (Syndromic RP)

Management

Currently Available

Emerging / Approved Therapies

Prognosis

• No cure currently; course is progressive and irreversible
• Rate of progression highly variable depending on genetic mutation and inheritance pattern
• AD: best prognosis (slow progression, later onset)
• XLR: worst prognosis (most severe, rapid progression)
• Patients often retain some useful central vision into middle age
• Regular follow-up critical to manage complications and access emerging therapies

Summary Box — Exam Points

Retinitis Pigmentosa

Definition

Inheritance

Clinical Features

1. Nyctalopia (night blindness) — earliest symptom; rod dysfunction
2. Peripheral visual field loss → ring scotoma → tunnel vision
3. Photopsia
4. Central vision loss — late

1. Bone-spicule pigmentation — dark, branching perivascular deposits in mid-periphery
2. Arteriolar attenuation — thread-like narrowed vessels
3. Waxy disc pallor — secondary optic atrophy

Investigations

• ERG (gold standard) — reduced scotopic → photopic → extinguished
• FAF — perimacular hyperautofluorescent ring; distinguishes RP in 95%
• OCT — detects CME (~15%), macular atrophy (~40%)
• Perimetry — ring scotoma → concentric constriction
• Genetic analysis — counselling and trial eligibility

Associated Syndromes

Management

• Luxturna — FDA-approved gene therapy for RPE65 mutations
• Vitamin A palmitate 15,000 IU/day + lutein 12 mg/day (may slow field loss)
• Cataract surgery when indicated
• Carbonic anhydrase inhibitors for CME
• Low vision aids and rehabilitation
• Annual follow-up; genetic counselling; smoking cessation

Prognosis