Eye Diseases > Retina

Sickle Cell Retinopathy

Evidence-based assessment and management of sickle cell retinopathy. Comprehensive guide covering haemoglobin genotypes, Goldberg classification, peripheral sea fan neovascularisation, diagnosis, and treatment protocols relevant to optometry practice.

Schematic fundus view of sickle cell retinopathy showing the Goldberg staging sequence: peripheral arteriolar occlusions (Stage I), arteriovenous anastomoses (Stage II), sea fan neovascularisation (Stage III), vitreous haemorrhage (Stage IV); alongside non-proliferative findings — salmon patch haemorrhage, black sunburst, iridescent spots, and angioid streaks.

Sickle cell retinopathy (SCR) encompasses the spectrum of retinal changes occurring in patients with sickle cell haemoglobinopathies. It results from sickling of abnormal erythrocytes within the retinal microvasculature, causing vaso-occlusion, ischaemia, and — in its proliferative form — neovascularisation. SCR is classified as non-proliferative (NPSCR) or proliferative (PSCR), with the latter carrying significant risk of vision-threatening complications including vitreous haemorrhage and retinal detachment. Counterintuitively, the compound heterozygous genotype HbSC causes more severe proliferative retinopathy than homozygous HbSS, due to higher haematocrit and blood viscosity. SCR disproportionately affects people of sub-Saharan African, Mediterranean, Middle Eastern, and South Asian ancestry. With global migration patterns, optometrists in Singapore may encounter patients with sickle cell disease, particularly those from African or South Asian backgrounds. Systematic dilated fundal examination is the cornerstone of early detection and vision preservation.

Genetic Basis — Haemoglobin S Mutation

Sickle cell retinopathy is caused by mutations in the HBB gene encoding the beta-globin chain of haemoglobin. The pathological allele — haemoglobin S (HbS) — results from a single nucleotide substitution (GAG→GTG) at codon 6, replacing glutamic acid with valine. This creates an abnormal haemoglobin prone to polymerisation under deoxygenated conditions, causing erythrocyte distortion (sickling).

Clinically Relevant Haemoglobin Genotypes

Genotype	Name	Retinopathy Prevalence	Systemic Severity
HbSC	Haemoglobin SC disease	Highest (~70% proliferative SCR by age 40)	Moderate systemic disease; milder crises
HbSS	Sickle cell anaemia (SCA)	~14% proliferative SCR by age 40; more NPSCR	Most severe systemic disease; frequent crises
HbS-β⁰ thalassaemia	Sickle-beta-zero thalassaemia	Similar to HbSS	Severe; similar to HbSS clinically
HbS-β⁺ thalassaemia	Sickle-beta-plus thalassaemia	Moderate; some residual HbA produced	Milder than HbSS
HbAS	Sickle cell trait (carrier)	Minimal; rare peripheral findings under extreme hypoxia	Essentially asymptomatic systemically

The HbSC paradox: Despite less severe systemic disease, HbSC patients develop proliferative retinopathy more frequently and earlier than HbSS patients. This is because HbSC patients have higher haematocrit and blood viscosity than HbSS (who are more severely anaemic), leading to greater sludging in peripheral retinal vessels. HbSS patients are also more likely to auto-infarct sea fan lesions due to more severe sickling.

Inheritance

Autosomal recessive inheritance — HbSS requires homozygous mutations from both parents
HbSC requires one HbS allele and one HbC allele (HbC is a separate beta-globin variant: Glu6Lys)
Sickle cell trait (HbAS) occurs when only one HBB allele carries the HbS mutation; no significant retinopathy under normal conditions
Carrier prevalence: ~1 in 4 in parts of sub-Saharan Africa; ~1 in 10 in African-Caribbean populations in the UK; lower but present in South Asian and Mediterranean populations

HbS Polymerisation and Erythrocyte Sickling

Under deoxygenated conditions, HbS molecules polymerise into rigid fibres, distorting the erythrocyte into the characteristic sickle shape. Sickled cells are rigid, adhesive, and prone to haemolysis. In the retinal microvasculature — particularly the peripheral capillary beds, which have low oxygen tension — this sickling cascade leads to the sequence of events responsible for retinopathy.

Cascade of Retinal Vascular Events

Step 1 — Peripheral Arteriolar Occlusion

Sickled erythrocytes obstruct the small-calibre peripheral retinal arterioles, particularly in the temporal periphery where the retinal capillary network terminates
Results in abrupt arteriolar termination — vessels end in a sharp "comma" or hairpin configuration without normal arborisation
Creates an avascular peripheral retinal zone distal to the occlusion
Corresponds to Goldberg Stage I

Step 2 — Arteriovenous Anastomoses

Pre-existing capillary channels connecting arterioles to venules dilate in response to ischaemia, forming peripheral AV anastomoses
These represent remodelled capillaries — not true neovascularisation — and do not leak on fluorescein angiography
They form a boundary between perfused posterior retina and avascular peripheral retina
Corresponds to Goldberg Stage II

Step 3 — Sea Fan Neovascularisation

Retinal ischaemia distal to the occlusion drives VEGF upregulation by hypoxic Müller cells and retinal pigment epithelium
Pathological new vessels grow at the junction of perfused and non-perfused retina — typically at the AV anastomosis — and extend anteriorly over the avascular zone
The frond-like arborising pattern of new vessels resembles a sea fan (Gorgonia coral) — a pathognomonic finding of proliferative sickle cell retinopathy
Sea fans are fibrovascular and may be accompanied by a fibrous scaffolding that creates vitreoretinal traction
The temporal periphery is most frequently affected due to its greater extent of avascular retina and relatively poor collateral supply
Corresponds to Goldberg Stage III

Steps 4–5 — Haemorrhage and Detachment

Fragile sea fan vessels may rupture, causing vitreous haemorrhage (Stage IV)
Fibrovascular proliferation and vitreous traction may cause tractional, rhegmatogenous, or combined retinal detachment (Stage V)
Auto-infarction: A proportion of sea fans (more commonly in HbSS) spontaneously infarct, leaving white fibrotic "ghost" lesions — this is a self-limiting protective mechanism absent in HbSC

Non-Proliferative Lesion Formation

Salmon patch haemorrhage: Intraretinal or sub-ILM haemorrhage from sickling within a vessel; the characteristic salmon colour reflects partial haemolysis and oxyhaemoglobin content; located in the mid-peripheral retina along vessels
Black sunburst: RPE hyperplasia surrounding a previous haemorrhage that has been absorbed; the RPE proliferates and migrates into the retina, creating a spiculated black pigmented lesion resembling a starburst — a permanent marker of previous vascular event
Iridescent spots (schisis cavities): Glistening crystalline deposits at the site of a resolved salmon patch; represent haemosiderin or haematoidin crystals and retinoschisis; not clinically significant
Venous tortuosity: Peripheral venous engorgement and increased tortuosity from haemolytic anaemia and increased cardiac output
Angioid streaks: Breaks in Bruch's membrane from iron deposition and calcium in the elastic layer; appear as irregular dark reddish-brown lines radiating from the disc; predispose to choroidal neovascular membranes
Macular ischaemia: Sickling within perifoveal capillaries causes macular thinning and foveal avascular zone (FAZ) enlargement; may cause asymptomatic or symptomatic central vision loss independent of proliferative disease

Goldberg Classification (1971) — Proliferative Sickle Cell Retinopathy

The Goldberg classification is the standard staging system for proliferative sickle cell retinopathy, describing the sequential progression of peripheral retinal vascular changes. Non-proliferative changes (salmon patches, black sunbursts, etc.) are not staged within this system but occur concurrently.

Stage	Description	Fundus Finding	Visual Threat
Stage I	Peripheral arteriolar occlusions	Abrupt termination of peripheral arterioles; hairpin loops; avascular zone formation	None
Stage II	Peripheral arteriovenous anastomoses	Dilated capillary connections at the ischaemic border; non-leaking on FA	Minimal
Stage III	Sea fan neovascularisation and fibrous proliferation	Frond-like fibrovascular tufts at the perfused-avascular border; leaks profusely on FA; may auto-infarct in HbSS	Moderate — risk of haemorrhage
Stage IV	Vitreous haemorrhage	Blood in vitreous from sea fan rupture; may obscure view of underlying retina; often recurrent	High — acute vision loss
Stage V	Retinal detachment	Tractional (from fibrovascular contraction), rhegmatogenous (from retinal break), or combined; may be total	Severe — potential permanent vision loss

Non-Proliferative Sickle Cell Retinopathy (NPSCR)

Non-proliferative changes are not captured in the Goldberg system but are clinically important markers of sickle cell vascular disease in the eye. They may precede or coexist with proliferative disease and include:

Venous tortuosity — especially of peripheral veins
Salmon patch haemorrhage — mid-peripheral intraretinal or pre-retinal haemorrhage; may resolve completely or leave iridescent spots / black sunbursts
Black sunburst — RPE hyperplasia after haemorrhage absorption; permanent lesion
Iridescent / crystalline deposits — retinoschisis cavities at prior haemorrhage sites
Angioid streaks — Bruch's membrane fractures; risk of choroidal neovascular membrane (CNV)
Macular thinning / FAZ enlargement — from perifoveal capillary drop-out; detectable on OCT and OCTA
Comma-shaped conjunctival vessels — isolated sickled cells visible in bulbar conjunctival capillaries; a pathognomonic sign of sickle cell disease

Genotype-Related Risk Factors

HbSC genotype: The single greatest risk factor for proliferative SCR; ~70% develop PSCR by age 40 compared with ~14% in HbSS
High HbS percentage: Greater proportion of sickle haemoglobin correlates with increased sickling tendency
High haematocrit: Higher haematocrit (as in HbSC and less anaemic patients) increases blood viscosity and promotes vascular sludging in the peripheral retina
Concurrent alpha-thalassaemia trait: Paradoxically may be protective by reducing HbS polymerisation; alpha-thalassaemia co-inheritance in HbSS patients is associated with lower retinopathy rates

Demographic and Clinical Risk Factors

Male sex: Proliferative SCR is more prevalent in males across all genotypes — hormonal and haematological differences may play a role
Increasing age: Cumulative vascular damage; PSCR incidence rises with age, particularly in the third and fourth decades
Lack of regular ophthalmic screening: Missed opportunities to detect and treat Stage III disease before haemorrhage or detachment
Poorly controlled systemic sickle cell disease: Frequent vaso-occlusive crises may correlate with greater retinal ischaemic burden
Low fetal haemoglobin (HbF) levels: Higher HbF inhibits HbS polymerisation; low HbF is associated with more severe disease
Geographic / seasonal factors: Dehydration, hypoxia (high altitude, aviation), extreme cold, and infection can precipitate sickling crises including retinal vascular events
Pregnancy: Associated with increased haematological stress and potential worsening of sickle cell complications

Proliferative Signs (Goldberg Stages I–V)

Peripheral arteriolar occlusions (Stage I): Abrupt termination of retinal arterioles in the far periphery, most frequently in the superior and inferior temporal quadrants; hairpin-loop configurations at the vessel ends; clear demarcation between vascularised posterior retina and avascular peripheral retina
Peripheral AV anastomoses (Stage II): Dilated capillary channels at the border of perfused and avascular retina; may appear as abnormal retinal shunting vessels; non-leaking on fluorescein angiography (distinguishes from true neovascularisation)
Sea fan neovascularisation (Stage III): Pathognomonic of PSCR; frond-like, arborising new vessel complexes arising at the perfused-avascular junction; typically flat initially, may become elevated and fibrovascular; brilliant red when active; white/grey when auto-infarcted (HbSS); most commonly temporal periphery; profuse leakage on FA
Vitreous haemorrhage (Stage IV): Blood in the vitreous cavity from sea fan vessel rupture; may range from small floaters to total vitreous obscuration; often recurrent; tends to clear more slowly than in diabetic or other aetiologies due to sickle cell-related haemostatic changes
Retinal detachment (Stage V): Tractional detachment from fibrovascular membrane contraction; may convert to combined tractional-rhegmatogenous if a retinal break forms; high-water mark retinal folds are characteristic; may be bullous and funnel-shaped in advanced cases

Non-Proliferative Signs

Salmon patch haemorrhage: Distinctive oval or round intraretinal / pre-retinal haemorrhage in the mid-periphery; salmon-pink to orange colour; located along retinal vessels; may have associated retinoschisis cavity as it resolves
Black sunburst lesion: Flat, pigmented, stellate-shaped lesion with radiating spoke-like projections; permanent marker of previous salmon patch haemorrhage; most frequent in HbSS; usually innocuous but may obscure retinal details
Iridescent spots: Small, glistening crystalline deposits at the inner retinal surface; located at sites of prior haemorrhage or schisis cavity; represent haemosiderin or haematoidin
Peripheral retinal degenerations: Lattice degeneration and retinoschisis adjacent to avascular zones; increase risk of retinal breaks and rhegmatogenous RD
Venous tortuosity: Peripheral venous dilatation and increased tortuosity; more prominent in HbSS due to severe anaemia and compensatory increased cardiac output
Angioid streaks: Irregular crack-like lines in Bruch's membrane extending radially from the optic disc; brownish-red; may underlie retinal vessels; predispose to CNV and subretinal haemorrhage following even minor trauma
Macular changes: Temporal macular thinning; enlarged FAZ; reduced vessel density on OCTA; central scotoma from perifoveal ischaemia; may be subclinical or cause reduced visual acuity and colour discrimination
Conjunctival comma-shaped vessels: Isolated, segmented sickled-cell capillary segments in the bulbar conjunctiva; pathognomonic of sickle cell disease; visible on slit-lamp with appropriate illumination

Clinical note: Sickle cell retinopathy is typically asymptomatic until Stage IV or V. Patients may have extensive peripheral neovascularisation (Stage III) without any visual symptoms — making regular dilated screening examinations essential for early detection and timely intervention.

Asymptomatic Stages (I–III)

Stages I–III are typically entirely asymptomatic; patients maintain full central visual acuity
Peripheral visual field may be subtly reduced due to avascular zone formation, but is rarely noticed by the patient
Macular ischaemia — when present — may cause mild central visual disturbance detectable only on careful VA testing or Amsler grid

Symptomatic Stages (IV–V)

Floaters: The earliest symptom of vitreous haemorrhage (Stage IV) — patients notice dark spots, cobwebs, or a shower of "smoke" in the vision; sudden onset
Blurred or hazy vision: As vitreous haemorrhage increases; ranges from mild blur to severe visual reduction
Visual field loss: Sectoral or peripheral loss from retinal detachment (Stage V); central loss from macular involvement in Stage V or macular ischaemia
Sudden severe visual loss: From massive vitreous haemorrhage or retinal detachment involving the macula
Photopsia (flashing lights): From vitreoretinal traction as fibrovascular membranes contract; a warning symptom of impending retinal detachment
Metamorphopsia: Distorted central vision if macular detachment or macular traction is present

Vision-Threatening Ocular Complications

Vitreous haemorrhage (Stage IV): The most common vision-threatening complication of PSCR; may clear spontaneously but often recurs; dense haemorrhage may take weeks to months to clear; hemosiderin deposition from chronic haemorrhage can cause persistent vitreitis
Tractional retinal detachment (Stage V): From fibrovascular membrane contraction; high-water mark folds are characteristic; difficult surgical anatomy; recurrence rates higher than in other proliferative conditions
Rhegmatogenous retinal detachment: From retinal breaks at the edge of sea fans or at the border of avascular retina; may combine with tractional component; wide bullous detachments possible
Macular infarction: Ischaemic destruction of the foveal photoreceptors and inner retinal layers from perifoveal capillary sickling; causes central scotoma and permanent visual acuity reduction; detectable as FAZ enlargement on OCTA and macular thinning on OCT
Choroidal neovascular membrane (CNV): Complicating angioid streaks — subretinal haemorrhage and exudation from neovascular membrane growth through Bruch's breaks; may cause sudden central visual disturbance
Neovascular glaucoma: Rare; from anterior segment ischaemia in severe proliferative disease with rubeosis iridis
Anterior segment ischaemia: Following excessive scleral buckling surgery in sickle cell patients (who have tenuous ciliary circulation); leads to corneal oedema, anterior chamber inflammation, iris atrophy — a specific surgical risk

Complications of Treatment

After laser photocoagulation: Choroidal neovascularisation at laser scars; scotoma from burns; vitreous haemorrhage from sea fan contraction after laser
After vitrectomy: Retinal breaks during surgery (fragile tissue); haemorrhage; re-detachment; the sickle cell patient is at particular risk of anterior segment ischaemia from scleral indentation techniques — exchange transfusion may be required peri-operatively
Anti-VEGF injections: Risk of sudden worsening — fibrovascular membrane contraction after VEGF reduction can precipitate acute tractional detachment if used without laser consolidation in PSCR

Sickle Cell Disease as a Multisystem Disorder

Sickle cell retinopathy is one manifestation of a systemic vasculopathy. The same sickling mechanism that causes retinal vascular occlusion operates throughout the body. Clinicians caring for patients with SCR must understand the broader systemic disease context.

Vaso-occlusive crisis (painful crisis): Episodes of ischaemic pain, most commonly in the long bones, spine, and chest; triggered by dehydration, infection, cold, or hypoxia; the most frequent acute complication; does not directly correlate with retinopathy severity
Acute chest syndrome (ACS): Life-threatening pulmonary vaso-occlusion — new pulmonary infiltrate with hypoxia, chest pain, and fever; the leading cause of death in SCD; hypoxia during ACS can precipitate retinal sickling
Stroke and cerebrovascular disease: Silent cerebral infarcts detectable on MRI in ~35% of HbSS children; overt stroke in ~10%; transcranial Doppler screening and prophylactic transfusions are standard of care; cerebrovascular disease is the leading cause of neurological disability
Chronic haemolytic anaemia: HbSS patients have severe chronic anaemia (Hb ~6–8 g/dL); jaundice, cholelithiasis (pigment gallstones), and aplastic crises (from parvovirus B19) are common sequelae
Splenic sequestration and autosplenectomy: Repeated splenic infarctions lead to progressive loss of splenic function; patients are functionally asplenic by adulthood (HbSS) or have enlarged spleen (HbSC); increased susceptibility to encapsulated bacteria (pneumococcus, Haemophilus)
Avascular necrosis (AVN): Osteonecrosis of the femoral and humeral heads from vascular insufficiency; causes chronic pain and disability
Sickle cell nephropathy: Hyperfiltration, microalbuminuria, and progressive CKD from medullary and glomerular ischaemia; renal failure in 4–18% of adults
Pulmonary hypertension: Elevated tricuspid regurgitant velocity on echocardiography in ~30%; associated with haemolytic anaemia-related endothelial dysfunction and nitric oxide depletion
Leg ulcers: Chronic, painful ulcers at the medial or lateral malleoli from ischaemia; more common in HbSS
Priapism: Prolonged involuntary erection from vaso-occlusion of penile vasculature in males; can cause erectile dysfunction

Correlation Between Retinopathy and Systemic Severity

Unlike diabetic retinopathy (where eye disease severity broadly mirrors systemic control), sickle cell retinopathy does not reliably correlate with overall disease severity. HbSC patients — who have milder systemic disease — have the highest rates of proliferative retinopathy. Patients with few systemic crises may still have advanced PSCR. This dissociation underscores the importance of regular ophthalmic screening regardless of the severity of systemic symptoms.

Systemic Treatments and Ocular Relevance

Hydroxyurea (hydroxycarbamide): Increases HbF production, reduces sickling tendency, decreases vaso-occlusive crises; may reduce the frequency and severity of retinal vascular events; limited evidence for direct impact on established PSCR
Chronic transfusion therapy: Dilutes HbS with HbA; used for stroke prevention; may have ocular benefit by reducing sickling in the retinal vasculature
Haematopoietic stem cell transplantation (HSCT): The only curative option currently; corrects the underlying haematological defect; retinopathy progression may halt post-transplant
Gene therapy: Emerging curative approaches (lentiviral vectors introducing HbA or HbF genes; CRISPR-mediated reactivation of HbF); long-term ocular outcomes under investigation

Dilated Fundus Examination — The Gold Standard Screen

Binocular indirect ophthalmoscopy with scleral indentation: Essential for thorough examination of the far peripheral retina where early Stage I–II changes and sea fans are located; direct ophthalmoscopy is insufficient for peripheral assessment
Slit-lamp biomicroscopy with 78D/90D lens: For detailed posterior pole and macular assessment; detects macular thinning, cystoid changes, and macular ischaemia
Mydriasis: Full pupil dilation is mandatory; tropicamide 1% + phenylephrine 2.5% standard; note that hypertonic phenylephrine can in theory increase blood viscosity — use 2.5% rather than 10% in sickle cell patients
Frequency: Annual dilated fundus examination recommended from age 10 for HbSC and HbSS; some guidelines recommend every 1–2 years from age 5 in HbSS

Wide-Field Fundus Photography and Imaging

Ultra-wide-field (UWF) fundus photography: Provides 200° field-of-view in a single capture; dramatically improves detection of peripheral neovascularisation, salmon patches, and black sunbursts; now recommended as the imaging modality of choice for SCR screening in centres where available
Standard fundus photography (7-field): Documents posterior pole and peripheral findings; useful for baseline and serial comparison

Fluorescein Angiography (FA)

Gold standard for peripheral ischaemia assessment: Delineates the extent of the avascular zone; identifies non-perfused areas not visible on clinical examination
Sea fan characterisation: Active sea fans leak profusely (hyperfluorescence); auto-infarcted sea fans are non-perfused (hypofluorescence); distinguishes Stage II AV anastomoses (non-leaking) from Stage III neovascularisation (leaking)
Macular ischaemia: Demonstrates FAZ enlargement, perifoveal capillary dropout, and retinal arteriolar occlusions
Treatment planning: Guides laser treatment extent and target location
Ultra-wide-field FA (e.g., Optos) is particularly valuable for documenting peripheral non-perfusion and neovascularisation in a single image

Optical Coherence Tomography (OCT and OCTA)

Macular OCT: Detects macular thinning (inner retinal layer loss from ischaemia); identifies schisis cavities near salmon patches; measures central macular thickness as baseline
OCT angiography (OCTA): Non-invasive quantification of foveal avascular zone (FAZ) size and parafoveal vessel density; FAZ enlargement is an early, sensitive marker of macular ischaemia in SCR, detectable before visual acuity changes; increasingly used as a monitoring tool
Optic disc OCT: Retinal nerve fibre layer (RNFL) thinning occurs as a result of inner retinal ischaemia; provides baseline for monitoring

Systemic / Haematological Investigations

Haemoglobin electrophoresis / HPLC: Confirms genotype (HbSS, HbSC, HbS-β thal); essential for risk stratification
Full blood count: Haemoglobin level, haematocrit, reticulocyte count — markers of haemolytic severity
HbF percentage: Higher HbF is protective; may guide hydroxyurea dosing
Serum LDH, bilirubin: Markers of haemolysis

Singapore Optometry Scope Note: Optometrists in Singapore use a fundus camera to examine the fundus in known sickle cell patients as part of structured annual screening. Detection and documentation of Goldberg Stage I–II disease allows appropriate monitoring intervals to be set. Any proliferative disease (Stage III — sea fan neovascularisation) or higher must be referred promptly to a retinal specialist for laser treatment consideration. Optometrists do not perform laser or surgical treatment but play a pivotal role in early detection. Wide-field fundus camera imaging should be used where available to maximise peripheral retinal coverage. Patients should be counselled on the importance of regular screening even if they feel well.

Observation — Stages I–II

No treatment required for Stages I and II
Annual dilated fundus examination with wide-field imaging or FA to monitor for progression to Stage III
Document baseline OCTA for macular FAZ assessment

Laser Photocoagulation — Stage III (Sea Fan Neovascularisation)

Indication: Active (leaking on FA) sea fan neovascularisation — Stage III; treatment intent is to induce sea fan regression and prevent haemorrhage or detachment
Scatter (sectoral) laser photocoagulation: 500 µm burns applied to the avascular retina between the vascular arcade and the sea fan; reduces VEGF drive by ablating ischaemic peripheral retina; most widely used technique
Direct feeder vessel photocoagulation: Laser applied to the arteriole supplying the sea fan; effective but risk of haemorrhage during treatment
Cryotherapy: For peripheral sea fans not accessible with laser; applied transsclerally
Observation for auto-infarction: In HbSS patients, a proportion of sea fans will auto-infarct without treatment — some clinicians elect to observe Stage III HbSS disease with 3-monthly FA and treat only if sea fans remain active or enlarge
Evidence: Landmark Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) and the ongoing PISCES studies have refined treatment indications; prophylactic laser of avascular zones before sea fan formation has not shown clear benefit

Vitreous Haemorrhage — Stage IV

Conservative management: Initial observation for spontaneous clearing — many haemorrhages in SCR clear over 6–12 weeks; head-of-bed elevation and avoidance of aspirin/NSAIDs
Pars plana vitrectomy (PPV): Indicated for dense, non-clearing haemorrhage (>3–6 months); haemorrhage obscuring treatment of underlying neovascularisation; or associated retinal detachment
Surgical precautions specific to sickle cell: Pre-operative exchange transfusion to reduce HbS to <30% before general anaesthesia; avoidance of scleral buckling (risk of anterior segment ischaemia); maintain adequate oxygenation and hydration throughout peri-operative period
Intraoperative considerations: Minimise hypotony; avoid use of air tamponade under hypoxic conditions; prefer silicone oil in high-risk detachments

Retinal Detachment — Stage V

Surgical intervention: Pars plana vitrectomy preferred over scleral buckling (significant risk of anterior segment ischaemia from buckling in sickle cell patients)
Silicone oil tamponade: Often preferred in SCR-associated detachments due to complex nature of vitreoretinal adhesions and high re-detachment risk
Exchange transfusion: Pre-operatively reduces HbS percentage and perioperative sickling risk
Prognosis is guarded: Anatomical reattachment rates reasonable but functional visual outcomes often limited, particularly if the macula was detached or if macular ischaemia pre-exists

Anti-VEGF Therapy — Limited and Cautious Use

Caution with anti-VEGF in sickle cell retinopathy: Intravitreal anti-VEGF agents (bevacizumab, ranibizumab) may cause rapid regression of sea fan vessels — but fibrovascular membranes may simultaneously contract, precipitating acute tractional retinal detachment. Anti-VEGF should not be used as monotherapy in PSCR. If used (e.g., as an adjunct prior to surgery), it should be combined with laser consolidation. Evidence for anti-VEGF in SCR is limited to case series.

Management of Non-Proliferative Complications

Macular ischaemia: No effective treatment to restore ischaemic macular function; low vision rehabilitation if significant central scotoma; optimise systemic disease control
Choroidal neovascular membrane (CNV) from angioid streaks: Intravitreal anti-VEGF therapy (bevacizumab, ranibizumab); generally well tolerated for CNV treatment without the fibrovascular traction risk seen with sea fans; photodynamic therapy (PDT) is second-line
Screening interval adjustment: More frequent monitoring (3–6 months) in patients with advanced NPSCR or treated PSCR

Visual Outcomes by Stage

Stage / Finding	Visual Prognosis	Notes
Stage I–II (NPSCR)	Excellent; VA fully preserved	Annual monitoring sufficient; low progression risk with stable systemic disease
Stage III — treated (laser)	Good; sea fan regression in ~80% with scatter laser	HbSS auto-infarction rate ~30–40%; HbSC rarely auto-infarcts
Stage IV — vitreous haemorrhage	Good if cleared and sea fan treated; guarded if recurrent	Spontaneous clearing in many cases over 6–12 weeks; recurrence common
Stage V — retinal detachment (macula on)	Guarded; anatomical success ~60–70% with PPV	Functional vision reasonable if macula was attached; pre-existing macular ischaemia limits recovery
Stage V — retinal detachment (macula off)	Poor; permanent central visual loss common	Macular ischaemia may pre-exist; structural reattachment does not restore ischaemic fovea
Macular ischaemia (NPSCR)	Irreversible; degree of visual loss proportional to FAZ enlargement	No treatment available; low vision rehabilitation; systemic optimisation

Natural History and Long-term Considerations

The majority of patients with sickle cell disease will develop some degree of retinopathy by middle age; HbSC patients face a higher cumulative PSCR burden
Sea fans in HbSS patients may auto-infarct at a higher rate than in HbSC, providing a degree of spontaneous protection in HbSS despite higher overall systemic disease severity
Blindness from sickle cell retinopathy is preventable in the vast majority of cases with timely screening and treatment
Systemic disease control — particularly hydroxyurea adherence and regular haematology follow-up — has potential to reduce retinal sickling events over time
Patients require lifelong ophthalmological follow-up; the risk of new neovascularisation or haemorrhage persists throughout adulthood

Key prognostic message: The majority of visual loss from sickle cell retinopathy is preventable. The critical window for intervention is at Goldberg Stage III, before haemorrhage or detachment occurs. Because Stages I–III are asymptomatic, only systematic annual dilated screening can identify patients at this treatable stage. A single episode of vitreous haemorrhage or retinal detachment can cause permanent visual impairment in a young person — making prevention through early detection the highest priority.

The peripheral neovascularisation and non-proliferative findings of sickle cell retinopathy must be distinguished from other causes of peripheral retinal vascular disease and proliferative retinopathy. Haemoglobin electrophoresis and the clinical context are essential for confirmation.

Condition	Shared Features	Key Differentiating Features
Proliferative Diabetic Retinopathy (PDR)	Peripheral and posterior neovascularisation, vitreous haemorrhage, tractional retinal detachment	NVD/NVE at disc and posterior pole (not exclusively peripheral); microaneurysms throughout retina; dot-blot haemorrhages; hard exudates; DM history and HbA1c; no avascular peripheral zone; no sea fans or salmon patches
Branch Retinal Vein Occlusion (BRVO) with Neovascularisation	Peripheral neovascularisation in the affected sector, vitreous haemorrhage	Strictly sectoral distribution (one quadrant); dilated tortuous venule in the occluded segment; haemorrhages in a sector; associated with hypertension and AV nicking; no systemic sickle cell disease; no black sunbursts or salmon patches
Familial Exudative Vitreoretinopathy (FEVR)	Peripheral avascularity, fibrovascular proliferation, tractional detachment	Term-born patient; family history (autosomal dominant); bilateral peripheral avascularity; macular dragging; no systemic haemoglobin abnormality; genetic testing (FZD4, LRP5, NDP mutations); no salmon patches or black sunbursts
Eales Disease	Peripheral retinal vasculitis, neovascularisation, vitreous haemorrhage in young men	Inflammatory vasculitis (sheathing of peripheral vessels); predominantly young South Asian males; no sickle cell haemoglobin; associated with tuberculosis sensitisation (Mantoux test); no characteristic salmon patches or sunbursts; responds to systemic anti-tuberculosis therapy and steroids
Sarcoidosis	Peripheral neovascularisation, sea fan-like lesions, vitreous haemorrhage	Bilateral; periphlebitis (candle-wax drippings); granulomatous uveitis; systemic sarcoidosis signs (bilateral hilar lymphadenopathy, skin nodules, elevated ACE/SACE); no sickle haemoglobin
Incontinentia Pigmenti	Peripheral avascularity, neovascularisation, retinal detachment	X-linked dominant (usually female); characteristic skin lesions following Blaschko lines; dental and CNS anomalies; no sickle cell haemoglobin; IKBKG gene mutation
Retinopathy of Prematurity (ROP) Sequelae	Peripheral fibrovascular proliferation, tractional detachment, macular dragging	History of prematurity; macular dragging (temporal macular ectopia); ridge at vascular–avascular border; no sea fans; no salmon patches or black sunbursts; no sickle haemoglobin
Retinitis Pigmentosa (RP)	Peripheral pigmentary changes (bone spicules may superficially resemble black sunbursts)	Bone spicule pattern follows vessels differently; attenuated arterioles; waxy pale disc; peripheral field loss on VF; reduced/absent ERG; no sea fans; no vitreous haemorrhage; no sickle cell history; genetic testing

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Clinical Illustration

Overview

Etiology