Sickle cell disease and the retina: why have your eyes examined when your sight is perfect

Sickle cell retinopathy causes sight loss through vitreous haemorrhage or retinal detachment, in patients who had never had any complaints about their vision. Among 84 patients with SS sickle cell disease examined in Cameroon while they had no visual symptoms at all, 62% had retinopathy and 35% already had a proliferative form. The disease begins at the extreme periphery of the retina, far from the area used for reading: years can pass between the first blocked vessel and the first symptom. Here is what screening actually shows, how often it should be done, and what is actually proven when it comes to treatment.

UNDERSTANDING

20/20 vision doesn’t mean the retina is healthy

A patient with sickle cell disease can already have a badly damaged retina and still read the smallest letters on the chart without hesitation. This is not a curiosity, it is the usual situation. In a study carried out in Cameroon on 84 patients homozygous for SS, all selected because they had no visual symptoms, the examination found retinopathy in 52 of them, or 62%. Twenty-nine, or 35% of the group, already had a proliferative form — the stage at which abnormal new vessels have developed and the risk of haemorrhage becomes real.

The large series tell the same story. In the Cooperative Study of Sickle Cell Disease, which examined 1,904 patients, 96.4% had visual acuity better than 20/40 in their better-seeing eye. Good vision, then. And yet occlusion of a peripheral retinal artery was bilateral in 20.3% of patients and unilateral in 6.9%. The explanation lies in the geography of the retina: occlusions strike the finest arterioles of the extreme periphery first, at a distance from the macula. There is also a further quirk: the tendency of “sea fan” new vessels to infarct and regress on their own. The disease therefore stays silent for a long time, and its course is not a straight line.

The cost of this silence can be measured. A school screening campaign in Ghana identified 24 pupils with sickle cell disease out of 8,168 respondents: only one had ever had a dilated fundus examination, and four already had retinopathy, two of them at the proliferative stage (Goldberg stage 3), for whom treatment was recommended. This gap is not unique to West Africa: in the United Kingdom, where more than 15,000 people live with sickle cell disease, the authors of a national study find that no national recommendation for retinal screening exists. This is a silent, screenable disease whose screening is not organised — the very same logic that justifies monitoring diabetic retinopathy, except that the reflex has not yet been adopted.

MECHANISM

What is proliferative sickle cell retinopathy?

This is the form in which the retina, starved of blood, makes new vessels to compensate for it — fragile vessels that bleed and pull on the retina. The starting point is haematological: the abnormal haemoglobin aggregates inside the red blood cell, the cell loses its flexibility, blood flow slows and then stagnates in the precapillary arterioles, a thrombosis forms and the territory downstream becomes ischaemic. Three circumstances favour this chain of events: hypoxia, acidosis and hyperosmolarity.

The reference description remains the Goldberg classification, published in 1971 and still used as the standard. It describes five stages. First, occlusion of the peripheral arterioles. Then arteriovenous anastomoses, short-circuits that bypass the blocked areas. Next, “sea fan” neovascularisation, which marks the entry into the proliferative form and is the main target of screening. Then vitreous haemorrhage, when one of these new vessels ruptures. Finally, retinal detachment, through traction or a tear.

These lesions are not theoretical. A multicentre series from Burkina Faso of 274 patients, almost all of the SC genotype, gives a sense of the scale: sea fan new vessels (33.2%) and arteriovenous anastomoses (28.4%) were the main lesions found on fundus examination, the proliferative form affected 92.7% of the 271 patients with retinopathy, and on angiography, Goldberg stage 3 predominated, accounting for about 37% of eyes. The last two stages are the ones that cause sight loss: vitreous haemorrhage and retinal detachment are the mechanisms through which this disease leads to severe visual impairment. The whole value of screening lies in the interval, long and silent, between the first blocked vessel and the first drop of blood in the vitreous.

GENOTYPE

Why does the SC form, thought to be milder, affect the retina more?

Because what spares the rest of the body does not spare the eye. Patients with the HbSC genotype have a milder systemic disease than HbSS homozygotes: fewer crises, less organ damage. But the reference reviews state it in black and white: they are the ones who run the highest risk of proliferative retinopathy and visual loss. Many arrive at their appointment convinced they have “the less severe form”. For the retina, it is the opposite.

The data agree from one continent to another. Another analysis of the Cooperative Study of Sickle Cell Disease, in 1,867 patients, found a frequency of proliferative retinopathy that differed significantly by genotype, with SC in the lead. In Mali, screening of 1,604 patients at a referral centre found retinopathy in 12.4% of SC patients against 5.2% of SS patients. In children, the gap appears early: in a cohort of 398 children followed in Philadelphia, the proliferative form affected 5% of SC patients against 1% of SS patients, and the youngest diagnosis was at 12.2 years in SC patients against 15.4 years in SS patients.

Several series point in a paradoxical direction: it is not the most anaemic patient who has the most damaged retina. A Portuguese study compared patients with and without a proliferative form and found, in those who had one, a lower mean corpuscular volume, lower fetal haemoglobin and lower lactate dehydrogenase — a marker of haemolysis. The most discriminating parameter was mean corpuscular volume, and the authors conclude that the driving factor may be hypoxia rather than haemolysis. The same signal is seen in Mali and Cameroon, where a higher haemoglobin level was associated with retinopathy. The SC patient is less anaemic; the hypothesis, which these studies do not prove, is that their more viscous blood circulates less well through the finest capillaries.

SCREENING

How often should you have your retina examined?

The 2014 American expert panel report recommends a fundus examination after dilation from the age of 10, repeated every 1 to 2 years for as long as it remains normal; if retinopathy is suspected, it asks for the patient to be referred to a retina specialist. It is worth saying where this figure comes from: a 2024 systematic review, covering 44 studies and 4,928 patients, notes that the evidence supporting it is of low quality and that it rests on expert consensus. That is not a reason to do nothing, it is a reason not to turn an approximate interval into a rigid rule, and to adapt it to genotype.

This same review measured how good the examinations actually are. Dilated fundus examination has moderate performance for detecting the proliferative form, with a positive likelihood ratio of 8.0 and a negative likelihood ratio of 0.3. Ultra-widefield fundus photography does markedly better: 32.5 and 0.03. OCT angiography is also very good at picking up the proliferative form: analysed by machine learning, it reaches the same values (32.5 and 0.03); read by a human observer, its results vary more from one study to the next, with a negative likelihood ratio of 0.1 to 0.2. One point is worth remembering: most of these examinations are more reliable for spotting the proliferative form than for detecting early stages or pinning down the exact stage.

On the age to start, the Philadelphia paediatric cohort offers a pragmatic reading: looking for non-proliferative forms means starting around age 5, but targeting the lesions that warrant treatment allows a start around age 9 for SC patients and age 13 for SS patients. Its authors add a counter-intuitive finding: in this cohort, no marker of general severity — emergency visits or hospital admissions for crises, transfusions, hydroxyurea treatment — was associated with retinopathy. A patient whose sickle cell disease is quiet is therefore not exempt from examination. In practice, a full assessment combines visual acuity, slit-lamp examination, a dilated fundus examination that carefully explores the periphery, macular OCT, and, depending on the equipment available, OCT angiography.

MACULA

What OCT angiography has shown in patients with perfect sight

It has shown that the macula is affected far more often than was thought, without acuity necessarily being reduced. This damage is called sickle cell maculopathy, and for a long time it was poorly described: it can go unnoticed on fundus examination as well as on conventional angiography, while OCT reveals it. A systematic review of 12 studies published in 2019 puts its prevalence at 45.6%, a prevalence that increases with age. A German review puts it simply: independently of any peripheral retinopathy, up to about half of patients can develop maculopathy early in the course of the disease.

Two abnormalities are seen on these images. Thinning first: an Italian study of 30 patients and 30 controls found maculopathy in 43% of patients, in the form of areas of thinning located mainly on the temporal side; compared with controls, the thinning affected both the inner and outer layers. Capillary dropout second: a study from Guadeloupe of 151 eyes in 78 adults found maculopathy in 44% of eyes and identified areas with no flow in eyes with no thinning at all. The perfusion abnormality therefore appears to precede the loss of tissue. This damage does not follow the genotype distribution of the proliferative form: here this maculopathy was more common in HbSS patients.

The most telling figure comes from a series of 69 children and adolescents whose acuity ranged from 20/20 to 20/40. Fundus examination found signs of retinopathy in 11 of them; OCT found thinning of the inner retina temporal to the fovea in 47 of 68, and made the diagnosis 1.78 years earlier on average. A Boston study of 606 children’s eyes goes further: imaging parameters correlated better with systemic events — strokes, hospital admissions — than visual acuity did, which correlated with neither the number of admissions, nor the haemoglobin level, nor the velocities measured on transcranial Doppler. In this disease, vision as measured in the consulting room is a poor indicator.

TREATMENT

What is proven when it comes to treatment, and what is not

Let’s start with the most uncomfortable point: there is currently no consensus on the management of sickle cell retinopathy. That is the explicit conclusion of the most recent review; a 2019 review already judged the evidence in favour of laser to be weak. What follows describes practices backed by case series, not by randomised trials. Laser photocoagulation remains the standard approach for progressive neovascularisation: the 2014 American expert panel report strongly recommends referring both children and adults with a proliferative form to a specialist to consider it. No standardised criteria exist, however, for when to treat.

Intravitreal anti-VEGF injections are the option progressing fastest. A retrospective series published in 2026 followed 45 eyes at stages 3 and 4: in the month after the injection, acuity had improved by at least two lines in 18 eyes, stayed stable in 26 and worsened in just one. For stage 4 eyes, median acuity went from 20/200 to 20/30. The disease could be controlled without vitrectomy in 42 of the 45 eyes. These results are encouraging, but retrospective and in a modest number of patients: recent reviews call for more robust research.

Surgery comes into play when the blood fails to clear on its own or when the retina detaches, and its outlook depends on the indication. In a series of 65 eyes operated on between 2014 and 2021, the 13 eyes operated on for vitreous haemorrhage went from a mean acuity of 20/944 to 20/56; for the 52 detachments, anatomical success after a single procedure was 72.4% with a scleral buckle combined with vitrectomy against 47.8% with vitrectomy alone, a difference that does not reach the threshold of statistical significance. None of these series report anterior segment ischaemia, a complication once greatly feared.

That leaves hydroxyurea, and this is where caution matters most. A 2026 meta-analysis concludes that its use is not associated with a statistically significant reduction in retinopathy: overall odds ratio of 0.90, 95% confidence interval of 0.41 to 1.97. Secondary analyses not planned in the protocol find a favourable signal, but the authors themselves describe the certainty of the evidence as very low. A paediatric cohort of 630 patients points towards a benefit: 30% retinopathy on hydroxyurea against 42%. The accurate way to put it is this: hydroxyurea is prescribed for the systemic disease, a protective effect on the eye is plausible, it is not established — and the effect of recent gene therapies on retinopathy remains unknown, for want of in-depth studies.

SICKLE TRAIT (AS)

And what about sickle cell trait? What is documented, without alarm

Sickle cell trait — a single mutated gene, haemoglobin AS — is not a disease and should not be presented as one. It affects 8% of African Americans according to the ophthalmological literature. It is traditionally considered benign and often remains without symptoms, but retinal damage, up to and including the proliferative form, has been described with it. The 2014 screening recommendations are aimed at people with sickle cell disease: in practice, in the absence of a symptom or a particular circumstance, a trait carrier does not fall under the regular retinal follow-up given to a patient with sickle cell disease. One study even found, in 100 diabetic trait carriers compared with 100 non-carriers, less sight-threatening diabetic retinopathy: 58% against 95%. The authors see this as a hypothesis to be confirmed, not a conclusion.

That said, “healthy carrier, so nothing to report” is too short a formula, and two documented situations are worth knowing about as emergencies. The first is eye trauma: an Indian study reports two young men who, after a blunt injury, developed a rapidly progressing vaso-occlusive retinopathy within less than two months, which went on to the proliferative form in both, with vitreous haemorrhage in one of them — independently of any rise in intraocular pressure, and while the trait had until then gone unrecognised.

The second concerns intraocular pressure and its treatment. A Paris-based team reports a 24-year-old man treated for hypertensive herpetic uveitis in whom the sharp drop in pressure achieved with systemic acetazolamide caused decompression retinopathy and multiple arterial occlusions; haemoglobin electrophoresis then revealed a sickle cell trait. The authors recommend testing for a haemoglobinopathy in patients of African or Mediterranean origin presenting with acute raised pressure, particularly before starting a carbonic anhydrase inhibitor. Other reported cases round out the picture without making it bleaker: central retinal artery occlusion in a teenager, proliferative retinopathy after repeated exposure to high altitude, vitreous haemorrhage in a 21-year-old man. Several occur in a particular context, but not all of them: the teenager’s central retinal artery occlusion is described as spontaneous. In practice, the usual approach is not systematic monitoring, but knowing your status, mentioning it, and seeking care without delay if a symptom appears.

EMERGENCY

Which signs mean you should see a doctor without delay

Three symptoms call for a retinal examination without delay, as the 2014 American expert panel report requires — in practice within the following hours, without waiting for the next scheduled appointment. A sudden drop in vision in one eye, without pain. The sudden appearance of a shower of black dots or strands — what are known as floaters — especially if it is heavy and comes with flashes of light. And a dark veil, a fixed shadow, a curtain rising or falling across the field of vision. Eye trauma calls for the same urgency: in a patient with sickle cell disease, this report asks for immediate examination for bleeding in the front chamber of the eye (hyphaema).

These presentations can point to either of the two complications that cause sight loss. A shower of floaters or a sudden drop in vision can signal vitreous haemorrhage: a new vessel has ruptured and blood is filling the vitreous cavity. A sudden drop can also reveal occlusion of a retinal artery, which has been described even in trait carriers. A veil or a curtain suggests retinal detachment, through traction or a tear. One practical point that is often overlooked: mention your sickle cell disease and your genotype as soon as you arrive, even if you are only a trait carrier. This changes the doctor’s reasoning and guides the choice of treatments for intraocular pressure.

Frequently asked questions

Consultations in Cachan, Paris 13 and at the Sorbonne Saint-Michel practice (Paris 5th) · Tel. +33 1 45 47 08 11

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This article is intended for information purposes and does not replace a medical consultation. Indications, expected benefits and risks depend on each individual situation. For any question concerning your vision, consult an ophthalmologist.