Anti-VEGF Improves Outcomes in Proliferative Sickle Cell Retinopathy

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Within one month of treatment, anti-VEGF therapy improves anatomic and visual outcomes among eyes with stage 3 and 4 proliferative sickle cell retinopathy.

Anti-vascular endothelial growth factor (VEGF) therapies for eyes with stage 3 or 4 proliferative sickle cell retinopathy were associated with improvements in anatomic and visual outcomes, according to new data presented at the 2024 Association for Research in Vision and Ophthalmology (ARVO) Meeting.1

Across the analysis, the utility of intravitreal anti-VEGF therapy showed stability or improvements in visual acuity (VA) in many patients, and a significant clearing of vitreous hemorrhage, within one month of treatment.

“This case series showed that anti-VEGF therapy can safely result in resolution of the abnormal blood vessels and can also result in resolution of bleeding in eyes with sickle cell eye disease,” wrote the investigative team, led by Jennifer I. Lim, MD, department of ophthalmology, University of Illinois Chicago.

Anti-VEGF drugs are the standard of care when treating eyes with retinal diseases, due to targeting the formation of new blood vessels in the eye.2 These treatments can resolve blood vessels that would otherwise lead to bleeding and loss of vision.

Sickle cell disease (SCD), the most common inherited blood disorder in the United States, can also lead to the formation of new blood vessels in the retina.3 Laser treatment has previously been used to treat SCD-related retinal disease, but the introduction of anti-VEGF therapy has transformed clinical practice.

In this analysis, Lim and colleagues assessed the Anti-VEGF versus Laser (APLS) cohort, involving 23 retina specialists, on their experience using anti-VEGF agents for PSR.1 Of that cohort, 6 specialists reported using anti-VEGF treatment for stage 3 and 4 PSR.

Institutional review board approval was then acquired to review the retrospective use of anti-VEGF therapy for PSR. The de-identified data collected for the analysis involved baseline demographics, including age and sickle cell subtype, ocular history, PSR stage, anti-VEGF therapy parameters, and visual and anatomic outcomes.

The outcomes included sea fan activity and fibrosis, vitreous hemorrhage, and the development of new sea fans or vitreous hemorrhage. Complications, including endophthalmitis, retinal tears, traction (TRD), or rhegmatogenous detachment (RRD), were also measured by investigators.

Previously non-published cases were only included in this series. Overall, across the US and Nigeria, there were 38 eyes treated with intravitreal anti-VEGF injections. After 5 eyes were excluded due to diabetic retinopathy (n = 4) and choroidal neovascularization (n = 1), 33 eyes of 31 patients were included for analysis.

This included 22 eyes with hemoglobin SC (HbSC), 6 eyes with hemoglobin SS (HbSS), 1 with sickle thalassemia (SThal), and 2 unknowns. Meanwhile, 15 eyes were designated stage 3 and 18 as stage 4 PSR. Moreover, 10 of the 33 eyes had undergone prior laser photocoagulation for PSR.

Anti-VEGF drugs in the study included bevacizumab (n = 24), aflibercept (n = 6), and ranibizumab (n = 3). The treatment regimens included anti-VEGF agents alone in 13 eyes and anti-VEGF followed by laser photocoagulation in 20 eyes. The follow-up period ranged from 1 to 36 months, with four eyes experiencing only 1-month follow-up.

Among eyes treated only with anti-VEGF, sea fan regression to inactivity in 9 (69%) eyes at the 1-month and final follow-up periods. Lim and colleagues indicated that 3 of 4 persistent sea fans occurred in eyes at the 1-month follow-up.

At the last follow-up, for eyes with follow-up >1 month, sea fans were inactive in 7 of 8 (88%) eyes in the anti-VEGF-only cohort. Sea fans were inactive in 17 of 20 (85%) combination treatment eyes.

In eyes at stage 4, within 1 month of anti-VEGF treatment, VA improved >3 lines in 12 of 18 eyes and remained stable in 5 eyes (20/20 or 20/25 at baseline) — a single eye experienced worsening at the 1-month mark. For eyes at stage 4 with baseline VA 20/40 or worse, most (12 of 13; 92%) improved >3 lines by 1 month post anti-VEGF treatment.

Lim and colleagues identified no cases of endophthalmitis or rhegmatogenous retinal detachment (RRD) during the study period.

“Within one month of treatment, anti-VEGF therapy of PSR eyes resulted in high rates of sea fan-like regression, significant clearing of vitreous hemorrhage, and stable or improved VA in a large majority,” Lim and colleagues wrote.


  1. Lim JI, Okonkwo O, Regillo C, Wykoff CC, Cao J, Mansour H, Miao BA. Anti-VEGF Therapy for Stages 3 and Stage 4 Proliferative Sickle Cell Retinopathy Results in Improved Anatomic and Visual Outcomes. Poster presented at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Meeting, May 5–9, 2024.
  2. Anti-VEGF treatments. American Academy of Ophthalmology. July 26, 2023. Accessed May 13, 2024.
  3. Feroze KB, Azevedo AM. Retinopathy Hemoglobinopathies. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: