The Sickle I project: Prevalence of sight loss associated with sickle cell retinopathy and maculopathy and the impact on vision-related quality of life

Research question What is the prevalence of visual impairment due to sickle cell retinopathy and maculopathy in the UK?

Background Proliferative sickle cell retinopathy (SCR) is the most common ophthalmic manifestation of Sickle Cell Disease (SCD) and can result in significant sight loss, although the prevalence in the U.K is unknown. Retinal screening provision is variable.

There are 5 stages of SCR described; stages 1-3 are asymptomatic and stage 4 and 5 associated with significant visual loss often requiring surgical intervention with guarded outcomes.

The severity classification has remained unchanged for 50-years and may not reflect new insight on disease progression provided by modern imaging technologies.

Laser treatment and intravitreal anti-vascular endothelial growth factor therapy have shown efficacy for treatment of stage 3 SCR but conclusive evidence is lacking.

Retrospective evidence suggests Hydroxycarbamide, used to prevent painful crises, has a protective effect against progression of SCR and maculopathy by elevating levels of fetal haemoglobin (HbF).

Rationale Ultrawide field fundus photography, Optical Coherence Tomography (OCT) and OCT-angiography are proven to detect SCR and maculopathy more reliably than traditional eye examination.

This affords the opportunity to establish the true burden of sight loss due to SCR and prevalence of each stage of SCR and maculopathy in a representative population, with implications for public health policy on screening, therapeutic development for prevention and treatment of SCR and preventable vision loss through improved compliance.

Objectives Primary objective: Determine the prevalence of visual impairment (best corrected visual acuity BCVA ≤ 6/12) due to SCR and/or maculopathy. Secondary objectives: 1.

Determine prevalence of each stage of SCR and presence of maculopathy and correlation with i) severity of SCD ii) HbF level. 2. Determine impact of SCR and maculopathy on vision-related quality of life 3. Determine acceptability to patients of retinal imaging and routine screening for SCR and maculopathy 4.

Develop updated severity classification system for SCR and maculopathy incorporating definitions generated by modern ophthalmic imaging technology Design: Multi-center, prospective, cross-sectional, study.

Setting: 12 NHS sites Inclusion criteria: Willingness to participate Age ≥16 Diagnosis of SCD of any genotype Exclusion criteria Other causes of visual impairment such as cataract, glaucoma, and diabetic retinopathy.

Methods After consent the following will be recorded: medical and ocular history; Best Corrected Visual Acuity (BCVA); slit lamp biomicroscopy; ultrawide field fundus photography; OCT and OCT-angiography; vision-related quality of life tool (NEI-VFQ 25) and acceptability questionnaire.

Timelines Prefunding: Protocol development, staff recruitment Months 1-6: Site set-up, ethics, HRA and R&D approval, site training and initiation, development of image grading protocol Months 7-18: Recruitment and data collection Months 19-24: Site close down, analysis and report writing Anticipated impact and dissemination Our data will inform: education of people with SCD and their clinicians; configuration of services for sight impairment due to SCR and maculopathy; cost-benefit analysis of introducing standardized retinal imaging for screening in SCD; enable the design of clinical trials.

Results will be shared widely engaging integrated care boards, policy groups and patients in conjunction with our PPI Group and Sickle Cell Society.