Characterization of West African crystalline macular dystrophy in the Ghanaian population

Objective/purpose: West African Crystalline Maculopathy (WACM) is characterized by the presence of macular hyper-refractile crystal-like deposits. Although the underlying pathophysiology has not been elucidated, a few biological drivers have been proposed. We analysed a large WACM case series to gain a more robust understanding of its features and etiology.

Design: Prospective, Cross-sectional cohort study.

Subjects/participants: Participants with WACM were selected from the large cohort recruited into the Ghana Age-Related Macular Degeneration Study (Ghana AMD Study).

Methods: Demographic and detailed medical histories, full ophthalmic examinations, digital colour fundus photographs and optical coherence tomography (OCT) images were obtained. All WACM cases were evaluated by three retina experts. Crystal numbers, location, and distribution were determined. Associations between WACM and Caucasian AMD risk variants were assessed using Firth's bias-reduced logistic regression, including age and gender as covariates.

Main outcome measures: Phenotypic features of, and genetic associations with, WACM.

Results: WACM was identified in 106 eyes of 53 participants: 22 were bilateral and 24 unilateral. Grading for AMD was not possible in one eye of seven WACM participants; therefore, laterality was not assessed in these subjects. Thirty-eight participants were female, and 14 male; gender was unrecorded for one participant. Mean age was 68.4 years (range 45-101). OCT demonstrated typical WACM crystals, which were more easily identified at high contrast and predominantly located at the inner limiting membrane (ILM). In eyes with co-pathology, crystals localised deeper in the inner retina with wider retinal distribution over co-pathology lesions. There was no age or gender association. A significant association was observed between the complement factor H (CFH) 402H risk variant and WACM.

Conclusion: This study confirms localization of crystals adjacent to the ILM, and distribution over lesions in eyes with co-pathology. Evaluation of OCT images under high contrast allows improved identification. WACM may be associated with the CFH-CFHR5 AMD-risk locus identified amongst Caucasians; however, it is also possible that combination of crystals and the CFH 402H allele increases the risk for developing late AMD. Further analyses using larger sample sizes are warranted to identify causalities between genotype and WACM phenotype.