Cystoid maculopathy is a frequent feature of Cohen syndrome-associated retinopathy

Abstract

Cohen syndrome (CS) is a rare syndromic form of rod-cone dystrophy. Recent case reports have suggested that cystoid maculopathy (CM) could affect CS patients with an early onset and high prevalence. Our study aims at improving our understanding and management of CM in CS patients through a retrospective case series of ten CS patients with identified pathogenic variants in VPS13B. Longitudinal optical coherence tomography (OCT) imaging was performed and treatment with carbonic anhydrase inhibitors (CAI) was provided to reduce the volume of cystoid spaces. CM affected eight out of ten patients in our cohort. The youngest patient showed a strong progression of macular cysts from the age of 4.5 to 5 years despite oral CAI medication. Other teenage and young adult patients showed stable macular cysts with and without treatment. One patient showed a moderate decrease of cystoid spaces in the absence of treatment at 22 years of age. Through a correlative analysis we found that the volume of cystoid spaces was positively correlated to the thickness of peripheral and macular photoreceptor-related layers. This study suggests that CAI treatments may not suffice to improve CM in CS patients, and that CM may resolve spontaneously during adulthood as photoreceptor dystrophy progresses.

Ophthalmic findings in Cohen syndrome patient without subjective ophthalmic complaints: A case report

“…Gabrielle et al reported that topical and systemic carbonic anhydrase IV inhibitors were administered for the treatment of cystoid maculopathy but failed to reduce or prevent the disease progression. [12] Many patients with Cohen syndrome cannot speak complete sentences by age 6, have some degree of intellectual disability, and up to 22% show significant delays. [18] In our case, the patient was unable to express himself and interact with others due to an underlying disorder affecting his language development.…”

“…Pigmentary retinopathy was seen in 91% of Finnish patients, retinal involvement in 83% of Japanese patients, and 32% of other Caucasians. [11] Gabrielle et al [12] reported that cystoid maculopathy is a frequent finding in Cohen syndrome, with a prevalence of about 80%. Nasser et al [13] described bull’s-eye maculopathy, cystic changes, and atrophy of outer retinal layers in 5 patients, while Beck et al [14] described a patient with non-leaking cystoid macular edema on fluorescein angiography.…”

“…Gabrielle et al reported that topical and systemic carbonic anhydrase IV inhibitors were administered for the treatment of cystoid maculopathy but failed to reduce or prevent the disease progression. [12]…”

Value of Combining Optical Coherence Tomography with Fundus Photography in Screening Retinopathy in Patients with High Myopia

“…Because highly myopic patients have a higher diopter accompanied by astigmatism, vitreous opacity and other features, and their fundus lesions are not easily visible under direct test lens, so fundus fluorography is the best method for screening fundus lesions in them [ 17 , 18 ]. Fundus fluorescence imaging can present retinal and choroidal blood circulation, and dynamically and objectively record small changes in the center and periphery of the macula in affected eyes of patients with high myopia, which is beneficial for providing an objective basis for clinical treatment.…”

VPS13B is localized at the cis-trans Golgi complex interface and is a functional partner of FAM177A1

“…In conclusion, our studies provide new insight into the site of action of VPS13B, suggest the possibility that this protein may mediate bridge-like lipid transport between Golgi subcompartments, and identify FAM177A1 as one of its potential functional partners. They provide a foundation for further investigations of the cellular (Seifert et al, 2011;Duplomb et al, 2014;Zorn et al, 2022) and organismal (Da Costa et al, 2019;Kim et al, 2019;Gabrielle et al, 2021;Montillot et al, 2023) phenotypes produced by VPS13B loss-of-function.…”