Fleck-like lesions in CEP290-associated leber congenital amaurosis: a case series

ABSTRACT

Purpose

To provide a detailed ophthalmic phenotype of a small cohort of patients with Leber Congenital Amaurosis (LCA) caused by mutations in CEP290 (CEP290-LCA) with a focus on elucidating the origin of yellow-white lesions observed in 30% of patients with this condition.

Methods

This is a retrospective review of records of five patients with CEP290-LCA. Patients had comprehensive ophthalmic evaluations. Visual function was assessed with full-field electroretinograms (ffERGs) and full-field sensitivity testing (FST). Multimodal imaging was performed with spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) with short- (SW) and near-infrared (NIR) excitation wavelengths.

Results

All patients showed relative structural preservation of the foveal and near midperipheral retina separated by a pericentral area of photoreceptor loss. Yellow-white, fleck-like lesions in an annular distribution around the near midperiphery co-localized with hyperreflective lesions on SD-OCT. The lesions located between the inner segment ellipsoid signal and the apical retinal pigment epithelium (RPE). The inner retina was normal. Longitudinal observations in one of the patients indicates the abnormalities may represent an intermediate stage in the degenerative process between the near normal appearing retina previously documented in young CEP290-LCA patients and the pigmentary retinopathy observed along the same region in older individuals.

Conclusions

We speculate that fleck-like lesions in CEP290-LCA correspond to malformed, rudimentary or degenerated, including shed, photoreceptor outer segments. The topography and possible origin of the abnormalities may inform the planning of evolving genetic therapies for this disease.

KEYWORDS:

• Flecks
• marbleized
• CEP290
• LCA10
• leber congenital amaurosis
• Joubert syndrome
• OCT

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authorship

All authors attest that they meet the current ICMJE criteria for authorship. Two of the patients were seen as part of their standard of care; images have been de-identified in compliance of HIPPA regulations. The other three patients were examined as part of both clinical visits and as part of an observational study and consent and assent were obtained and procedures adhered to the institutional guidelines of the University of Pennsylvania (protocol number 815348), and complied with the Declaration of Helsinki.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13816810.2022.2147960

Additional information

Funding

The work was supported by the Center for Advanced Retinal and Ocular Therapeutics of the Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania.