Hyperautofluorescent Dots are Characteristic in Ceramide Kinase Like-associated Retinal Degeneration

Jesse D Sengillo,Maarjaliis Paavo,Eugenia White,Winston Lee,Ruben Jauregui,Galaxy Y Cho,Rando Allikmets,Stephen H Tsang,Janet R Sparrow

doi:10.1038/s41598-018-37578-4

Jesse D Sengillo, Maarjaliis Paavo + Show 7 more

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https://doi.org/10.1038/s41598-018-37578-4

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There is a lack of studies which seek to discern disease expression in patients with mutations that alter retinal ceramide metabolism, specifically in the ceramide kinase like (CERKL) gene. This cross-sectional case series reports a novel phenotypic manifestation of CERKL-associated retinopathy. Four unrelated patients with homozygous CERKL mutations underwent a complete ocular exam, spectral-domain optical coherence tomography, short-wavelength fundus autofluorescence (SW-AF), quantitative autofluorescence (qAF), and full-field electroretinogram (ffERG). Decreased visual acuity and early-onset maculopathy were present in all patients. All four patients had extensive hyperautofluorescent foci surrounding an area of central atrophy on SW-AF imaging, which has not been previously characterized. An abnormal spatial distribution of qAF signal was seen in one patient, and abnormally elevated qAF8 signal in another patient. FfERG recordings showed markedly attenuated rod and cone response in all patients. We conclude that these patients exhibit several features that, collectively, may warrant screening of CERKL as a first candidate: early-onset maculopathy, severe generalized retinal dysfunction, peripheral lacunae, intraretinal pigment migration, and hyperautofluorescent foci on SW-AF.

Highlights

In one cohort of 272 Spanish retinitis pigmentosa (RP) patients, ceramide kinase like (CERKL) was found to be a commonly mutated gene, with the p.Arg257Stop mutation being the most frequent[15]
This typical ERG finding and early involvement of the macula have led some to categorize the condition as a cone-rod dystrophy rather than autosomal recessive retinitis pigmentosa[18], as it is traditionally cited[7,15,16,17]
Key features seen on ophthalmoscopy, spectral-domain optical coherence tomography (SD-OCT), en face short-wavelength fundus autofluorescence (SW-AF), quantitative autofluorescence, and full-field electroretinography are described

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Introduction

In one cohort of 272 Spanish retinitis pigmentosa (RP) patients, CERKL was found to be a commonly mutated gene, with the p.Arg257Stop mutation being the most frequent[15]. Patients typically exhibit an early maculopathy with severely depressed rod- and cone-responses, which vary in relation to each other This typical ERG finding and early involvement of the macula have led some to categorize the condition as a cone-rod dystrophy rather than autosomal recessive retinitis pigmentosa (arRP)[18], as it is traditionally cited[7,15,16,17]. Identification and diagnosis are important in the management of patients with CERKL-associated retinopathy, as it manifests more severely than most appearing cone-rod and rod-cone dystrophies. This retrospective analysis seeks to further illustrate the CERKL-associated retinopathy phenotype, expand on the previously described imaging and electrodiagnostic characteristics, and report a novel SW-AF imaging feature. Key features seen on ophthalmoscopy, spectral-domain optical coherence tomography (SD-OCT), en face short-wavelength fundus autofluorescence (SW-AF), quantitative autofluorescence (qAF), and full-field electroretinography (ffERG) are described

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