Yuchen Lin1,2, Christine L Xu1,3, Mark P Breazzano3,4, Akemi J Tanaka5, Joseph Ryu1,3, Sarah R Levi1,3, Ke Yao2, Janet R Sparrow1,3,5, Stephen H Tsang1,3,5. 1. Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, USA. 2. Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China. 3. Department of Ophthalmology, New York-Presbyterian Hospital, New York, New York, USA. 4. Department of Ophthalmology, New York University School of Medicine, New York, New York, USA. 5. Department of Pathology & Cell Biology, Institute of Human Nutrition, and Columbia Stem Cell Initiative, Columbia University, New York, New York, USA.
Abstract
Background: To evaluate the long-term progression of autosomal recessive retinitis pigmentosa (RP) due to mutations in KIZ using multimodal imaging and a quantitative analytical approach. Methods: Whole exome sequencing (WES) and targeted capture sequencing were used to identify mutation. Fundus photography, short-wavelength autofluorescence (SW-AF), spectral-domain optical coherence tomography (SD-OCT) imaging, and electroretinography (ERG) were analyzed. Serial measurements of peripheral retinal pigment epithelium (RPE) atrophy area with SW-AF, as well as the ellipsoid zone (EZ) width using SD-OCT were performed. Results: Two homozygous variants in KIZ-a c.226C>T mutation as well as a previously unreported c.119_122delAACT mutation-were identified in four unrelated patients. Fundus examination and ERG revealed classic rod-cone dysfunction, and SD-OCT demonstrated outer retinal atrophy with centrally preserved EZ line. SW-AF imaging revealed hyperautofluorescent rings with surrounding parafoveal, mid-peripheral and widespread loss of autofluorescence. The RPE atrophy area increased annually by 4.9%. Mean annual exponential rates of decline for KIZ patients were 8.5% for visual acuity and 15.9% for 30 Hz Flicker amplitude. The average annual reduction distance of the EZ distance was 66.5 μm per year.Conclusions: RPE atrophy progresses along with a loss of photoreceptors, and parafoveal RPE hypoautofluorescence is commonly seen in KIZ-associated RP patients. KIZ-associated RP is an early-onset severe rod-cone dystrophy.
Background: To evaluate the long-term progression of autosomal recessive retinitis pigmentosa (RP) due to mutations in KIZ using multimodal imaging and a quantitative analytical approach. Methods: Whole exome sequencing (WES) and targeted capture sequencing were used to identify mutation. Fundus photography, short-wavelength autofluorescence (SW-AF), spectral-domain optical coherence tomography (SD-OCT) imaging, and electroretinography (ERG) were analyzed. Serial measurements of peripheral retinal pigment epithelium (RPE) atrophy area with SW-AF, as well as the ellipsoid zone (EZ) width using SD-OCT were performed. Results: Two homozygous variants in KIZ-a c.226C>T mutation as well as a previously unreported c.119_122delAACT mutation-were identified in four unrelated patients. Fundus examination and ERG revealed classic rod-cone dysfunction, and SD-OCT demonstrated outer retinal atrophy with centrally preserved EZ line. SW-AF imaging revealed hyperautofluorescent rings with surrounding parafoveal, mid-peripheral and widespread loss of autofluorescence. The RPE atrophy area increased annually by 4.9%. Mean annual exponential rates of decline for KIZ patients were 8.5% for visual acuity and 15.9% for 30 Hz Flicker amplitude. The average annual reduction distance of the EZ distance was 66.5 μm per year.Conclusions: RPE atrophy progresses along with a loss of photoreceptors, and parafoveal RPE hypoautofluorescence is commonly seen in KIZ-associated RP patients. KIZ-associated RP is an early-onset severe rod-cone dystrophy.
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