PMID- 34003923 OWN - NLM STAT- MEDLINE DCOM- 20210628 LR - 20210628 IS - 2164-2591 (Electronic) IS - 2164-2591 (Linking) VI - 10 IP - 2 DP - 2021 Feb 5 TI - Multimodal Retinal Imaging and Microperimetry Reveal a Novel Phenotype and Potential Trial End Points in CRB1-Associated Retinopathies. PG - 38 LID - 10.1167/tvst.10.2.38 [doi] LID - 38 AB - PURPOSE: Biallelic crumbs cell polarity complex component 1 (CRB1) mutations can present as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), or cystic maculopathy. This study reports a novel phenotype of asymptomatic fenestrated slit maculopathy (AFSM) and examines macular volume profile and microperimetry as clinical trial end points in CRB1-associated retinopathies. METHODS: Twelve patients from nine families with CRB1 mutation were recruited. Ultra-widefield (UWF) color fundus photography and autofluorescence (AF), spectral-domain optical coherence tomography (SD-OCT), microperimetry, and adaptive optics (AO) imaging were performed. Macular volume profiles were compared with age-matched healthy controls. Genotyping was performed using APEX genotyping microarrays, targeted next-generation sequencing, and Sanger sequencing. RESULTS: We identified one patient with LCA, five patients with RP, and four patients with macular dystrophy (MD) with biallelic CRB1 mutations. Two siblings with compound heterozygote genotype (c.[2843G>A]; [498_506del]) had AFSM characterized by localized outer retinal disruption on SD-OCT and parafoveal cone loss on AO imaging despite normal fundus appearance, visual acuity, and foveal sensitivity. UWF AF demonstrated preserved para-arteriolar retinal pigment epithelium (PPRPE) in all patients with RP. Microperimetry documented preserved central retinal function in six patients. The ratio of perifoveal-to-foveal retinal volume was greater than controls in 89% (8/9) of patients with RP or MD, whereas central subfield and total macular volume were outside normal limits in 67% (6/9). CONCLUSIONS: AO imaging was helpful in detecting parafoveal cone loss in asymptomatic patients. Macular volume profile and microperimetry parameters may have utility as CRB1 trials end points. TRANSLATIONAL RELEVANCE: Macular volume and sensitivity can be used as structural and functional end points for trials on CRB1-associated RP and MD. FAU - Roshandel, Danial AU - Roshandel D AD - Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Australia. FAU - Thompson, Jennifer A AU - Thompson JA AD - Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia. FAU - Heath Jeffery, Rachael C AU - Heath Jeffery RC AD - Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Australia. AD - Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia, Australia. FAU - Sampson, Danuta M AU - Sampson DM AD - Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Australia. AD - Surrey Biophotonics, Centre for Vision, Speech and Signal Processing and School of Biosciences and Medicine, The University of Surrey, Guildford, UK. FAU - Chelva, Enid AU - Chelva E AD - Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia. FAU - McLaren, Terri L AU - McLaren TL AD - Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Australia. AD - Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia. FAU - Lamey, Tina M AU - Lamey TM AD - Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Australia. AD - Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia. FAU - De Roach, John N AU - De Roach JN AD - Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Australia. AD - Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia. FAU - Durkin, Shane R AU - Durkin SR AD - Discipline of Ophthalmology and Visual Science, The University of Adelaide, South Australia, Australia. AD - Department of Ophthalmology, The Royal Adelaide and Queen Elizabeth Hospital, Adelaide, South Australia, Australia. FAU - Chen, Fred K AU - Chen FK AD - Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Australia. AD - Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia, Australia. AD - Department of Ophthalmology, Perth Children's Hospital, Nedlands, Western Australia, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Transl Vis Sci Technol JT - Translational vision science & technology JID - 101595919 RN - 0 (CRB1 protein, human) RN - 0 (Eye Proteins) RN - 0 (Membrane Proteins) RN - 0 (Nerve Tissue Proteins) SB - IM MH - *Eye Proteins/genetics MH - Humans MH - Membrane Proteins/genetics MH - Nerve Tissue Proteins/genetics MH - Phenotype MH - Retina MH - *Retinitis Pigmentosa/diagnosis MH - Visual Field Tests PMC - PMC7910635 COIS- Disclosure: D. Roshandel, None; J.A. Thompson, None; R.C. Heath Jeffery, None; D.M. Sampson, None; E. Chelva, None; T.L. McLaren, None; T.M. Lamey, None; J.N. De Roach, None; S.R. Durkin, None; F.K. Chen, None EDAT- 2021/05/19 06:00 MHDA- 2021/06/29 06:00 PMCR- 2021/02/25 CRDT- 2021/05/18 17:22 PHST- 2021/05/18 17:22 [entrez] PHST- 2021/05/19 06:00 [pubmed] PHST- 2021/06/29 06:00 [medline] PHST- 2021/02/25 00:00 [pmc-release] AID - 2772331 [pii] AID - TVST-20-3139 [pii] AID - 10.1167/tvst.10.2.38 [doi] PST - ppublish SO - Transl Vis Sci Technol. 2021 Feb 5;10(2):38. doi: 10.1167/tvst.10.2.38.