CRB1-Associated Retinal Dystrophies: A Prospective Natural History Study in Anticipation of Future Clinical Trials

Abstract

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CRB1-Associated Retinal Dystrophies: Genetics, Clinical Characteristics, and Natural History

“…The latter is in agreement with Talib and Mathijssen et al, 20,46 while Nguyen et al recommended treatment before the third decade of life, having seen in their cohort a faster decline around that period. 37 Furthermore, in our cohort, VA deterioration was significantly associated with age in all EOSRD/LCA, RP, and MD sub-cohorts. This association was also found in CRB1-RP by Mathijssen et al, 20 but not by Talib et al, despite their cohort being mostly RP phenotype.…”

“…Regarding BCVA asymmetry, we report a smaller proportion than previous cohorts (19% in this report vs 33% and 31% in other groups). 45,46 Progressive visual decline was also reported during long follow up studies, 20 however this was not picked up in the 2-year follow up study by Nguyen et al 37 The rate of progression of our patients was greater than the one reported by Talib et al, 45 possibly reflecting an overall earlier onset and more severe disease stage in our patients.…”

“…Macular OCTs were divided into three categories regarding their qualitative features and associations subsequently explored: group 1, characterized by normal lamination; group 2, where the retinal layers are generally discernible but appear ill-defined; and group 3, defined by a disorganised retina with coalescent layers (particularly within the inner retina) and a degree of increased reflectivity of the nuclear layers (Figure 1). 36,37 To allow direct comparison between normal and abnormal retinal architecture, we also compared normal (group 1) and abnormal OCT lamination (groups 2 and 3). Patients with macular cysts, edema, and/or only line scans due to poor fixation were excluded from quantitative assessments (details in Supplementary Methods).…”

“…Our results are comparable with some previous investigations e.g., where 38 to 52% eyes were categorised as group 3. 37,45 However, we consider that the classification of OCTs into groups 2 and 3 can be somewhat subjective and it is also dependant on the quality of the scan, intrinsically difficult in patients with EOSRD/LCA and nystagmus. To mitigate this potential limitation and thereby minimize possible bias, we added the comparison of normal and abnormal lamination groups.…”

CRB1-Related Retinal Dystrophies in a Cohort of 50 Patients: A Reappraisal in the Light of Specific Müller Cell and Photoreceptor CRB1 Isoforms

“…Tsang et al reported the first cases of macular dystrophy with bi-allelic pathogenic variants in CRB1 [7]. Prior to this, CRB1 had only been associated with EORD (where it was responsible for 10 to 13% of LCA cases) or RP (responsible for 8% of cases) with specific clinical features, such as para-arteriolar preservation of the retinal pigment epithelium, peripheral nummular pigmentation or Coats-like disease [8][9][10][11][12][13][14][15][16].…”