Dataset Information

Foveal Hypoplasia in CRB1-Related Retinopathies.

ABSTRACT: The CRB1 gene plays a role in retinal development and its maintenance. When disrupted, it gives a range of phenotypes such as early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa (RP), cone-rod dystrophy (CORD) and macular dystrophy (MD). Studies in CRB1 retinopathies have shown thickening and coarse lamination of retinal layers resembling an immature retina. Its role in foveal development has not yet been described; however, this retrospective study is the first to report foveal hypoplasia (FH) presence in a CRB1-related retinopathy cohort. Patients with pathogenic biallelic CRB1 variants from Moorfields Eye Hospital, London, UK, were collected. Demographic, clinical data and SD-OCT analyses with FH structural grading were performed. A total of 15 (48%) patients had EOSRD/LCA, 11 (35%) MD, 3 (9%) CORD and 2 (6%) RP. FH was observed in 20 (65%; CI: 0.47-0.79) patients, all of whom were grade 1. A significant difference in BCVA between patients with FH and without was found (p = 0.014). BCVA continued to worsen over time in both groups (p < 0.001), irrespective of FH. This study reports FH in a CRB1 cohort, supporting the role of CRB1 in foveal development. FH was associated with poorer BCVA and abnormal retinal morphology. Nonetheless, its presence did not alter the disease progression.

SUBMITTER: Rodriguez-Martinez AC

PROVIDER: S-EPMC10531165 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Foveal Hypoplasia in CRB1-Related Retinopathies.

Rodriguez-Martinez Ana Catalina AC Higgins Bethany Elora BE Tailor-Hamblin Vijay V Malka Samantha S Cheloni Riccardo R Collins Alexander Mark AM Bladen John J Henderson Robert R Moosajee Mariya M

International journal of molecular sciences 20230911 18

The CRB1 gene plays a role in retinal development and its maintenance. When disrupted, it gives a range of phenotypes such as early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa (RP), cone-rod dystrophy (CORD) and macular dystrophy (MD). Studies in CRB1 retinopathies have shown thickening and coarse lamination of retinal layers resembling an immature retina. Its role in foveal development has not yet been described; however, this retros ...[more]

PMID: 37762234

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Project description:BackgroundFoveal hypoplasia is characterized by the persistance of inner retinal layers at the macular center. We evaluated using spectral-domain optical coherence tomography (SD-OCT) morphological parameters of the macular center of eyes with foveal hypoplasia and describe the presence of hyporeflective zones in the Henle fiber layer (HFL) of eyes with high-grade foveal hypoplasia.MethodsEyes with foveal hypoplasia were classified into two groups: high-grade foveal hypoplasia with thick inner retinal layers at the macular center (thickness above 100 μm; 16 eyes of 9 subjects) and low-grade foveal hypoplasia with thinner inner retinal layers at the macular center (thickness below 100 μm; 25 eyes of 13 subjects). As comparison, SD-OCT images of normal control eyes (n = 75) were investigated.ResultsEyes with foveal hypoplasia displayed shorter central photoreceptor outer segments (POS), a thinner central myoid zone, and a thicker central HFL compared to control eyes. Eyes with high-grade foveal hypoplasia also displayed a thinner central outer nuclear layer (ONL) compared to eyes with low-grade foveal hypoplasia and control eyes. There was a negative correlation between the thicknesses of the central ONL and HFL in eyes with foveal hypoplasia; however, the total thickness of both ONL and HFL was similar in all eye populations investigated. Visual acuity of subjects with foveal hypoplasia was negatively correlated to the thickness of the central inner retinal layers and positively correlated to the length of central POS. In contrast to central POS, the length of paracentral POS (0.5 and 1.0 mm nasal from the macular center) was not different between the three eye populations investigated. The paracentral ONL was thickest in eyes with high-grade foveal hypoplasia and thinnest in control eyes. Hyporeflective zones in the HFL were observed on SD-OCT images of eyes with high-grade foveal hypoplasia, but not of eyes with low-grade foveal hypoplasia and control eyes. OCT angiography images recorded at the level of the HFL of eyes with high-grade foveal hypoplasia showed concentric rings of different reflectivity around the macular center; such rings were not observed on images of eyes with low-grade foveal hypoplasia and control eyes.ConclusionsIt is suggested that the hyporeflective zones in the HFL of eyes with high-grade foveal hypoplasia represent cystoid spaces which are surrounded by Henle fiber bundles. Cystoid spaces are likely formed because there are fewer Henle fibers and a thinner central ONL despite an unchanged thickness of both ONL and HFL. Cystoid spaces may cause the concentric rings of different reflectivity around the macular center in the HFL of eyes with high-grade foveal hypoplasia.

Project description:PurposeTo characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH).DesignMulticenter, observational study.ParticipantsA total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n = 523) or extracted from publicly available datasets from previously reported literature (n = 384).MethodsIndividuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans.Main outcome measuresGrade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS-), molecular diagnosis, and visual acuity (VA).ResultsThe most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS- (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P < 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH.ConclusionsWe characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms of FH. In typical FH, our data suggest that arrested retinal development occurs earlier in SLC38A8, OA, HPS, and AHR variants and later in FRMD7 variants. The defined time period of foveal developmental arrest for OCA and PAX6 variants seems to demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH and have significant prognostic and diagnostic value.

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Foveal Hypoplasia in CRB1-Related Retinopathies.

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Foveal Hypoplasia in <i>CRB1</i>-Related Retinopathies.

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Dataset Information

Foveal Hypoplasia in CRB1-Related Retinopathies.

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Foveal Hypoplasia in &lt;i&gt;CRB1&lt;/i&gt;-Related Retinopathies.

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OmicsDI is part of the ELIXIR infrastructure

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Foveal Hypoplasia in <i>CRB1</i>-Related Retinopathies.