Scleral Pits in Choroideremia

Alqahtani, Abdullah Ali; Ba‐Ali, Shakoor; Alabduljalil, Talal; Coyner, Aaron S.; Patel, Rajan S.; Weleber, Richard G.; Girach, Aniz; Christensen, Søren Kirchhoff; Larsen, Michael; Pennesi, Mark E.; Yang, Paul

doi:10.1097/iae.0000000000001957

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…They are thought to represent remodeling of the photoreceptors that have lost their outer segments after degeneration of the underlying RPE. Occasionally, the degeneration in choroideremia could be associated with foveal schisis or scleral pits resulting from severe retinal thinning [31] and may even be complicated by choroidal neovascularization [32]. These retinal changes need to be taken into account when selecting patients for gene therapy, because structural fragility of the retina could make subretinal injection of vector surgically challenging.…”

Section: Introductionmentioning

confidence: 99%

Ocular gene therapy for choroideremia: clinical trials and future perspectives

MacLaren

2018

Expert Review of Ophthalmology

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Introduction Gene therapy offers the potential for targeted replacement of single gene defects in inherited retinal degenerations. Areas covered Choroideremia is an X-linked blinding retinal disease resulting from deficiency of the CHM gene product, REP1. The disease represents an ideal target for retinal gene therapy, as it is readily diagnosed in the clinic, relatively homogenous in phenotype and slow progressing, thereby providing a wide therapeutic window for intervention. Ongoing clinical trials of retinal gene therapy for choroideremia using an adeno-associated viral vector have demonstrated safety and early efficacy. We review the clinical characteristics of the disease with a view to interpreting the findings of gene therapy clinical trials and discuss future directions. Expert commentary Choroideremia gene therapy has so far demonstrated good safety profile and early functional visual acuity gains in a proportion of trial participants, which appear to be sustained.

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Section: Introductionmentioning

confidence: 99%

Ocular gene therapy for choroideremia: clinical trials and future perspectives

MacLaren

2018

Expert Review of Ophthalmology

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“…Numerous ophthalmic imaging studies have studied morphological and functional alterations in CHM. [11][12][13][14][15][16][17][18][19] However, no study has thoroughly investigated quantitative alterations occurring in retinal layers.…”

Section: Introductionmentioning

confidence: 99%

Reduced vessel density in deep capillary plexus correlates with retinal layer thickness in choroideremia

et al. 2020

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BackgroundTo assess retinal layer thickness in choroideremia (CHM) and to reveal its correlation with optical coherence tomography (OCT) angiography (OCTA) findings.MethodsThe study was designed as an observational, cross-sectional clinical series of patients with CHM, which included 14 CHM eyes and 14 age-matched controls. Multimodal imaging included OCT and OCTA. The vessel density (VD) of superficial capillary (SCP), deep capillary (DCP) and choriocapillaris (CC) plexuses was analysed by OCTA. The apparently preserved retinal islet and atrophic regions were investigated separately. Main outcome measures were as follows: best-corrected visual acuity (BCVA), total retinal layers, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), ellipsoid zone–retinal pigment epithelium (EZ-RPE) layer, choroidal thickness and VDs of SCP, DCP and of CC.ResultsMean BCVA was 0.0±0.0 LogMAR in both groups. GCL, ONL, EZ-RPE and choroid were significantly thinned in CHM, particularly in the atrophic region. OPL was unaffected in the apparently preserved islet, whereas INL and IPL were similarly thinned in the atrophic and apparently preserved retina. DCP appeared severely affected in both regions, while CC was only altered in the atrophic retina. Significant correlations were found between OCT and OCTA parameters.ConclusionsOur study showed severe alterations in both outer and inner retinal layers of patients with CHM. The extended retinal involvement might be the consequence of neuronal and vascular trophic factor reduction produced by the primarily altered RPE and/or secondary Müller glial cell reaction.

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CHM mutation spectrum and disease: An update at the time of human therapeutic trials

et al. 2021

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Choroideremia is an X‐linked inherited retinal disorder (IRD) characterized by the degeneration of retinal pigment epithelium, photoreceptors, choriocapillaris and choroid affecting males with variable phenotypes in female carriers. Unlike other IRD, characterized by a large clinical and genetic heterogeneity, choroideremia shows a specific phenotype with causative mutations in only one gene, CHM. Ongoing gene replacement trials raise further interests in this disorder. We describe here the clinical and genetic data from a French cohort of 45 families, 25 of which carry novel variants, in the context of 822 previously reported choroideremia families. Most of the variants represent loss‐of‐function mutations with eleven families having large (i.e. ≥6 kb) genomic deletions, 18 small insertions, deletions or insertion deletions, six showing nonsense variants, eight splice site variants and two missense variants likely to affect splicing. Similarly, 822 previously published families carry mostly loss‐of‐function variants. Recurrent variants are observed worldwide, some of which linked to a common ancestor, others arisen independently in specific CHM regions prone to mutations. Since all exons of CHM may harbor variants, Sanger sequencing combined with quantitative polymerase chain reaction or multiplex ligation‐dependent probe amplification experiments are efficient to achieve the molecular diagnosis in patients with typical choroideremia features.

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Scleral Pits in Choroideremia

Abstract: Scleral pits are, to the best of our knowledge, a novel optical coherence tomography finding in advanced choroideremia that likely represents the abnormal juxtaposition of penetrating short posterior ciliary arteries with the retina.

Cited by 4 publications

References 26 publications

Ocular gene therapy for choroideremia: clinical trials and future perspectives

Ocular gene therapy for choroideremia: clinical trials and future perspectives

Reduced vessel density in deep capillary plexus correlates with retinal layer thickness in choroideremia

CHM mutation spectrum and disease: An update at the time of human therapeutic trials

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