Choroideremia

Rubin, Melvin L.; Fishman, Ronald S.; McKAY, Richard A.

doi:10.1001/archopht.1966.03850010565015

Cited by 23 publications

(5 citation statements)

References 7 publications

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“…Although the primary site of disease in CHM remains debatable with later trends pointing toward the RPE, our findings are consistent with a rod POS abnormality resulting in rod dysfunction as the earliest detectable abnormality within the central retina in CHM, consistent with previous observations and with reports of impaired night vision, early rod dysfunction and histological evidence of rod disease in CHM. 7,8,51,70,75,76 Although our findings point strongly at rod photoreceptors as the primary site of insult as a result of the loss of REP1 function the possibility still exists that rods may be particularly vulnerable to a primary RPE abnormality that takes place before obvious RPE disease becomes clinically detectable as demelanization. Evidence for early (and late) cone photoreceptor disease has accumulated for over four decades and was corroborated in this cohort.…”

Section: Discussionmentioning

confidence: 66%

“…Evidence for early (and late) cone photoreceptor disease has accumulated for over four decades and was corroborated in this cohort. 7,8,10,50,51,66,70, Measurable ONL in blind regions of severe RPE demelanization and choroidal thinning suggests survival of photoreceptors, likely cones, in severe RPE and choroidal disease. This indeed departs from the sequence of primary rod photoreceptor disease where RPE demelanization and choroidal abnormalities tend to occur following total photoreceptor loss.…”

Section: Discussionmentioning

confidence: 99%

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Natural History of the Central Structural Abnormalities in Choroideremia

et al. 2017

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Purpose To describe in detail the central retinal structure of a large group of patients with Choroideremia (CHM). Design prospective, cross-sectional, descriptive study. Subjects Patients (n=97, age 6-71 years) with CHM and subjects with normal vision (n=44; ages 10-50 years) were included. Methods Subjects were examined with spectral domain optical coherence tomography (SD-OCT) and near infrared reflectance imaging. Visual acuity (VA) was measured during their encounter or obtained from recent ophthalmic examinations. Visual thresholds were measured in a subset of patients (n=24) with automated static perimetry within the central regions (±15°) examined with SD-OCT. Main outcome measures VA and visual thresholds, total, inner and outer nuclear layer (ONL) thicknesses, and the horizontal extent of the ONL and of the photoreceptor outer segment (POS) interdigitation zone. Results Earliest abnormalities in regions with normally appearing RPE were the loss of the POS and EZ zone associated with rod dysfunction. Transition zones (TZs) from relatively preserved retina to severe ONL thinning and inner retinal thickening moved centripetally with age. Most patients (88%) retained VAs better than 20/40 until their fifth decade of life. VA decline coincided with migration of the TZ near the foveal center. There were outer retinal tubulations in degenerated, non-atrophic retina in the majority (69%) of patients. In general, retinal pigment epithelium (RPE) abnormalities paralleled photoreceptor degeneration, although there were regions with detectable but abnormally thin ONL co-localizing with severe RPE depigmentation and choroidal thinning. Conclusions Abnormalities of the POS and rod dysfunction are the earliest central abnormalities observed in CHM. Foveal function is relatively preserved until late disease. TZ migration to the foveal center with foveal thinning and structural disorganization heralded central VA loss. The relationships established may help outline the eligibility criteria and outcome measures for clinical trials for CHM.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Natural History of the Central Structural Abnormalities in Choroideremia

et al. 2017

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“…Significant visual impairment in female carriers of choroideremia is uncommon, and typically attributed to skewed X-inactivation leading to a high percentage of cells expressing the mutant X chromosome 1 , although subretinal neovascularization or fibrosis has been reported in at least 2 cases 2,3 . Full-field ERG recordings in carrier females are typically normal or very mildly reduced 4,5 ; multifocal ERGs may be more sensitive given the patchy nature of cellular loss in the carrier state 6 .…”

Section: Introductionmentioning

confidence: 99%

Choroideremia: Analysis of the Retina from a Female Symptomatic Carrier

Bonilha

Trzupek

et al. 2008

Ophthalmic Genetics

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Purpose To define the retinal pathology in a 91 year-old affected matriarch of a three-generation choroideremia family with multiple manifesting carriers. Methods Tissue from three different retinal areas was processed for immunohistochemistry. The macular area was processed for transmission electron microscopy. Cryosections were studied by indirect immunofluorescence, using well-characterized antibodies to cone cytoplasm, rhodopsin and cone opsins. The affected donor eyes were compared to a postmortem matched normal eye. Results The retina displayed areas of severe degeneration, with no photoreceptor outer segments, photoreceptor nuclear atrophy, and atrophy of the inner retina. Other retinal areas were near to normal. The RPE was severely degenerated, with thinning, pigment clumping and sub-epithelial debris deposition in all the areas examined. The choroid displayed depigmentation. Labeling with cone opsin antibodies revealed that cones were drastically affected: blue opsin was almost completely absent, while red/green opsins were distributed along the entire plasma membrane of the cell. Rhodopsin was also distributed along the entire rod plasma membrane. Ultrastructural analysis of the affected macula revealed the absence of RPE apical microvilli and basal infoldings. Instead, RPE’s basal surface and choroid displayed the presence of banded fibers composed of clumps of wide-spacing collagen. Bruch’s membrane was filled with vesicular structures, some smooth and others with bristle-like projections. Conclusions The histological data suggests that the clinical manifestation in this donor is related to degenerative changes in the retina, RPE and choroid.

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“…Choroideremia is a rare X-linked disorder causing progressive degeneration of the retina, retinal pigment epithelium (RPE), and choroid [123]. Affected male patients develop night blindness with progressive peripheral vision loss and central vision loss, usually observed later in their lives [4].…”

Section: Introductionmentioning

confidence: 99%

Identification of Pathogenic Variants in the CHM Gene in Two Korean Patients With Choroideremia

et al. 2017

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Choroideremia is a rare X-linked disorder causing progressive chorioretinal atrophy. Affected patients develop night blindness with progressive peripheral vision loss and eventual blindness. Herein, we report two Korean families with choroideremia. Multimodal imaging studies showed that the probands had progressive loss of visual field with characteristic chorioretinal atrophy, while electroretinography demonstrated nearly extinguished cone and rod responses compatible with choroideremia. Sanger sequencing of all coding exons and flanking intronic regions of the CHM gene revealed a novel small deletion at a splice site (c.184_189+3delTACCAGGTA) in one patient and a deletion of the entire exon 9 in the other. This is the first report on a molecular genetic diagnosis of choroideremia in Korean individuals. Molecular diagnosis of choroideremia should be widely adopted for proper diagnosis and the development of new treatment modalities including gene therapy.

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Choroideremia

Cited by 23 publications

References 7 publications

Natural History of the Central Structural Abnormalities in Choroideremia

Natural History of the Central Structural Abnormalities in Choroideremia

Choroideremia: Analysis of the Retina from a Female Symptomatic Carrier

Identification of Pathogenic Variants in the CHM Gene in Two Korean Patients With Choroideremia

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