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Recent advances and future prospects in choroideremia.

Zinkernagel MS, MacLaren RE - Clin Ophthalmol (2015)

Bottom Line: Choroideremia is a complex and rare disease that is frequently misdiagnosed due to its similar appearance to classic retinitis pigmentosa.Recent advances in genetic testing have identified specific genetic mutations in many retinal dystrophies, and the identification of the mutation of the CHM gene on the X chromosome 25 years ago has paved the way for gene replacement therapy with the first human trials now underway.This article reviews the epidemiological and pathological features of choroideremia and new prospects in imaging to monitor disease progression, as well as potential treatment approaches for choroideremia.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland ; Department of Clinical Research, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.

ABSTRACT
Choroideremia is a complex and rare disease that is frequently misdiagnosed due to its similar appearance to classic retinitis pigmentosa. Recent advances in genetic testing have identified specific genetic mutations in many retinal dystrophies, and the identification of the mutation of the CHM gene on the X chromosome 25 years ago has paved the way for gene replacement therapy with the first human trials now underway. This article reviews the epidemiological and pathological features of choroideremia and new prospects in imaging to monitor disease progression, as well as potential treatment approaches for choroideremia.

No MeSH data available.


Related in: MedlinePlus

Multimodal imaging of a patient with choroideremia.Notes: (A) Fundus AF showing an island of hyperfluorescent intact retina (delineated by white arrows). (B) IR image with corresponding OCT scan line (the green line represents the OCT scan direction) and (C) OCT images of the same patient. In OCT, the marked atrophy of the retinal pigment epithelium with homogenously increased reflectivity in OCT corresponds well with the borders seen in AF. There is a marked thinning of the outer nuclear layers and the choroidea is virtually absent, both hallmarks of choroideremia.Abbreviations: AF, autofluorescence; OCT, optical coherence tomography; IR, infrared.
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f2-opth-9-2195: Multimodal imaging of a patient with choroideremia.Notes: (A) Fundus AF showing an island of hyperfluorescent intact retina (delineated by white arrows). (B) IR image with corresponding OCT scan line (the green line represents the OCT scan direction) and (C) OCT images of the same patient. In OCT, the marked atrophy of the retinal pigment epithelium with homogenously increased reflectivity in OCT corresponds well with the borders seen in AF. There is a marked thinning of the outer nuclear layers and the choroidea is virtually absent, both hallmarks of choroideremia.Abbreviations: AF, autofluorescence; OCT, optical coherence tomography; IR, infrared.

Mentions: In the last decade, advances in retinal imaging have led to an improved understanding of morphological changes occurring during the disease course of choroideremia. Optical coherence tomography (OCT) can be used to diagnose macular changes associated with choroideremia such as choroidal neovascularization,14 cystoid macular edema,15 epiretinal membrane formation,16 outer retinal tubulations,17 macular hole formation,18 and macular hole complicated by retinal detachment.19 Fundus autofluorescence shows a characteristic speckled pattern of low- and high-density fundus autofluorescence (Figure 2).20 Increased lipofuscin accumulation originating from digestion of degenerating rods by RPE cells is thought to cause increased autofluorescence in choroideremia, whereas low density fluorescence reflects loss of the RPE layer whilst the choroid is still intact. This is corroborated by functional tests, showing an association of multifocal electroretinogram (mfERG) deterioration with major fundus autofluorescence changes.20,21 Despite high resolution OCT and genetic characterization of choroideremia, the sequence of morphological changes leading to vision loss remains unknown. There are several theories on which retinal layers are primarily affected by choroideremia. Whereas some reports show that the RPE is the first layer to degenerate, followed by loss of photoreceptors,22 others claim that the photoreceptor layer,23 in particular the rods,24 is primarily affected, followed by degeneration of the RPE and the choriocapillaris. The latter hypothesis is not however supported by the observations from patients with dominant RPE65 mutations who have a very similar choroidal atrophy appearance to CHM. Since the RPE65 gene is known to be expressed only in the RPE and being dominantly negative, we assume it causes RPE cell death; this phenotype provides an alternative pathway for the choroidal atrophy being RPE-driven in both diseases. Conversely, if CHM were a disease primarily of rod photoreceptor loss, then we might expect it to appear similar to the other forms of rod-cone dystrophy (retinitis pigmentosa).


Recent advances and future prospects in choroideremia.

Zinkernagel MS, MacLaren RE - Clin Ophthalmol (2015)

Multimodal imaging of a patient with choroideremia.Notes: (A) Fundus AF showing an island of hyperfluorescent intact retina (delineated by white arrows). (B) IR image with corresponding OCT scan line (the green line represents the OCT scan direction) and (C) OCT images of the same patient. In OCT, the marked atrophy of the retinal pigment epithelium with homogenously increased reflectivity in OCT corresponds well with the borders seen in AF. There is a marked thinning of the outer nuclear layers and the choroidea is virtually absent, both hallmarks of choroideremia.Abbreviations: AF, autofluorescence; OCT, optical coherence tomography; IR, infrared.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664510&req=5

f2-opth-9-2195: Multimodal imaging of a patient with choroideremia.Notes: (A) Fundus AF showing an island of hyperfluorescent intact retina (delineated by white arrows). (B) IR image with corresponding OCT scan line (the green line represents the OCT scan direction) and (C) OCT images of the same patient. In OCT, the marked atrophy of the retinal pigment epithelium with homogenously increased reflectivity in OCT corresponds well with the borders seen in AF. There is a marked thinning of the outer nuclear layers and the choroidea is virtually absent, both hallmarks of choroideremia.Abbreviations: AF, autofluorescence; OCT, optical coherence tomography; IR, infrared.
Mentions: In the last decade, advances in retinal imaging have led to an improved understanding of morphological changes occurring during the disease course of choroideremia. Optical coherence tomography (OCT) can be used to diagnose macular changes associated with choroideremia such as choroidal neovascularization,14 cystoid macular edema,15 epiretinal membrane formation,16 outer retinal tubulations,17 macular hole formation,18 and macular hole complicated by retinal detachment.19 Fundus autofluorescence shows a characteristic speckled pattern of low- and high-density fundus autofluorescence (Figure 2).20 Increased lipofuscin accumulation originating from digestion of degenerating rods by RPE cells is thought to cause increased autofluorescence in choroideremia, whereas low density fluorescence reflects loss of the RPE layer whilst the choroid is still intact. This is corroborated by functional tests, showing an association of multifocal electroretinogram (mfERG) deterioration with major fundus autofluorescence changes.20,21 Despite high resolution OCT and genetic characterization of choroideremia, the sequence of morphological changes leading to vision loss remains unknown. There are several theories on which retinal layers are primarily affected by choroideremia. Whereas some reports show that the RPE is the first layer to degenerate, followed by loss of photoreceptors,22 others claim that the photoreceptor layer,23 in particular the rods,24 is primarily affected, followed by degeneration of the RPE and the choriocapillaris. The latter hypothesis is not however supported by the observations from patients with dominant RPE65 mutations who have a very similar choroidal atrophy appearance to CHM. Since the RPE65 gene is known to be expressed only in the RPE and being dominantly negative, we assume it causes RPE cell death; this phenotype provides an alternative pathway for the choroidal atrophy being RPE-driven in both diseases. Conversely, if CHM were a disease primarily of rod photoreceptor loss, then we might expect it to appear similar to the other forms of rod-cone dystrophy (retinitis pigmentosa).

Bottom Line: Choroideremia is a complex and rare disease that is frequently misdiagnosed due to its similar appearance to classic retinitis pigmentosa.Recent advances in genetic testing have identified specific genetic mutations in many retinal dystrophies, and the identification of the mutation of the CHM gene on the X chromosome 25 years ago has paved the way for gene replacement therapy with the first human trials now underway.This article reviews the epidemiological and pathological features of choroideremia and new prospects in imaging to monitor disease progression, as well as potential treatment approaches for choroideremia.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland ; Department of Clinical Research, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.

ABSTRACT
Choroideremia is a complex and rare disease that is frequently misdiagnosed due to its similar appearance to classic retinitis pigmentosa. Recent advances in genetic testing have identified specific genetic mutations in many retinal dystrophies, and the identification of the mutation of the CHM gene on the X chromosome 25 years ago has paved the way for gene replacement therapy with the first human trials now underway. This article reviews the epidemiological and pathological features of choroideremia and new prospects in imaging to monitor disease progression, as well as potential treatment approaches for choroideremia.

No MeSH data available.


Related in: MedlinePlus