choroidal sclerosis

Choroidal Dystrophy, Central Areolar 1

Clinical Characteristics
Ocular Features: 

The primary feature of this form of macular dystrophy is atrophy of the RPE and choriocapillaris centralized to the macula.  In early stages among young patients in the second decade of life, some pigment changes are seen in the parafoveal area.  Later, the central macula develops hypopigmentation followed by atrophy of the choriocapillaris.  The area is usually sharply defined but fluorescein angiography often shows multiple window defects beyond the edges.  The same region often has speckled autofluorescence.  Secondary dysfunction of the photoreceptors in this area leads to some mild degree of vision loss in adults between the ages of 30 and 60 years but this progressive disease may eventually result in legal blindness.  The ERG demonstrates a cone dystrophy. The rate of disease progression is highly variable.  Visual acuity varies considerably as does the appearance of the macula.  Older individuals may be misdiagnosed as having age-related macular degeneration. 

Systemic Features: 

There is no associated systemic disease. 

Genetics

CACD1 is caused by a hterozygous mutations in GUCY2D gene localized to 17p13.  One large three generation Irish family has been reported.

For a somewhat similar disorder see choroidal dystrophy, central areolar 2 (613105).

CACD is a genetically heterogeneous disorder with mutations in several genes responsible.  The majority of patients have one of several mutations in the PRPH2 gene (6p21.1-cen) and the inheritance pattern seems to be autosomal recessive (CACD2).  However, other family trees in which mutations in PRPH2 were excluded suggest autosomal dominant inheritance (CACD3; 613144) suggesting genetic heterogeneity such as the CACD1 condition described here.   

 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no treatment of the macular disease.  However, some patients can benefit from low vision aids. 

References
Article Title: 

Central areolar choroidal dystrophy

Boon CJ, Klevering BJ, Cremers FP, Zonneveld-Vrieling MN, Theelen T, Den Hollander AI, Hoyng CB. Central areolar choroidal dystrophy. Ophthalmology. 2009 Apr;116(4):771-82, 782.e1.

PubMed ID: 
19243827

Choroideremia

Clinical Characteristics
Ocular Features: 

Choroideremia is characterized by a progressive atrophy of photoreceptors, retinal pigment epithelium (RPE) and choroid. Areas of RPE atrophy are present early in the mid-periphery and progress centrally.  This is associated with loss of photoreceptors and the choriocapillaris.

Night blindness is the first symptom often with onset during childhood. A ring-like perimacular scotoma develops that progresses into the periphery during life with corresponding visual field loss (peripheral constriction).  Symptoms and fundus changes are highly variable. Visual acuity is generally well maintained into later stages of the disease but some males are blind by age 30 years whereas others over the age of 50 are symptom-free.  An increased prevalence of myopia has been noted.

Males with choroideremia (and some females) have progressive loss of the choriocapillaris eventually baring the sclera beneath. Female carriers can exhibit patchy areas of RPE atrophy in the periphery and these may enlarge. Female carriers are typically not symptomatic, but there are reports of females being fully affected.  Females may also have visual field changes and defective dark adaptation.  OCT in young women shows dynamic changes and remodeling of the outer retina with time with focal retinal thickening, drusenlike deposits and disruptions in photoreceptor inner and outer segment junctions even in younger individuals.  The phenotype is more severe in older females as well suggesting that the retinal degeneration is progressive in both sexes.

Electroretinography (ERG) initially shows a decreased dark-adapted response with  intact light-adapted responses, indicating general dysfunction of rod photoreceptors. Cone dysfunction, however, develops with progression of the disease.

Systemic Features: 

No general systemic manifestations are associated with choroideremia. This may be explained by systemic expression of REP2, Rab escort protein-2, compensating for the decreased level of REP1.

There are occasional reports of associated deafness and obesity in some families with choroideremia (303110) but it is uncertain if this represents a unique disorder.

Genetics

Choroideremia is an X-linked recessive disorder affecting males and occasional female carriers.  The disorder is caused by mutations in the CHM gene on the X chromosome (Xq21.2) which leads to absence or truncation of the protein Rab escort protein-1 (REP1) that is part of Rab geranylgeranyltransferase, an enzyme complex involved in intracellular vesicular transport. A few patients with chromosomal translocations involving the relevant region of the X chromosome have been reported.

A homozygous mutation in the CYP4V2 gene has been reported to be responsible for a choroideremia-like clinical phenotype.

Pedigree: 
X-linked recessive, carrier mother
X-linked recessive, father affected
Treatment
Treatment Options: 

Visual function can be improved with low vision aids.  Recent early trials using adeno-associated viral vectors containing DNA coding for normal REP1 protein have documented improved rod and cone function with better visual acuity in affected males.

References
Article Title: 

CHANGES IN RETINAL SENSITIVITY AFTER GENE THERAPY IN CHOROIDEREMIA


Fischer MD, Ochakovski GA, Beier B, Seitz IP, Vaheb Y, Kortuem C, Reichel FFL, Kuehlewein L, Kahle NA, Peters T, Girach A, Zrenner E, Ueffing M, MacLaren RE, Bartz-Schmidt K, Wilhelm B. CHANGES IN RETINAL SENSITIVITY AFTER GENE THERAPY IN CHOROIDEREMIA. Retina. 2018 Oct 9. doi: 10.1097/IAE.0000000000002360. [Epub ahead of print].
 

PubMed ID: 
30308560

Clinical and Genetic Features of Choroideremia in Childhood

Khan KN, Islam F, Moore AT, Michaelides M. Clinical and Genetic Features of Choroideremia in Childhood. Ophthalmology. 2016 Aug 6. pii: S0161-6420(16)30583-8. doi: 10.1016/j.ophtha.2016.06.051. [Epub ahead of print] PubMed.

PubMed ID: 
27506488

Optical

Jain N, Jia Y, Gao SS, Zhang X, Weleber RG, Huang D, Pennesi ME. Optical
Coherence Tomography Angiography in Choroideremia: Correlating Choriocapillaris
Loss With Overlying Degeneration
. JAMA Ophthalmol. 2016 May 5. doi:
10.1001/jamaophthalmol.2016.0874. [Epub ahead of print].

PubMed ID: 
27149258
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