Choroideremia (CHM) is a progressive, X-linked condition that results in slow degeneration of the retinal pigment epithelium (RPE), choroid, and photoreceptors.

Pediatric Considerations

Although many patients with choroideremia may not present with symptoms until their early teens, others develop nyctalopia in the first decade.



Estimated to be around 1:50,000


• Male gender with family history of choroideremia

– Although extremely rare, female carriers can manifest signs and symptoms of CHM, but it is usually mild.


X-linked recessive


• The CHM gene, located on the X chromosome (Xq21.2), codes for a component of rab geranylgeranyltransferase (GGTase), otherwise known as Rab escort protein (REP), an important component of RPE cell function.

• Strunnikova et al. studied monocytes and primary skin fibroblasts from CHM individuals. Monocytes showed impaired phagocytosis and intracellular vesicle transport, decreased lysosomal acidification, and hampered rates of proteolytic degradation compared to controls. Fibroblasts showed decreased secretion of several cytokines/growth factors (1).

• The RPE serves multiple functions including phagocytosis/degradation of shed outer photoreceptor segments, as well as processing/transport of Vitamin A and other nutrients. Altered lysosomal function and cell trafficking may contribute to the RPE degeneration seen in CHM patients.


Multiple types of mutations including full deletions, partial deletions, nonsense mutations, and splice site mutations have been reported (over 100 different mutations have been described overall (2)). All mutations are thought to lead to complete loss of REP-1.



• Affected males usually present with trouble with night vision (nyctalopia). Some males may not develop any symptoms until their teen years, whereas others develop nyctalopia during the first decade.

• Nyctalopia is followed by gradual loss of peripheral vision.


• The visual field loss starts as annular scotomas which progresses to concentric field loss.

– By 40 years of age, affected males will typically have a severely impaired peripheral visual field at or near the level of legal blindness.

• Central visual acuity is usually good until age 60 years or greater (3).

• Funduscopic findings include pigmentary stippling and areas of RPE and choroidal atrophy in the equatorial fundus that eventually progress to involve the peripheral retina and posterior pole.

• In advanced stages, the RPE and choroid loss is so severe that the only apparent retinal vasculature being apparent is in the far periphery, the macula, and around the optic disc. The underlying sclera is visible through the areas of atrophy.



• CHM is a clinical diagnosis. However, genetic testing is valuable.

– Duplication/deletion analysis, sequence analysis, and targeted mutation analysis are available.

– If the above mentioned tests fail to identify a mutation, reverse transcriptase PCR, northern blot analysis, protein truncation testing, and immunoblot analysis are available (primarily as research tools only).

Immunoblot analysis is used to detect anti-REP-1 antibody. Because all CHM gene mutations are thought to result in absence of REP-1, most cases can be diagnosed by this method 2.


Initial approach

• To establish extent of disease and to obtain a baseline for monitoring, obtain the following:

– Dilated ophthalmologic examination

– Goldmann visual field testing

– Electroretinography (ERG)

In the early stages, patients may have a nonspecific rod-cone degenerative pattern which eventually becomes non-recordable. Carriers typically have normal ERG studies.

Follow-up & special considerations

Annual exams, along with ERG and visual field testing, may be helpful to follow disease progression.

Diagnostic Procedures/Other

Fluorescein angiography may show large areas of capillary non-perfusion/loss.

Pathological Findings

• Earlier reports suggested choroidal atrophy was the primary event that led to secondary loss of RPE and photoreceptors (4)

• More recent reports suggest independent degeneration of the retina, RPE, and choriocapillaris (5)

• Focal choroidal T-lymphocyte infiltration and retinal gliosis occur, suggesting inflammation may play a role (5)


• CHM may be difficult to distinguished from:

– Retinitis Pigmentosa

– Diffuse Choriocapillaris Atrophy

– Gyrate Atrophy of the retina and choroid

– Usher Syndrome Type I

– Kearns-Sayre Syndrome



General Measures

In the future, gene therapy may be effective in delaying progression of CHM. Using a recombinant adenovirus, Anand et al. were able to successfully deliver human cDNA coding for REP-1 to CHM-affected lymphocytes and fibroblasts. It is still uncertain whether or not delivery of REP-1 to retinal cells in CHM patients would stop or slow the progression of CHM, but this was an important first step in gene therapy development for CHM (bib6).

Issues for Referral

• As patient symptoms progress and peripheral and central vision worsen, patients may benefit from referral to a specialist in low vision services to help them learn to optimize residual vision.

• As vision declines, patients may have to cope with multiple social difficulties which may include job loss, loss of independence, and depression. Patients may benefit from referral to appropriate professionals to enable them to better cope with these issues.

Additional Therapies

Precautions from UV exposure may be beneficial, thus affected individuals should wear UV-blocking sunglasses when outdoors (7).


Nearly one-third of affected males are found to have posterior subcapsular cataracts that can be removed as needed.



• Patients should be examined periodically, and be monitored for progression with ERG and peripheral visual field analysis.

• Refer for low vision services as indicated.


• Lutein supplementation (20 mg daily) may be helpful, but this data is weak (8).

• Omega-3 fatty acids, fresh fruit, dark green leafy vegetables, and antioxidant supplements may be beneficial (7).


• Patients and their families should undergo genetic counseling to educate them regarding the X-linked recessive nature of transmission of CHM:

– A mother of more than 1 affected male is an obligate carrier (A proband with no family history of CHM may have a de novo mutation, and it is appropriate to examine the retina of the mother to look for signs of carrier status.)

– A carrier mother has a 50% chance of passing on the CHM gene mutation to each offspring; each male child has a 50% chance of having CHM and each female child has a 50% chance of being a CHM carrier.

– The father of an affected male does not have CHM nor would be a CHM carrier.

– All daughters of an affected male will receive the abnormal gene and will be CHM carriers, however, it is impossible for an affected male to pass the disease on to his sons.

– Prenatal testing for at-risk pregnancies is possible using cells obtained from amniocentesis or chorionic villous sampling, however, the disease-causing allele of an affected family member must be identified prior to prenatal testing.


• Most affected males will have severely reduced peripheral vision by age 40 years.

• Visual acuity in affected males is typically preserved until later in life, but is also eventually lost, resulting in blindness.

• Most carrier females are asymptomatic, but a small percentage will demonstrate symptoms and exam findings of CHM (typically much more mild than affected males).


Blindness as disease progresses


1. Strunnikova NV, Barb J, Sergeev YV, et al. Loss-of-function mutations in Rab escort protein 1 (REP-1) affect intracellular transport in fibroblasts and monocyctes in choroideremia patients. PLoS ONE 2009;4(12):e8402.

2. MacDonald IM, Mah DY, Ho YK, et al. A practical diagnostic test for choroideremia. Ophthalmology 1998;105(9):1637–40.

3. Roberts MF, Fishman GA, Roberts DK, et al. Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia. Br J Ophthalmol 2002;86(6):658–62.

4. McCulloch JC. The pathologic findings in two cases of choroideremia. Trans Am Acad Ophthalmol Otolaryngol 1950;56:565–72.

5. MacDonald IM, Russel L, Chan CC. Choroideremia: New findings from ocular pathology and review of recent literature. Surv Ophthalmol 2009;54(3):401–07.

6. Anand V, Barral DC, Zeng Y, et al. Gene therapy for choroideremia: In vitro rescue mediated by recombinant adenovirus. Vision Research 2000;43:919–26.

7. MacDonald IM, Meltzer MR, Smaoui N, et al. Choroideremia. In: Pagon RA, Bird TC, Dolan CR, Stephens K (eds). GeneReviews, Univ. Of Washington: Seattle, 1993–2003, May 2008 update.

8. Duncan JL, Aleman TS, Gardner LM, et al. Macular pigment and lutein supplementation in choroideremia. Exp. Eye Res 2002;74:371–81.

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Nov 9, 2016 | Posted by in OPHTHALMOLOGY | Comments Off on Choroideremia

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