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Clinical Findings and Management of Choroideremia
Matt Goodman, OD
[email protected]
Abstract
A 12-year-old male presents with bilateral vision loss. The exam reveals bilateral acuity
reduction, fundus changes, and constricted visual fields. Genetic testing reveals a deletion
on the CHM gene consistent with the diagnosis of choroideremia.
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I. Case History
A 12-year-old Caucasian male was referred to the Bascom Palmer Eye Institute neuroophthalmology service with decreased vision. The mother stated that he frequently bumps
into objects, especially at night. The patient and mother denied any redness, photophobia,
or discharge. The patient reported only wears spectacles while at school. Personal ocular
history was unremarkable. Personal medical history was significant for a hospitalization
at the age of 18 months for Kawasaki disease. Family history was remarkable for
“retinitis pigmentosa” that inflicted the patient’s maternal grandfather, who had since
passed on. He was living with both parents and doing well in school. The patient was not
taking any medications, and there were no known drug allergies. Review of systems was
unremarkable.
II. Pertinent Findings
Best corrected visual acuity was 20/40 OD and 20/50 OS with a moderate myopic
refraction. Pupils were unremarkable and intraocular pressures were within normal limits
OU. Motilities were full, and the patient showed a small flick esotropia at both distance
and near. Notably, the patient was unable to count fingers during confrontation visual
fields testing, but his fields were full to hand motion. Slit lamp examination was
unremarkable for anterior segment findings.
Fundus examination with a 90D lens revealed a very blonde appearance to the fundus and
prominent choroidal vasculature OU. There appeared to be an island of normally
pigmented retina centrally OU. The appearance of the ONH and the retinal vasculature
was unremarkable OU. Peripheral retinal examination with the BIO showed mild pigment
clumping 360 degrees OU. There were no tears, holes, or breaks anywhere in the retina
OU. Fundus examination of the mother was unremarkable. Fundus photos of the posterior
pole of the patient are pictured below.
Of note, skin and hair pigmentation appeared normal. No obvious limb or neurologic
abnormalities were present. Facies appeared normal with no findings to suggest a
systemic syndrome was present.
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Stratus macular OCT, while of low image quality, showed mild sub-retinal fluid present
OU. Goldmann visual field testing showed a normal response to a Size-V stimulus, but a
severely concentrically constricted field to all other size targets OU. A full-field ERG
showed a rod-cone dysfunction with the rod ERG being completely undetectable.
Macular OCT and Goldmann visual fields are pictured below.
III. Differential Diagnosis
Leading diagnoses included X-linked retinitis pigmentosa and choroideremia. Others
included on the differential diagnosis list were gyrate atrophy, diffuse choroidal atrophy,
albinism, post-inflammatory retinal atrophy, and high myopia.
The clinical picture of this patient did not fit the typical presentation of X-linked retinitis
pigmentosa. First, there is almost always a marked attenuation of the retinal vasculature
and a very significant amount of pigment migration3. Second, carriers of the mutated RP
gene often show bone spicules in their peripheral retina, even when no symptoms are
present3. All of these findings were absent in this particular patient.
IV. Diagnosis and Discussion
The presumed clinical diagnosis was choroideremia. This was confirmed with genetic
testing that showed hemizygous deletion of exons 9-11 on the CHM gene. Mutation
specific carrier testing was recommended to all first degree female relatives.
The prevalence of choroideremia is estimated to be 1 in every 50,000 to 75,000 people1.
It is thought that roughly 6% of patients initially diagnosed with retinitis pigmentosa
actually have choroideremia3. It shows an X-linked recessive inheritance pattern and is
characterized by progressive chorioretinal degeneration4. Initial symptoms often include
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progressive reduction of central acuity, nyctalopia, and constriction of the visual field1.
The chorioretinal degeneration begins in the mid-peripheral fundus and spreads towards
the posterior pole and the ora serrata4. The typical blonde appearance to the fundus is a
result of the atrophy of the RPE and choriocapillaris6. However, the deep choroidal
vasculature is usually preserved and very prominent on fundus examination6. The central
macular pigment is typically preserved until very late in the disease process4. Acuity
reduction early in the disease often occurs secondary to the development of cystoid
macular edema7. The development of cystoid macular edema was previously thought to
be rare, but a recent study found 10 of 16 choroideremia patients to have cystic edema
present on OCT examination7. For this reason, macular OCT is a useful tool to help in
identifying the cause of reduced acuity in this patient population8.
The CHM gene is the only gene isolated thus far for choroideremia2. The gene encodes
for the REP-1 protein, which is involved in intracellular protein trafficking2. A mutation
in the gene leads to disabled protein movement and apoptosis3. The REP-2 protein
provides redundancy in other bodily tissues, but is absent from the retinal cells2. Large
deletions can lead to a host of associated findings systemically, including sensorineural
hearing loss, cognitive deficits, absence of the corpus callosum, and cleft palate1.
Diagnosis of choroideremia is primarily a clinical one. Common clinical findings include
poor dark adaptation, the characteristic fundus appearance described above, a ring
scotoma or generally constricted visual field, and reduced or absent rod-cone response on
full-field ERG1. Genetic testing is now commonly done to confirm the diagnosis3. It is
also possible to assess for reduced levels of the REP-1 protein in peripheral lymphocytes,
but this is not commonly done3.
Interestingly, female carries may show similar chorioretinal degeneration on fundus
exam, but are completely asymptomatic5. The chorioretinal degeneration found in carriers
is not visible until much later in life, typically the 3rd-4th decade5. If tested with ERG,
carriers may show occasional abnormalities, but ERG is not a reliable indicator for
identifying carries of the mutated CHM gene5.
V. Treatment
There is no cure for choroideremia9. Management typically includes genetic counseling
and genetic testing for all female relatives, including prenatal genetic testing9. Low vision
support is often utilized, especially late in the disease process9. Progression of the disease
is generally monitored with Goldmann visual fields and clinical examination9.
Several interventions to help slow the progression of the disease have been proposed,
with limited efficacy. They include UV protection, lutein supplementation, increasing
leafy vegetable intake, and supplementation of Omega-3 fatty acids through diet9. A
current therapeutic study that shows promise is the ciliary neutrophic factor (CNTF)
capsular implant. The implant is filled with cells genetically modified to produce CNTF
and is clipped to a suture on the ciliary body. The release of the CNTF into the vitreous
has shown promise for rescuing dying retinal cells and has potential to improve vision in
choroideremia patients9.
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Several recent studies have shown that topical carbonic anhydrase inhibitors, such as
dorzolamide, are more effective at decreasing cystoid macular edema in choroideremia
patients compared to standard topical anti-inflammatory drops7.
Long-term prognosis for choroideremia patients is poor7. A recent study looked at 115
males choroideremia confirmed via genetic testing and found a trend of slow central
acuity loss until the 5th-7th decade of life1. In general, patients under 60 years of age
maintained fairly good acuity, with 84% having acuity of 20/40 or better1. However,
patients over the age of 60 did not fare as well, with 35% having acuity of 20/200 or
worse1.
VI. Conclusion
Choroideremia is an X-linked recessive disorder characterized by chorioretinal
degeneration that begins in mid-peripheral fundus early in life1. Genetic testing is
confirmatory, but clinical suspicion is required. Various mutations in only the CHM gene
have been identified in choroideremia2. Currently, there is no cure for choroideremia, and
long-term visual prognosis remains poor9.
Bibliography
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Katz BJ et al. Fundus appearance of choroideremia using optical coherence tomography.
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