Widespread primary retinal or RPE disease that causes advanced atrophy of the choriocapillaris occurs in choroideremia, gyrate atrophy, Bietti crystalline dystrophy, and phenothiazine-related retinal toxicity (see also Chapter 15). In fundus autofluorescence imaging, hypoautofluorescence in the areas of atrophy is typically observed in all of these conditions and is therefore helpful for monitoring the disease progression.
Patients with choroideremia have night blindness and show progressive peripheral visual field loss over 3–5 decades. Most patients maintain good visual acuity until a central island of foveal vision is lost. The degeneration initially manifests as mottled areas of pigmentation in the anterior equatorial region and macula. The anterior areas gradually degenerate to confluent scalloped areas of RPE and choriocapillaris loss; larger choroidal vessels are preserved (Fig 13-9). Furthermore, the retinal vessels appear normal, and there is no optic atrophy.
Figure 13-9 Fundus photograph of a patient with choroideremia.
(From Fishman GA, Birch DG, Holder GE, Brigell MG. Electrophysiologic Testing in Disorders of the Retina, Optic Nerve, and Visual Pathways. 2nd ed. Ophthalmology Monograph 2. San Francisco: American Academy of Ophthalmology; 2001:67.)
On fluorescein angiography imaging, the changes are pronounced: the scalloped areas of missing choriocapillaris appear hypofluorescent next to brightly hyperfluorescent areas of perfused choriocapillaris with intact overlying RPE. Fundus autofluorescence imaging shows a characteristic speckled pattern of autofluorescence in the nonatrophic areas. The ERG response is abnormal early in the course of the disease and is generally extinguished by midlife. Because phenotypes can overlap with other conditions, especially other choroidal dystrophies, the clinical and imaging features should not be considered pathognomonic.
Choroideremia is X-linked and caused by mutations in CHM, which is constitutively expressed and encodes geranylgeranyl transferase Rab escort protein. Carriers of choroideremia are usually asymptomatic and have normal ERGs. However, they often show patches of subretinal black mottled pigment, and on occasion, older female carriers show a lobular pattern of choriocapillaris and RPE loss. Gene-therapy trials for choroideremia are ongoing.
Edwards TL, Jolly JK, Groppe M, et al. Visual acuity after retinal gene therapy for choroideremia. N Engl J Med. 2016;374(20):1996–1998.
MacLaren RE, Groppe M, Barnard AR, et al. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet. 2014;383(9923):1129–1137.
Patients affected by gyrate atrophy usually develop night blindness during the first decade of life, and experience progressive loss of visual field and visual acuity later in the course of the disease. Macular edema is commonly present. In the early stages of the disease, patients have large, geographic, peripheral paving-stone–like areas of atrophy of the RPE and choriocapillaris, which gradually coalesce to form a characteristic scalloped border at the junction of normal and abnormal RPE (Fig 13-10). Gyrate atrophy is an autosomal recessive dystrophy caused by mutations in the gene for ornithine aminotransferase (OAT). The diagnosis is supported by elevated plasma levels of ornithine. If started at a young age, aggressive dietary restriction of arginine intake and, in some cases, vitamin B6 supplementation can slow or halt progression of the retinal degeneration. The clinical diagnosis can be confirmed by measuring elevated serum or plasma ornithine levels as well as by genetic testing for mutations of OAT.
Figure 13-10 Gyrate atrophy. Wide-angle color fundus photograph shows scalloped edges of the remaining posterior retina, as is typically seen in gyrate atrophy. A crescent of nasal macular atrophy is also present.
(Courtesy of Colin A. McCannel, MD.)
Bietti crystalline dystrophy
Individuals with Bietti crystalline dystrophy develop symptoms of nyctalopia, decreased vision, and paracentral scotomas in the second to fourth decades. On examination, intraretinal yellow-white crystals are visible in the posterior retina and in the peripheral cornea near the limbus. As the disease progresses, widespread retinochoroidal atrophy develops and peripheral vision worsens. In eyes with advanced disease, the intraretinal crystals may not be evident. This condition is a very rare, autosomal recessive disorder caused by mutations in the gene CYP4V2. There is no known treatment.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.