History of present illness
A 59-year-old White woman of German descent presented with progressive visual difficulty in the dark for 5 years. The right eye was amblyopic secondary to anisometropia. She was otherwise healthy.
Ocular examination findings
Her best corrected visual acuities were 20/400 in the right eye and 20/50 in the left eye. Anterior segment examination was normal in both eyes. Fundus examination showed multiple islands of geographical atrophy (GA) involving most of the posterior pole and temporal retina in each eye. There were yellow drusen-like flecks in the nasal retina, without islands of atrophy.
Imaging
Fundus photograph of the right eye showed multiple islands of GA involving the posterior pole ( Figs. 19.1 and 19.2 ) and temporal retina ( Figs. 19.3 and 19.4 ). Many of the patches of atrophy abutted neighboring patches leaving scalloped areas of preserved retina between them. Fine yellow drusen-like flecks were seen in the nasal retina, without islands of atrophy ( Fig. 19.5 ). The fluorescein angiogram showed window defects corresponding to the GA ( Fig. 19.6 ), and the corresponding atrophic areas showed reduced autofluorescence ( Fig. 19.7 ). Optical coherence tomography revealed outer retinal atrophy corresponding to the GA but sub–retinal pigment epithelium (RPE) thickening/deposits in the intact areas ( Fig. 19.8 ).
Questions to ask
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Is there a family history of similar symptoms? If there is a family history suggestive of autosomal dominant inheritance, one should consider Sorsby fundus dystrophy, peripherin/RDS dystrophy, and late-onset retinal macular degeneration (LORMD). Lack of family history suggests an autosomal recessive inheritance condition such as Gyrate atrophy or sporadic extensive macular atrophy with pseudodrusen.
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Yes. Father was adopted and had poor vision late in life.
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Is there a history of long-term use of certain medications? Thioridazine (Mellaril), used in treatment of psychosis, and didanosine, previously used in treatment of HIV, can cause widespread chorioretinal atrophy resembling LORMD.
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The patient has no history of long-term use of medications.
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Thioridazine accumulates in the melanin granules of the RPE and uveal melanocytes and affects rhodopsin synthesis resulting in disintegration of rod outer segments. Beginning as a coarse granular salt-and-pepper pigmentary retinopathy in the periphery, the lesions progress as nummular areas of GA of the RPE and choriocapillaris that can eventually enlarge and become confluent, involving the entire fundus.
Didanosine is a nucleoside reverse transcriptase inhibitor postulated to deplete mitochondrial DNA. The clinical features begin with coarse pigment speckling in the midperipheral and peripheral fundus and progress to well-circumscribed round areas of RPE and choriocapillaris atrophy that are sharply demarcated from the posterior pole. These enlarge over time despite discontinuation of the drug, with only a few scalloped ares of remaining RPE. Patients can report nyctalopia.
Assessment
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This 59-year-old woman reports with a history of visual loss and nyctalopia of 5 years’ duration and a similar history in her father. The patient demonstrates punctate drusen in the nasal retina and extensive GA in the macula and temporal retina.
Differential diagnosis
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Sorsby fundus dystrophy
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LORMD
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Peripherin/RDS retinal dystrophy
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Extensive macular atrophy with pseudodrusen
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Gyrate atrophy
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Thioridazine toxicity
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Didanosine toxicity
Working diagnosis
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Sorsby fundus dystrophy
Nyctalopia is a late feature of Sorsby fundus dystrophy. The macula would show extensive drusen and RPE changes along with gradually increased drusen and pseudodrusen from the posterior pole toward the periphery. Choroidal neovascularization is much more common, and an autosomal dominant family history of “early-onset wet age-related macular degeneration” is often elicitable.
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LORMD
Early findings are drusen-like flecks in asymptomatic patients. Nyctalopia begins after age 50 and worsens rapidly over 4 to 5 years. The widespread islands of GA are seen in the macula, midperiphery, and periphery. The peripheral lesions may not be uniformly distributed, with some areas, especially the nasal area, being spared until very late. Choroidal neovascularization is uncommon. It is dominantly inherited and was first described in people of Scottish descent.
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Extensive macular atrophy with pseudodrusen
This condition is generally sporadic, with no known family history. The islands of GA arise in the central macula and are limited to the posterior pole, but the pseudodrusen are extensive and found up to the equator and beyond.
Other features
Patients with LORMD can have long zonules attached to the anterior surface of the lens, which this patient did not have.
Multimodal testing and results
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Goldmann visual field
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Central scotoma and marked constriction on the right and moderate constriction on the left ( Figs. 19.9 and 19.10 )
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