April 12, 2016
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Severe macular disease detected in patient with no symptoms

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A 50-year-old Caucasian female presented to the clinic in November 2014 for a periodic eye exam with complaints of blurry vision at distance and near without correction. She also reported difficulty in adjusting to changes in lighting conditions, specifically, that she was not able to see when walking in a darkened room, which she attributed to aging. Her medical history was significant for mild osteoarthritis, for which she takes no medications. She reported taking only a multivitamin and had no allergies. She also denied use of tobacco products. Her family medical and ocular history was unremarkable.

Upon examination the patient’s best-corrected visual acuity was 20/20 OD and 20/20 OS at distance and near with a small hyperopic astigmatic correction and appropriate add. IOP measured 14 mm Hg OD and 14 mm Hg OS by Tonopen. Pupils were equal, round and well reactive to light with no afferent pupillary defect. Confrontation fields were full in both eyes. Extraocular movements were smooth and intact without restriction. She was orthophoric at distance and near by cover test. Anterior segment examination was unremarkable.

Dilated fundus exam revealed healthy, well-perfused optic nerves with a cup-to-disc ratio of 0.3:0.3 in each eye. Her posterior pole findings are demonstrated in the fundus photos shown. Irregular pigment clumping was observed throughout the midperiphery in each eye, with hypopigmented “flecks” more prominent in the left eye. There was mild vitreous syneresis in each eye. Spectral domain optical coherence tomography testing was also obtained in the macula at a later exam.

David Otto

Given the clinical picture, several differential diagnoses were considered, including: central areolar choroidal dystrophy, geographic atrophy from age-related macular degeneration, retinal toxicity induced by Plaquenil (hydroxychloroquine sulfate, Sanofi-Aventis) and Stargardt’s disease.

Fundus photo demonstrating extensive pericentral C-shaped retinal pigment epithelium (RPE) atrophy with sparing of the papillomacular bundle and an intact foveal RPE island in the right eye.

Images: Otto D

Central areolar choroidal dystrophy

Central areolar choroidal dystrophy is a hereditary retinal disorder that primarily affects the macula. Inheritance can be in an autosomal dominant or autosomal recessive pattern. Patients usually become symptomatic in the third to fourth decade of life with a dramatic decline in central acuity occurring in the fourth to seventh decade of life.

With time, macular depigmentation progresses into a well-defined area of atrophy of the retinal pigment epithelium (RPE) and choriocapillaris in the center of the macula, leading to profound vision loss. This was considered unlikely given the patient’s lack of symptoms and the presence of good vision.

Age-related macular degeneration

Fundus photo demonstrating almost complete circumferential RPE atrophy with sparing inferiorly and an intact foveal RPE island in the left eye. Deep choroidal vessels are clearly visible.

A well-known cause of geographic atrophy is the advanced stage of AMD. The clinical appearance of geographic atrophy represents the nearly complete loss of the RPE cells under the retina. The atrophic areas have clearly defined borders to healthy retina, and deep choroidal vasculature is usually visible.

This stage represents the most common cause of severe vision loss from dry AMD. We ruled out this diagnosis based on clinical appearance.

Bull’s eye maculopathy

The hallmark of hydroxychloroquine-induced retinal toxicity is bilateral pigmentary retinopathy. Late stages demonstrate a bull’s eye appearance with sparing of the fovea. Initially visual acuity remains excellent despite the presence of paracentral visual field defects.

The recommendations for screening for chloroquine and hydroxychloroquine retinopathy were revised in 2011 by the American Academy of Ophthalmology. The risk for retinopathy sharply increases after a cumulative dose of 1,000 g. The current guidelines recommend baseline testing at the start of treatment to serve as a reference and annual screening after 5 years, or sooner if risk factors are present. The new guidelines recommend 10-2 automated visual field testing along with at least one objective test, such as multifocal electroretinogram, SD-OCT or fundus autofluorescence. These tests can be more sensitive to detecting early changes. Because our patient was taking no medications, we ruled this out as a potential diagnosis.

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Stargardt’s disease

Stargardt’s disease is the most common recessively inherited macular dystrophy of children. Autosomal dominant modes of inheritance have also been documented. A hallmark of the disease is the accumulation of discrete “pisciform” flecks at the level of the RPE. These lesions are concentrated primarily in the posterior pole. When these flecks accumulate throughout the fundus starting in adulthood, the disease is termed fundus flavimaculatus, or late-onset Stargardt’s disease.

A defect in the ABCA4 gene causes an error in a protein-encoding cascade that is essential in the process of photoreceptor breakdown. The result is an accumulation of a protein in the photoreceptor outer segments that is toxic to the RPE. This stress eventually leads to the destruction of the RPE and overlying photoreceptors. Typically, Stargardt’s disease causes rapid visual deterioration between childhood and early adulthood. More profound vision loss is linked to an earlier age of onset.

Diagnosis, management

Given our patient’s young age and fundus appearance she was tentatively diagnosed with late-onset Stargardt’s disease or fundus flavimaculatus. The diagnosis was confirmed with fluorescein angiography.

There is no proven treatment for Stargardt’s disease. Management involves several subspecialties depending on the stage of visual impairment. Low vision consultation is beneficial. Genetic testing and counseling is not routinely performed; however, it should be considered if there is a known family history.

The dietary guidelines we give to our AMD patients would also serve these patients well. Limiting dietary intake of vitamin A is beneficial, as excess amounts can cause additional stress to the RPE and overlying photoreceptors.

SD-OCT through the fovea of the right eye demonstrating absent RPE and disruption of the ellipsoidal zone (also referred to as the PIL or photoreceptor integrity line) corresponding to the areas of atrophy. The photoreceptors in the foveal pit remain intact.

SD-OCT through the fovea of the right eye demonstrating absent RPE and disruption of the ellipsoidal zone (also referred to as the PIL or photoreceptor integrity line) corresponding to the areas of atrophy. The photoreceptors in the foveal pit remain intact.

Any steps that can be taken to reduce the stress on the RPE would benefit these patients. UV protection is never a bad idea and theoretically could help maintain the health of the RPE for a longer period. While we are unsure of the potential benefit of blue light protection, blue-blocking lens treatments will not make things worse.

This patient’s management

A retinal specialist discussed the future option of stem-cell transplantation once her disease progresses to the point of considering such a treatment. Low vision rehabilitation has also been discussed. It is not known at this time how long her foveal island will remain intact. She was given the option of genetic counseling; however, she has chosen not to pursue any further study at this time. Our patient reports that she has four grown children with no abnormal eye exams to date.

Over the past year, there has been slight enlargement of the atrophic zone in both eyes, but with no definitive pattern. Despite her fundus appearance, her vision is still correctable to 20/20 in each eye. This patient will be followed with dilated exams at 6-month intervals.

SD-OCT through the fovea of the left eye demonstrating absent RPE and disruption of the ellipsoidal zone corresponding to the areas of atrophy. The photoreceptors in the foveal pit remain intact.

SD-OCT through the fovea of the left eye demonstrating absent RPE and disruption of the ellipsoidal zone corresponding to the areas of atrophy. The photoreceptors in the foveal pit remain intact.

Better long-term visual outcomes are associated with an older age of diagnosis; however, no prediction can be made regarding the actual level of visual acuity to expect. The average visual acuity at diagnosis ranges from 20/20 to 20/40, but very few patients get the range of hand motion vision.

It would be reasonable to assume that this patient will retain relatively good central vision for years; however, this depends on how long the central foveal sparing remains undisturbed.

Disclosure: Otto reports no relevant financial disclosures.