History of present illness
A 47-year-old woman presented to our clinic with a chief report of “spots in vision.” She denied other changes in her vision, flashes, or floaters and had no past history of ocular conditions or surgeries.
Ocular examination findings
Visual acuity with correction was 20/20 in both eyes. Intraocular pressures were normal. External and anterior segment examinations were unremarkable. Dilated fundus examination showed pigmentary changes in the perimacular areas in both eyes and a large cotton wool spot along the arcade.
Imaging
Color fundus photography showed retinal pigment epithelium (RPE) hyperpigmentary changes and subtle yellow spots surrounding the macular area ( Fig. 11.1 ). Optical coherence tomography (OCT) showed that the hyperpigmented areas corresponded to a hyperreflective dome-shaped lesion on the RPE ( Fig. 11.2 , green arrow ), and the outer retina was markedly attenuated ( Fig. 11.2 , yellow arrow ).
Fundus autofluorescence (AF) showed alternating hyper- and hypoautofluorescent lesions in the perifoveal area and nasal to the optic nerve ( Fig. 11.3 ).
Questions to ask
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Is there a previous history of ocular disease and/or relapsing vision loss? Previous history of subretinal fluid is associated with retinal pigment epitheliopathy abnormalities due to central serous chorioretinopathy (CSC)/pachychoroid disease. Geographical atrophy and RPE changes could also be observed in dry age-related macular degeneration (AMD) in older patients.
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No
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What medications does the patient take? Pentosan polysulfate maculopathy may be associated with RPE and outer retinal atrophy.
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Patient was on no medications and had no history of pentosan polysulfate usage.
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Is there a history of systemic medical illness? Inflammatory diseases, including syphilis and sarcoidosis, might be accompanied by ocular manifestations. A thorough history and review of systems are helpful. When multiple systems are affected without another obvious explanation, mitochondrial retinal disease should be suspected. Diabetes mellitus (DM), especially maternally inherited, and clinical or subclinical hearing loss (maternally inherited diabetes and deafness [MIDD] syndrome) are the most common features associated with the A3243G mitochondrial mutation.
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Yes. She has a history of DM.
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Does the patient have a family history of ocular conditions or consanguinity? A family history would be essential to ascertain inherited retinal disorders. MIDD and stroke-like episodes are caused by various mitochondrial DNA mutations. MIDD also has been shown to have a high correlation with pattern dystrophies.
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No history of ocular conditions.
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Assessment
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This is a case of a 47-year-old woman with no past ocular or surgical history demonstrating bilateral macular dystrophy and subretinal hyperreflective flecks on OCT and a ring of alternating hyper- and hypoautofluorescence surrounding the fovea. She has DM.
Differential diagnosis
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Syphilitic chorioretinitis
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Pseudoxanthoma elasticum maculopathy
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Pattern dystrophy: RDS peripherin/RDS gene
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Mitochondrial retinopathy
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Central areolar choroidal dystrophy
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AMD
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CSC/pachychoroid disease
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Pentosan polysulfate maculopathy
Working diagnosis
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DNA testing revealed A3243G mitochondrial DNA point mutation.
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The diagnosis is m.3243A>G-associated maculopathy.
Multimodal testing and results
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Fundus photographs
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On fundus examination, hyperpigmented lesions surrounding the macula are typically visualized involving the peripapillary retina ( Fig. 11.1 ). ,
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OCT
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As mentioned earlier, OCT showed hyperreflective areas and outer retinal attenuation. OCT also showed ellipsoid zone and RPE thinning in areas without atrophy and outer retinal attenuation in areas of chorioretinal atrophy ( Fig. 11.2 ). ,
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Fundus AF
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Our patients’ AF showed alternating hyper- and hypoautofluorescence in the perifoveal area and nasal to the optic nerve. AF examination revealed hyperautofluorescence due to yellow-white spots/flecks (RPE thickening on OCT) and hypoautofluorescence due to atrophic changes ( Fig. 11.3 ).
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Genetic testing
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Genetic testing of mitochondrial DNA identified a point mutation at locus 3243 that confirmed this disorder. Our patient has a history of DM at a young age. mtDNA genome sequencing and heteroplasmy analysis can now be effectively performed in blood, although it may be necessary to test other tissues in affected organs. Analysis in urine can selectively be more informative and accurate than testing in blood alone, especially in older individuals.
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Management
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Because this patient was asymptomatic and visual acuity was 20/20 in both eyes, the patient was observed.
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There is currently no effective treatment for m.3243A>G-associated maculopathy.
Follow-up care
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There are no previously established guidelines for follow-up.
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Our patient is followed on a biannual basis.
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Our patient’s visual acuity remains 20/20 but the area of perifoveal degeneration has progressed ( Fig. 11.4 ).
