Juvenile-onset macular dystrophy associated with ABCA4 gene characterized by progressive loss of central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina.
Stargardt disease (STGD1) or fundus flavimaculatus (FFM) is a juvenile-onset macular dystrophy associated with ABCA4 gene characterized by progressive loss of central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina.
M/C inherited macular dystrophy
Autosomal recessive inheritance
Rod & cone photoreceptors and ABCA4 mechanism in OS disc membranes: In both rod and cone cells, the light-sensitive OS is attached to the inner segment (IS) by a connecting cilium (CC). Rhodopsin, the visual pigment in rod cells, comprises the protein opsin bound to the chromophore 11-cis-retinal, which is isomerized to all-trans-retinal upon photon absorption. Once released from opsin, all-trans-retinal then reacts with PE to form a Schiff base. ABCA4 then “flips” all-trans-retinal to the outer portion of the disc membrane to access the visual cycle. | Sears, A. E., Bernstein, P. S., Cideciyan, A. V., Hoyng, C., Charbel Issa, P., Palczewski, K., Rosenfeld, P. J., Sadda, S., Schraermeyer, U., Sparrow, J. R., Washington, I., & Scholl, H. (2017). Towards Treatment of Stargardt Disease: Workshop Organized and Sponsored by the Foundation Fighting Blindness. Translational vision science & technology, 6(5), 6. https://doi.org/10.1167/tvst.6.5.6
Clinical features
Symptoms typically develop within the first two decades of life and include progressive, irreversible loss of central and color vision and delayed dark adaptation. The peripheral visual field is normal and there is no complaint of night blindness. Nevertheless, the natural course of the disease is characterized by marked clinical variability with regards to the age of onset, the pattern of fundus lesions, and the rate of progression.
Bilateral central visual loss
Dyschromatopsia
Central scotomata
Diagnosis
Fundus examination:
Characteristic macular atrophy and yellow–white flecks at the level of the retinal pigment epithelium (RPE) at the posterior pole
(A) Colour fundus photograph showing typical yellow–white retinal flecks with macular atrophy. (B) Corresponding fundus autofluorescence image showing flecks of both increased and decreased autofluorescence and reduced central macular autofluorescence surrounded by an increased signal. | Tanna, P., Strauss, R. W., Fujinami, K., & Michaelides, M. (2017). Stargardt disease: clinical features, molecular genetics, animal models and therapeutic options. The British journal of ophthalmology, 101(1), 25–30. https://doi.org/10.1136/bjophthalmol-2016-308823
Fundus autofluorescence (FAF):
Hypoautofluorescence at level of RPE atrophy
Hyperautofluorescence corresponding to flecks
Angiographic examinations:
Fundus fluorescein angiography (FFA) & indocyanine green angiography (ICGA)
Silent choroid/dark choroid due to masking of background choroidal fluorescence by diffuse RPE abnormality
Optical coherence tomography (OCT):
Shows changes in the outer nuclear layer
Photoreceptor loss
RPE abnormalities
Choroidal neovascularization (CNV) (rare)
Multimodal imaging of the right eye of a molecularly proven 15-year-old patient with Stargardt disease. (A) Fundus autofluorescence image. The yellow line indicates the scanning level of the optical coherence tomography (OCT) scan in (B). (B) OCT scan showing central loss of outer retinal structure. The yellow arrows indicate the location and extent of the adaptive optics scanning light ophthalmoscopy (AOSLO) montages in (C) and (D) through the transition zone. (C) Confocal AOSLO montage of the photoreceptor mosaic. (D) Split-detection AOSLO montage of the photoreceptor mosaic. The far left side of (C) and (D) is closer to the fovea and lacks cone structure, corresponding with the lack of outer hyper-reflective layers in (B). Moving towards the right of (C) and (D), away from the fovea and superiorly on the retina, (C) shows structural changes that are relatively challenging to interpret, whereas (D) clearly shows the presence of cones. Scale bars represent 100 µm | Scoles D, Sulai YN, Langlo CS, et al. . In vivo imaging of human cone photoreceptor inner segments. Invest Ophthalmol Vis Sci 2014;55:4244–51. 10.1167/iovs.14-14542
