A 58-year-old woman presented with complaints of bilateral decreased vision and dissatisfaction with her current spectacle correction. Her past medical history was unremarkable. Family history was significant, as she reported having four sisters, all of whom experienced reduced distance visual acuity, raising suspicion for an inherited retinal disorder.
On comprehensive ophthalmologic examination, best-corrected visual acuity was 0.5 (decimal) in both eyes. Intraocular pressure was within normal limits bilaterally. Anterior segment examination was unremarkable.
Dilated fundus examination of both eyes revealed widespread, discrete to confluent yellowish subretinal deposits diffusely distributed across the posterior pole and midperipheral retina. These lesions demonstrated a characteristic honeycomb-like pattern, particularly prominent in the macular and perimacular regions. The optic discs and retinal vasculature appeared within normal limits, with no signs of hemorrhage, exudation, or pigmentary changes suggestive of advanced age-related macular degeneration.
Color fundus photography demonstrated numerous bilateral, diffuse yellowish subretinal deposits distributed across the posterior pole and extending into the midperipheral retina. The lesions were discrete to confluent, round to irregular in shape, and arranged in a characteristic honeycomb-like pattern, particularly prominent in the macular and perimacular regions. The retinal vasculature and optic disc appeared unremarkable, with no associated hemorrhage, exudation, or signs of choroidal neovascularization.
Fundus autofluorescence imaging revealed numerous, diffusely distributed hyperautofluorescent spots corresponding to the yellowish subretinal deposits observed on color fundus photography. These lesions were scattered across the posterior pole and extended into the midperipheral retina, forming a characteristic speckled and honeycomb-like pattern. Areas of relatively reduced autofluorescence were interspersed between the hyperautofluorescent deposits, consistent with heterogeneous lipofuscin accumulation at the level of the retinal pigment epithelium. No large confluent hypoautofluorescent areas suggestive of advanced retinal pigment epithelium atrophy were observed.
Spectral-domain optical coherence tomography demonstrated multiple subretinal and subretinal pigment epithelium (sub-RPE) hyperreflective deposits corresponding to the clinically observed yellowish lesions. These deposits were predominantly located between the retinal pigment epithelium and Bruch’s membrane, resulting in focal elevations and irregularities of the RPE layer. Overlying outer retinal layers, including the ellipsoid zone, showed variable degrees of disruption, while the inner retinal architecture remained relatively preserved. No intraretinal or subretinal fluid was observed.
Doyne honeycomb retinal dystrophy is a rare inherited retinal disorder characterized by the accumulation of diffuse subretinal and subretinal pigment epithelium (sub-RPE) deposits, classically arranged in a honeycomb-like pattern. The disease is most commonly associated with mutations in the EFEMP1 gene and is inherited in an autosomal dominant manner. Clinically, it presents in mid-adulthood with gradually progressive bilateral visual impairment. The deposits represent abnormal extracellular matrix material located between the retinal pigment epithelium and Bruch’s membrane, leading to structural disruption of the outer retina. Although the funduscopic appearance may resemble age-related macular degeneration, the earlier age of onset, strong family history, and distinctive distribution of lesions support its classification as a hereditary retinal dystrophy rather than a degenerative condition.
Malattia Leventinese and Doyne honeycomb retinal dystrophy are now widely recognized as phenotypic variants of the same underlying disorder rather than distinct clinical entities. Although they were historically described separately, subsequent genetic studies have demonstrated that both conditions arise from mutations in the EFEMP1 gene, most commonly the Arg345Trp mutation. Clinically, patients may exhibit different drusen patterns, such as the characteristic radial or spoke-like deposits seen in Malattia Leventinese or the honeycomb-like configuration described in Doyne honeycomb dystrophy. However, these variations represent differences in expression rather than differences in disease mechanism. Consequently, both disorders are best classified under the unified term EFEMP1-related autosomal dominant drusen dystrophy, reflecting their shared genetic basis and pathophysiology.
Clinical and Imaging Characteristics
Multimodal imaging plays a central role in the diagnosis of Doyne honeycomb retinal dystrophy. Color fundus photography typically reveals numerous yellowish subretinal deposits distributed across the posterior pole and midperipheral retina, forming a characteristic honeycomb pattern. Fundus autofluorescence demonstrates corresponding hyperautofluorescent spots, reflecting altered lipofuscin metabolism at the level of the retinal pigment epithelium. Optical coherence tomography further delineates the pathology, showing hyperreflective sub-RPE deposits with associated focal elevations and irregularities of the RPE layer, while inner retinal layers are generally preserved. Over time, progressive outer retinal and ellipsoid zone disruption may occur, accounting for gradual visual decline. Recognition of these characteristic imaging features is essential to differentiate this entity from age-related macular degeneration and adult-onset vitelliform dystrophy, thereby preventing misdiagnosis and inappropriate management.
Credit: M. Giray Ersoz, MD, FEBO
Memorial Bahçelievler Hospital, Department of Ophthalmology, Istanbul, Turkey
Instagram accounts: @retina.review and @retina.dr.girayersoz
and Sepideh Lotfi, MD
Biruni University School of Medicine, Department of Ophthalmology, Istanbul, Turkey
Instagram accounts: @sepidls
