Purpose. To evaluate and compare the value of fundus autofluorescence (FAF) imaging and multifocal electroretinography (mfERG) in early detection of retinal alterations in patients using chloroquine/hydroxychloroquine (CQ/HCQ). methods. FAF imaging was performed in a consecutive series of 25 patients with long-term CQ or HCQ treatment (duration, >1 year), with or without visual disturbances. In addition, mfERG was performed in accordance with ISCEV (International Society for Clinical Electrophysiology of Vision) guidelines in 23/25 patients. results. In 10/25 patients alterations of FAF were observed. Mild changes were limited to a pericentral ring of increased FAF. More advanced stages presented as pericentral mottled loss of FAF with increased FAF in the adjacent retina and later on a complete loss of pericentral FAF. In one case, a pericentral ring was observed when ophthalmoscopy and fluorescein angiography were normal. Marked progression of FAF abnormalities was observed during a 3-year follow-up in two of three patients. With the mfERG, pericentral, central, or generalized amplitude reductions were detected in all patients with FAF abnormalities and in an additional four patients with normal FAF. conclusions. FAF imaging can be reliably used to detect early retinal pigment epithelial alterations in CQ/HCQ retinopathy. Ophthalmoscopy and fluorescein angiography appear to be less sensitive. With the mfERG, more retinal abnormalities were detected compared with FAF imaging.

The purpose of this study was to compare near-infrared fundus autofluorescence (NIA, excitation 787 nm, emission >800 nm) with fundus autofluorescence (FAF, excitation 488 nm, emission >500 nm) in patients with age-related macular degeneration (AMD). Fundus autofluorescence and NIA were obtained using a confocal scanning-laser ophthalmoscope (HRA2) in 308 eyes (172 patients) with AMD [age-related maculopathy (n = 116), geographic atrophy (n = 77), and neovascular AMD (n = 115)]. Retinal pigment epithelial alterations were detected with FAF and NIA in all eyes and showed a similar lesion size in 81.8%. In age-related maculopathy, spots of increased FAF (87.9%) were more frequent than spots of reduced FAF (26.7%). Spots of increased and reduced NIA were of similar frequency (66.4%). A higher relative intensity of FAF was more frequent (72.4%) than higher relative NIA intensity (16.4%), suggesting that loss of NIA usually precedes loss of FAF. The junctional zone of geographic atrophy presented with increased NIA (19.5%), increased FAF (10.4%), or an increase of both (22.1%). In neovascular AMD, exudative changes were better visualized with FAF (56.5%) compared with NIA (33.9%). Patterns of FAF and NIA indicate different involvement of lipofuscin and melanin in the pathophysiological process and provide further insight into the development of AMD and noninvasive monitoring of future therapeutic interventions.

Mutations in genes encoding components of the mitochondrial DNA (mtDNA) replication machinery cause mtDNA depletion syndromes (MDSs), which associate ocular features with severe neurological syndromes. Here, we identified heterozygous missense mutations in single-strand binding protein 1 (SSBP1) in 5 unrelated families, leading to the R38Q and R107Q amino acid changes in the mitochondrial single-stranded DNA-binding protein, a crucial protein involved in mtDNA replication. All affected individuals presented optic atrophy, associated with foveopathy in half of the cases. To uncover the structural features underlying SSBP1 mutations, we determined a revised SSBP1 crystal structure. Structural analysis suggested that both mutations affect dimer interactions and presumably distort the DNA-binding region. Using patient fibroblasts, we validated that the R38Q variant destabilizes SSBP1 dimer/tetramer formation, affects mtDNA replication, and induces mtDNA depletion. Our study showing that mutations in SSBP1 cause a form of dominant optic atrophy frequently accompanied with foveopathy brings insights into mtDNA maintenance disorders.