Our results show that in stages of retinitis pigmentosa, before atrophic lesions spread inside the vascular arcades, the pattern of fundus autofluorescence correlates well with functional tests such as perimetry and electroretinography. The ring of increased AF appears to represent the border between functional and dysfunctional retina. This shows that autofluorescence, as a quick and non-invasive imaging tool, may be related to retinal function as well.

Usher syndrome (USH), the most prevalent cause of hereditary deafness–blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1–3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods.

Purpose of this study was to characterize retinal disease in Usher syndrome using fundus autofluorescence and optical coherence tomography. Study included 54 patients (26 male, 28 female) aged 7-70 years. There were 18 (33%) USH1 and 36 (67%) USH2 patients. 49/52 (94%) patients were found to carry at least one mutation in Usher genes. Ophthalmological examination included assessment of Snellen visual acuity, color vision with Ishihara tables, Goldmann visual fields (targets II/1-4 and V/4), microperimetry, fundus autofluorescence imaging and optical coherence tomography. Average age at disease onset (nyctalopia) was significantly lower in USH1 than USH2 patients (average 9 vs. 17 years, respectively; p<0.01); however no significant differences were found regarding type of autofluorescence patterns, frequency of foveal lesions and CME, rate of disease progression and age at legal blindness. All representative eyes had abnormal fundus autofluorescence of either hyperautofluorescent ring (55%), hyperautofluorescent foveal patch (35%) or foveal atrophy (10%). Disease duration of more than 30 years was associated with a high incidence of abnormal central fundus autofluorescence (patch or atrophy) and visual acuity loss.

In Leber hereditary optic neuropathy, a reduced N95 component of PERG and severely reduced VEP P100 may be present already in the acute stage of disease, before optic disc pallor appears, suggesting primary dysfunction of retinal ganglion cells.

Purpose To evaluate retinal sensitivity and fixation patterns in patients with Best's dystrophy by microperimetry (MP) and to correlate the results with static perimetry and retinal morphology seen by autofluorescence (AF). Methods Central 101 visual fields in 11 patients with Best's dystrophy (VA: 0.570.38) were recorded by the Octopus M2 TOP program and by MP (MP1, Nidek Technologies). AF was recorded by HRA (Heidelberg Engineering). Results High correlation (R ¼ 0.75, À0.76, À0.48) was found between static perimetry (MS, MD and CLV indices) and MP. Based on MP and AF results, three groups of patients were formed. Patients in the first two groups fixated inside the central nonuniform hypoand hyperfluorescent AF ring area, next to relative (Group 1) or absolute scotoma (Group 2). Inner parts of the retina close to the fovea were most affected, whereas regions closer to the periphery of the 101 visual field showed near normal function. As the disease progressed, there was an evident shift of fixation to preferential retinal locus (PRL) in eight eyes with visual acuity 0.2 or less (Group 3). Fixation shift was superior in four eyes, temporal in two eyes, and nasal in two eyes. Conclusion MP enabled a highly sensitive topographic monitoring of retinal function, showing central or pericentral fixation in the early stages, until loss of central function, in eyes with VA 0.2 or less, caused evident shift of fixation to PRL. PRL was never situated inside the central uniform hypofluorescent area, but corresponded with the hyperfluorescent ring seen with AF imaging.