Multiple evanescent white dot syndrome: clinical course and factors influencing visual acuity recovery.

OBJECTIVE: To report the demographics and the clinical course of patients with multiple evanescent white dot syndrome (MEWDS) and to investigate for those factors which influence visual acuity (VA) recovery. METHODS: This is a retrospective single-centre observational study. Electronic medical records and retinal imaging of patients with a diagnosis of MEWDS with a minimum follow-up of 3 months were reviewed. Patients were categorised into three groups according to the VA at presentation and at the last visit: group 1 >0.48 logarithm of the minimum angle of resolution (LogMAR), group 2 ≤0.48 and ≥0.18 LogMAR and group 3 <0.18 LogMAR. All patients had non-invasive multimodal imaging including optical coherence tomography, near-infrared reflectance imaging and blue fundus autofluorescence at presentation and during follow-up. RESULTS: A total of 51 eyes from 51 patients (41 women, mean age 29.8±7.8 years) were included. Significantly more patients presented in the autumn (X2=8.69, p=0.034). The percentage of eyes recovering vision to 0.0 LogMAR or better was 80.3% (41/51). Worse presenting vision and young age at presentation were independent significant predictive variables for poorer final VA (p=0.002 and p=0.02, respectively). No imaging features were significantly predictive of complete versus incomplete recovery, but disc hyperfluorescence on fluorescein angiography was more common in those with incomplete recovery. CONCLUSIONS: Although the majority of cases have a benign prognosis, the clinical spectrum of MEWDS includes incomplete visual recovery. In our series, poor presenting VA and young age were associated with poor VA outcome. Further study is warranted to confirm these findings.

Quantifying the Separation Between the Retinal Pigment Epithelium and Bruch's Membrane using Optical Coherence Tomography in Patients with Inherited Macular Degeneration.

Purpose: To describe and quantify Bruch's membrane (BM) and retinal pigment epithelium (RPE) separation using spectral-domain (SD) optical coherence tomography (OCT) in patients affected by inherited macular degenerations associated with BM thickening. Methods: Patients with molecularly confirmed Sorsby fundus dystrophy (SFD), dominant drusen (DD), and late-onset retinal degeneration (L-ORD) were included in this retrospective study. Each disease was classed as early stage if subjects were asymptomatic, intermediate stage if they had nyctalopia alone, and late stage if they described loss of central vision. The main outcome was measurement of BM-RPE separation on SD-OCT. The BM-RPE separation measurements were compared against those in normal age-matched controls. Results: Seventeen patients with SFD, 22 with DD, and eight with L-ORD were included. BM-RPE separation on SD-OCT demonstrated a high test-retest and interobserver reproducibility (intraclass correlation coefficients >0.9). BM-RPE separation was not identified in normal subjects. In SFD, there was greater BM-RPE separation in late-stage disease compared with intermediate-stage patients both at subfoveal (P < 0.05) and juxtafoveal (P < 0.01) locations. In DD, there was increased BM-RPE separation in late-stage disease compared with early stage at subfoveal (P < 0.001) and juxtafoveal (P < 0.05) topographies. There was no significant difference in BM-RPE separation between disease stages in L-ORD. Conclusions: BM-RPE separation is a novel, quantifiable phenotype in the three monogenic macular dystrophies studied, and may be an optical correlate of the histopathological thickening in BM that is known to occur. BM-RPE separation, as measured by OCT, varies with stage of disease in SFD and DD, but not in L-ORD. Translational Relevance: SFD, DD, and L-ORD are associated with BM thickening. In this group of patients, OCT assessment of macular structure identifies a separation of the usually single, hyperreflective line thought to represent BM and the overlying RPE. This separation is a novel and quantifiable feature of disease staging in SFD and DD.

Whole genome sequencing reveals novel mutations causing autosomal dominant inherited macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a common sight threatening condition. However, there are a number of monogenic macular dystrophies that are clinically similar to AMD, which can potentially provide pathogenetic insights. METHODS: Three siblings from a non-consanguineous Greek-Cypriot family reported central visual disturbance and nyctalopia. The patients had full ophthalmic examinations and color fundus photography, spectral-domain ocular coherence tomography and scanning laser ophthalmoscopy. Targeted polymerase chain reaction (PCR) was performed as a first step to attempt to identify suspected mutations in C1QTNF5 and TIMP3 followed by whole genome sequencing. RESULTS: The three patients were noted to have symptoms of nyctalopia, early paracentral visual field loss and, in older patients, central vision loss. Imaging identified pseudodrusen, retinal atrophy and RPE-Bruch's membrane separation. Whole genome sequencing of the proband revealed two novel heterozygous variants in C1QTNF5, c.556C>T, and c.569C>G. The mutation segregated with disease in this family, occurred in cis, and resulted in missense amino acid changes P186S and S190W in C1QTNF5. In silico modeling of the variants revealed that the S190W mutations was likely to have the greatest pathologic effect and that the combination of the mutations was likely to have an additive effect. CONCLUSIONS: The novel mutations in C1QTNF5 identified here expand the genotypic spectrum of mutations causing late-onset retinal dystrophy.