Classification and heritability of macular pigment spatial profile phenotypes using two-wavelength fundus autofluorescence

Purpose: We investigated the frequency and heritability of macular pigment (MP) spatial profile phenotypes determined by objective and subjective profile classification based on fundus autofluorescence (FAF). Methods: Between scans Coefficient of Repeatability (CoR) of MP optical density (MPOD) was calculated from two FAF scans (Spectralis, Heidelberg, Germany) of 40 participants (39±8.6 years) acquired in a single session. We then analyzed two FAF scans acquired in a single session from 314 twins (157 pairs; 39±8.8 years) and classified each MP profile as exponential, ring-like or central dip by subjective visual assessment. Profiles were also classified objectively based on deviations larger than the CoR away from the exponential fit. We calculated Kappa agreement of the profiling methods, case-wise concordance of non-exponential profiles for the 88 mono- (MZ) and 69 dizygotic (DZ) twin pairs, and profile heritability. Results: Following visual subjective profiling, 64% showed an exponential profile, 27% presented ring-like and 9% central dip profiles; case-wise concordance was 0.80 for MZ and 0.41 for DZ twins. Following objective classification, 71% showed an exponential profile, 29% ring-like profile and no central dip profiles were identified; case-wise concordance was 0.74 for MZ and 0.36 for DZ twins. Heritability was calculated as 81.5% (95% CI 61.1 to 93.1). Between scan repeatability of profile classification showed good agreement objectively (κ=0.85, 95% CI 0.69 to 1.00; P<0.0005) and moderate agreement visually (κ=0.48, 95% CI 0.23 to 0.73; P<0.0005). Agreement of subjective versus objective profiling was low (κ=0.23, 95% CI 0.04 to 0.42; P=0.02). Conclusions: MP profiles showed high heritability. Compared to visual assessment, objective profile classification is a more reliable method for future experimental studies using FAF

Electrophysiological Assessment in Birdshot Chorioretinopathy: Flicker Electroretinograms Recorded With a Handheld Device

Purpose: The flicker electroretinogram (ERG) is a sensitive indicator of retinal dysfunction in birdshot chorioretinopathy (BCR). We explored recordings from a handheld device in BCR, comparing these with conventional recordings in the same patients and with handheld ERGs from healthy individuals. Methods: Non-mydriatic flicker ERGs, using the handheld RETeval system (LKC Technologies), were recorded with skin electrodes at two centers. At one center (group 1), the stimuli (85 Td·s, 850 Td background) delivered retinal illuminance equivalent to international standards; at the other center (group 2), a different protocol was used (32 Td·s, no background). Patients also underwent international standard flicker ERG recordings with conventional electrodes following mydriasis. Portable ERGs from patients were also compared with those from healthy individuals. Results: Thirty-two patients with BCR (mean age ± SD, 56.4 ± 11.3 years) underwent recordings. Portable and standard ERG parameters correlated strongly (r > 0.75, P < 0.01) in both groups. Limits of agreement for peak times were tighter in group 1 (n = 21; −4.3 to+2.0ms [right eyes], −3.9to1.5ms [left eyes]) than in group 2(n=11;−3.4 to +6.9 ms [right eyes], −4.8 to +9.0 ms [left eyes]). Compared with healthy controls (n =66 and n =90 for groups 1 and 2, respectively), patients with BCR showed smaller mean amplitudes and longer peak times. Conclusions: Portable ERGs correlated strongly with conventional recordings, suggesting potential in rapid assessment of cone system function in office settings. Translational Relevance: Flicker ERGs, known to be useful in BCR, can be obtained rapidly with a portable device with skin electrodes and natural pupils

Prevalence of refractive error in Europe: the European Eye Epidemiology (E3) Consortium

To estimate the prevalence of refractive error in adults across Europe. Refractive data (mean spherical equivalent) collected between 1990 and 2013 from fifteen population-based cohort and cross-sectional studies of the European Eye Epidemiology (E3) Consortium were combined in a random effects meta-analysis stratified by 5-year age intervals and gender. Participants were excluded if they were identified as having had cataract surgery, retinal detachment, refractive surgery or other factors that might influence refraction. Estimates of refractive error prevalence were obtained including the following classifications: myopia ≤−0.75 diopters (D), high myopia ≤−6D, hyperopia ≥1D and astigmatism ≥1D. Meta-analysis of refractive error was performed for 61,946 individuals from fifteen studies with median age ranging from 44 to 81 and minimal ethnic variation (98 % European ancestry). The age-standardised prevalences (using the 2010 European Standard Population, limited to those ≥25 and <90 years old) were: myopia 30.6 % [95 % confidence interval (CI) 30.4–30.9], high myopia 2.7 % (95 % CI 2.69–2.73), hyperopia 25.2 % (95 % CI 25.0–25.4) and astigmatism 23.9 % (95 % CI 23.7–24.1). Age-specific estimates revealed a high prevalence of myopia in younger participants [47.2 % (CI 41.8–52.5) in 25–29 years-olds]. Refractive error affects just over a half of European adults. The greatest burden of refractive error is due to myopia, with high prevalence rates in young adults. Using the 2010 European population estimates, we estimate there are 227.2 million people with myopia across Europe

KCNV2-associated retinopathy: genotype–phenotype correlations – KCNV2 study group report 3

BACKGROUND/AIMS: To investigate genotype–phenotype associations in patients withKCNV2retinopathy. METHODS: Review of clinical notes, best-corrected visual acuity (BCVA), molecular variants, electroretinography (ERG) and retinal imaging. Subjects were grouped according to the combination ofKCNV2variants—two loss-of-function (TLOF), two missense (TM) or one of each (MLOF)—and parameters were compared. RESULTS: Ninety-two patients were included. The mean age of onset (mean±SD) in TLOF (n=55), TM (n=23) and MLOF (n=14) groups was 3.51±0.58, 4.07±2.76 and 5.54±3.38 years, respectively. The mean LogMAR BCVA (±SD) at baseline in TLOF, TM and MLOF groups was 0.89±0.25, 0.67±0.38 and 0.81±0.35 for right, and 0.88±0.26, 0.69±0.33 and 0.78±0.33 for left eyes, respectively. The difference in BCVA between groups at baseline was significant in right (p=0.03) and left eyes (p=0.035). Mean outer nuclear layer thickness (±SD) at baseline in TLOF, MLOF and TM groups was 37.07±15.20 µm, 40.67±12.53 and 40.38±18.67, respectively, which was not significantly different (p=0.85). The mean ellipsoid zone width (EZW) loss (±SD) was 2051 µm (±1318) for patients in the TLOF, and 1314 µm (±965) for MLOF. Only one patient in the TM group had EZW loss at presentation. There was considerable overlap in ERG findings, although the largest DA 10 ERG b-waves were associated with TLOF and the smallest with TM variants. CONCLUSIONS: Patients with missense alterations had better BCVA and greater structural integrity. This is important for patient prognostication and counselling, as well as stratification for future gene therapy trials