The Clinical Use of Vernier Acuity: Resolution of the Visual Cortex Is More Than Meets the Eye

Vernier acuity measures the ability to detect a misalignment or positional offset between visual stimuli, for example between two vertical lines when reading a vernier scale. It is considered a form of visual hyperacuity due to its detectable thresholds being considerably smaller than the diameter of a foveal cone receptor, which limits the spatial resolution of classical visual acuity. Vernier acuity relies heavily on cortical processing and is minimally affected by optical media factors, making it a useful indicator of cortical visual function. Vernier acuity can be measured, usually in seconds of arc, by freely available automated online tools as well as via analysis of steady state visual-evoked potentials, which allows measurement in non- or pre-verbal subjects such as infants. Although not routinely measured in clinical practice, vernier acuity is known to be reduced in amblyopia, glaucoma and retinitis pigmentosa, and has been explored as a measure of retinal or neural visual function in the presence of optical media opacities. Current clinical utility includes a home-based vernier acuity tool, preferential hyperacuity perimetry, which is used for screening for choroidal neovascularisation in age-related macular degeneration. This review will discuss the measurement of vernier acuity, provide a current understanding of its neuro-ophthalmic mechanisms, and finally explore its utility through a clinical lens, along with our recommendations for best practice

Test-Retest Repeatability of Microperimetry at the Border of Deep Scotomas

Citation: Wu Z, Jung CJ, Ayton LN, Luu CD, Guymer RH. Test-retest repeatability of microperimetry at the border of deep scotomas. Invest Ophthalmol Vis Sci. 2015;56:2606-2611. DOI:10.1167/iovs.14-15977 PURPOSE. The purpose of this study was to examine the test-retest repeatability of microperimetric sensitivity at the border of deep scotomas. METHODS. Thirty normal participants underwent two examinations, each on the Macular Integrity Assessment (MAIA) microperimeter and on the MP-1 microperimeter (four examinations in total). A customized stimulus pattern allowed microperimetric sensitivity to be measured at the border of the optic nerve head (ONH), which acted as a model for the border of a deep scotoma-and also at the macular and peripapillary region. RESULTS. There were no significant changes in average point-wise sensitivity (PWS) values between the two examinations for all three regions using the MAIA microperimeter (P ‡ 0.262). The PWS coefficient of repeatability (CoR) was 612.99 dB at the border of the ONH, which was significantly larger than points in the macular and peripapillary regions (P > 0.001). A significant decrease in average PWS, using the MP-1 microperimeter at the macular and peripapillary region (P < 0.001), meant that the PWS CoR could not be determined in these regions. No significant changes in average PWS were observed at the border of the ONH (P ¼ 0.223), and the PWS CoR was 67.52 dB in this region. CONCLUSIONS. Microperimetric test-retest repeatability at the border of a deep scotoma was worse than at other areas of normal retina, and this highlights the limitation of applying a single estimate of test-retest repeatability to determine whether significant functional decline has occurred at the border of a deep scotoma

Analysis of the outer retinal bands in ABCA4 and PRPH2-associated retinopathy using OCT

Purpose: To evaluate the outer retinal bands using OCT in ABCA4- and PRPH2-associated retinopathy and develop a novel imaging biomarker to differentiate between these 2 genotypes. Design: Multicenter case-control study. Participants: Patients with a clinical and genetic diagnosis of ABCA4- or PRPH2-associated retinopathy and an age-matched control group. Methods: Macular OCT was used to measure the thickness of the outer retinal bands 2 and 4 by 2 independent examiners at 4 retinal loci. Main Outcome Measures: Outcome measures included the thicknesses of band 2, band 4, and the band 2/band 4 ratio. Linear mixed modeling was used to make comparisons across the 3 groups. Receiver operating characteristic (ROC) analysis determined the optimal cutoff for the band 2/band 4 ratio to distinguish PRPH2- from ABCA4-associated retinopathy. Results: We included 45 patients with ABCA4 variants, 45 patients with PRPH2 variants, and 45 healthy controls. Band 2 was significantly thicker in patients with PRPH2 compared with ABCA4 (21.4 vs. 15.9 m, P \u3c 0.001) variants, whereas band 4 was thicker in patients with ABCA4 variants than those with PRPH2 variants (27.5 vs. 21.7 m, P \u3c 0.001). Similarly, the band 2/band 4 ratio was significantly different (1.0 vs. 0.6 for PRPH2 vs. ABCA4, P \u3c 0.001). The area under the ROC curve was 0.87 for either band 2 ( \u3e 18.58 m) or band 4 ( \u3c 26.17 μm) alone and 0.99 (95% confidence interval: 0.97–0.99) for the band 2/band 4 ratio with a cutoff threshold of 0.79, providing 100% specificity. Conclusions: We report an altered outer retinal band profile whereby the band 2/band 4 ratio was able to discriminate between PRPH2- and ABCA4-associated retinopathy. This may have future clinic utility in predicting the genotype and provide further insight into the anatomic correlate of band 2. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients

PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P \u3c 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P \u3c 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. CONCLUSIONS: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials

Developmental eye movement test: What is it really measuring?

C1 - Journal Articles Referee

Female carriers of X-linked inherited retinal diseases – Genetics, diagnosis, and potential therapies

Inherited retinal diseases (IRDs) are a group of heterogeneous conditions that cause progressive vision loss, typically due to monogenic mutations. Female carriers of X-linked IRDs have a single copy of the disease-causing gene, and therefore, may exhibit variable clinical signs that vary from near normal retina to severe disease and vision loss. The relationships between individual genetic mutations and disease severity in X-linked carriers requires further study.This review summarises the current literature surrounding the spectrum of disease seen in female carriers of choroideremia and X-linked retinitis pigmentosa. Various classification systems are contrasted to accurately grade retinal disease. Furthermore, genetic mechanisms at the early embryonic stage are explored to potentially explain the variability of disease seen in female carriers.Future research in this area will provide insight into the association between genotype and retinal phenotypes of female carriers, which will guide in the management of these patients. This review acknowledges the importance of identifying which patients may be at high risk of developing severe symptoms, and therefore should be considered for emerging treatments, such as retinal gene therapy.</p

Image processing for visual prostheses: A clinical perspective

Recent advances in the field of visual prostheses or 'bionic eyes' have shown that it is possible to use electrical stimulation to produce basic phosphenised vision to patients who are profoundly vision impaired or blind. In particular, retinal prostheses have been implanted in a number of clinical trials for a degenerative eye disease known as retinitis pigmentosa. To date, the visual improvements in these trials have been small and not easily quantified. The aim of this paper is to highlight the inherent complexities in the assessment of visual function in the profoundly vision impaired, and discuss the potential for improvement in outcomes using image processing technology.</p

Perspectives of carriers of X-linked retinal diseases on genetic testing and gene therapy: A global survey

Female carriers of X-linked inherited retinal diseases (IRDs) are burdened with potentially passing their disease-causing variant to future generations, as well as exhibiting signs of retinal disease themselves. This study aimed to investigate carriers' experiences of genetic testing, emotions relating to having affected children, and their knowledge regarding genetic testing and gene therapy. An online survey was advertised to self-identified carriers worldwide. Two hundred and twenty-eight carriers completed the survey with mean age of 51 years (SD ± 15.0). A majority of respondents resided in the United States of America (51%), Australia (19%), and the United Kingdom (14%). Most carriers identified with feelings of guilt (70%), concern (91%), and anxiety (88%) for their child. Female carriers who had given birth to children had significantly greater gene therapy knowledge compared to carriers who had not (p < 0.05). Respondents agreed that their eyecare provider and general practitioner helped them understand their condition (63%), however, few carriers reported receiving psychological counselling (9%) or family planning advice (5%). Most respondents (78%) agreed that gene therapy should be available to carriers. This study emphasises the importance of providing appropriate counselling to female carriers and illustrates the motivation of many to participate in emerging treatment options, such as gene therapy.</p