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BackgroundOptical coherence tomography is commonly used to measure the retinal nerve fibre layer thickness in both normal and diseased eyes; however, variation among normal eyes is common and may limit the usefulness of the results. The aim of this study was to explore the interocular asymmetries in retinal nerve fibre layer thickness in a group of normal eyes and to investigate the influence of blood vessel diameter on local retinal nerve fibre layer thickness.MethodsIn this prospective study, retinal nerve fibre layer thickness and blood vessel diameter across 100 healthy participants were measured using two optical coherence tomography instruments. Individuals were categorised into two groups based on the presence or absence of interocular retinal nerve fibre layer thickness asymmetry beyond the 75th percentile of all participants.ResultsThe superonasal sectoral retinal nerve fibre layer thickness was significantly greater in the left eye compared to the right, across all three sectors. Mean blood vessel diameter showed a corresponding difference in thickness at one of the superonasal sectors. Linear regression showed a positive and moderate correlation between blood vessel diameter and focal retinal nerve fibre layer thickness. This trend persisted across both arteries and veins, but veins showed larger variability between left and right eye in participants with marked superonasal retinal nerve fibre layer asymmetry.ConclusionRetinal nerve fibre layer thickness and blood vessel diameter vary significantly between eyes even in healthy individuals. These asymmetries in a normal population should be taken into consideration when interpreting the retinal nerve fibre layer thickness measurements from optical coherence tomography to assist in distinguishing normal variations from disease.

Optic nerve head (ONH) assessment and its interpretation in healthy patients and those with glaucoma remains a pivotal topic specifically considering rapid advancements in imaging technologies. We undertook a large-scale, mixed cohort, comparative study to assess the correlation of optic disc measurements between different imaging modalities and investigated the impact of patient and disc associated parameters.ONH sizes were obtained from one randomly selected eye of each of 209 patients using stereophotography, confocal scanning laser ophthalmoscopy and two different optical coherence tomographers (OCT). Patient related data, glaucoma status and optic disc variables, specifically oblique insertion, torsion, presence of beta PPA and spherical equivalent were recorded. Measurements between imaging modalities were analysed using Pearson correlation, linear regression analysis and Blend-Altman plots. Individual variables were compared applying multivariate regression analysis, ANOVA and chi square statistics was used to determine correlations between patient and clinical characteristics.Absolute measurements significantly differed between imaging modalities generally producing smaller measurements for OCT derived measurements of Bruch's membrane opening (BMO). Pairwise correlations between imaging modalities were between 0.83 and 0.93 for discs without myopia, oblique insertion, or beta PPA. These features impacted on measurements for individual modalities and consequently contributed to inconsistencies and variability.In comparison to planimetry, OCT derived BMO measurements are more variable in the presence of oblique insertion, beta PPA or magnification errors due to myopia. Impact of these factors, however, differs between instruments and needs to be considered to accurately interpret optic disc features in particular within the context of glaucoma diagnosis.

Mutations in the BEST1 gene constitute an underlying cause of juvenile macular dystrophies, a group of retinal disorders commonly referred to as bestrophinopathies and usually diagnosed in early childhood or adolescence. The disease primarily affects macular and paramacular regions of the eye leading to major declines in central vision later in life. Currently, there is no cure or surgical management for BEST1-associated disorders. The recently characterized human disease counterpart, canine multifocal retinopathy (cmr), recapitulates a full spectrum of clinical and molecular features observed in human bestrophinopathies and offers a valuable model system for development and testing of therapeutic strategies. In this study, the specificity, efficiency and safety of rAAV-mediated transgene expression driven by the human VMD2 promoter were assessed in wild-type canine retinae. While the subretinal delivery of rAAV2/1 vector serotype was associated with cone damage in the retina when BEST1 and GFP were co-expressed, the rAAV2/2 vector serotype carrying either GFP reporter or BEST1 transgene under control of human VMD2 promoter was safe, and enabled specific transduction of the RPE cell monolayer that was stable for up to 6 months post injection. These encouraging studies with the rAAV2/2 vector lay the groundwork for development of gene augmentation therapy for human bestrophinopathies.