En face OCT imaging for the assessment of glaucoma

Glaucoma is a leading cause of irreversible vision loss globally, and demands early and accurate diagnosis. OCT has become a key investigative technique in glaucoma, and, although it provides invaluable clinical support, detection of early glaucoma remains imperfect. Recent OCT developments enabled direct assessment of retinal nerve fibre bundle (RNFB) reflectance in en face OCT images. The technique has considerable potential in the assessment of glaucoma, yet it has limited clinical usability due to an incomplete understanding of RNFB features in healthy and glaucoma eyes and the lack of accepted methods to identify reflectance defects. This thesis aimed to better understand characteristics of RNFB reflectance in en face OCT imaging and to develop objective methods to extract defects in this domain. Structural and functional measures of glaucoma changes were collected in eyes with established glaucoma and age-similar controls. Results showed that the healthy configuration of RNFB varies across the retina and between different eyes. We developed a method for automated and objective examination of reflectivity changes in en face images. This method considers individual anatomy and varying RNFB configuration, and found more abnormalities than previous approaches. Measures of en face reflectance and conventional retinal nerve fibre layer thickness were strongly related. The agreement between changes of reflectance and visual function was moderate-to-good, and both testing domains presented concordant abnormalities in all tested eyes. Following further minimisation of artefacts in en face images, direct use of reflectance analysis or its combination with perimetry appear viable and with significant potential for clinical examination of glaucoma

A Natural History Study of RP2-Related Retinopathy

X-linked retinitis pigmentosa (RP) is a severe form of RP, often with early macular involvement. This study aimed to characterise the natural history of patients with a diagnosis of X-linked RP due to RP2 mutations. Clinical details, best-corrected visual acuity (BCVA) and multimodal retinal imaging were retrospectively collected from patients with RP2 variants from Moorfields Eye Hospital (London, UK). Measures of the ellipsoid-zone (EZ) width, central retinal thickness (CRT), and thickness of the photoreceptor and retinal pigment epithelium complex (PR+RPE, taken between the external limiting membrane and RPE) were extracted from spectral-domain optical coherence tomography (SD-OCT) scans. A total of 47 affected males (median baseline age: 20 years, IQR: 12.5–36.5) were included, and 41 had two or more visits (median follow-up: 8.0 years, IQR: 3.2–14.5). A total of 24 RP2 variants were identified, 13 of which were novel. BCVA dropped from 0.66 LogMAR at baseline (IQR, 0.35–1.4) to 1.3 LogMAR at the most recent visit (IQR: 0.6–1.4). SD-OCT revealed a prevalent outer retinal atrophy (n = 23/35, 65.7%), and measurable EZ width at baseline in 34.3% of patients (n = 12). Age significantly affected all quantitative measures (p < 0.001) except EZ width (p = 0.58), with exponential decays of 46–49% and 12.6–33.9% per decade for BCVA and SD-OCT measures, respectively. RP2 patients exhibited rapid progression to outer retina atrophy and early macular involvement with substantial vision loss by age 30–40

Concordance of objectively-detected retinal nerve fiber bundle defects in en face OCT images with conventional structural and functional changes in glaucoma.

YesTo assess how objectively-detected defects of retinal nerve fibre bundle (RNFB) reflectance in en face OCT images relate to circumpapillary retinal nerve fibre layer thickness (cpRNFLT) and visual field defects. Cross-sectional study. 16 participants with early-glaucoma and 29 age-similar healthy controls, among which 22 had usable en face images to establish normative levels of RNFB reflectance. All participants underwent cpRNFLT scans, visual field examination and wide-field OCT. En face reflectivity was assessed objectively using the Summary of Multiple Anatomically-Adjusted Slabs (SMAS) method. En face defects were deemed concordant with cpRNFLT when they had at least one cpRNFLT point with

Longitudinal structure-function analysis of molecularly-confirmed CYP4V2 Bietti Crystalline Dystrophy

Objectives: Bietti Crystalline Dystrophy (BCD) is an autosomal recessive progressive retinal disease caused by mutations in CYP4V2. We have characterised the natural history including structural and functional measures to identify potential outcome metrics for future clinical trials. Methods: Molecularly-confirmed BCD patients with biallelic variants in CYP4V2 were retrospectively identified from Moorfields Eye Hospital (UK). Clinical details including results of molecular genetic testing, best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (OCT) scans were extracted. From OCT scans, ellipsoid zone (EZ) measures, foveal thickness of the whole retina, outer retina and choroid were measured. Age-related changes of clinical parameters were assessed with linear mixed models. Results: Twenty-eight BCD patients were identified, with median age at baseline of 37 years (interquartile range [IQR]: 30–49.5). Median follow-up was 7.7 years (IQR: 3.4–14.5). Most patients (41.7%) showed chorioretinal atrophy at baseline. All OCT parameters showed significant age-related loss (p < 0.05), with EZ measures and choroidal thickness displaying the most rapid degeneration (2.3–3.3% per year vs 0.6–1.5% per year). Median BCVA was 0.2 LogMAR (IQR: 0–0.5) at baseline and showed small age-related loss ( + 0.016 LogMAR per year, p = 0.0019). Patients exhibited substantial phenotypic variability. Conclusions: BCD presents between age 25 and 40, and slowly progresses to an advanced chorioretinal atrophy and vision loss by age 60. BCVA may be preserved until late, and is seemingly poorly representative of disease progression. OCT parameters capturing EZ and choroid changes may afford more suitable trial outcome measures

Depth-resolved variations in visibility of retinal nerve fibre bundles across the retina in enface OCT images of healthy eyes.

YesRecent developments in optical coherence tomography (OCT) technology enable direct enface visualisation of retinal nerve fibre bundle (RNFB) loss in glaucoma. However, the optimum depth at which to visualise RNFBs across the retina is unknown. We aimed to evaluate the range of depths and optimum depth at which RNFBs can be visualised across the retina in healthy eyes. The central ± 25° retina of 10 healthy eyes from 10 people aged 57–75 years (median 68.5 years) were imaged with spectral domain OCT. Slab images of maximum axial resolution (4 μm) containing depth‐resolved attenuation coefficients were extracted from 0 to 193.5 μm below the inner limiting membrane (ILM). Bundle visibility within 10 regions of a superimposed grid was assessed subjectively by trained optometrists (n = 8), according to written instructions. Anterior and posterior limits of RNFB visibility and depth of best visibility were identified for each grid sector. Effects of retinal location and individual eye on RNFB visibility were explored using linear mixed modelling with likelihood ratio tests. Intraclass correlation coefficient (ICC) was used to measure overall agreement and repeatability of grading. Spearman’s correlation was used to measure correlation between depth range of visible RNFBs and retinal nerve fibre layer thickness (RNFLT). Retinal location and individual eye affected anterior limit of visibility (χ2(9) = 58.6 and 60.5, both p < 0.0001), but none of the differences exceeded instrument resolution, making anterior limit consistent across the retina and different eyes. Greater differences were observed in the posterior limit of visibility across retinal areas (χ2(9) = 1671.1, p < 0.0001) and different eyes (χ2(9) = 88.7, p < 0.0001). Optimal depth for visualisation of RNFBs was around 20 µm below the ILM in most regions. It varied slightly with retinal location (χ2(9) = 58.8, p < 0.0001), but it was not affected by individual eye (χ2(9) = 10.7, p = 0.29). RNFB visibility showed good agreement between graders (ICC 0.89, 95%CI 0.87–0.91), and excellent repeatability (ICC 0.96–0.99). Depth range of visible RNFBs was highly correlated with RNFLT (ρ = 0.9, 95%CI: 0.86–0.95). The range of depths with visible RNFBs varies markedly across the healthy retina, consistently with RNFLT. To extract all RNFB information consistently across the retina, slab properties should account for differences across retinal locations and between individual eyes.This work was supported by a College of Optometrists Research Fellowship (JD)

Referral in a routine Italian optometric examination: towards an evidence-based model.

Italian optometrists refract patients and prescribe optical appliances. The routine optometric examination that is currently conducted in Italy, however, does not include a comprehensive ocular health assessment. Like many other countries, in Italy ophthalmologists are solely responsible for the diagnosis and treatment of ocular pathologies, yet, the care an optometrist provides must be done with the aim of promoting the general and ocular health of patients seen in practice. Such scope has to be pursued using a close collaboration with ophthalmologists, ultimately facilitating the earliest medical diagnosis and minimisation of visual impairment. Referral represents the basis of optometrist-ophthalmologist collaboration, yet, no guidance is available to Italian optometrists indicating when referral is warranted. The purpose of this study was to identify the circumstances deserving a referral in a routine Italian optometric examination in adults, ultimately constituting preliminary evidence-based indications of a referral model oriented to enhance the ocular and general health of patients. A literature review was conducted on Pubmed and the Cochrane Library, mainly targeting high quality secondary literature such as systematic reviews, meta-analysis and clinical guidelines. Several reasons for referral were identified. Further, while a wide range of anomalies of the visual system are likely to be discovered by the Italian optometric examination, up to 20% of patients could suffer an underlying condition undetected by the current assessment. This results in the need to refer seemingly healthy patients if they have not attended routine ophthalmological examinations within optimal time frames. In Italy, and countries with similar settings, the referral is an essential instrument that optometrists must largely use to ensure early diagnosis of ocular conditions by ophthalmologists and minimisation of avoidable visual impairment

Foveal Hypoplasia in CRB1-Related Retinopathies

The CRB1 gene plays a role in retinal development and its maintenance. When disrupted, it gives a range of phenotypes such as early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa (RP), cone-rod dystrophy (CORD) and macular dystrophy (MD). Studies in CRB1 retinopathies have shown thickening and coarse lamination of retinal layers resembling an immature retina. Its role in foveal development has not yet been described; however, this retrospective study is the first to report foveal hypoplasia (FH) presence in a CRB1-related retinopathy cohort. Patients with pathogenic biallelic CRB1 variants from Moorfields Eye Hospital, London, UK, were collected. Demographic, clinical data and SD-OCT analyses with FH structural grading were performed. A total of 15 (48%) patients had EOSRD/LCA, 11 (35%) MD, 3 (9%) CORD and 2 (6%) RP. FH was observed in 20 (65%; CI: 0.47–0.79) patients, all of whom were grade 1. A significant difference in BCVA between patients with FH and without was found (p = 0.014). BCVA continued to worsen over time in both groups (p &lt; 0.001), irrespective of FH. This study reports FH in a CRB1 cohort, supporting the role of CRB1 in foveal development. FH was associated with poorer BCVA and abnormal retinal morphology. Nonetheless, its presence did not alter the disease progression

A Natural History Study of <i>RP2</i>-Related Retinopathy

X-linked retinitis pigmentosa (RP) is a severe form of RP, often with early macular involvement. This study aimed to characterise the natural history of patients with a diagnosis of X-linked RP due to RP2 mutations. Clinical details, best-corrected visual acuity (BCVA) and multimodal retinal imaging were retrospectively collected from patients with RP2 variants from Moorfields Eye Hospital (London, UK). Measures of the ellipsoid-zone (EZ) width, central retinal thickness (CRT), and thickness of the photoreceptor and retinal pigment epithelium complex (PR+RPE, taken between the external limiting membrane and RPE) were extracted from spectral-domain optical coherence tomography (SD-OCT) scans. A total of 47 affected males (median baseline age: 20 years, IQR: 12.5–36.5) were included, and 41 had two or more visits (median follow-up: 8.0 years, IQR: 3.2–14.5). A total of 24 RP2 variants were identified, 13 of which were novel. BCVA dropped from 0.66 LogMAR at baseline (IQR, 0.35–1.4) to 1.3 LogMAR at the most recent visit (IQR: 0.6–1.4). SD-OCT revealed a prevalent outer retinal atrophy (n = 23/35, 65.7%), and measurable EZ width at baseline in 34.3% of patients (n = 12). Age significantly affected all quantitative measures (p p = 0.58), with exponential decays of 46–49% and 12.6–33.9% per decade for BCVA and SD-OCT measures, respectively. RP2 patients exhibited rapid progression to outer retina atrophy and early macular involvement with substantial vision loss by age 30–40

Global prevalence of diabetic retinopathy: protocol for a systematic review and meta-analysis

With increasing diabetes trends worldwide, morbidity, mortality and associated costs due to diabetes-related complications are a global public health concern. Diabetic retinopathy (DR) is among the leading causes of vision loss at the global level; accurate estimates of DR burden is of crucial importance for planning, implementing and evaluating DR prevention and care interventions.The available evidence on DR prevalence at the global level, dating back to 2008, only considered data from selected regions. Taking into account the rapidly changing patterns in DR epidemiology, the aim of the current study is to carry out a systematic review and meta-analysis to derive solid and updated estimates on global and setting-specific DR prevalence

Physical Properties and Interaction With the Ocular Surface of Water-Gradient Contact Lenses

Since the introduction of silicone hydrogel contact lenses, many silicone-hydrogel materials have been produced, including water-gradient contact lenses with a silicone hydrogel core and a thin hydrogel outer layer (e.g., delefilcon A, verofilcon A, and lehfilcon A). Their properties have been investigated in various studies assessing both the chemical-physical characteristics and the comfort, but the overall picture is not always consistent. In this study, water-gradient technology is reviewed by looking at basic physical properties both in vitro and in vivo and at the interaction with the human ocular surface. Surface and bulk dehydration, surface wetting and dewetting, shear stress, interaction with tear components and with other environmental compounds, and comfort are discussed. [Abstract copyright: Copyright © 2023 Contact Lens Association of Ophthalmologists.