Background: To characterise stromal curvature and curvature ratios in keratoconus (KCN) using anterior segment OCT, and to evaluate the implications of using single-, two-, and three-surface refractive models for corneal power estimation in ectatic eyes.
Methods: Retrospective observational study. Anterior segment OCT measurements (MS-39, CSO) were analysed. Anterior, stromal, and posterior curvature radii were computed across five concentric zones (2.0-6.0 mm) using a floating best-fit sphere, and curvature ratios were subsequently derived: anterior-to-stromal (ASR), stromal-to-posterior (SPR), and anterior-to-posterior (APR). Corneal power was calculated using one-, two-, and three-surface models. KCN severity was classified according to the Belin ABC grading stage and ASR, SPR, and APR were stratified accordingly.
Results: Data from 944 keratoconic eyes were analysed. Peripheral zones (6.0 mm) exhibited reduced variability in curvature measurement compared to central zones (3.0 mm). Differences between simplified (one- and two-surface) and three-surface power models correlated moderately with increased APR and SPR values. ASR, SPR, and APR all increased progressively with advancing ABC grade.
Conclusion: In advanced keratoconus, three-surface modelling yields different corneal power estimates versus simplified models in KC; prospective outcome studies are needed to assess clinical impact. Stromal curvature and its derived ratios provide novel structural metrics that change with KCN severity. Curvature ratio increase -especially APR and SPR- reflects posterior steepening and anterior-posterior decoupling, with possible implications for staging and surgical planning.
Background: Uveal melanoma (UM) is the most common primary intraocular tumour. Despite effective local therapies, UM has a high risk of metastatic recurrence, most frequently to the liver. A significant proportion of patients treated definitively for primary UM eventually experience metastatic disease. Systemic surveillance to detect recurrence is critical to maximise therapeutic options. Whilst international guidelines exist, there are currently no standardised Australian guidelines for surveillance imaging. This systematic review examines the literature regarding systemic surveillance methods following local treatment for UM.
Methods: Medline, Embase and PubMed databases were searched, from 2010 to 01-07-2024, using keywords related to uveal melanoma and surveillance. Eligible studies were identified by two independent reviewers, and a systematic review was undertaken.
Results: Of 840 records, six guidelines and institutional consensus statements were identified, and an additional 13 studies were included. Most studies were cohort studies (n = 7), with the rest being case-control studies and reliability analyses. Risk stratification methods and surveillance strategies varied, with most studies recommending increased frequency (at least every 6 months) and higher-resolution imaging modalities (MRI over ultrasound) for higher-risk patients.
Conclusion: Despite several published guidelines, existing evidence regarding optimal surveillance strategies in localised primary UM is of variable quality, relying on cohort studies and limited by heterogeneity, as assessed by the modified Newcastle-Ottawa Scale. There is a clear need to further define local practices and outcomes to direct future guidelines.
Background: To evaluate the 10-year cumulative incidence, progression rates, and risk factors for macular atrophy (MA) in neovascular age-related macular degeneration (nAMD) patients receiving long-term anti-vascular endothelial growth factor (VEGF) therapy.
Methods: Retrospective, multicenter, cohort study including 148 eyes from 140 nAMD patients treated with a pro-re-nata (PRN) anti-VEGF regimen and followed for ≥ 10 years. Annual multimodal imaging-including blue autofluorescence [BAF], spectral-domain optical coherence tomography [SD-OCT] and near-infrared reflectance-was reviewed to detect and quantify MA using RegionFinder. Kaplan-Meier analysis estimated cumulative MA incidence, while mixed-effects Cox and linear regressions identified risk factors and progression rates.
Results: Baseline MA prevalence was 23.0%, increasing to 64.9% at 5 years and 79.8% at 10 years. Foveal involvement occurred in 47.4% of cases. Significant predictors for MA included baseline BCVA < 20/40 (HR = 1.50, p = 0.02), greater central subfield thickness (CST) fluctuations (HR = 1.04, p = 0.01), and more frequent submacular haemorrhages (HR = 1.34, p = 0.04). Type 3 macular neovascularization was associated with fovea-involving MA (HR = 2.03, p = 0.02). Mean MA size increased from 0.34 to 2.27 mm at 10 years, progressing at 0.20 mm/year (β = 0.15, p < 0.001). Eyes with incident MA exhibited faster progression (β = 0.03, p = 0.01) and worse BCVA decline compared to those with baseline MA (-1.96 vs. -1.42 letters/year, p < 0.001).
Conclusions: nAMD patients treated with PRN anti-VEGF therapy demonstrated a high 10-year cumulative incidence of MA (79.8%), with poor baseline BCVA and CST fluctuations as key risk factors. Eyes with incident MA progressed faster and were associated with greater visual decline, suggesting a more visually impactful atrophy.
Background: Reticular pseudodrusen (RPD) signify a critical phenotype driving vision loss in age-related macular degeneration (AMD). This study sought to develop and externally test a deep learning (DL) model to detect RPD on optical coherence tomography (OCT) scans with expert-level performance.
Methods: RPD were manually segmented in 9800 OCT B-scans from individuals enrolled in a multicentre randomised trial. A DL model for instance segmentation of RPD was developed and evaluated against four retinal specialists in an internal test dataset. The primary outcome was the performance of the DL model for detecting RPD in OCT volumes in five external test datasets compared to two retinal specialists.
Results: In an internal test dataset consisting of 250 OCT B-scans, the DL model produced RPD segmentations that had higher agreement with four retinal specialists (Dice similarity coefficient [DSC] = 0.76) than the agreement amongst the specialists (DSC = 0.68; p < 0.001). In the five external test datasets consisting of 1017 eyes from 812 individuals, the DL model detected RPD in OCT volumes with a similar level of performance as two retinal specialists (area under the receiver operator characteristic curve [AUC] = 0.94, 0.95 and 0.96 respectively; p ≥ 0.32).
Conclusions: We present a DL model for automatic detection of RPD with expert-level performance, which could be used to support the clinical management of AMD. This model has been made publicly available to facilitate future research to understand this critical, yet enigmatic, AMD phenotype.
To explore the prevalence of serious adverse events (SAEs) associated with retinal viral gene therapy and to examine trends influencing SAE occurrences in human gene therapy surgeries and pre-clinical animal trials.
Literature review was performed to identify peer-reviewed human and animal studies relevant to viral gene therapy, subretinal injections, and intravitreal injections. For clinical trials and post-approval LUXTURNA studies, only those that examined SAEs were included.
Of included clinical trial studies (n = 31), SAEs were recorded in 51 out of 438 eyes (11.6%) that received subretinal injections and in 11 out of 348 eyes (3.2%) that received intravitreal injections. There were fewer intravitreal-related SAEs and less vision loss compared to subretinal gene therapy. Inflammation was the predominant SAE following intravitreal injections, whereas unexplained vision loss was the most common for subretinal injections. Clinical trials utilising subretinal injections met primary or secondary efficacy endpoints more than intravitreal trials. Eighteen studies (429 eyes) of post-approval LUXTURNA were reviewed, and SAEs were reported in 24.7% of eyes, retinal degeneration being most common (20.7%). For 58 animal studies, SAEs were recorded in 17.3% of eyes that received subretinal injections and 8.7% of eyes that received intravitreal injections.
Subretinal injections show higher efficacy than intravitreal injections but are associated with more serious adverse events. Consistent adverse event patterns in humans and large animals highlight their predictive value for safety. There is a need for optimised delivery methods, refined dosing protocols, and improved post-treatment monitoring to improve safety and effectiveness in gene therapy.
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