Lyndell L. Lim

Geographic atrophy is a leading cause of severe vision loss and is estimated to affect around 100,000 people in Australia alone. This survey is topical for clinical optometrists as the first treatment for geographic atrophy has just been approved by the Australian Therapeutics Goods Administration and may soon become available in Australia. Considering that treatments for geographic atrophy secondary to age-related macular degeneration are likely imminent, a survey of Australian optometrists was conducted to gauge their readiness in caring for people with geographic atrophy. The Royal Australian and New Zealand College of Ophthalmologists age-related macular degeneration referral guidelines working group determined 26 survey questions relating to management of geographic atrophy. Strength of agreement questions utilised a 5-point Likert scale. Optometrists answered anonymously during January to March 2024. There were 101 survey responses. Almost all (97%) respondents have access to colour fundus photography, three-quarters (74%) to optical coherence tomography, and almost half (44%) to fundus autofluorescence. Almost all (97%) see patients with GA regularly, with 73% seeing at least two geographic atrophy patients per month and the majority reviewing them every 6 months. Around half were confident in differentiating geographic atrophy from inherited retinal disease (49%) and confident in identifying early signs of atrophy (44%). Around half (46%) nominated that they would refer over 50% of their current geographic atrophy patients to ophthalmology for assessment of their suitability for new treatments. Eighty-three percent would refer a patient with good vision (6/12 or better) to initiate treatment to save encroachment on the fovea. Respondents were keen to receive more education about diagnosis (88%) and new treatments (93%). Optometrists are preparing for changes in the clinical management of geographic atrophy and are keen to receive further education to ensure optimal patient-centric care as new treatments become available.

Secondary causes of cataract contribute to significant morbidity, but their pathogeneses are not well understood. This RNA sequencing study aimed to be the first to quantify and compare the transcriptome of the uveitic, steroid-induced, and post-vitrectomy cataract, using age-related cataracts (ARCs) as the study control. Between March and July 2023 in Melbourne (VIC, Australia), human anterior lens capsules were prospectively collected during surgery from ARCs (n = 36), as well as steroid-induced (n = 23), uveitic (n = 25), and post-vitrectomy (n = 13) cataracts, and they were stabilized in RNAlater reagent. The Australian Genome Research Facility performed RNA isolation with RNeasy Mini and library preparation and sequencing using the Illumina workflow. Quality control was performed with the Agilent 2200 TapeStation. Bioinformatic analysis of RNA sequencing data identified differentially expressed genes (DEGs), defined as those with a log fold change ≥ 1 and false discovery rate (FDR) < 0.05. Differential gene expression analysis demonstrated significant differences between the transcriptome of age-related versus uveitic cataract (345 DEGs), steroid-induced versus uveitic cataract (117 DEGs), and age-related versus post-vitrectomy cataract (30 DEGs in the subgroup without removal of silicone oil [ROSO] and 1347 DEGs in the subgroup with ROSO). No DEGs were identified between age-related and steroid-induced cataracts. To our knowledge, this is the first large-scale gene expression study focusing on these secondary cataracts. This dataset will assist in forming a broader knowledge base of secondary cataract pathogenesis and inform future research in this area, particularly in the selection of specific genes and investigating their impact on cataract development through animal model studies.

Sarcoidosis is the exemplar sterile granulomatous disease and can affect any organ system. Tattoo uveitis (TU) resembles sarcoidosis clinically and histologically but is distinguished by the absence of systemic lymphadenopathy, with inflammation restricted to skin and eyes. In this study, our objectives were, first, to resolve whether TU is a subset of sarcoidosis or a different antigen-driven condition and, second, by comparing TU and sarcoidosis, to identify blood-borne signatures of active and quiescent sterile granulomatous diseases. We recruited patients with active and inactive TU, sarcoidosis and healthy controls on whom we performed blood cell phenotyping and transcriptomics. Unlike sarcoidosis, active TU is characterised by marked CXCR5 down-regulation on B cells and CD4+ T cells that normalises on remission. TCR-VDJ sequencing reveals an antigen-driven response in sarcoidosis, but not in TU, with clonally expanded cytotoxic and terminally differentiated CD8+ effectors. Both active TU and sarcoidosis exhibit gene signatures of epithelial-to-mesenchymal transition (EMT) in circulating monocytes, whereas epithelioid macrophages are a hallmark of active granulomas. We have identified both shared and specific phenotypes in TU and sarcoidosis. Marked CXCR5 down-regulation occurs in active TU and could explain the unique absence of lymphadenopathy. Both TU and sarcoidosis are characterised by inflammatory monocyte phenotypes and transcriptional signatures of EMT.

Background: To identify predictive factors of uveitis refractory to treatment in initial-onset acute Vogt-Koyanagi-Harada disease. Methods: This was a retrospective chart review of patients with initial-onset acute Vogt-Koyanagi-Harada disease presenting to the Royal Victorian Eye and Ear Hospital, Melbourne, Australia between July 2001 and March 2023 inclusive. Factors predictive of uveitis refractory to treatment were determined using logistic regression models with, and without, adjustment for initial use of intravenous methylprednisolone. Results: Thirty-eight patients with initial-onset acute Vogt-Koyanagi-Harada were included, 27 of whom received initial intravenous corticosteroids (71%) and 23 met the criteria for uveitis refractory to treatment (61%). Comparing those who received intravenous corticosteroids to those who did not, the incidence of complications, time-to-quiescence, time-to-relapse, time-to-low dose corticosteroid or corticosteroid-sparing control of inflammation and time-to-remission were not statistically different (all p > 0.164). Factors at onset of treatment that were predictive for uveitis refractory to treatment included greater anterior chamber inflammation (p = 0.008), greater vitreous inflammation (p = 0.015), the absence of bacillary layer detachments on macular optical coherence tomography (p = 0.010) and commencement of systemic steroid therapy 1 week or longer after ocular symptom onset (p = 0.013). Absence of intravenous corticosteroids as initial therapy was not a statistically significant predictive factor for refractory disease (p = 0.802). Conclusions: Delayed commencement of systemic steroid therapy and higher severity of intraocular inflammation at presentation are predictive of initial-onset acute Vogt-Koyanagi-Harada disease evolving into disease refractory to treatment.

The choroidal thickening and serous retinal detachments that characterize Vogt-Koyanagi-Harada (VKH) disease can be imaged in detail using spectral domain optical coherence tomography (SD-OCT). Whether specific qualitative and quantitative SD-OCT features at presentation were associated with visual outcomes in a randomized controlled trial comparing methotrexate to mycophenolate for steroid-sparing control of uveitis were evaluated. An exploratory subanalysis of data from the FAST trial in which SD-OCT images from VKH participants were analyzed for presence/absence of bacillary detachments, retinal pigment epithelium (RPE) folds, and internal limiting membrane (ILM) fluctuations was performed. A modified RPE undulation index was calculated to provide a quantifiable surrogate marker for choroidal folds. SD-OCT images were available from 158 eyes with VKH. At baseline, bacillary detachments were present in 23.5% of eyes, RPE folds in 22.8% of eyes, and ILM fluctuations in 35.2% of eyes. For each 0.1 unit increase in modified RPE undulation index, there was an associated 0.13 increase in mean logMAR BSCVA at baseline. None of the SD-OCT features were associated with BSCVA at the 6-month primary endpoint. Indeed, mean final BSCVA was similar in those with and without the SD-OCT features of interest at baseline, and was between 0.1 and 0.2 logMAR (Snellen visual acuity 20/25 to 20/30). While eyes with VKH may present with a variety of SD-OCT imaging pathology prior to starting immunosuppression with methotrexate or mycophenolate mofetil, final visual outcome in our study was excellent. With appropriate immunosuppression, good visual outcomes are possible in VKH.ClinicalTrials.gov Identifier NCT01829295Date of Registration: April 11, 2013.

Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial

Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial

First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial

Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial

A Phase IV Randomised Clinical Trial of Laser Therapy for Peripheral Retinal Ischaemia Combined With Intravitreal Aflibercept (Eylea®) Versus Intravitreal Aflibercept Monotherapy for Diabetic Macular Oedema