Prediction of vitreomacular traction syndrome outcomes with deep learning: A pilot study.

PURPOSE: To investigate the potential of an Optical Coherence Tomography (OCT) based Deep-Learning (DL) model in the prediction of Vitreomacular Traction (VMT) syndrome outcomes. DESIGN: A single-centre retrospective review. METHODS: Records of consecutive adult patients attending the Royal Adelaide Hospital vitreoretinal clinic with evidence of spontaneous VMT were reviewed from January 2019 until May 2022. All patients with evidence of causes of cystoid macular oedema or secondary causes of VMT were excluded. OCT scans and outcome data obtained from patient records was used to train, test and then validate the models. RESULTS: For the deep learning model, ninety-five patient files were identified from the OCT (SPECTRALIS system; Heidelberg Engineering, Heidelberg, Germany) records. 25% of the patients spontaneously improved, 48% remained stable and 27% had progression of their disease, approximately. The final longitudinal model was able to predict 'improved' or 'stable' disease with a positive predictive value of 0.72 and 0.79, respectively. The accuracy of the model was greater than 50%. CONCLUSIONS: Deep-learning models may be utilised in real-world settings to predict outcomes of VMT. This approach requires further investigation as it may improve patient outcomes by aiding ophthalmologists in cross-checking management decisions and reduce the need for unnecessary interventions or delays.

Calciphylaxis, beware the ophthalmic mimic: A case series.

PURPOSE: We present two atypical cases of calciphylaxis presenting with ocular ischemic pathology - both without the hallmark cutaneous manifestations - to raise awareness of this rare yet highly disabling condition. OBSERVATIONS: We report two cases of ophthalmic calciphylaxis presenting as (1) anterior ischemic optic neuropathy (AION) and cilioretinal artery occlusion in a 76-year-old woman with pre-dialysis kidney failure, and (2) AION with contralateral central retinal artery occlusion (CRAO) in a 44-year-old man on hemodialysis. CONCLUSION AND IMPORTANCE: These cases highlight the need for judicious clinical suspicion of calciphylaxis in patients with kidney failure, presenting with microvascular ischemic ophthalmic pathology such as AION or CRAO. Confirmation with temporal artery biopsy is essential to direct targeted individualized multi-disciplinary treatment of calciphylaxis and avoid unnecessary steroid exposure in cases masquerading as giant cell arteritis (GCA).

Disturbed glucose and pyruvate metabolism in glaucoma with neuroprotection by pyruvate or rapamycin.

Intraocular pressure-sensitive retinal ganglion cell degeneration is a hallmark of glaucoma, the leading cause of irreversible blindness. Here, we used RNA-sequencing and metabolomics to examine early glaucoma in DBA/2J mice. We demonstrate gene expression changes that significantly impact pathways mediating the metabolism and transport of glucose and pyruvate. Subsequent metabolic studies characterized an intraocular pressure (IOP)-dependent decline in retinal pyruvate levels coupled to dysregulated glucose metabolism prior to detectable optic nerve degeneration. Remarkably, retinal glucose levels were elevated 50-fold, consistent with decreased glycolysis but possibly including glycogen mobilization and other metabolic changes. Oral supplementation of the glycolytic product pyruvate strongly protected from neurodegeneration in both rat and mouse models of glaucoma. Investigating further, we detected mTOR activation at the mechanistic nexus of neurodegeneration and metabolism. Rapamycin-induced inhibition of mTOR robustly prevented glaucomatous neurodegeneration, supporting a damaging role for IOP-induced mTOR activation in perturbing metabolism and promoting glaucoma. Together, these findings support the use of treatments that limit metabolic disturbances and provide bioenergetic support. Such treatments provide a readily translatable strategy that warrants investigation in clinical trials.

Software for Quantifying and Batch Processing Images of Brn3a and RBPMS Immunolabelled Retinal Ganglion Cells in Retinal Wholemounts.

Purpose: The ability to accurately quantify immunohistochemically labeled retinal ganglion cells (RGCs) on wholemounts is an important histopathological determinant in experimental retinal research. Traditionally, this has been performed by manual or semi-automated counting of RGCs. Here, we describe an automated software that accurately and efficiently counts immunolabeled RGCs with the ability to batch process images and perform whole-retinal analysis to permit isodensity map generation. Methods: Retinal wholemounts from control rat eyes, and eyes subjected to either chronic ocular hypertension or N-methyl-D-aspartate (NMDA)-induced excitotoxicity, were labeled by immunohistochemistry for two different RGC-specific markers, Brn3a and RNA-binding protein with multiple splicing (RBPMS). For feasibility of manual counting, images were sampled from predefined retinal sectors, totaling 160 images for Brn3a and 144 images for RBPMS. The automated program was initially calibrated for each antibody prior to batch analysis to ensure adequate cell capture. Blinded manual RGC counts were performed by three independent observers. Results: The automated counts of RGCs labeled for Brn3a and RBPMS closely matched manual counts. The automated script accurately quantified both physiological and damaged retinas. Efficiency in counting labeled RGC wholemount images is accelerated 40-fold with the automated software. Whole-retinal analysis was demonstrated with integrated retinal isodensity map generation. Conclusions: This automated cell counting software dramatically accelerates data acquisition while maintaining accurate RGC counts across different immunolabels, methods of injury, and spatial heterogeneity of RGC loss. This software likely has potential for wider application. Translational Relevance: This study provides a valuable tool for preclinical RGC neuroprotection studies that facilitates the translation of neuroprotection to the clinic.

Neuroprotection in glaucoma: recent advances and clinical translation.

Intraocular pressure (IOP) reduction is currently the only evidence-based treatment strategy for glaucoma. However, IOP control in some individuals is challenging. Despite optimal treatment, a significant proportion of individuals will progress, with loss of visual field, loss of driving vision and impaired quality of life. A new modality that could augment current treatment and reduce the rate of neurodegeneration to preserve vision throughout life would be a major breakthrough. A vast number of studies have reported effective neuroprotection in animal models of glaucoma; however, translation to the clinic remains a major hurdle. Herein, we explore the therapeutic advancements in non-IOP-dependent neuroprotection research based upon potential pathogenic mechanisms and propose strategies to improve the clinical translation of neuroprotective research in glaucoma.

The AgED Study. Age-related eye disease (AgED) in South Australian general practice: are we blind to early detection and intervention?

The AgED Study aimed to evaluate the detection, awareness and management of age-related eye disease (AgED) in South Australian general practice. Three South Australian metropolitan general practices were recruited and all patients aged 75 years and older were invited to participate. A cross-sectional postal questionnaire and retrospective audit of consenting patients' medical records was performed. On average, patients had their last eye check 9 months ago; the majority (64.9%) performed by an optometrist. Only 7.6% had visited their GP for their last eye check, mostly (90.5%) for a mandatory 'Fitness to Drive' medical assessment. There were marked differences in GP recording v. self-reported AgED and a marked discrepancy in the prevalence rates of AgED, visual impairment and blindness in this study compared with Australian population-based prevalence surveys. Despite the lack of GP documentation of eye disease, the majority of patients engaged in timely eye checks with either an optometrist or ophthalmologist, and their overall visual function and vision-related quality of life (QoL) were satisfactory.

Successful treatment of disseminated mucormycosis in a neutropenic patient with T-cell acute lymphoblastic leukaemia.

Mucormycosis is a rare angioinvasive fungal infection, more commonly seen in immunosuppressed patients, with reported mortality rates of 95% in disseminated disease. We present a case report of a patient with T-cell acute lymphoblastic leukaemia who developed disseminated infection with mucormycosis (involving the pancreas, left occipital lobe, right lower lobe of lung, appendix and right kidney) after having completed induction and consolidation chemotherapy. Growth of Lichtheimia corymbifera was initially isolated following a right pleural tap with fungal elements identified repeatedly on subsequent pathology specimens. Following radical surgical debridement and concurrent treatment with combination antifungal therapy, the patient survived. This case demonstrates that aggressive multisite surgical de-bulking of disseminated fungal foci, in conjunction with combination antifungal therapy and reversal of immunosuppression, can result in survival despite the grave prognosis associated with disseminated mucormycosis.