Retinal vascular profile in predicting incident cardiometabolic diseases among individuals with diabetes.

OBJECTIVE: To determine the longitudinal associations between retinal vascular profile (RVP) and four major cardiometabolic diseases; and to quantify the predictive improvements when adding RVP beyond traditional risk factors in individuals with diabetes. METHODS: Subjects were enrolled from the Singapore Epidemiology of Eye Disease (SEED) study, a multi-ethnic population-based cohort. Four incident cardiometabolic diseases, calculated over a ~ 6-year period, were considered: cardiovascular disease (CVD), hypertension (HTN), diabetic kidney disease (DKD), and hyperlipidemia (HLD). The RVP-vessel tortuosity, branching angle, branching coefficient, fractal dimension, vessel caliber, and DR status-was characterized at baseline using a computer-assisted program. Traditional risk factors at baseline included age, gender, ethnicity, smoking, blood pressure (BP), HbA1c, estimated glomerular filtration rate (eGFR), or cholesterol. The improvements in predictive performance when adding RVP (compared with only traditional risk factors) was calculated using several metrics including area under the receiver operating characteristics curve (AUC) and net reclassification improvement (NRI). RESULTS: Among 1770 individuals with diabetes, incidences were 6.3% (n = 79/1259) for CVD, 48.7% (n = 166/341) for HTN, 14.6% (n = 175/1199) for DKD, and 59.4% (n = 336/566) for HLD. DR preceded the onset of CVD (RR 1.85[1.14;3.00]) and DKD (1.44 [1.06;1.96]). Narrower arteriolar caliber preceding the onset of HTN (0.84 [0.72;0.99]), and changes in arteriolar branching angle preceded the onset of CVD (0.78 [0.62;0.98]) and HTN (1.15 [1.03;1.29]). The largest predictive improvement was found for HTN with AUC increment of 3.4% (p = .027) and better reclassification of 11.4% of the cases and 4.6% of the controls (p = .008). CONCLUSION: We found that RVPs improved the prediction of HTN in individuals with diabetes, but add limited information for CVD, DKD, and HLD predictions.

Intraocular Pressure and Glaucoma in Thyroid Eye Disease.

PURPOSE: Current literature lacks a summary of knowledge on intraocular pressure (IOP) elevation and glaucoma in thyroid eye disease (TED). This review aims to augment existing literature by providing such a summary. It qualitatively evaluates current knowledge on the pathogenesis, prevalence, and management of concomitant ocular hypertension or glaucoma in TED patients. METHODS: In this narrative review, relevant publications were identified through a computerized database search. Search results were screened for relevance. Correspondence, Editorials, and Letters to the Editors were excluded. References cited within the identified articles were used to further augment the search. Information extracted for qualitative analysis included epidemiologic data, methods of IOP assessment, management protocols, and response to treatment. RESULTS: Studies in current literature are relatively heterogenous, differing in country of origin, TED cohort sizes, and IOP measurement techniques. Further studies are required to elucidate the true epidemiologic relationship between TED and ocular hypertension or glaucoma. Proposed models of IOP elevation include elevation of episcleral venous pressure, mucopolysaccharide deposition within the trabecular meshwork, restrictive myopathy, steroid-induced glaucoma, and secondary glaucoma. IOP-reducing effects of TED treatment options are discussed. CONCLUSIONS: While raised IOP in TED is a common phenomenon, the diagnosis of glaucoma in TED requires a high index of suspicion before any intervention.

The Global Extent of Undetected Glaucoma in Adults: A Systematic Review and Meta-analysis.

TOPIC: Glaucoma is the leading cause of irreversible blindness, despite having good prognosis with early treatment. We evaluated the global extent of undetected glaucoma and the factors associated with it in this systematic review and meta-analysis. CLINICAL RELEVANCE: Undetected glaucoma increases the risk of vision impairment, which leads to detrimental effects on the quality-of-life and socioeconomic well-being of those affected. Detailed information on the extent and factors associated with undetected glaucoma aid in the development of public health interventions. METHODS: We conducted a systematic review and meta-analysis of population-based studies published between January 1, 1990, and June 1, 2020. Article search was conducted in online databases (PubMED, Web-of-Science), grey literatures (OpenGrey), and nongovernment organization reports. Our outcome measure was the proportion of glaucoma cases that were undetected previously. Manifest glaucoma included any form of glaucoma reported in the original studies and may include primary open-angle glaucoma (POAG), primary angle-closure-glaucoma, secondary glaucoma, or a combination thereof. Undetected glaucoma was defined as glaucoma cases that were undetected prior to diagnosis in the respective study. Random-effect meta-analysis was used to estimate the pooled proportion of undetected glaucoma. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines in our study. RESULTS: We identified 61 articles from 55 population-based studies (n = 189 359 participants; n = 6949 manifest glaucoma). Globally, more than half of all glaucoma cases were undetected previously on average in each geographical region. Africa (odds ratio [OR], 12.70; 95% confidence interval [CI], 4.91-32.86) and Asia (OR, 3.41; 95% CI, 1.63-7.16) showed higher odds of undetected glaucoma as compared with Europe. Countries with low Human Development Index (HDI; <0.55) showed a higher proportion of undetected manifest glaucoma as compared with countries of medium to very high HDI (≥0.55; all P < 0.001). In 2020, 43.78 million POAG cases were projected to be undetected, of which 76.7% were in Africa and Asia. DISCUSSION: Undetected glaucoma is highly prevalent across diverse communities worldwide and more common in Africa and Asia. Strategies to improve detection are needed to prevent excess visual disability and blindness resulting from glaucoma.

Standalone XEN45 Gel Stent implantation versus combined XEN45-phacoemulsification in the treatment of open angle glaucoma-a systematic review and meta-analysis.

PURPOSE: The XEN45 Gel Stent is currently the only FDA-approved sub-conjunctival minimally invasive glaucoma surgery (MIGS) procedure. It has been used worldwide either as a standalone implantation procedure or in combination with phacoemulsification surgery. Concomitant phacoemulsification is understood to influence outcomes of traditional subconjunctival filtering surgery. However, the comparative efficacy between standalone XEN45 Gel Sent implantation ("Standalone XEN45") and combined XEN-phacoemulsification surgery ("XEN45-Phaco") remains unclear. This study aims to appraise current literature to compare the efficacy of Standalone XEN45 and XEN45-Phaco in open-angle glaucoma. METHODS: A comprehensive search of PubMed, CINAHL, CENTRAL databases was performed with the terms "Xen surgery" followed by selective vetting. Pilot, cohort, observational studies and randomised controlled trials that included at least 10 patients undergoing either Standalone XEN45 or XEN45-Phaco surgeries for the treatment of open-angle glaucoma were deemed eligible for inclusion after independent assessment by 2 authors. The search workflow was reported according to the PRISMA guidelines. Data was pooled using random-effects model. A meta-analysis of continuous outcome and proportions was performed using the meta routine in R v3.2.1. RESULTS: Ten studies were included. There was a statistically significant difference in IOP reduction favouring Standalone XEN45 at post-operative day 1, week 1, months 1, 3 and 6. There was a statistically significant difference in decrease in IOP-lowering medications favouring Standalone XEN45 at post-operative week 1 and month 1. CONCLUSION: Standalone XEN45 has superior IOP-lowering outcomes compared to XEN45-Phaco in the early post-operative period, up to 6 months after surgery.

Clinics of ocular tuberculosis: A review.

Ocular tuberculosis (OTB) is an extrapulmonary mycobacterial infection, which still sees variations in incidence, manifestations, diagnostic and therapeutic approaches. While the disease is gaining more recognition as a differential in ocular inflammation, it remains a difficult entity to detect and treat. Global efforts to synthesize and standardize the approach to OTB could prove useful in delivering quicker, more effective care. We summarize recent insights in appropriate nomenclature, clinical presentations, diagnostic modalities and courses of treatment.

Comparison of Peripapillary Choroidal Thickness Between Primary Open-angle Glaucoma, Normal Tension Glaucoma, and Normal Eyes: A Systematic Review and Meta-analysis.

TOPIC: To investigate differences in peripapillary choroidal thickness (PPCT) between primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and healthy eyes, additionally comparing differences between POAG and NTG eyes. CLINICAL RELEVANCE: Peripapillary choroidal thickness is a well-established OCT parameter in eyes with glaucoma and other ocular pathologies. The relationship between PPCT and glaucoma, if better understood, may facilitate the development of PPCT as a potential diagnostic and monitoring metric for glaucoma. In particular, there has yet to be a synthesis that directly compares PPCT between POAG eyes and NTG eyes. METHODS: A comprehensive literature search was performed on PubMed, EMBASE, and Cochrane Library, identifying studies from inception to December 2022. We included studies that measured PPCT using OCT in POAG, NTG, and healthy eyes. Mean difference (MD) among groups was calculated. Statistical analysis was performed using R version 4.2.0. Risk of bias of included studies was assessed using the Newcastle Ottawa Scale (NOS). RESULTS: Eighteen studies were included in this meta-analysis, with a pooled total of 935 healthy control eyes, 446 NTG eyes, and 934 POAG eyes. There was a significant reduction of PPCT in POAG eyes compared with healthy eyes [MD = -16.32; 95% confidence interval (CI) (-27.55 to -5.09)]. Reduction in PPCT was also significant in NTG eyes compared with healthy eyes [MD = -34.96; 95% CI (-49.97 to -19.95)]. NTG eyes had significantly reduced PPCT compared with POAG eyes [MD = -26.64; 95% CI (-49.00 to -4.28)]. CONCLUSIONS: Glaucomatous eyes appear to have significantly reduced PPCT compared with normal healthy eyes. In addition, PPCT in NTG eyes appear significantly thinner compared with that in POAG eyes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Assessing the value of the water drinking test in glaucoma-a systematic review and meta-analysis.

This systematic review and meta-analysis examines the relationship between intraocular pressure (IOP) parameters derived from the water drinking test (WDT) and diurnal IOP monitoring, and evaluates the reproducibility of the WDT and its association with future glaucomatous visual field (VF) loss. A literature search was performed on PubMed, EMBASE, and Cochrane Library from inception to 31 March 2023. Cohort, cross-sectional and observational studies reporting WDT results in glaucoma patients were included. Meta analysis with random-effect model was performed using "metafor" package in R version 3.2.1. 641 studies were identified on initial literature search. 38 studies (2479 subjects) were included in final analysis. Meta-analytic estimates of 5 studies (310 subjects) found strong positive correlation in peak IOP between the WDT and diurnal IOP monitoring (r = 0.92, 95% CI = 0.75, 1.08, p < 0.0001). However, there was only weak positive correlation for IOP fluctuation between both methods (r = 0.26, 95% CI = 0.06,0.47, p < 0.0001). Meta-analytic estimates of 3 studies (189 subjects) suggested a trend of the diurnal peak IOP being lower than that derived from the WDT (MD = -2.37 mmHg, 95% Limit of Agreement (LOA) =-5.58,0.84, p = 0.147). Two studies found that a higher WDT peak IOP was associated with greater future VF progression. Two studies demonstrated good reproducibility in peak IOP measurements for WDTs conducted across different days. In conclusion, there was a strong positive correlation between IOP peak measurements from the WDT and diurnal IOP monitoring in glaucoma patients. The WDT peak IOP demonstrated good reproducibility and may be associated with greater future VF progression.

A deep dive into hyperbaric environments and intraocular pressure-a systematic review.

Purpose: SCUBA diving exposes participants to a unique hyperbaric environment, but few studies have examined the effects of such an environment on intraocular pressure (IOP) and glaucoma. This systematic review aims to consolidate recent literature findings regarding the impact of increased atmospheric pressure on IOP and glaucoma. Methods: Three online databases were searched to identify publications encompassing the subjects of diving or increased atmospheric pressure in conjunction with IOP or glaucoma. Three reviewers independently screened the publications and identified eligible articles. Relevant data was extracted from each article. The heterogeneity of the data precluded the conduct of a meta-analysis. Results: Nine studies met the inclusion criteria. Six experimental studies employed hyperbaric chambers to measure IOP under simulated diving conditions. Among these, IOP exhibited a reduction with increased atmospheric pressures in four studies, while the findings of two studies were inconclusive. One study measured IOP pre- and post-dive and another measured IOP with and without a diving mask. Post-dive, a decrease in IOP was observed, and a statistically significant reduction was noted when subjects wore a diving mask. A retrospective study examining the incidence of acute angle closure glaucoma attack found no association with weather or atmospheric pressure. Conclusion: The majority of studies found IOP to decrease with increased atmospheric pressure and after diving. The mechanisms underlying this reduction remain incompletely understood, with potential contributors including changes in ocular blood flow, sympathetic responses, and increased oxygenation. Hyperbaric chambers may have potential in future glaucoma treatments, but more studies are required to draw reliable conclusions regarding the safety of diving for glaucoma patients.

Combined Phacoemulsification and Hydrus Microstent Implantation in Asian Eyes with Moderate-to-Severe Normal Tension Glaucoma - 12-Month Outcomes.

PRECIS: This study reports 12-month outcomes of combined phacoemulsification and Hydrus Microstent implantation in Asian eyes with moderate-to-severe normal tension glaucoma, demonstrating a significant reduction in glaucoma medications with an excellent intra- and post-operative safety profile. PURPOSE: To evaluate the 12-month safety and efficacy outcomes of combined phacoemulsification and Hydrus Microstent (Ivantis Inc., Irvine, CA) implantation in Asian eyes with moderate to severe normal tension glaucoma (NTG). METHODS: Retrospective study of consecutive surgeries performed from August 2019 to August 2021 in a single tertiary eye centre in Singapore. Outcome measures included reduction in intraocular pressure (IOP), number of glaucoma medications, and intra- and post-operative complications. RESULTS: Data from 21 eyes of 21 subjects was analysed. All subjects were ethnic Chinese and majority were male (14, 66.7%). At baseline, mean IOP was 13.3 (2.3) mmHg, all eyes had a Humphrey Visual Field (HVF) mean deviation (MD) of ≥-6 dB [mean -13.9 (4.3) dB] and all eyes were on at least one glaucoma medication. There was no statistically significant reduction in IOP at all timepoints compared to baseline (all P>0.05). However, median number of medications was reduced from 2 to 0 at all timepoints, up to POM12 (all P<0.001). There were no intraoperative complications. No eyes underwent secondary glaucoma procedures nor lost any Snellen's line of visual acuity by POM12. One (4.8%) eye experienced numerical hypotony at POD1, which resolved conservatively. Two (9.5%) eyes underwent laser iridoplasty for stent occlusion by iris. There was no deterioration in HVF MD at POM12 compared to baseline (n=20, P>0.05). CONCLUSION: Combined phacoemulsification and Hydrus Microstent implantation was effective in reducing medication burden in Asian eyes with moderate to severe NTG, up to 12 months post-operatively.

Intermediate Uveitis: A Review.

PURPOSE: This review aims to provide an update on the clinical presentation, etiologies, complications, and treatment options in intermediate uveitis (IU). METHODS: Narrative literature review. RESULTS: IU affects all age groups with no clear gender predominance and has varied etiologies including systemic illnesses and infectious diseases, or pars planitis. In some instances, IU may be the sole presentation of an underlying associated condition or disease. Management of IU and its complications include administration of corticosteroids, antimetabolites, T-cell inhibitors, and/or biologics, along with surgical interventions, with varying degrees of effectiveness across literature. In particular, increasing evidence of the safety and efficacy of immunomodulatory agents and biologics has seen greater adoption of these therapies in clinical practice. CONCLUSIONS: IU is an anatomical description of uveitis, involving intraocular inflammation of the vitreous, peripheral retinal vasculature, and pars plana. Various treatment options for intermediate uveitis are currently used in practice.

Complications and post-operative interventions in XEN45 gel stent implantation in the treatment of open angle glaucoma-a systematic review and meta-analysis.

BACKGROUND: The XEN45 Gel Stent is a subconjunctival filtering device that has demonstrated promising efficacy. This meta-analysis quantitatively evaluates reported complications and interventions after XEN45 implantation in the treatment of open angle glaucoma (OAG). METHODS: Pilot, cohort, observational studies, and randomised controlled trials that included at least ten patients undergoing ab interno or externo XEN45 surgery, with or without phacoemulsification were deemed eligible for inclusion. A meta-analysis of proportions with random-effect models was performed using the meta routine in R version 3.2.1. Outcomes included the rate of complications and post-operative interventions. RESULTS: One hundred and fifty-two studies were identified on initial literature search and 33 were included in final analysis. Numerical hypotony was the most common post-operative complication, involving 20% of patients (95% CI: 10-31%). Post-operative gross hyphema occurred in 14% (95% CI: 7-22%) and transient intra-ocular pressure (IOP) spikes (>30 mmHg) in 13% (95% CI: 4-27%). Stent exposure occurred in 1% (95% CI: 0-2%). Stent migration occurred in 1% (95% CI: 0-3%). XEN45 revision and/or a second XEN45 implantation was performed in 5% of patients (95% CI: 3-7%). Stent relocation was performed in 3% (95% CI: 1-7%). A second glaucoma procedure was performed in 11% (95% CI: 8-15%). 26% underwent one (95% CI: 17-36%), 13% underwent two (95% CI: 5-24%) while 4% underwent three (95% CI: 2-6%) bleb needling procedures. 35% of patients (95% CI: 29-40%) required at least one needling. The average rate of needling per patient was 0.38 (95% CI: 0.20-0.59). However, there is a lack of high-quality data, with 8 of the 33 studies assessed to have a moderate to high risk of bias. CONCLUSIONS: While literature suggests that XEN45 Gel Stent implantation is safe in the treatment of OAG, the overall current level of evidence is low and further studies are needed. More than a third of patients require at least one post-operative bleb needling procedure.

Anti-tubercular therapy in the treatment of tubercular uveitis: A systematic review and meta-analysis.

We quantitatively evaluated the efficacy of antitubercular therapy (ATT) in tubercular uveitis (TBU) patients. Main outcome measures include inflammation recurrence, inflammation reduction, complete resolution of inflammation, improved visual acuity (VA), ability to taper corticosteroids to < 10 mg/day without inflammatory progression, and use of adjunctive immunosuppressants while on ATT. This review is prospectively registered in PROSPERO (CRD42020206845). Forty-nine studies reporting data for 4,017 TBU patients were included. In comparative studies, the odds ratio (OR) of inflammatory recurrence was 0.33 (95%CI:0.19-0.60) for TBU patients treated with ATT±corticosteroid versus no ATT. For TBU patients treated with ATT±corticosteroid, the pooled absolute incidences of inflammatory recurrence, inflammatory reduction, complete resolution of inflammation, and visual acuity improvement were 13% (n=310/2,216; 95%CI:9-18), 81% (n=217/276; 95%CI: 62-95), 83% (n=1,167/1,812; 95%CI: 77-89), and 65% (n=347/542; 95%CI:51-78), respectively. Corticosteroids were tapered to <10 mg/day without inflammatory progression in 91% (n=326/395; 95%CI:78-99) of patients, 9% (n=121/1,376; 95%CI:6-13) of whom were administered concomitant immunosuppressive agents alongside ATT. We conclude that treatment of TBU with ATT±corticosteroid is associated with a high level of control or improvement of inflammation. More prospective studies with detailed reporting of ATT regimens, patient subgroups, and outcomes are required to better evaluate ATT effectiveness.

Recent Advancements in Glaucoma Surgery-A Review.

Surgery has long been an important treatment for limiting optic nerve damage and minimising visual loss in patients with glaucoma. Numerous improvements, modifications, and innovations in glaucoma surgery over recent decades have improved surgical safety, and have led to earlier and more frequent surgical intervention in glaucoma patients at risk of vision loss. This review summarises the latest advancements in trabeculectomy surgery, glaucoma drainage device (GDD) implantation, and minimally invasive glaucoma surgery (MIGS). A comprehensive search of MEDLINE, EMBASE, and CENTRAL databases, alongside subsequent hand searches-limited to the past 10 years for trabeculectomy and GDDs, and the past 5 years for MIGS-yielded 2283 results, 58 of which were included in the final review (8 trabeculectomy, 27 GDD, and 23 MIGS). Advancements in trabeculectomy are described in terms of adjunctive incisions, Tenon's layer management, and novel suturing techniques. Advancements in GDD implantation pertain to modifications of surgical techniques and devices, novel methods to deal with postoperative complications and surgical failure, and the invention of new GDDs. Finally, the popularity of MIGS has recently promoted modifications to current surgical techniques and the development of novel MIGS devices.

A Duration-Dependent Interaction Between High-Intensity Light and Unrestricted Vision in the Drive for Myopia Control.

Purpose: To evaluate the duration-dependent and synergetic impact of high-intensity light (HL) and unrestricted vision (UnV) on lens-induced myopia (LIM) development in chickens. Methods: Myopia was induced in one eye in chicks (10 groups, n = 126) from day 1 posthatching (D1) until day 8 (D8) using -10 diopter (D) lenses. Fellow eyes remained uncovered as controls. Nine groups were exposed daily to 2, 4, or 6 hours of HL (15,000 lux), UnV (removal of -10 D lens), or both (HL + UnV). One group served as the LIM group without any interventions. Ocular axial length (AL), refractive error, and choroidal thickness were measured on D1, D4, and D8. Outcome measures are expressed as interocular difference (IOD = experimental eye - control eye) ± SEM. Results: By D8, LIM increased AL (0.36 ± 0.04 mm), myopic refraction (-9.02 ± 0.37 D), and choroidal thinning (-90.27 ± 16.44 µm) in the LIM group (all, P < 0.001). Compared to the LIM group, exposure to 2, 4, or 6 hours of HL, UnV, or HL + UnV reduced myopic refraction in a duration-dependent manner, with UnV being more effective than HL (P < 0.05). Only 6 hours of HL + UnV (not 2 or 4 hours) prevented LIM and was more effective than UnV (P = 0.004) or HL (P < 0.001) in reducing myopic refraction and more effective than HL (P < 0.001) in reducing axial elongation. Conclusions: Daily exposure to 2, 4, or 6 hours of HL, UnV, or HL + UnV reduced lens-induced myopic refraction in a duration-dependent manner in chickens. Only 6 hours of HL + UnV completely stopped LIM development. The synergetic effect of HL and UnV is dependent on the duration of the interventions.

Oral Ibuprofen is Associated With Reduced Likelihood of Early Bleb Failure After Trabeculectomy in High-Risk Glaucoma Patients.

PRCIS: Individuals prescribed ibuprofen after trabeculectomy have better postoperative intraocular pressure (IOP) control and a higher chance of bleb survival despite being at a higher risk of scarring. PURPOSE: To investigate the effects of early adjunctive oral ibuprofen treatment on IOP and bleb failure in eyes at high risk of scarring. METHODS: In these retrospective analyses, 288 eyes of 273 patients (mean ± SD age: 68.56 ± 10.47 y; 32.60% females) with primary glaucoma who underwent trabeculectomy/phacotrabeculectomy at the Singapore National Eye Centre between April 2020 and April 2021 with a follow-up duration ≥1 year were included. Of these, 77 (26.7%) eyes deemed to be at high risk of scarring were administered oral ibuprofen ≥3 months postoperatively (mean ± SD ibuprofen administration duration: 4.08 ± 2.28 wk). Participant's IOPs at baseline and at postoperative weeks 1, 2-3; and months 1, 2, 3, 6, and 12 were recorded. Bleb failure was defined as 2 consecutive IOP readings of >21, >18, and >15 mm Hg, and/or requiring remedial postoperative laser or surgery. RESULTS: The ibuprofen group experienced significantly greater postoperative IOP reductions at week 1 [mean difference, 95%CI: -2.89 (-5.22, -0.56) mm Hg] and month 1 [-2.29 (-4.53, -0.05) mm Hg]; and substantially lower odds of bleb failure at the >18 mm Hg [odds ratio, 95% CI: 0.39 (0.20-0.79)] and >15 mm Hg [0.52 (0.29-0.94)] thresholds, compared with the non-ibuprofen group. No differences in adverse ocular hypotony events were observed. CONCLUSION: Early adjunctive oral ibuprofen administered to individuals at high risk of posttrabeculectomy scarring is associated with greater IOP reductions and reduced likelihood of bleb failure. Our results suggest that oral nonsteroidal anti-inflammatory drugs may be a safe way of improving trabeculectomy survival in high-risk eyes.

Deep learning algorithms to detect diabetic kidney disease from retinal photographs in multiethnic populations with diabetes.

OBJECTIVE: To develop a deep learning algorithm (DLA) to detect diabetic kideny disease (DKD) from retinal photographs of patients with diabetes, and evaluate performance in multiethnic populations. MATERIALS AND METHODS: We trained 3 models: (1) image-only; (2) risk factor (RF)-only multivariable logistic regression (LR) model adjusted for age, sex, ethnicity, diabetes duration, HbA1c, systolic blood pressure; (3) hybrid multivariable LR model combining RF data and standardized z-scores from image-only model. Data from Singapore Integrated Diabetic Retinopathy Program (SiDRP) were used to develop (6066 participants with diabetes, primary-care-based) and internally validate (5-fold cross-validation) the models. External testing on 2 independent datasets: (1) Singapore Epidemiology of Eye Diseases (SEED) study (1885 participants with diabetes, population-based); (2) Singapore Macroangiopathy and Microvascular Reactivity in Type 2 Diabetes (SMART2D) (439 participants with diabetes, cross-sectional) in Singapore. Supplementary external testing on 2 Caucasian cohorts: (3) Australian Eye and Heart Study (AHES) (460 participants with diabetes, cross-sectional) and (4) Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) (265 participants with diabetes, cross-sectional). RESULTS: In SiDRP validation, area under the curve (AUC) was 0.826(95% CI 0.818-0.833) for image-only, 0.847(0.840-0.854) for RF-only, and 0.866(0.859-0.872) for hybrid. Estimates with SEED were 0.764(0.743-0.785) for image-only, 0.802(0.783-0.822) for RF-only, and 0.828(0.810-0.846) for hybrid. In SMART2D, AUC was 0.726(0.686-0.765) for image-only, 0.701(0.660-0.741) in RF-only, 0.761(0.724-0.797) for hybrid. DISCUSSION AND CONCLUSION: There is potential for DLA using retinal images as a screening adjunct for DKD among individuals with diabetes. This can value-add to existing DLA systems which diagnose diabetic retinopathy from retinal images, facilitating primary screening for DKD.

Large language models and their impact in ophthalmology.

The advent of generative artificial intelligence and large language models has ushered in transformative applications within medicine. Specifically in ophthalmology, large language models offer unique opportunities to revolutionise digital eye care, address clinical workflow inefficiencies, and enhance patient experiences across diverse global eye care landscapes. Yet alongside these prospects lie tangible and ethical challenges, encompassing data privacy, security, and the intricacies of embedding large language models into clinical routines. This Viewpoint highlights the promising applications of large language models in ophthalmology, while weighing up the practical and ethical barriers towards their real-world implementation. This Viewpoint seeks to stimulate broader discourse on the potential of large language models in ophthalmology and to galvanise both clinicians and researchers into tackling the prevailing challenges and optimising the benefits of large language models while curtailing the associated risks.

Artificial Intelligence in Predicting Systemic Parameters and Diseases From Ophthalmic Imaging.

Artificial Intelligence (AI) analytics has been used to predict, classify, and aid clinical management of multiple eye diseases. Its robust performances have prompted researchers to expand the use of AI into predicting systemic, non-ocular diseases and parameters based on ocular images. Herein, we discuss the reasons why the eye is well-suited for systemic applications, and review the applications of deep learning on ophthalmic images in the prediction of demographic parameters, body composition factors, and diseases of the cardiovascular, hematological, neurodegenerative, metabolic, renal, and hepatobiliary systems. Three main imaging modalities are included-retinal fundus photographs, optical coherence tomographs and external ophthalmic images. We examine the range of systemic factors studied from ophthalmic imaging in current literature and discuss areas of future research, while acknowledging current limitations of AI systems based on ophthalmic images.

Anterior segment imaging in minimally invasive glaucoma surgery - A systematic review.

Minimally invasive glaucoma surgery (MIGS) has grown in popularity over the past decade. This systematic review explores the peri-operative and intraoperative application of anterior segment imaging to maximize the efficacy and safety of MIGS. A review of the PubMed, EMBASE and CINAHL databases was conducted, with inclusion criteria restricted to MIGS that had received United States Food and Drug Administration (FDA) premarket approval, FDA 510(K) premarket notification, or were listed as a class 1 device exempt from FDA approval or notification. 21 manuscripts from 21 unique studies were identified pertaining to MIGS devices including the XEN Gel Stent, Trabectome, iStent Inject, 1st-generation iStent and the Kahook Dual Blade (KDB). Anterior segment imaging modalities included anterior segment optical coherence tomography (AS-OCT), ultrasound biomicroscopy (UBM), aqueous angiography, OCT volumetric scans and in vivo confocal microscopy. Identification and evaluation of aqueous outflow pathways before and after MIGS have potential for improving patient preoperative patient selection and postoperative outcomes. Intraoperative imaging potentially provides the resolution needed for good visualization of angle anatomy and accurate evaluation of surgical endpoints in angle-based MIGS. Anterior segment imaging has been used to identify procedural complications, provide objective information on implant location in relation to surrounding anatomy, assess the post-implantation structural impact of MIGS devices and manage bleb failure and scarring. Technical difficulties in incorporating imaging modalities into the surgical microscope, variable quality of images and optical interference from ocular structures or surgical instruments are remaining barriers, which discourage the widespread clinical use of this technology.

Standalone XEN45 Gel Stent implantation in the treatment of open-angle glaucoma: A systematic review and meta-analysis.

The XEN45 Gel Stent (Allergan Inc., Irvine, CA) allows the drainage of aqueous into the sub-conjunctival space, through a minimally-invasive approach. This systematic review and meta-analysis evaluates its intraocular pressure (IOP)-lowering efficacy and complications in the treatment of open-angle glaucoma. Fourteen studies comprising 963 eyes were included. IOP decreased significantly (P < 0.001) across all timepoints (1 day, 1 week, 1, 3, 6, 12, 18, and 24 months) with a mean decrease of 7.44 mm Hg (95%CI:4.91-9.97) at 24 months. IOP-lowering medications decreased significantly (P < 0.001) across all timepoints (1 week, 1, 3, 6, 12, 18, 24 months) with a mean reduction of 1.67 medications (95%CI:1.28-2.06) at 24 months. Numerical hypotony occurred in 39% (95%CI:14%-67%) and stent exposure in 1% (95%CI:0%-2%) of eyes. 38% (95%CI:30%-46%) of eyes required at least one postoperative needling, with an average of 0.6 (95%CI:0.37-0.81) needlings per eye. Standalone XEN45 Gel Stent implantation is effective in lowering IOP in open-angle glaucoma. Transient numerical hypotony is the most common postoperative complication. Sight-threatening complications are rare. Postoperative needling may be required to maintain IOP-lowering outcomes; however, the overall quality of current evidence is low, with the need for more randomized controlled trials and outcomes measured with a clinically meaningful definition of success.