Faricimab Treat-and-Extend for Diabetic Macular Edema: Two-Year Results from the Randomized Phase 3 YOSEMITE and RHINE Trials.

PURPOSE: To evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2 and vascular endothelial growth factor (VEGF) A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend (T&E)-based regimen with up to every-16-week dosing in the YOSEMITE and RHINE (ClinicalTrials.gov identifiers, NCT03622580 and NCT03622593, respectively) phase 3 trials of diabetic macular edema (DME). DESIGN: Randomized, double-masked, noninferiority phase 3 trials. PARTICIPANTS: Adults with visual acuity loss (best-corrected visual acuity [BCVA] of 25-73 letters) due to center-involving DME. METHODS: Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg every 8 weeks. The T&E up to every-16-week dosing regimen was based on central subfield thickness (CST) and BCVA change. MAIN OUTCOME MEASURES: Included changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. RESULTS: In YOSEMITE and RHINE (n = 940 and 951, respectively), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92, 96, and 100 average) with faricimab every 8 weeks (YOSEMITE and RHINE, +10.7 letters and +10.9 letters, respectively) or T&E (+10.7 letters and +10.1 letters, respectively) were comparable with aflibercept every 8 weeks (+11.4 letters and +9.4 letters, respectively). The median number of study drug injections was lower with faricimab T&E (YOSEMITE and RHINE, 10 and 11 injections, respectively) versus faricimab every 8 weeks (15 injections) and aflibercept every 8 weeks (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was improved further during year 2, with > 60% of patients receiving every-16-week dosing and approximately 80% receiving every-12-week or longer dosing at week 96. Almost 80% of patients who achieved every-16-week dosing at week 52 maintained every-16-week dosing without an interval reduction through week 96. Mean CST reductions were greater (YOSEMITE/RHINE weeks 92/96/100 average: faricimab every 8 weeks -216.0/-202.6 µm, faricimab T&E -204.5/-197.1 µm, aflibercept every 8 weeks -196.3/-185.6 µm), and more patients achieved absence of DME (CST < 325 µm; YOSEMITE/RHINE weeks 92-100: faricimab every 8 weeks 87%-92%/88%-93%, faricimab T&E 78%-86%/85%-88%, aflibercept every 8 weeks 77%-81%/80%-84%) and absence of intraretinal fluid (YOSEMITE/RHINE weeks 92-100: faricimab every 8 weeks 59%-63%/56%-62%, faricimab T&E 43%-48%/45%-52%, aflibercept every 8 weeks 33%-38%/39%-45%) with faricimab every 8 weeks or T&E versus aflibercept every 8 weeks through year 2. Overall, faricimab was well tolerated, with a safety profile comparable with that of aflibercept. CONCLUSIONS: Clinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to every 16 weeks were maintained through year 2. Faricimab given as a personalized T&E-based dosing regimen supports the role of dual angiopoietin-2 and VEGF-A inhibition to promote vascular stability and to provide durable efficacy for patients with DME. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

International Classification System for Ocular Complications of Anti-Vascular Endothelial Growth Factor Agents in Clinical Trials.

OBJECTIVE: Complications associated with intravitreal anti-vascular endothelial growth factor (VEGF) therapies are inconsistently reported in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process. DESIGN: Systematic review and Delphi consensus process. PARTICIPANTS: 25 international retinal specialists participated in the Delphi consensus survey. METHODS: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists that voted on inclusion, exclusion, rephrasing, and addition of complications. As well, surveys determined specifiers for the selected complications. This iterative process helped refine the final classification system. MAIN OUTCOME MEASURES: The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration. RESULTS: After screening 18,229 articles, 130 complications were initially categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 (70%) complications after three rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 (52%) complications in the final list. A total of 14 (11%) complications met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds were also excluded from the final classification system after the Delphi process terminated. In addition, 47 out of 75 (63%) proposed complication specifiers were included based on participant agreement. CONCLUSION: Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses.

Recent evidence of economic evaluation of artificial intelligence in ophthalmology.

PURPOSE OF REVIEW: Health economic evaluation (HEE) is essential for assessing value of health interventions, including artificial intelligence. Recent approaches, current challenges, and future directions of HEE of artificial intelligence in ophthalmology are reviewed. RECENT FINDINGS: Majority of recent HEEs of artificial intelligence in ophthalmology were for diabetic retinopathy screening. Two models, one conducted in the rural USA (5-year period) and another in China (35-year period), found artificial intelligence to be more cost-effective than without screening for diabetic retinopathy. Two additional models, which compared artificial intelligence with human screeners in Brazil and Thailand for the lifetime of patients, found artificial intelligence to be more expensive from a healthcare system perspective. In the Thailand analysis, however, artificial intelligence was less expensive when opportunity loss from blindness was included. An artificial intelligence model for screening retinopathy of prematurity was cost-effective in the USA. A model for screening age-related macular degeneration in Japan and another for primary angle close in China did not find artificial intelligence to be cost-effective, compared with no screening. The costs of artificial intelligence varied widely in these models. SUMMARY: Like other medical fields, there is limited evidence in assessing the value of artificial intelligence in ophthalmology and more appropriate HEE models are needed.

The impact of artificial intelligence on retinal disease management: Vision Academy retinal expert consensus.

PURPOSE OF REVIEW: The aim of this review is to define the "state-of-the-art" in artificial intelligence (AI)-enabled devices that support the management of retinal conditions and to provide Vision Academy recommendations on the topic. RECENT FINDINGS: Most of the AI models described in the literature have not been approved for disease management purposes by regulatory authorities. These new technologies are promising as they may be able to provide personalized treatments as well as a personalized risk score for various retinal diseases. However, several issues still need to be addressed, such as the lack of a common regulatory pathway and a lack of clarity regarding the applicability of AI-enabled medical devices in different populations. SUMMARY: It is likely that current clinical practice will need to change following the application of AI-enabled medical devices. These devices are likely to have an impact on the management of retinal disease. However, a consensus needs to be reached to ensure they are safe and effective for the overall population.

Current status and practical considerations of artificial intelligence use in screening and diagnosing retinal diseases: Vision Academy retinal expert consensus.

PURPOSE OF REVIEW: The application of artificial intelligence (AI) technologies in screening and diagnosing retinal diseases may play an important role in telemedicine and has potential to shape modern healthcare ecosystems, including within ophthalmology. RECENT FINDINGS: In this article, we examine the latest publications relevant to AI in retinal disease and discuss the currently available algorithms. We summarize four key requirements underlining the successful application of AI algorithms in real-world practice: processing massive data; practicability of an AI model in ophthalmology; policy compliance and the regulatory environment; and balancing profit and cost when developing and maintaining AI models. SUMMARY: The Vision Academy recognizes the advantages and disadvantages of AI-based technologies and gives insightful recommendations for future directions.

Polypoidal Choroidal Vasculopathy: Consensus Nomenclature and Non-Indocyanine Green Angiograph Diagnostic Criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup.

PURPOSE: To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV) and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiography (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photography findings. DESIGN: Evaluation of diagnostic test results. PARTICIPANTS: Panel of retina specialists. METHODS: As part of the Asia-Pacific Ocular Imaging Society, an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV, and proposed an updated consensus nomenclature that reflects our latest understanding based on imaging and histologic reports. The workgroup evaluated a set of diagnostic features based on OCT images and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria that does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts. MAIN OUTCOME MEASURES: Consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD. RESULTS: The workgroup recommended the terms polypoidal lesion and branching neovascular network for the 2 key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based major criteria (sub-retinal pigment epithelium [RPE] ring-like lesion, en face OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 80 eyes achieved an accuracy of 82%. CONCLUSIONS: We propose updated terminology for PCV lesion components that better reflects the nature of these lesions and is based on international consensus. A set of practical diagnostic criteria applied easily to spectral-domain OCT results can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not performed routinely.

Prevalence and Pattern of Geographic Atrophy in Asia: The Asian Eye Epidemiology Consortium.

PURPOSE: Although there have been many population-based studies of age-related macular degeneration (AMD), only limited information is available in Asia on the epidemiology of geographic atrophy (GA). We aimed to determine the prevalence and patterns of GA through an analysis of multiple studies conducted within the Asian Eye Epidemiology Consortium (AEEC). DESIGN: Cross-sectional meta-analyses. PARTICIPANTS: A total of 97 213 individuals aged 40 years and older. METHODS: Data from 22 population-based studies from countries belonging to the AEEC were included. In all studies, AMD was defined on the basis of standardized grading systems. Geographic atrophy was defined as an area of pallor in the fundus with visibility of the underlying choroidal blood vessels and sharply defined borders. Random-effects meta-analysis was performed to estimate overall and age-, gender-, and region-specific pooled prevalence of GA. MAIN OUTCOME MEASURES: Prevalence of GA per 1000 persons. RESULTS: The mean age was 60.8 ± 10.0 years, and 42 673 (43.9%) were male. Overall, a total of 223 individuals (0.2%) had GA. The pooled overall prevalence of GA was 1.57 per 1000 persons (95% confidence interval [CI], 1.04-2.10), which was 3 times less than that of neovascular AMD of 5.20 per 1000 persons (95% CI, 3.97-6.43). Compared with those aged 50 to 59 years, the prevalence of GA increased from 0.34 per 1000 persons (95% CI, 0.07-0.62) to 2.90 per 1000 persons (95% CI, 1.55-4.25) in those aged ≥70 years. The GA prevalence per 1000 persons was similar between urban (2.22; 95% CI, 1.22-3.23) and rural residents (1.33; 95% CI, 0.70-1.96). Geographic atrophy was more prevalent in South Asia (based on studies from India and Nepal, 3.82 per 1000 persons; 95% CI, 1.72-5.93) compared with East Asia (based on studies from China, Korea, Hong Kong, Taiwan, and Japan, and the Singapore Chinese Eye Study, 0.76 per 1000 persons; 95% CI, 0.31-1.22, P = 0.005). CONCLUSIONS: Geographic atrophy is uncommon in Asian populations compared with those of European ancestry. Even within Asia, geographic differences in GA prevalence were seen. The findings of this meta-analysis suggest that better dissection of risk factors in the Asian population for GA may provide insights into the biological pathways that drive these late-stage manifestations, thus suggesting better targets for prevention.

A real-world study of effectiveness of intravitreal bevacizumab and ranibizumab injection for treating retinal diseases in Thailand.

BACKGROUND: To evaluate the effectiveness of intravitreal bevacizumab (IVB) and intravitreal ranibizumab (IVR) in actual practice for treating patients with retinal diseases in Thailand. METHODS: A prospective, multi-centre, observational study was conducted among eight hospitals in their ophthalmology outpatient departments. Participants consisted of patients who had previously not received any IVB or IVR treatment between 2013 and 2014. The primary outcome measurement was the change in best-corrected visual acuity (BCVA) at the end of the follow-up period compared to baseline. RESULTS: There were 1629 treatment-naïve patients for the pro re nata (PRN) treatment pattern and 226 treatment-naive patients for the three-injections (3Inj) treatment pattern. BCVA improvements were found in 35% of the PRN group and 47% of the 3Inj group; however, it was not clinically meaningful between the IVB and IVR groups (P-value = 0.568 for PRN, P-value = 0.103 for 3Inj). A multivariable logistic regression (using the propensity score) showed that positive factors associated with vision improvement for the PRN pattern were the number of drug injections, having retinal vein occlusion, and under 60 years of age, while good BCVA at baseline was a negative predictive factor. For the 3Inj pattern, under 60 years of age and baseline BCVA were statistically significant predictors. Nonetheless, diabetes mellitus (DM) without other comorbidities was a statistically significant predictor of low response to vision improvement compared to DM with other comorbidities. CONCLUSIONS: This study was the first observational, prospective study to evaluate the real-life effectiveness of IVB and IVR in Thailand. The majority of participants who used IVB or IVR showed improvements in BCVA after treatment. Further evaluation such as long-term follow-ups and subsequent comparison of effectiveness between IVB and IVR should be investigated due to the limited sample of IVR patients. TRIAL REGISTRATION: Thai Clinical Trial Registry TCTR20141002001 . Registered 02 October 2014 (retrospectively registered).

Polypoidal Choroidal Vasculopathy: Definition, Pathogenesis, Diagnosis, and Management.

Polypoidal choroidal vasculopathy (PCV) is an age-related macular degeneration (AMD) subtype and is seen particularly in Asians. Previous studies have suggested disparity in response to intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents between PCV and typical AMD, and thus, the preferred treatment for PCV has remained unclear. Recent research has provided novel insights into the pathogenesis of PCV, and imaging studies based on OCT suggest that PCV belongs to a spectrum of conditions characterized by pachychoroid, in which disturbance in the choroidal circulation seems to be central to its pathogenesis. Advances in imaging, including enhanced depth imaging, swept-source OCT, en face OCT, and OCT angiography, have facilitated the diagnosis of PCV. Importantly, 2 large, multicenter randomized clinical trials evaluating the safety and efficacy of anti-VEGF monotherapy and combination with photodynamic therapy (PDT) recently reported initial first-year outcomes, providing level I evidence to guide clinicians in choosing the most appropriate therapy for PCV. In this review, we summarize the latest updates in the epidemiologic features, pathogenesis, and advances in imaging and treatment trials, with a focus on the most recent key clinical trials. Finally, we propose current management guidelines and recommendations to help clinicians manage patients with PCV. Remaining gaps in current understanding of PCV, such as significance of polyp closure, high recurrence rate, and heterogeneity within PCV, are highlighted where further research is needed.

Guidelines on Diabetic Eye Care: The International Council of Ophthalmology Recommendations for Screening, Follow-up, Referral, and Treatment Based on Resource Settings.

Diabetes mellitus (DM) is a global epidemic and affects populations in both developing and developed countries, with differing health care and resource levels. Diabetic retinopathy (DR) is a major complication of DM and a leading cause of vision loss in working middle-aged adults. Vision loss from DR can be prevented with broad-level public health strategies, but these need to be tailored to a country's and population's resource setting. Designing DR screening programs, with appropriate and timely referral to facilities with trained eye care professionals, and using cost-effective treatment for vision-threatening levels of DR can prevent vision loss. The International Council of Ophthalmology Guidelines for Diabetic Eye Care 2017 summarize and offer a comprehensive guide for DR screening, referral and follow-up schedules for DR, and appropriate management of vision-threatening DR, including diabetic macular edema (DME) and proliferative DR, for countries with high- and low- or intermediate-resource settings. The guidelines include updated evidence on screening and referral criteria, the minimum requirements for a screening vision and retinal examination, follow-up care, and management of DR and DME, including laser photocoagulation and appropriate use of intravitreal anti-vascular endothelial growth factor inhibitors and, in specific situations, intravitreal corticosteroids. Recommendations for management of DR in patients during pregnancy and with concomitant cataract also are included. The guidelines offer suggestions for monitoring outcomes and indicators of success at a population level.

Genome-wide association study of neovascular age-related macular degeneration in the Thai population.

We performed a genome-wide association study on 377 cases of neovascular age-related macular degeneration (AMD) and 1074 controls to determine the association of previously reported genetic variants associated with neovascular AMD in the Thai population. All patients were of Thai ancestry. We confirmed the association of age-related maculopathy susceptibility 2 (ARMS2) rs10490924 (P=7.38 × 10-17), HTRA1 rs11200638 (P=5.47 × 10-17) and complement factor H gene (CFH) rs800292 (P=2.53 × 10-8) with neovascular AMD, all loci passing the genome-wide significance level (P<5.22 × 10-8). We also found association of the previously reported CFH rs10737680 (P=1.76 × 10-6) locus in the discovery sample. Two loci not previously reported to be associated with neovascular AMD were selected for replication in 222 cases and 623 controls. The loci included LINCO1317 rs6733379 and rs2384550 on chromosome 12. LINCO1317 rs6733379 (P=3.85 × 10-2) remained significantly associated with neovascular AMD after replication. In conclusion, we confirm that ARMS2, HTRA1 and CFH variants are associated with neovascular AMD in the Thai population. Findings from this study also suggest that variants contributing to the susceptibility of neovascular AMD in the Thai population are mostly similar to other Asians with additional local genetic risks that may specifically be identified in Thai population.

Diabetic Retinopathy: Current Treatment and Thailand Perspective.

Diabetes mellitus is a common and chronic metabolic disorder involving multiple organ systems. Major eye involvements include diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). With a significantly increasing global number of cases of diabetes and the tendency towards an aging population, sight-threatening diabetic retinopathies are expected to increase from 37.3 million in 2011 to 56.3 million worldwide by 2030. Besides good glycemic and metabolic disease control, appropriate diabetic retinopathy (DR) screening and prompt treatments are crucial in order to minimize visual impairment from DR. The first-line therapy of DME is anti-vascular endothelial growth factor while panretinal photocoagulation laser remains the main treatment for PDR. Fortunately, in Thailand, these conditions have been included in the fundamental rights to eye care treatment, though an extension of geographic coverage and equal accessibility to care is needed. The Ministry of Public Health of Thailand has recently launched an area health initiative named the Service Plan, integrating 13 centers of excellence for certain specialties. As one of the 13 specialties, ophthalmic care includes centers of excellence in retina diseases. The policy implementation is aimed at drastically reducing preventable visual impairment resulting from various retinal diseases.

Update on central retinal artery occlusion.

The medical condition referred to as "central retinal artery occlusion" (CRAO) was first documented by Albrecht von Graefe in 1859. Subsequently, CRAO has consistently been identified as a serious medical condition that leads to substantial visual impairment. Furthermore, it is correlated with vascular complications that have the potential to affect crucial organs such as the brain and heart. A considerable amount of research has been extensively published on the various aspects of this topic, which is marked by notable debates and misconceptions, especially regarding its management and outcomes. The primary aim of this review article is to analyze the latest developments in the understanding of CRAO, which includes its causes, techniques for retinal imaging, systemic evaluation, and therapeutic strategies, such as vitrectomy. This review article offers readers a comprehensive learning experience to gain knowledge on the fundamental principles and recent advancements in CRAO.

Six-Year Outcomes in Subjects with Polypoidal Choroidal Vasculopathy in the EVEREST II Study.

INTRODUCTION: The EVEREST II study previously reported that intravitreally administered ranibizumab (IVR) combined with photodynamic therapy (PDT) achieved superior visual gain and polypoidal lesion closure compared to IVR alone in patients with polypoidal choroidal vasculopathy (PCV). This follow-up study reports the long-term outcomes 6 years after initiation of the EVEREST II study. METHODS: This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVEREST II study. The long-term outcomes were assessed during a recall visit at about 6 years from commencement of EVEREST II. RESULTS: The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year 6 was not different between the monotherapy and combination groups; - 7.4 ± 23.0 versus - 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year 6 (- 179.9 vs - 74.2 µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year 6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year 6 include BCVA (year 2), CST (year 2), presence of SRF/IRF at year 2, and number of anti-VEGF treatments (years 2-6). Factors associated with presence of SRF/IRF at year 6 include combination arm (OR 0.45, p = 0.033), BCVA (year 2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year 2) (OR 2.59, p = 0.042). CONCLUSION: At 6 years following the EVEREST II study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01846273.

Polypoidal choroidal vasculopathy: evidence-based guidelines for clinical diagnosis and treatment.

BACKGROUND: Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy affecting vision, with clinical features distinct from neovascular age-related macular degeneration. Currently, no evidence-based guidelines exist for its diagnosis and treatment. METHODS: A panel of experts analyzed a systematic literature search on PCV together with results of the EVEREST trial, the only published randomized controlled clinical trial in PCV. At a subsequent Roundtable meeting, recommendations for the management of PCV were agreed based on this analysis and their own expert opinion. RESULTS: Diagnosis of PCV should be based on early-phase nodular hyperfluorescence from choroidal vasculature visualized using indocyanine green angiography. Recommended initial treatment of juxtafoveal and subfoveal PCV is either indocyanine green angiography-guided verteporfin photodynamic therapy or verteporfin photodynamic therapy plus 3 × 0.5 mg ranibizumab intravitreal injections 1 month apart. If there is incomplete regression of polyps by indocyanine green angiography, eyes should be retreated with verteporfin photodynamic therapy monotherapy or verteporfin photodynamic therapy plus ranibizumab. If there is complete regression of polyps by indocyanine green angiography, but there is leakage on fluorescein angiography and other clinical or anatomical signs of disease activity, eyes should be retreated with ranibizumab. CONCLUSION: Practical guidance on the clinical management of PCV is proposed based on expert evaluation of current evidence.

Artificial Intelligence for Diabetic Retinopathy Screening Using Color Retinal Photographs: From Development to Deployment.

Diabetic retinopathy (DR), a leading cause of preventable blindness, is expected to remain a growing health burden worldwide. Screening to detect early sight-threatening lesions of DR can reduce the burden of vision loss; nevertheless, the process requires intensive manual labor and extensive resources to accommodate the increasing number of patients with diabetes. Artificial intelligence (AI) has been shown to be an effective tool which can potentially lower the burden of screening DR and vision loss. In this article, we review the use of AI for DR screening on color retinal photographs in different phases of application, ranging from development to deployment. Early studies of machine learning (ML)-based algorithms using feature extraction to detect DR achieved a high sensitivity but relatively lower specificity. Robust sensitivity and specificity were achieved with the application of deep learning (DL), although ML is still used in some tasks. Public datasets were utilized in retrospective validations of the developmental phases in most algorithms, which require a large number of photographs. Large prospective clinical validation studies led to the approval of DL for autonomous screening of DR although the semi-autonomous approach may be preferable in some real-world settings. There have been few reports on real-world implementations of DL for DR screening. It is possible that AI may improve some real-world indicators for eye care in DR, such as increased screening uptake and referral adherence, but this has not been proven. The challenges in deployment may include workflow issues, such as mydriasis to lower ungradable cases; technical issues, such as integration into electronic health record systems and integration into existing camera systems; ethical issues, such as data privacy and security; acceptance of personnel and patients; and health-economic issues, such as the need to conduct health economic evaluations of using AI in the context of the country. The deployment of AI for DR screening should follow the governance model for AI in healthcare which outlines four main components: fairness, transparency, trustworthiness, and accountability.

Potential Ocular Biomarkers for Early Detection of Alzheimer's Disease and Their Roles in Artificial Intelligence Studies.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Early detection is believed to be essential to disease management because it enables physicians to initiate treatment in patients with early-stage AD (early AD), with the possibility of stopping the disease or slowing disease progression, preserving function and ultimately reducing disease burden. The purpose of this study was to review prior research on the use of eye biomarkers and artificial intelligence (AI) for detecting AD and early AD. The PubMed database was searched to identify studies for review. Ocular biomarkers in AD research and AI research on AD were reviewed and summarized. According to numerous studies, there is a high likelihood that ocular biomarkers can be used to detect early AD: tears, corneal nerves, retina, visual function and, in particular, eye movement tracking have been identified as ocular biomarkers with the potential to detect early AD. However, there is currently no ocular biomarker that can be used to definitely detect early AD. A few studies that used AI with ocular biomarkers to detect AD reported promising results, demonstrating that using AI with ocular biomarkers through multimodal imaging could improve the accuracy of identifying AD patients. This strategy may become a screening tool for detecting early AD in older patients prior to the onset of AD symptoms.

Color vision restrictions for medical school admission: a discussion on regulations in ASEAN countries compared to countries across the world.

Color vision deficiency impairs one's ability to perceive and discriminate colors. Color-deficient individuals may face discrimination in various occupations, particularly in medical school admissions. This discussion seeks to compare the existing color vision requirements for entry to medical school in Southeast Asian countries as compared to countries across the world. Following this, we explore the published evidence in this field, to provide recommendations for future guidelines that will maximize the occupational opportunities for color-deficient individuals.

Clinical Correlation of Retinal Fluid Fluctuation Represented by Fluctuation Index in Wet Age-Related Macular Degeneration: TOWER Study Report 2.

Purpose: To explore outcomes and biomarkers associated with retinal fluid instability represented by a new parameter in neovascular age-related macular degeneration (nAMD). Methods: Patients with treatment-naïve nAMD receiving anti-vascular endothelial growth factor (VEGF) injections for a duration of 1 to 3 years were consecutively reviewed. Fluctuation Index (FI) of each eye, calculated by averaging the sum of differences in 1-mm central subfield thickness between each follow-up from months 3 to 24, was arranged into ascending order from the lowest to the highest and split equally into low, moderate, and high fluctuation groups. Outcomes were analyzed at 24 months. Results: Of 558 eyes, FI values showed a negative correlation with a degree-response gradient with 24-month visual improvement. After controlling for baseline best-corrected visual acuity and potential confounders, eyes with low fluctuation gained more Early Treatment Diabetic Retinopathy Study letters than those in the moderate and high fluctuation group (Δ, 10.1 and 14.0 letters, respectively). Significant best-corrected visual acuity improvement from baseline to month 24 (11.8 letters) was observed exclusively in the low fluctuation group despite the indifference in the number of injections and types of anti-VEGF drug used among groups. Patients presenting with central subfield thickness of ≥405 µm or intraretinal fluid coinciding with subretinal fluid showed a significant association with foveal thickness instability during the maintenance phase. Conclusions: Apart from the central subfield thickness values, unstable macular thickening represented by the FI was associated with some baseline features and may contribute to substandard visual outcomes. Translational Relevance: FI may be a valuable tool for assessing therapeutic adequacy in the treatment of nAMD.

Investigating public behavior with artificial intelligence-assisted detection of face mask wearing during the COVID-19 pandemic.

OBJECTIVES: Face masks are low-cost, but effective in preventing transmission of COVID-19. To visualize public's practice of protection during the outbreak, we reported the rate of face mask wearing using artificial intelligence-assisted face mask detector, AiMASK. METHODS: After validation, AiMASK collected data from 32 districts in Bangkok. We analyzed the association between factors affecting the unprotected group (incorrect or non-mask wearing) using univariate logistic regression analysis. RESULTS: AiMASK was validated before data collection with accuracy of 97.83% and 91% during internal and external validation, respectively. AiMASK detected a total of 1,124,524 people. The unprotected group consisted of 2.06% of incorrect mask-wearing group and 1.96% of non-mask wearing group. Moderate negative correlation was found between the number of COVID-19 patients and the proportion of unprotected people (r = -0.507, p<0.001). People were 1.15 times more likely to be unprotected during the holidays and in the evening, than on working days and in the morning (OR = 1.15, 95% CI 1.13-1.17, p<0.001). CONCLUSIONS: AiMASK was as effective as human graders in detecting face mask wearing. The prevailing number of COVID-19 infections affected people's mask-wearing behavior. Higher tendencies towards no protection were found in the evenings, during holidays, and in city centers.