Acceptance and Perception of Artificial Intelligence Usability in Eye Care (APPRAISE) for Ophthalmologists: A Multinational Perspective

Background: Many artificial intelligence (AI) studies have focused on development of AI models, novel techniques, and reporting guidelines. However, little is understood about clinicians' perspectives of AI applications in medical fields including ophthalmology, particularly in light of recent regulatory guidelines. The aim for this study was to evaluate the perspectives of ophthalmologists regarding AI in 4 major eye conditions: diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and cataract. Methods: This was a multi-national survey of ophthalmologists between March 1st, 2020 to February 29th, 2021 disseminated via the major global ophthalmology societies. The survey was designed based on microsystem, mesosystem and macrosystem questions, and the software as a medical device (SaMD) regulatory framework chaired by the Food and Drug Administration (FDA). Factors associated with AI adoption for ophthalmology analyzed with multivariable logistic regression random forest machine learning. Results: One thousand one hundred seventy-six ophthalmologists from 70 countries participated with a response rate ranging from 78.8 to 85.8% per question. Ophthalmologists were more willing to use AI as clinical assistive tools (88.1%, n = 890/1,010) especially those with over 20 years' experience (OR 3.70, 95% CI: 1.10–12.5, p = 0.035), as compared to clinical decision support tools (78.8%, n = 796/1,010) or diagnostic tools (64.5%, n = 651). A majority of Ophthalmologists felt that AI is most relevant to DR (78.2%), followed by glaucoma (70.7%), AMD (66.8%), and cataract (51.4%) detection. Many participants were confident their roles will not be replaced (68.2%, n = 632/927), and felt COVID-19 catalyzed willingness to adopt AI (80.9%, n = 750/927). Common barriers to implementation include medical liability from errors (72.5%, n = 672/927) whereas enablers include improving access (94.5%, n = 876/927). Machine learning modeling predicted acceptance from participant demographics with moderate to high accuracy, and area under the receiver operating curves of 0.63–0.83. Conclusion: Ophthalmologists are receptive to adopting AI as assistive tools for DR, glaucoma, and AMD. Furthermore, ML is a useful method that can be applied to evaluate predictive factors on clinical qualitative questionnaires. This study outlines actionable insights for future research and facilitation interventions to drive adoption and operationalization of AI tools for Ophthalmology

Accuracy of axial length measurements obtained by optical biometry and acoustic biometry in rhegmatogenous retinal detachment: a prospective study

Pear Pongsachareonnont, Sagol Tangjanyatam Vitreoretinal Research Unit, Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand Purpose: We compared the accuracy of axial length (AL) measurement obtained by optical biometry with that obtained by acoustic biometry in eyes with rhegmatogenous retinal detachment (RRD). Patients and methods: This prospective descriptive analytic study measured the AL of eyes with RRD preoperatively and 3 months postoperatively using optical biometry (intraocular lens [IOL] master group) and acoustic biometry (immersion A-scan group). Preoperative and postoperative measurements were compared by paired t-test. The agreement between preoperative and postoperative measurements was analyzed using a Bland–Altman plot. Subgroup analysis of macular involvement status was performed. Results: Twenty-seven eyes were analyzed in this study. The mean AL in the IOL master group was 23.58±0.97 mm preoperatively and 24.17±1.16 mm postoperatively; the mean difference was −0.59±0.90 mm (P = 0.007). The mean AL in the immersion A-scan group was 24.29±1.59 mm preoperatively and 24.27±1.69 mm postoperatively; the mean difference was 0.02±0.48 mm (P = 0.827). Bland–Altman analysis revealed disagreement between preoperative and postoperative AL measurements in both techniques. In subgroup analysis of macula with RRD, there were significant differences between preoperative and postoperative AL measurements in the IOL master group (P = 0.014). Conclusion: Significant underestimation of AL measurement was observed when using the IOL master in eyes with RRD with macular involvement, which could affect IOL power selection. Keywords: IOL biometry, phacoemulsification, phacovitrectomy, cataract surgery biometr

Intraocular cytokines in neovascular age-related macular degeneration non-responder to ranibizumab treatment

Purpose : To evaluate cytokines level in aqueous humor of ranibizumab (RN) non-responders with neovascular AMD (nAMD) who were treated with either combination of ranibizumab (RN), and photodynamic therapy (PDT) or aflibercept (AF) and explore the prediction cytokines for RN non-responders Methods : This prospective study collected aqueous specimen prospectively from RN non-responder receiving either AF or combination PDT (Study gr.) and RN responders patients (Control gr.) for cytokine analysis at baseline, month 1, 2 and 3 visit of treatment. Cytokines level and changes in 3 treatment groups were compared by using GLMM. Weighted propensity score was used to adjusted for covariate. VEGF, PDGF,PLGF and others angiogenesis/inflammatory cytokines were analyzed by Bio-Plex® Multiplex Immunoassays. Results : Eleven, 8 and 13 eyes received AF treatment, combined PDT, and control respectively. Mean change of visual acuity from baseline is improved [WC1] in the control gr. (P<0.05) while study gr. didn’t show significant changes. In PDT group, 75% of patients showed stabilization or improvement in AMD clinical activity while PLGF, PDGF and leptin level are significant increase at first month: At 2 months visit, VEGF-A level is increase while Endoglin and HB-EGF decline when compare to baseline. At 3 months visit, VEGF-C and HGF concentration are higher in AF group than control group (p=0.02 and 0.02). There are no different in PLGF,PDGF,VEGF-A levels between each treatment group in all visit. PLGF level was higher in study gr. while IL-7 was lower in study gr. (P=0.02 and 0.04 respectively). The combination level of Angiopoetin 2, IL-6, ICAM, Follistatin and IL-3 can predict the response of RN treatment with 83% sensitivity and 72% specificity. Conclusions : Switching to AF may not reduce major cytokines level but resulted in improvement of visual acuity. Combination of PDT and RN resulted increase angiogenesis cytokines. The lack of IL-7 was found in non-responder patient. Apart from cytokine levels, other factors such as cytokine receptors and immune system activity may play a role in non-response patient

Neovascular age-related macular degeneration: intraocular inflammatory cytokines in the poor responder to ranibizumab treatment

Pear Pongsachareonnont,1,2 Michael Ying Kit Mak,2 Cameron Paul Hurst,3 Wai-Ching Lam2,4 1Vitreo-Retinal Research Unit, Department of Ophthamology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; 2Department of Ophthalmology and Vision Sciences, University of Toronto Faculty of Medicine, Toronto, ON, Canada; 3Biostatistics Center, Department of Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 4Department of Ophthalmology, University of Hong Kong, Hong Kong, China Purpose: To determine the levels of interleukin (IL)-6, vascular endothelial growth factor-A, platelet-derived growth factor, placental growth factor (PLGF), and other cytokines in the aqueous fluid of patients with neovascular age-related macular degeneration who respond poorly to ranibizumab. Patients and methods: This is an observational, prospective study. Thirty-two eyes from 30 patients were included in the study: 11 patients who responded poorly to ranibizumab and were switched to aflibercept (AF group), 8 patients who received ranibizumab and photodynamic therapy (PDT group), and 13 patients who responded to ranibizumab (control group). Aqueous fluid samples were collected for analysis of cytokine levels at baseline and after 1, 2, and 3 months of treatment. The effect of treatment on cytokine levels was compared between the study groups and between different time points using a linear mixed-effect regression model. Results: In the AF group, there was an increase in vascular endothelial growth factor-C, IL-7, and angiopoeitin-2 levels (P=0.01) and a decrease in intercellular adhesion molecule and IL-17 levels (P=0.01) between baseline and 3 months. After adjustment for age, sex, race, and type of lesion at baseline, the PLGF level was higher (P=0.02) and the IL-7 level was lower (P=0.04) in the ranibizumab non-responder group than in the ranibizumab responder group. Conclusion: Switching from ranibizumab to aflibercept did not reduce intraocular levels of angiogenesis cytokines, but resulted in improvement of central subfield thickness. PLGF levels were higher in poor responders to ranibizumab. The response of lesions to medication might be related to the stage of choroidal neovascularization. Trial registration: www.ClinicalTrial.gov (NCT02218177c). Keywords: neovascular age-related macular degeneration, choroidal neovascularization, anti-VEGF non-responder, poor responder, ranibizumab and AM

Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials

Background: To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. Methods: YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593). Findings: 3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference −0·2 ETDRS letters [−2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [−0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [−1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [−1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]). Interpretation: Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema. Funding: F Hoffmann-La Roche