Development and Validation of Performance-Based Assessment of Daily Living Tasks in Age-Related Macular Degeneration.

Purpose: To establish the reliability and validity of five performance-based activities of daily living task tests (ADLTT), to correlate structure to function, to evaluate the impact of visual impairment (VI) on age-related macular degeneration (AMD), and to develop new outcome measures. Methods: A multidisciplinary team developed five ADLTTs: (1) reading test (RT); (2) facial expression (FE) recognition; (3) item search (IS) task; (4) money counting (MC) task; and (5) making a drink (MD), tested with binocular and monocular vision. ADLTTs were tested for known-group (i.e., difference between AMD group and controls) and convergent (i.e., correlation to other measures of visual function), validity metrics, and test-retest reliability in 36 patients with VI (visual acuity (logMAR VA > 0.4) in at least one eye caused by AMD versus 36 healthy controls without VI. Results: Compared to controls, AMD patients had a slower reading speed (-77.41 words/min; P < 0.001); took longer to complete MC using monocular worse eye and binocular vision (15.13 seconds and 4.06 seconds longer compared to controls, respectively; P < 0.001); and MD using monocular worse eye vision (9.37 sec; P = 0.033), demonstrating known-group validity. Only RT and MC demonstrated convergent validity, showing correlations with VA, contrast sensitivity, and microperimetry testing. Moderate to good test-retest reliability was observed for MC and MD (interclass correlation coefficient = 0.55 and 0.77; P < 0.001) using monocular worse eye vision. Conclusions: Real-world ADL functioning associated with VI-related AMD can be assessed with our validated ADLTTs, particularly MC and MD. Translational Relevance: This study validates visual function outcome measures that are developed for use in future clinical practice and clinical trials.

Initial experiences of switching to faricimab for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in an Asian population.

Purpose: To describe the early experiences of patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) whose treatment was switched to faricimab from other anti-vascular endothelial growth factor (VEGF) agents. Methods: This is a prospective cohort of eyes with nAMD and PCV that were previously treated with anti-VEGF agents other than faricimab. We evaluated visual acuity (VA), central subfield thickness (CST), macular volume (MV), pigment epithelial detachment (PED) height, and choroidal thickness (CT) after one administration of faricimab. Where present, fluid was further evaluated according to intraretinal fluid (IRF), subretinal fluid (SRF), or within PED. Results: Seventy-one eyes from 71 patients were included (45.07% PCV and 54.93% typical nAMD). The mean [standard deviation (± SD)] VA, CST, and MV improved from 0.50 logMAR (± 0.27 logMAR) to 0.46 logMAR (± 0.27 logMAR) (p = 0.20), 383.35 µm (± 111.24 µm) to 322.46 µm (± 103.89 µm (p < 0.01), and 9.40 mm3 (± 1.52 mm3) to 8.75 mm3 (± 1.17 mm3) (p < 0.01) from switch to post switch visit, respectively. The CT reduced from 167 µm (± 151 µm) to 149 µm (± 113 µm) (p < 0.01). There was also a significant reduction in the maximum PED height between visits [302.66 µm (± 217.97 µm)] and the post switch visit [236.66 µm (± 189.05 µm); p < 0.01]. This difference was greater in PEDs that were predominantly serous in nature. In the eyes with typical nAMD (n = 39), improvements were significant for CST, MV, CT, and PED. In the eyes with PCV (n = 32), only reductions in CT were statistically significant, while VA, CST, MV, and PED only showed numerically smaller improvements. One patient developed mild vitritis without vasculitis, which resolved with topical steroids with no sequelae. Conclusions: In our case series of Asian nAMD patients, switching to faricimab was associated with a stable VA and meaningful anatomical improvements, particularly with typical nAMD subtypes.

Efficacy of a novel personalised aflibercept monotherapy regimen based on polypoidal lesion closure in participants with polypoidal choroidal vasculopathy.

PURPOSE: To compare the efficacy of aflibercept using a personalised versus fixed regimen in treatment-naïve participants with polypoidal choroidal vasculopathy (PCV). DESIGN: A 52-week, randomised, open-label, non-inferiority, single-centre study that included participants with symptomatic PCV. Participants were randomised (3:1 ratio) to receive either personalised (n=40) or fixed 8-weekly treatment regimen (n=13). The personalised regimen allowed for either early treat and extend (T&E) after week 12 or late T&E with 3 additional 4-weekly aflibercept injections until week 24 in participants with residual polypoidal lesions (PL) on indocyanine green angiography (ICGA) at week 12. MAIN OUTCOMES AND MEASURES: Non-inferiority of personalised to fixed regimen for mean change in best-corrected visual acuity (BCVA) from baseline to week 52 (non-inferiority margin: -5 letters). The key secondary outcomes include reduction in central subfield thickness (CSFT) on optical coherence tomography and the anatomical closure of PL on ICGA. RESULTS: Of the 53 participants, the mean (SD) age was 69.2 (8.1) years, 19 (35.8 %) were male. Personalised group was non-inferior to fixed for the primary end point (+8.1 vs +7.9 letters at week 52, respectively; difference 0.16, 95% CI -2.8 to 2.4, p=0.79). There was greater reduction in mean CSFT (SD) in the personalised versus fixed group (-248.8 (169.9) vs -164.8 (148.9) µm, p=0.03). Closure of PL occurred in 21 (55.2%) and 5 (41.6%) of study eyes in personalised and fixed groups, respectively at week 52 (p=0.41). CONCLUSIONS: Personalised regimen achieved non-inferior BCVA gain and numerically higher PL closure compared with fixed regimen. TRIAL REGISTRATION NUMBER: NCT03117634.

Retinal microvascular signs in COVID-19.

BACKGROUND/AIMS: To explore if retinal findings are associated with COVID-19 infection. METHODS: In this prospective cross-sectional study, we recruited participants positive for COVID-19 by nasopharyngeal swab, with no medical history. Subjects underwent retinal imaging with an automated imaging device (3D OCT-1 Maestro, Topcon, Tokyo, Japan) to obtain colour fundus photographs (CFP) and optical coherence tomographic (OCT) scans of the macula. Data on personal biodata, medical history and vital signs were collected from electronic medical records. RESULTS: 108 patients were recruited. Mean age was 36.0±5.4 years. 41 (38.0%) had symptoms of acute respiratory infection (ARI) at presentation. Of 216 eyes, 25 (11.6%) had retinal signs-eight (3.7%) with microhaemorrhages, six (2.8%) with retinal vascular tortuosity and two (0.93%) with cotton wool spots (CWS). 11 eyes (5.1%) had hyper-reflective plaques in the ganglion cell-inner plexiform layer layer on OCT, of which two also had retinal signs visible on CFP (CWS and microhaemorrhage, respectively). There was no significant difference in the prevalence of retinal signs in symptomatic versus asymptomatic patients (12 (15.0%) vs 13 (9.6%), p=0.227). Patients with retinal signs were significantly more likely to have transiently elevated blood pressure than those without (p=0.03). CONCLUSION: One in nine had retinal microvascular signs on ocular imaging. These signs were observed even in asymptomatic patients with normal vital signs. These retinal microvascular signs may be related to underlying cardiovascular and thrombotic alternations associated with COVID-19 infection.

Identifying the content for an item bank and computerized adaptive testing system to measure the impact of age-related macular degeneration on health-related quality of life.

PURPOSE: We are developing an age-related macular degeneration (AMD) health-related quality of life (HRQoL) item bank, applicable to Western and Asian populations. We report primarily on content generation and refinement, but also compare the HRQoL issues reported in our study with Western studies and current AMD-HRQoL questionnaires. METHODS: In this cross-sectional, qualitative study of AMD patients attending the Singapore National Eye Centre (May-December 2019), items/domains were generated from: (1) AMD-specific questionnaires; (2) published articles; (3) focus groups/semi-structured interviews with AMD patients (n = 27); and (4) written feedback from retinal experts. Following thematic analysis, items were systematically refined to a minimally representative set and pre-tested using cognitive interviews with 16 AMD patients. RESULTS: Of the 27 patients (mean ± standard deviation age 67.9 ± 7.0; 59.2% male), 18 (66.7%), two (7.4%), and seven (25.9%) had no, early-intermediate, and late/advanced AMD (better eye), respectively. Whilst some HRQoL issues, e.g. activity limitation, mobility, lighting, and concerns were similarly reported by Western patients and covered by other questionnaires, others like anxiety about intravitreal injections, work tasks, and financial dependency were novel. Overall, 462 items within seven independent HRQoL domains were identified: Activity limitation, Lighting, Mobility, Emotional, Concerns, AMD management, and Work. Following item refinement, items were reduced to 219, with 31 items undergoing amendment. CONCLUSION: Our 7-domain, 219-item AMD-specific HRQoL instrument will undergo psychometric testing and calibration for computerized adaptive testing. The future instrument will enable users to precisely, rapidly, and comprehensively quantify the HRQoL impact of AMD and associated treatments, with item coverage relevant across several populations.

Retinal photograph-based deep learning algorithms for myopia and a blockchain platform to facilitate artificial intelligence medical research: a retrospective multicohort study.

BACKGROUND: By 2050, almost 5 billion people globally are projected to have myopia, of whom 20% are likely to have high myopia with clinically significant risk of sight-threatening complications such as myopic macular degeneration. These are diagnoses that typically require specialist assessment or measurement with multiple unconnected pieces of equipment. Artificial intelligence (AI) approaches might be effective for risk stratification and to identify individuals at highest risk of visual loss. However, unresolved challenges for AI medical studies remain, including paucity of transparency, auditability, and traceability. METHODS: In this retrospective multicohort study, we developed and tested retinal photograph-based deep learning algorithms for detection of myopic macular degeneration and high myopia, using a total of 226 686 retinal images. First we trained and internally validated the algorithms on datasets from Singapore, and then externally tested them on datasets from China, Taiwan, India, Russia, and the UK. We also compared the performance of the deep learning algorithms against six human experts in the grading of a randomly selected dataset of 400 images from the external datasets. As proof of concept, we used a blockchain-based AI platform to demonstrate the real-world application of secure data transfer, model transfer, and model testing across three sites in Singapore and China. FINDINGS: The deep learning algorithms showed robust diagnostic performance with areas under the receiver operating characteristic curves [AUC] of 0·969 (95% CI 0·959-0·977) or higher for myopic macular degeneration and 0·913 (0·906-0·920) or higher for high myopia across the external testing datasets with available data. In the randomly selected dataset, the deep learning algorithms outperformed all six expert graders in detection of each condition (AUC of 0·978 [0·957-0·994] for myopic macular degeneration and 0·973 [0·941-0·995] for high myopia). We also successfully used blockchain technology for data transfer, model transfer, and model testing between sites and across two countries. INTERPRETATION: Deep learning algorithms can be effective tools for risk stratification and screening of myopic macular degeneration and high myopia among the large global population with myopia. The blockchain platform developed here could potentially serve as a trusted platform for performance testing of future AI models in medicine. FUNDING: None.

The Ophthalmology Surgical Competency Assessment Rubric for Intravitreal Injections (ICO-OSCAR:IVI).

(1) Background: Intravitreal injections (IVIs) are the most commonly performed intraocular procedure worldwide. Ensuring correct learning is essential to avoid complications. Our purpose was to develop an internationally valid tool to assess skill in performing IVIs. (2) Methods: A panel of six content experts designed a rubric for assessing the IVI procedure by using a modified Dreyfus scale of skill acquisition, dividing it into steps and providing objective behavioral descriptors for each level of skill in each category, following the International Council of Ophthalmology (ICO) guidance. The rubric draft was then critically reviewed by 12 international content experts, and their constructive comments were considered for the final rubric. (3) Results: The Ophthalmology Surgical Competency Assessment Rubric for IVI (ICO-OSCAR:IVI) is the proposed tool for assessing healthcare professionals training to perform IVI. (4) Conclusions: The ICO-OSCAR:IVI is the result of the consensus of an international expert panel. The methodology used for its development provides this rubric with face and content validity. It can be used globally to assess healthcare professionals training to perform IVI, as well as the impact of different teaching methods on performance. Further studies are required to establish intra- and inter-rater reliability, as well as the predictive validity of this tool.

Intravitreal Injection with a Conjunctival Injection Device: A Single-Center Experience.

Purpose: To evaluate the clinical performance of the intravitreal injection assistant device (InVitria) compared with the conventional freehand technique for delivering intravitreal injections. Methods: Seventy patients were randomized to receive intravitreal injections via the conventional freehand technique while 70 received injections using the InVitria. Half of all procedures in each group were performed by junior surgeons, while the rest were performed by senior surgeons. Results: Mean injections times were 90.0 ± 23.3 seconds and 64.9 ± 26.8 seconds for conventional versus InVitria (P < 0.001). Mean injection times with the conventional technique were 85.5 ± 23.0 seconds vs. 94.2 ± 23.0 seconds for senior versus junior surgeons (P = 0.120). Mean injection times with the InVitria were 56.1 ± 26.1 seconds vs. 66.3 ± 26.9 seconds (P = 0.211) for senior versus junior surgeons. There were no significant differences in pain scores regardless of technique (conventional versus In Vitria: 2.03 ± 1.73 vs. 2.13 ± 2.20, P = 0.770). Conclusions: In our experience, the InVitria is a comparable alternative to the conventional freehand technique of delivering intravitreal injections, with the potential for faster injection times and without compromising on patient comfort. Translational Relevance: The study provides evidence to suggest that the InVitria may be deployed effectively in clinical practice.

Correction: Design, implementation, and evaluation of a nurse-led intravitreal injection programme for retinal diseases in Singapore.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Design, implementation, and evaluation of a nurse-led intravitreal injection programme for retinal diseases in Singapore.

BACKGROUND: To describe the design, implementation, and evaluation of a nurse-led intravitreal injection (NL-IVT) programme in a Singapore tertiary eye hospital. METHODS: Patients requiring anti-vascular endothelial growth factor (VEGF) IVT were recruited. Implementation and evaluation were done in the Singapore National Eye Centre, a tertiary centre. To assess safety, nurse injectors recorded details of procedures performed and complications for an 8-month period from February 2019. To evaluate patient experience, we used a modified patient questionnaire and recorded both patients' waiting time and IVT procedure duration. A retrospective audit of IVTs before and after the introduction of NL-IVT was performed from January 2017 to September 2019. Cost difference between NL-IVT and standard doctor-led (DL) IVT was evaluated. RESULTS: A total of 8599 NL-IVTs were performed. No cases of severe complication were detected in the follow-up. A total of 135 patients who received NL-IVT and DL-IVT were surveyed. General satisfaction, interpersonal manner, financial aspect, time spent with injector, and staff competence were higher in NL-IVTs than in DL-IVTs (p < 0.05). There were no differences in terms of technical quality and communication. For 934 patients, waiting time was significantly shorter in NL-IVT (3.6 ± 10.3 min) compared with DL-IVTs (35.3 ± 32.3 min); on average, 19.7 min were saved through NL-IVT (p < 0.01). The cost difference per IVT between NL-IVT and DL-IVT is estimated at 286 SGD (163 GBP). CONCLUSION: With a well-designed training programme, NL-IVT is a safe, acceptable, and cost savings procedure. With increasing demand for IVT, NL-IVT provides an alternative model of care for healthcare systems globally.

25-years Trends and Risk factors related to Surgical Outcomes of Giant Retinal Tear-Rhegmatogenous Retinal Detachments.

To describe the 25-year surgical trends, long-term outcomes and risk factors affecting the outcomes of giant retinal tear-related rhegmatogenous retinal detachments (GRT-RRD). Patients' demographics, pre-operative characteristics, risk factors, operative procedures and post-operative outcomes were collected and divided into three groups - Group A: 1991 to 2015 (overall); Group B: 1991 to 2005, and Group C: 2006 to 2015. Functional and anatomical successes were monitored over a 5-year period. Multivariate logistic regression analysis was performed to identify the risk factors related to functional and anatomical success.127 eyes of 127 patients were included in the study. At 5th year, 69.4% patients had visual acuity (VA) < logMAR 1.0 with 87.5% primary anatomical success rate. While the functional outcome remained the same between group B and C, there was an increase in the anatomical success from 89.7% to 100%, albeit not statistically significant. Patients with worse presenting VA, 150 degrees or more of giant retina tear, macula-detached status and presence of PVR were associated with VA of> logMAR 1.0 (all p < 0.05). The types of surgery (TPPV vs combined SB/TPPV), number of breaks, lens extraction and additional cryotherapy were not associated with the functional or anatomical success. In conclusion, the GRT-RRD functional and structural outcomes were comparable between 1991-2005 and 2006-2015, albeit a statistically insignificant improvement of anatomical outcome over the past 25 years. Worse presenting VA, 150 degrees or more of giant retinal tear, detached macula and presence of PVR were associated with poorer visual outcome.

Real-World Treatment Outcomes of Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Asians.

PURPOSE: To describe the 12-month outcomes of treatment-naïve eyes with choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) after initiation of intravitreal anti-vascular endothelial growth factor (VEGF) monotherapy or combination therapy with verteporfin photodynamic therapy (PDT). DESIGN: A 12-month single-center, retrospective, comparative, nonrandomized cohort study. PARTICIPANTS: Patients with AMD or PCV who initiated intravitreal anti-VEGF therapy during 2015. METHODS: Demographics, visual outcomes, OCT, and treatment data were collected at baseline and months 1, 3, 6, and 12 after treatment initiation. Multivariate analysis was performed to identify baseline features predictive of visual maintenance and improvement after 12 months of treatment. MAIN OUTCOME MEASURES: Primary end point was visual acuity (VA) change from baseline to month 12. Secondary end points were treatment exposure and change in central subfield thickness on OCT. RESULTS: A total of 364 patients (165 AMD and 199 PCV) were included. Baseline vision was 41 and 43 logarithm of the minimum angle of resolution (logMAR) letters for AMD and PCV patients, respectively. Patients with AMD and PCV received 5.5 and 5.3 injections (5.0 monotherapy vs. 5.6 combination therapy; mean, 1.2 PDT sessions), respectively. Patients with AMD gained 4.7 logMAR letters after 12 months (P = 0.002), whereas PCV patients gained 6.6 logMAR letters (P = 0.001) and 10.8 logMAR letters (P < 0.001) for monotherapy and combination therapy, respectively. Only patients with presenting VA of fewer than 35 letters (Snellen equivalent, 6/60) achieved significant visual improvement (10.4 letters for AMD, 17.1 letters for PCV with monotherapy, and 35.5 letters for PCV with combination therapy). Predictors of VA gain included number of intravitreal injections (AMD and PCV adjusted odds ratio, 12.1 [P = 0.001] and 12.5 [P = 0.004] for ≥7 injections, respectively) and baseline VA of 20 logMAR letters or fewer (adjusted odds ratio, 3.8 and 10.6 for AMD and PCV, respectively). Age, gender, race, use of PDT or focal laser therapy, and central subfield thickness were not predictive of significant visual gain at 12 months. CONCLUSIONS: In Asian patients, treatment of AMD with anti-VEGF therapy yielded 12-month visual outcomes comparable with those of other real-world studies from Western populations but poorer than those of controlled trials. In contrast, for PCV eyes, anti-VEGF monotherapy and combination therapy with PDT yielded comparable outcomes as those of controlled clinical trials.

IMPROVED DETECTION AND DIAGNOSIS OF POLYPOIDAL CHOROIDAL VASCULOPATHY USING A COMBINATION OF OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess the ability of optical coherence tomography (OCT) alone and in combination with OCT angiography (OCTA) to differentiate polypoidal choroidal vasculopathy (PCV) from neovascular age-related macular degeneration, as compared to fluorescein angiography and indocyanine green angiography. METHODS: This is a cross-sectional study. All participants had a standardized history, clinical examination including measurement of best-corrected visual acuity, slit-lamp biomicroscopy, and indirect fundus examination, and underwent standardized imaging (color photography, fluorescein and indocyanine green angiography, OCT, and OCTA) after predefined protocols. We used a 2-step approach (Step 1: spectral domain OCT; Step 2: addition of OCTA) combining structural OCT and OCTA to differentiate 50 treatment-naive eyes with PCV, choroidal neovascularization, and retinal angiomatous proliferation and compared with the diagnosis based on fluorescein angiography and indocyanine green angiography. Spectral domain OCT signs used to diagnose PCV included presence of two out of three of any retinal pigment epithelium detachment (pigment epithelial detachment/double-layer sign), notched or narrow-peaked pigment epithelial detachment, or round subretinal pigment epithelium structure. Optical coherence tomography angiography signs used to diagnose PCV included presence of a localized subretinal pigment epithelium hyperflow signal in the cross-sectional OCTA and/or presence of a focal hyperflow sign in en face OCTA based on outer retina slab. RESULTS: Based on fluorescein angiography and indocyanine green angiography, the diagnosis was choroidal neovascularization in 24 eyes, PCV in 23 eyes, and retinal angiomatous proliferation in 3 eyes. Based on spectral domain OCT signs, PCV was diagnosed in 19/23 (82.6%) eyes; however, specificity of OCT was only 51.9%. Cross-sectional OCTA showed a diffuse hyperflow signal in all 24 (100.0%) eyes with choroidal neovascularization, whereas a localized subretinal pigment epithelium hyperflow signal was detected in 19/23 (82.6%) eyes with PCV. En face OCTA only detected a nodular hyperflow signal in 10/23 eyes (43.5%) with PCV. Combination of OCT and OCTA achieved 82.6% sensitivity and 100.0% specificity for differentiating PCV from choroidal neovascularization/retinal angiomatous proliferation. CONCLUSION: Cross-sectional OCTA is more sensitive than en face OCTA in detecting flow signal in polyps. Combination of structural OCT and OCTA can be used to screen for PCV with a high level of sensitivity and specificity.

PEDIATRIC RETINAL DETACHMENT IN AN ASIAN POPULATION WITH HIGH PREVALENCE OF MYOPIA: Clinical Characteristics, Surgical Outcomes, and Prognostic Factors.

PURPOSE: To evaluate the clinical characteristics and surgical outcomes of pediatric retinal detachments (RDs) in an Asian population. METHODS: Retrospective review of 171 eyes of 152 pediatric patients with rhegmatogenous RD over a 20-year period. RESULTS: Myopia was the most common risk factor in our population. At 6 months, primary anatomical success was 60.7%, and overall anatomical success was 86.7%. A total of 46.8% had best-corrected visual acuity of 20/40 or better, and 81.6% had best-corrected visual acuity of 20/200 or better. In primary RDs, high myopia (≤-6D) patients had a lower primary anatomical success compared to patients with moderate myopia (≤-2D) (59.3 vs. 100% P = 0.03). Increasing age and absence of proliferative vitreoretinopathy were associated with anatomical and visual success. Pars plana vitrectomy as the primary procedure was associated with decreased odds of anatomical success. A longer duration of symptoms, cataract, and a larger RD extent were associated with poorer functional outcome. CONCLUSION: Myopia was the commonest risk factor for pediatric RD in our population. Good anatomical and functional outcome can be achieved with surgery. Increasing age at presentation and absence of proliferative vitreoretinopathy was associated with anatomical and functional success. High myopia was associated with poorer anatomical and functional outcome.

Incidence of Fellow Eye Involvement in Patients With Unilateral Exudative Age-Related Macular Degeneration.

Importance: Since the advent of optical coherence tomography angiography (OCT-A), nonexudative neovascularization has been described in the fellow eyes of unilateral exudative age-related macular degeneration (AMD). However, there is limited literature describing the natural course and optimal management of these lesions. Objective: To determine the incidence of fellow eye involvement in patients presenting with unilateral typical AMD or polypoidal choroidal vasculopathy and to evaluate the patterns of OCT-A changes within 6 months before the onset of exudative changes, especially focusing on nonexudative neovascularization. Design, Setting, and Participants: Data for this study were taken from a prospective, observational cohort study involving Asian patients with exudative AMD in the Asian AMD Phenotyping Study between October 2015 and March 2016. Analyses began in June 2017. Only patients who had gradable OCT-A and indocyanine green angiography (ICGA) scans of the fellow eye at baseline and follow-up at least 6 months apart were included for the analysis. The contralateral eye was evaluated for presence of nonexudative neovascularization based on multimodal imaging, which included ICGA, spectral domain optical coherence tomography, and OCT-A. Main Outcomes and Measures: The difference between the incidence of those with nonexudative choroidal neovascularization and those without as analyzed using log-rank test and qualitative analysis of OCT-A images. Results: We included 95 fellow eyes of 95 patients who presented with unilateral exudative AMD with a mean (SD) age of 68.6 (8.6) years. Nonexudative neovascularization was present in 18 eyes (19%) (8 [22.9%] and 10 [19.0%] fellow eyes with typical AMD and polypoidal choroidal vasculopathy, respectively; 8 [44.4%] on OCT-A; 5 [27.8%] on ICGA; and 5 [27.8%] on both OCT-A and ICGA). Development of exudative changes was noted in 6 fellow eyes (6.3%). Four eyes developed exudation from previously noted nonexudative neovascularization, and 2 eyes arose exudative changes from de novo. The probability of developing exudation within 6 months was significantly higher in eyes with baseline nonexudative neovascularization (0.087; 95% CI, 0.0033-0.210) compared with eyes without (0.010; 95% CI, 0.0026-0.041) (P = .008). In all eyes whose OCT-A images were available immediately before the onset of exudative changes, there was an increase in the size of network vessels compared with baseline. Conclusions and Relevance: The presence of nonexudative neovascularization may predispose to the development of exudative changes.

Identification of imaging features that determine quality and repeatability of retinal capillary plexus density measurements in OCT angiography.

PURPOSE: Optical coherence tomography angiography (OCT-A) potentially allows for rapid and non-invasive quantification of retinal capillary plexus density in various disease states. This study aims to identify the key features that influenced the repeatability of OCT-A measurements. METHODS: We obtained OCT-A images on two separate visits in 44 healthy eyes from 44 subjects, each imaged with using the Topcon DRI OCT Triton imaging system. The parafoveal vessel density within a 1.5 mm radius centred over the fovea was obtained with the built-in tool for the superficial and deep retinal plexuses. Repeatability of vessel density was determined by intraclass correlation (ICC) and mean variation. We evaluated several image parameters to determine their influence on the repeatability of vessel density measurement in each of the two capillary plexuses. RESULTS: The mean age of the subjects was 70.2±9.2 years, with 64% males. Mean parafoveal vessel density measurements for the first and second visits were 53.3±11.1 and 53.3±10.3 for the superficial plexus and 27.3±8.59 and 27.0±8.78 for the deep plexus. ICC analyses demonstrated that high fine vessel visibility, the absence of motion artefact and software-derived image quality score of 60 or above were necessary to obtain a good (ICC>0.6) or excellent (ICC>0.75) repeatability. CONCLUSIONS: Our study identified the imaging parameters that determined the repeatability of quantitative retinal vessel density measurements. These findings have implications in determining if OCT-A images can be used to accurately evaluate serial changes in retinal vessel density.

COMPARISON OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHIC CHANGES AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY ALONE OR IN COMBINATION WITH PHOTODYNAMIC THERAPY IN POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To compare changes in optical coherence tomography angiography in eyes with polypoidal choroidal vasculopathy after treatment with anti-vascular endothelial growth factor monotherapy or combined with photodynamic therapy. METHODS: This is a longitudinal case-controlled study. The authors performed optical coherence tomography angiography at baseline and Month 3 in patients with treatment-naive polypoidal choroidal vasculopathy undergoing monotherapy (n = 10) or combination therapy (n = 13). We analyzed flow signal within the outer retina and choriocapillaris using automated segmentation. The authors analyzed the presence of pachyvessels using a 10.4-µm segment through Haller layer. The changes in each layer were compared between treatments. RESULTS: At Month 3, both groups showed similar improvement in best-corrected visual acuity and central retinal thickness. However, flow signal within the polypoidal choroidal vasculopathy complex was decreased in more eyes after combination therapy than after monotherapy (84.6% vs. 40.0%, P = 0.04). Patchy reduction in flow signal within the choriocapillaris layer was noted in 15.4% and 10.0% after combination therapy and monotherapy, respectively (P = 0.61). Significant reduction in pachyvessel caliber was seen only after combination therapy but not after monotherapy (75.0% vs. 0.0%, P = 0.01). CONCLUSION: Longitudinal optical coherence tomography angiography demonstrates more significant reduction in lesion flow and pachyvessels in the short term after combination therapy than after monotherapy, although visual and structural OCT showed similar improvement.

CHOROIDAL VASCULAR HYPERPERMEABILITY AS A PREDICTOR OF TREATMENT RESPONSE FOR POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To investigate the influence of choroidal vascular hyperpermeability (CVH) and choroidal thickness on treatment outcomes in eyes with polypoidal choroidal vasculopathy (PCV) undergoing anti-vascular endothelial growth factor monotherapy or combination therapy of photodynamic therapy and anti-vascular endothelial growth factor injections. METHODS: The authors performed a prospective, observational cohort study involving 72 eyes of 72 patients with polypoidal choroidal vasculopathy (mean age 68.6 years, 51% men) treated with either monotherapy (n = 41) or combination therapy (n = 31). Each eye was imaged with color fundus photography, fluorescent angiography, indocyanine green angiography, and spectral domain optical coherence tomography. Indocyanine green angiography images were used to evaluate CVH, and spectral domain optical coherence tomography was used to measure central choroidal thickness. Changes in visual acuity over 12 months, and number of anti-vascular endothelial growth factor injections were investigated. RESULTS: Choroidal vascular hyperpermeability was present in 31 eyes (43.1%). Visual acuity change over 12 months was numerically better in the CVH group compared with the CVH (-) group (-0.099 and -0.366 logarithm of the minimal angle of resolution unit in the CVH (-) and CVH (+) groups, respectively, multivariate P = 0.063) and significantly better in a matched pair analysis (P = 0.033). Furthermore, in the combination therapy group, the number of injection was significantly lower in the CVH (+) group compared with the CVH (-) group (4.68 vs. 2.58 injections/year in the CVH (-) and CVH (+) groups; P = 0.0044). There was no significant relationship between treatment response and choroidal thickening. CONCLUSION: The presence of CVH is associated with better visual outcome in eyes with polypoidal choroidal vasculopathy and lower injection number in combination therapy. Thus, CVH, but not choroidal thickness, should be further evaluated as a potential biomarker for selecting patients for combination therapy.

Change in vision-related quality of life and influencing factors in Asians receiving treatment for neovascular age-related macular degeneration.

AIM: To assess the change in vision-related quality of life (VRQoL) after treatment for neovascular age-related macular degeneration (nAMD) and factors influencing this change in an Asian population. METHODS: In this longitudinal study, 116 patients (mean age±SD=66.5±9.9 years; 59.5% male) who underwent treatment for nAMD were recruited from a tertiary eye centre in Singapore. Best-corrected visual acuity (BCVA) and the Impact of Vision Impairment (IVI) questionnaire were evaluated at baseline and month 12. We defined three categories of BCVA change in the treated eye: BCVA gain ≥2 lines; no change in BCVA; BCVA loss ≥2 lines. The main outcome measures were the Rasch-derived IVI Reading, Mobility, and Emotional Scores. Multivariable linear regression analyses assessed the influence of sociodemographic, clinical and treatment-related factors on change in VRQoL. RESULTS: Following treatment, mean treated-eye BCVA improved by almost 2 lines (-0.22±0.40 logMAR, p<0.001) and 43% (n=50) patients reported a gain in BCVA of ≥2 lines. Mean±SD scores for Reading, Mobility and Emotional demonstrated positive changes of 0.43±1.73, 0.45±1.54 and 0.66±1.6, respectively (p<0.001 for all). In multivariable models, a ≥2 line improvement in BCVA was independently associated with a 47% (ß=0.20; CI 0.01 to 0.39) increase in Reading Scores, but was not independently associated with Mobility or Emotional Scores. CONCLUSION: Nearly half of patients undergoing treatment for nAMD reported a 2-line improvement in vision which was, in turn, associated with substantial positive increases in Reading Scores. Improvements in Mobility and Emotional Scores appear to be driven by factors other than visual acuity.

Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes.

Importance: A deep learning system (DLS) is a machine learning technology with potential for screening diabetic retinopathy and related eye diseases. Objective: To evaluate the performance of a DLS in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, possible glaucoma, and age-related macular degeneration (AMD) in community and clinic-based multiethnic populations with diabetes. Design, Setting, and Participants: Diagnostic performance of a DLS for diabetic retinopathy and related eye diseases was evaluated using 494 661 retinal images. A DLS was trained for detecting diabetic retinopathy (using 76 370 images), possible glaucoma (125 189 images), and AMD (72 610 images), and performance of DLS was evaluated for detecting diabetic retinopathy (using 112 648 images), possible glaucoma (71 896 images), and AMD (35 948 images). Training of the DLS was completed in May 2016, and validation of the DLS was completed in May 2017 for detection of referable diabetic retinopathy (moderate nonproliferative diabetic retinopathy or worse) and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse) using a primary validation data set in the Singapore National Diabetic Retinopathy Screening Program and 10 multiethnic cohorts with diabetes. Exposures: Use of a deep learning system. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity of the DLS with professional graders (retinal specialists, general ophthalmologists, trained graders, or optometrists) as the reference standard. Results: In the primary validation dataset (n = 14 880 patients; 71 896 images; mean [SD] age, 60.2 [2.2] years; 54.6% men), the prevalence of referable diabetic retinopathy was 3.0%; vision-threatening diabetic retinopathy, 0.6%; possible glaucoma, 0.1%; and AMD, 2.5%. The AUC of the DLS for referable diabetic retinopathy was 0.936 (95% CI, 0.925-0.943), sensitivity was 90.5% (95% CI, 87.3%-93.0%), and specificity was 91.6% (95% CI, 91.0%-92.2%). For vision-threatening diabetic retinopathy, AUC was 0.958 (95% CI, 0.956-0.961), sensitivity was 100% (95% CI, 94.1%-100.0%), and specificity was 91.1% (95% CI, 90.7%-91.4%). For possible glaucoma, AUC was 0.942 (95% CI, 0.929-0.954), sensitivity was 96.4% (95% CI, 81.7%-99.9%), and specificity was 87.2% (95% CI, 86.8%-87.5%). For AMD, AUC was 0.931 (95% CI, 0.928-0.935), sensitivity was 93.2% (95% CI, 91.1%-99.8%), and specificity was 88.7% (95% CI, 88.3%-89.0%). For referable diabetic retinopathy in the 10 additional datasets, AUC range was 0.889 to 0.983 (n = 40 752 images). Conclusions and Relevance: In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes.