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To investigate the relative effect of disorganization of the retinal inner layers (DRIL) and ellipsoid zone (EZ) loss on visual function in diabetic macular ischemia (DMI).Prospective cross-sectional observational study.Patients with stable treated proliferative diabetic retinopathy (PDR) without center-involved diabetic macular edema were recruited at the Moorfields Eye Hospital from December 2019 to November 2021. The main inclusion criteria were best-corrected visual acuity (BCVA) of ≥ 40 ETDRS letters (Snellen equivalent 20/160) with OCT angiography (OCTA) evidence of DMI in ≥ 1 eye.Each eligible eye of the recruited patients was assessed for BCVA, OCT, and OCTA metrics. The prespecified OCT parameters were DRIL and subfoveal EZ loss. Generalized estimating equations were used.The frequency of DRIL and EZ loss, their relative contributions to vision loss, and their associations with microvascular alterations were evaluated.A total of 125 eyes of 86 patients with PDR were enrolled; 104 (83%) eyes had a BCVA of ≥ 70 letters. Disorganization of the retinal inner layers was more prevalent than EZ loss (46% [58 eyes] vs. 19% [24 eyes]). On average, the presence of DRIL had a more pronounced impact on vision, retinal thickness, and microvascular parameters than EZ loss. After multivariable adjustment, the odds of coexisting DRIL increased by 12% with every letter decrease in BCVA; however, there was no statistically significant association of subfoveal EZ loss with BCVA. In eyes with DRIL in the absence of EZ loss, the BCVA declined significantly by 6.67 letters compared with eyes with no DRIL nor EZ loss (95% confidence interval [CI], -9.92 to -3.41; P0.001). However, if DRIL and EZ loss coexisted, the resultant BCVA was 13.22 letters less than eyes without these structural abnormalities (95% CI, -18.85 to -7.59; P0.001).In patients with DMI with a Snellen visual acuity of 20/160 or better, eyes with DRIL were associated with more visual function loss and retinal blood circulation alterations than those with subfoveal EZ loss only.

To evaluate the ability of handheld chromatic pupillometry to reveal and localise retinal neural dysfunction in diabetic patients with and without diabetic retinopathy (DR).This cross-sectional study included 82 diabetics (DM) and 93 controls (60.4 ± 8.4 years, 44.1% males). DM patients included those without (n = 25, 64.7 ± 6.3 years, 44.0% males) and with DR (n = 57, 60.3 ± 8.5 years, 64.9% males). Changes in horizontal pupil radius in response to blue (469 nm) and red (640 nm) light stimuli were assessed monocularly, in clinics, using a custom-built handheld pupillometer. Pupillometric parameters (phasic constriction amplitudes [predominantly from the outer retina], maximal constriction amplitudes [from the inner and outer retina] and post-illumination pupillary responses [PIPRs; predominantly from the inner retina]) were extracted from baseline-adjusted pupillary light response traces and compared between controls, DM without DR, and DR. Net PIPR was defined as the difference between blue and red PIPRs.Phasic constriction amplitudes to blue and red lights were decreased in DR compared to controls (p 0.001; p 0.001). Maximal constriction amplitudes to blue and red lights were decreased in DR compared to DM without DR (p 0.001; p = 0.02), and in DM without DR compared to controls (p 0.001; p = 0.005). Net PIPR was decreased in both DR and DM without DR compared to controls (p = 0.02; p = 0.03), suggesting a wavelength-dependent (and hence retinal) pupillometric dysfunction in diabetic patients with or without DR.Handheld chromatic pupillometry can reveal retinal neural dysfunction in diabetes, even without DR. Patients with DM but no DR displayed primarily inner retinal dysfunction, while patients with DR showed both inner and outer retinal dysfunction.

PURPOSE: To evaluate the occurrence of retinal micro-vasculopathy in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developed coronavirus disease (COVID-19). DESIGN: Systematic review and meta-analysis. METHODS: The Pubmed and Embase databases were comprehensively searched to identify studies that reported retina vascular changes in eyes with COVID-19. Two independent reviewers selected papers and extracted data for analysis. Data of interest were extracted and analysed in RevMan Web versions 3.3. Quality of evidence was assessed using the National institute of health (NIH) quality assessment tool of case-control study. RESULTS: Thirty one studies reporting on 1373 subjects (972 COVID-19 and 401 controls) were included. Only case control studies were included in the pooled analysis. There was a significantly higher likelihood of retinal micro-vasculopathy in subjects with COVID-19 compared to controls. (odds ratio [95% confidence interval], 8.86 [2.54-27.53], p

Objective To assess ‘time in range’ as a novel measure of treatment response in diabetic macular oedema (DMO). Methods This post hoc analysis of the Protocol T randomised clinical trial included 660 individuals with centre-involved DMO and best-corrected visual acuity (BCVA) letter score ≤78–≥24 (approximate Snellen equivalent 20/32–20/320). Study participants received intravitreal aflibercept 2.0 mg, repackaged (compounded) bevacizumab 1.25 mg, or ranibizumab 0.3 mg given up to every 4 weeks using defined retreatment criteria. Mean time in range was calculated using a BCVA letter score threshold of ≥69 (20/40 or better; minimum driving requirement in many regions), with sensitivity analyses using BCVA thresholds from 100 to 0 (20/10 to 20/800) in 1-letter increments. Results Time in range was defined as either the absolute or relative duration above a predefined BCVA threshold, measured in weeks or as a percentage of time, respectively. Using a BCVA letter score threshold of ≥69 (20/40 or better), the least squares mean time in range (adjusted for baseline BCVA) in Year 1 was 41.2 weeks with intravitreal aflibercept, 4.0 weeks longer (95% CI: 1.7, 6.3; p = 0.002) than bevacizumab and 3.6 weeks longer (1.3, 5.9; p = 0.004) than ranibizumab. Overall, mean time in range was numerically longer for intravitreal aflibercept for all BCVA letter score thresholds between 92 and 30 (20/20 to 20/250). In the Day 365–728 analysis, time in range was 3.9 (1.3, 6.5) and 2.4 (0.0, 4.9) weeks longer with intravitreal aflibercept vs bevacizumab and vs ranibizumab (p = 0.011 and 0.106), respectively. Conclusion BCVA time in range may represent another way to describe visual outcomes and potential impact on vision-related functions over time for patients with DMO and provide a better understanding, for physicians and patients, of the consistency of treatment efficacy.

A panel of imaging experts was assembled to review neovascular age-related macular degeneration optical coherence tomography angiography descriptors published to date, and test agreement on use of these terms, which was found to be low. Optical coherence tomography angiography (OCTA) has been used to identify and characterize macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). 1 , 2 , 3 , 4 Many studies have explored OCTA morphological features of MNV that might serve as biomarkers to assess disease activity and response to treatment. 1 , 2 , 3 , 4 , 5 , 6 The proliferation of studies however has resulted in an OCTA terminology that has been variable and inconsistent. To address inconsistency of nomenclature and allow harmonization, a multidisciplinary panel of retinal imaging experts with a history of relevant research contributions to the field was assembled with the purpose of reviewing published terminology and to recommend a reduced list of key terms pertinent to OCTA. The group was called UNICORN, because of its ultimate goal of generating a UNIfied COmmentary of the committee of inteRnational experts on the nomenclature for Neovascular AMD in OCTA. In this report we describe the first steps, which included a review of OCTA descriptors of neovascular AMD (nAMD) published to date, and an exercise that tested agreement of these terms among retinal imaging experts. Prior to the first UNICORN meeting, a non-systematic review of the literature was performed, using the search terms “optical coherence tomography angiography” or “OCT angiography” or “OCT-A”, AND “neovascular macular degeneration” or “neovascular age-related macular degeneration” or “neovascular AMD” or “nAMD” or “wet age-related macular degeneration” or “wet AMD” or “wet ARMD”. A dictionary of OCTA descriptors relating to the features of MNV in AMD was generated and circulated to the panel.

PURPOSE: We describe the large-scale self-initiated recruitment of patients to a self-monitoring initiative for macular pathologic features during the coronavirus disease 2019 (COVID-19) pandemic. DESIGN: Observational study with retrospective analysis. PARTICIPANTS: A total of 2272 patients from the Singapore National Eye Centre (SNEC) whose visits were rescheduled over lockdown (April 13-June 1, 2020) were offered participation in a self-monitoring initiative administered by SNEC with the Alleye application (Switzerland) as the testing instrument. METHODS: This was an observational study with retrospective analysis. Demographics and characteristics were compared between those who signed up and those who did not. Similar comparisons were made between patients who complied with the initiative versus those who did not. Outcomes were tracked for 6 months starting from the commencement of lockdown. MAIN OUTCOME MEASURES: Participation and compliance rates and characteristics of patients who were more likely to participate and comply with the initiative. RESULTS: Seven hundred thirty-two patients (32%) participated in this self-monitoring initiative. Those who participated were younger (62 years of age vs. 68 years of age; P < 0.001), men, and living with family. Patients not receiving treatment and those with poorer vision in the worse-seeing eye were more likely to participate. When grouped according to diagnosis, the proportion who participated was highest for diabetic macular edema (52%), nonneovascular age-related macular degeneration (AMD; 42%), diabetic retinopathy (35%), retinal vein occlusions (18%), and neovascular AMD (15%; P < 0.001). Testing compliance rate was 43% (315/732). Patients who complied with the initiative were older, were receiving treatment, and had poorer vision in the worse-seeing eye. Trigger events occurred in 33 patients, with 5 patients having clinically verified disease progression (1.6%). CONCLUSIONS: We provide clinical data on characteristics of patients with stable retinal diseases who were offered, participated in, and complied with a self-monitoring program. The lower participation rate compared with standardized clinical studies reflects the difficulties in implementation for such initiatives in clinical settings. Despite this, self-monitoring continues to show promise in relieving clinic resources, suggesting the feasibility of scaling such programs beyond the COVID-19 pandemic.

PURPOSE: To develop a fully-automatic hybrid algorithm to jointly segment and quantify biomarkers of polypoidal choroidal vasculopathy (PCV) on indocyanine green angiography (ICGA) and spectral domain-OCT (SD-OCT) images. DESIGN: Evaluation of diagnostic test or technology. PARTICIPANTS: Seventy-two participants with PCV enrolled in clinical studies at Singapore National Eye Center. METHODS: The dataset consisted of 2-dimensional (2-D) ICGA and 3-dimensional (3-D) SD-OCT images which were spatially registered and manually segmented by clinicians. A deep learning-based hybrid algorithm called PCV-Net was developed for automatic joint segmentation of biomarkers. The PCV-Net consisted of a 2-D segmentation branch for ICGA and 3-D segmentation branch for SD-OCT. We developed fusion attention modules to connect the 2-D and 3-D branches for effective use of the spatial correspondence between the imaging modalities by sharing learned features. We also used self-supervised pretraining and ensembling to further enhance the performance of the algorithm without the need for additional datasets. We compared the proposed PCV-Net to several alternative model variants. MAIN OUTCOME MEASURES: The PCV-Net was evaluated based on the Dice similarity coefficient (DSC) of the segmentations and the Pearson’s correlation and absolute difference of the clinical measurements obtained from the segmentations. Manual grading was used as the gold standard. RESULTS: The PCV-Net showed good performance compared to manual grading and alternative model variants based on both quantitative and qualitative analyses. Compared to the baseline variant, PCV-Net improved the DSC by 0.04 to 0.43 across the different biomarkers, increased the correlations, and decreased the absolute differences of clinical measurements of interest. Specifically, the largest average (mean ± standard error) DSC improvement was for intraretinal fluid, from 0.02 ± 0.00 (baseline variant) to 0.45 ± 0.06 (PCV-Net). In general, improving trends were observed across the model variants as more technical specifications were added, demonstrating the importance of each aspect of the proposed method. CONCLUSION: The PCV-Net has the potential to aid clinicians in disease assessment and research to improve clinical understanding and management of PCV. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

OBJECTIVES For patients with polypoidal choroidal vasculopathy (PCV), intravitreal anti-vascular endothelial growth factor (anti-VEGF) combination therapy has been shown to be cost-saving relative to monotherapy in a clinical trial setting. However, whether this also applies to real-world settings is unclear. We aim to compare the real-world functional outcomes and cost-effectiveness of intravitreal anti-VEGF combination therapy relative to monotherapy, to investigate whether combination therapy is truly cost-saving. METHODS We used a Markov model to simulate a hypothetical cohort of PCV patients treated at Singapore National Eye Centre. Model parameters were informed by coarsened exact matched estimates of a two-year retrospective study of patients who initiated treatment in 2015. Treatment options included intravitreal aflibercept, bevacizumab, or ranibizumab, as monotherapy or in combination with full-fluence verteporfin photodynamic therapy. RESULTS The two-year logMAR letters gains were significant for combination therapy ( + 10.6, P = 0.006) but not monotherapy (-2.2, P = 0.459). Over 20 years, a PCV patient would cost the health system SGD 48,790 under monotherapy and SGD 61,020 under combination therapy. Quality-adjusted life-years (QALYs) were estimated to be 7.41 for monotherapy and 7.80 for combination therapy. The incremental cost-effectiveness ratio of combination therapy was SGD 31,460/QALY, which is less than the common willingness-to-pay threshold of per capita gross domestic product of Singapore (SGD 88,990/QALY). Sensitivity analysis showed that combination therapy remained incrementally cost-effective, but not cost-saving. CONCLUSIONS Our study shows that combination therapy is good value for money but is likely to increase costs when applied in real-world settings.

Age-related macular degeneration (AMD) is a global leading cause of visual impairment in older populations. 'Wet' AMD, the most common subtype of this disease, occurs when pathological angiogenesis infiltrates the subretinal space (choroidal neovascularization), causing hemorrhage and retinal damage. Gold standard anti-vascular endothelial growth factor (VEGF) treatment is an effective therapy, but the long-term prevention of visual decline has not been as successful. This warrants the need to elucidate potential VEGF-independent pathways. We generated blood out-growth endothelial cells (BOECs) from wet AMD and normal control subjects, then induced angiogenic sprouting of BOECs using a fibrin gel bead assay. To deconvolute endothelial heterogeneity, we performed single-cell transcriptomic analysis on the sprouting BOECs, revealing a spectrum of cell states. Our wet AMD BOECs share common pathways with choroidal neovascularization such as extracellular matrix remodeling that promoted proangiogenic phenotype, and our 'activated' BOEC subpopulation demonstrated proinflammatory hallmarks, resembling the tip-like cells in vivo. We uncovered new molecular insights that pathological angiogenesis in wet AMD BOECs could also be driven by interleukin signaling and amino acid metabolism. A web-based visualization of the sprouting BOEC single-cell transcriptome has been created to facilitate further discovery research. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University Published version The team from Nanyang Technological University Singapore was funded by the Nanyang Assistant Professorship and Academic Research Fund grants (MOE2018-T2-1-042 and RG88/21) from the Ministry of Education, Singapore. N.J.Y.Y and V.W. were supported by the Nanyang President’s Graduate Scholarship. C.C. and C.M.G.C. were funded by the SERI-IMCB Program in Retinal Angiogenic Diseases (SIPRAD) grant (SPF2014/002) from Agency for Science, Technology and Research, Singapore.

The natural history and clinical significance of pachydrusen is unclear. This study aims to compare the longitudinal changes of eyes with pachydrusen and soft drusen and progression to exudative macular neovascularisation (MNV). Patients with a diagnosis of MNV in one eye only and the fellow eye was selected as the study eye. Study eyes were required to have pachydrusen or soft drusen on fundus photographs and follow up of at least 2 years or until exudative MNV occurred. Systematic grading was performed at baseline and change in drusen area and onset of exudative MNV recorded over the period of follow up. A total of 75 eyes from 75 patients (29 with pachydrusen and 46 with soft drusen) were included. There was no difference in the rate of progression to exudative MNV in the soft and pachydrusen groups (13.3% versus 24.1%, p = 0.38). Pachydrusen, as compared to soft drusen, was associated with polypoidal choroidal vasculopathy subtype (85.7% versus 16.7%, p

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 angiograph (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photograph findings. Design Evaluation of diagnostic test Participants Panel of retina specialists. Methods As part of the Asia-Pacific Ocular Imaging Society (APOIS), 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, which reflects our latest understanding based on imaging and histology reports. The workgroup evaluated a set of diagnostic features based on OCT 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 which does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts. Main Outcome Measures A 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 two key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based ‘major criteria’ (sub-RPE ring-like lesion, enface 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 110 eyes achieved an accuracy of 82%. Conclusions We propose updated terminology for PCV lesion components which better reflect the nature of these lesions which was based on international consensus. A set of practical diagnostic criteria that are easily applied to SD-OCT can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not routinely performed.

The results of the study show that the updated ATN grading system is an accurate and reliable tool to classify patients with pathologic myopia. These findings show that best-corrected visual acuity is more compromised in eyes with severe pathologic myopia, particularly those graded ≥A3 or T3, Purpose: To assess the reliability of the atrophy-traction-neovascularization (ATN) classification in patients with pathologic myopia (PM) and its correlation with best-corrected visual acuity (BCVA). Methods: Cross-sectional study. Hundred highly myopic eyes with a spherical equivalent of >−6.0 diopters or axial length of >26 mm and a total ATN score of ≥3 underwent a complete ophthalmological examination, including fundus photography and swept-source optical coherence tomography. Five observers graded each eye using the ATN system. Mean A, T, and N scores were calculated and correlated with age, BCVA (in logarithm of the minimum angle of resolution), and axial length. Patients were considered to present severe PM if either A or T components were ≥3 and/or N was ≥2. Results: Hundred eyes (53 left) from 91 patients (78 women) were classified. Mean age, BCVA, and axial length values were, respectively, 65.1 ± 11.7 years (range, 36–97 years), −0.63 ± 0.62 (−3.00 to 0.00), and 29.26 ± 2.7 mm (26.01–37.66 mm). Mean ATN grades for each component were as follows: A = 2.51 ± 0.78 (0.6–4.0), T = 0.88 ± 1.14 (0.0–5.0), and N = 1.31 ± 1.40 (0.0–3.0). Weighted interobserver agreement was 98.1%, 98.7%, and 94.6%, for A, T and N, respectively. In eyes with severe PM, BCVA was significantly lower and axial length was significantly longer. Conclusion: The excellent interobserver rate in this study demonstrates that the updated ATN grading system is an accurate and reliable tool to classify patients with PM. These findings show that BCVA is more compromised in eyes with severe PM, particularly those graded ≥A3 and/or T3.

The COVID-19 pandemic has put strain on healthcare systems and the availability and allocation of healthcare manpower, resources and infrastructure. With immediate priorities to protect the health and safety of both patients and healthcare service providers, ophthalmologists globally were advised to defer nonurgent cases, while at the same time managing sight-threatening conditions such as neovascular Age-related Macular Degeneration (AMD). The management of AMD patients both from a monitoring and treatment perspective presents a particular challenge for ophthalmologists. This review looks at how these pressures have encouraged the acceptance and speed of adoption of digitalization. A literature review was conducted on the use of digital technology during COVID-19 pandemic, and on the transformation of medicine, ophthalmology and AMD screening through digitalization. In the management of AMD, the implementation of artificial intelligence and "virtual clinics" have provided assistance in screening, diagnosis, monitoring of the progression and the treatment of AMD. In addition, hardware and software developments in home monitoring devices has assisted in self-monitoring approaches. Digitalization strategies and developments are currently ongoing and underway to ensure early detection, stability and visual improvement in patients suffering from AMD in this COVID-19 era. This may set a precedence for the post COVID-19 new normal where digital platforms may be routine, standard and expected in healthcare delivery. [Abstract copyright: Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.]

Diabetic macular ischemia (DMI) is a common complication of diabetic retinopathy that can lead to progressive and irreversible visual loss. Despite substantial clinical burden, there are no treatments for DMI, no validated clinical trial endpoints, and few clinical trials focusing on DMI. Therefore, generating consensus on validated endpoints that can be used in DMI for the development of effective interventions is vital. In this review, we discuss potential endpoints appropriate for use in clinical trials of DMI, and consider the data required to establish acceptable and meaningful endpoints. A combination of anatomical, functional, and patient-reported outcome measures will provide the most complete picture of changes that occur during the progression of DMI. Potential endpoint measures include change in size of the foveal avascular zone measured by optical coherence tomography angiography and change over time in best-corrected visual acuity. However, these endpoints must be supported by further research. We also recommend studies to investigate the natural history and progression of DMI. In addition to improving understanding of how patient demographics and comorbidities such as diabetic macular edema affect clinical trial endpoints, these studies would help to build the consensus definition of DMI that is currently missing from clinical practice and research.

Aim The aim of this study is to evaluate the frequency and types of anti-retinal autoantibodies (ARAs) in highly myopic patients and to explore any association between ARAs and the severity of myopic macular degeneration (MMD). Methods This was a clinic-based study of 16 patients with high myopia (spherical equivalent worse than -6 dioptres or axial length (AL) ≥ 26.5 mm) recruited from the High Myopia clinic of the Singapore National Eye Centre. MMD was graded from fundus photographs according to the Meta-analysis for Pathologic Myopia (META-PM) classification. Severe MMD was defined as META-PM category 3 or 4. AL and logarithm of the minimal angle of resolution (logMAR) best corrected visual acuity (BCVA) were measured. Sera were obtained from subjects and analysed for the presence of ARAs with the western blot technique. Results The mean AL was significantly longer in patients with severe MMD (n = 8) than those without severe MMD (n = 8) (31.50 vs. 28.51, p = 0.005). There was at least one ARA identified in all patients. The most common ARA was anti-carbonic anhydrase II (anti-CAII), present in nine patients (56.3%). Anti-CAII was detected in more patients with severe MMD than those without (75 vs. 37.5%, p = 0.32). LogMar BCVA was also worse in subjects with anti-CAII (0.5 ± 0.38 vs. 0.22 ± 0.08, p = 0.06). The number of ARAs significantly correlated with increasing AL (r = 0.61, p = 0.012). Conclusions ARAs are prevalent in patients with high myopia, and this increases with increasing AL. In particular, anti-CAII antibodies were highly prevalent in patients with severe MMD, suggesting that ARAs may be associated with MMD. Further studies are necessary to confirm these observations in larger cohorts.

Purpose The aim of this consensus article was to provide comprehensive recommendations in the management of diabetic macular edema (DME) by reviewing recent clinical evidence. Design A questionnaire containing 47 questions was developed which encompassed clinical scenarios such as treatment response to anti-vascular endothelial growth factor and steroid, treatment side effects, as well as cost and compliance/reimbursement in the management of DME using a Dephi questionnaire as guide. Methods An expert panel of 12 retinal specialists from Singapore, Malaysia, Philippines, India and Vietnam responded to this questionnaire on two separate occasions. The first round responses were compiled, analyzed and discussed in a round table discussion where a consensus was sought through voting. Consensus was considered achieved, when 9 of the 12 panellists (75%) agreed on a recommendation. Results The DME patients were initially profiled based on their response to treatment, and the terms target response, adequate response, nonresponse, and inadequate response were defined. The panellists arrived at a consensus on various aspects of DME treatment such as need for classification of patients before treatment, first-line treatment options, appropriate time to switch between treatment modalities, and steroid-related side effects based on which recommendations were derived, and a treatment algorithm was developed. Conclusions This consensus article provides comprehensive, evidence-based treatment guidelines in the management of DME in Asian population. In addition, it also provides recommendations on other aspects of DME management such as steroid treatment for stable glaucoma patients, management of intraocular pressure rise, and recommendations for cataract development.

Purpose To report long-term changes in intraocular pressure (IOP) in eyes receiving vascular endothelial growth factor (VEGF) inhibitors for various retinal conditions over 12 and 24 months in routine clinical practice. Design Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project. Participants Treatment-naive eyes receiving monotherapy with VEGF inhibitors (ranibizumab [0.5 mg], aflibercept [2 mg], or bevacizumab [1 mg]) with at least 3 injections from December 2013 through December 31, 2018, and at least 12 months of follow-up. Methods Intraocular pressure was measured at each clinical visit for all eyes as part of routine practice. Main Outcome Measures The primary outcome was the mean change in IOP (in millimeters of mercury) at 12 months. The following secondary IOP outcome measures were investigated at 12 and 24 months: (1) mean change in IOP from baseline and (2) proportion of clinically significant IOP increase defined as an elevation of at least 6 mmHg to an IOP of more than 21 mmHg at any point during the follow-up. Results We identified 3429 treatment-naive eyes (395 receiving bevacizumab, 1138 receiving aflibercept, and 1896 receiving ranibizumab) with complete IOP data from 3032 patients with 12 months of follow-up data, of which 2125 (62%) had 24 months of follow-up data. The overall mean IOP change was –0.5 mmHg (95% confidence interval CI, –0.6 to –0.3 mmHg) at 12 months and –0.4 mmHg (95% CI, –0.6 to –0.3 mmHg) at 24 months, whereas the proportions of clinically significant IOP increases were 5.6% and 8.8%, respectively. A lower mean IOP change and fewer IOP elevations at 12 and 24 months was observed in eyes receiving aflibercept than in those receiving bevacizumab and ranibizumab (P ≤ 0.01 for both comparisons at each time point and outcome). Eyes with pre-existing glaucoma demonstrated more IOP increases over 12 and 24 months (odds ratio [OR], 2.2 [95% CI, 1.2–3.8; P = 0.012] and 2.1 [95% CI, 1.1–3.8; P = 0.025], respectively). Conclusions Mean IOP did not change significantly from baseline to 12 and 24 months in eyes receiving VEGF inhibitors, whereas clinically significant IOP elevations occurred in a small proportion of eyes. Aflibercept was associated with fewer clinically significant IOP elevations, whereas eyes with pre-existing glaucoma were at a higher risk.

Polypoidal choroidal vasculopathy (PCV) is a condition characterized by multiple, recurrent, serosanguineous pigment epithelial detachments, and neurosensory retinal detachments due to abnormal aneurysmal neovascular lesions. It is generally considered as a variant of neovascular age-related macular degeneration, but there are some differences between the clinical presentation, natural history, and treatment response between patients with PCV and typical neovascular age-related macular degeneration patients. Over the past decade, new research and technological advancements have greatly improved our understanding of the PCV disease process and the management of PCV. This review aims to summarize the recent research findings to highlight the epidemiology, pathogenesis, genetics, the application of various diagnostic tools for PCV, and the available treatment options for PCV.

Introduction: Since July 2021, a worldwide shortage of verteporfin (Visudyne (R)) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of indications in ophthalmology, including chronic central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal haemangioma. For these disorders, PDT is either the first-choice treatment or regarded as a major treatment option. Materials and methods: A questionnaire was sent to key opinion leaders in the field of medical retina throughout the world, to assess the role of PDT in their country and the effects of the shortage of verteporfin. In addition, information on the application of alternative treatments during shortage of verteporfin was obtained, to further assess the impact of the shortage. Results: Our questionnaire indicated that the shortage of verteporfin had a major impact on ophthalmic care worldwide and was regarded to be a serious problem by most of our respondents. However, even though there is ample evidence to support the use of PDT in several chorioretinal diseases, we found notable differences in its use in normal patient care throughout the world. Various alternative management strategies were noted during the verteporfin shortage, including lowering the dose of verteporfin per patient, the use of alternative treatment strategies and the use of a centralized system for allocating the remaining ampoules of verteporfin in some countries. Conclusion: The shortage of verteporfin has had a large effect on the care of ophthalmic patients across the world and may have resulted in significant and irreversible vision loss. Mitigation strategies should be developed in consultation with all stakeholders to avoid future medication shortages of verteporfin and other unique ophthalmic medications. These strategies may include mandatory stock keeping, compulsory licensing to an alternative manufacturer or incentivizing the development of competition, for example through novel public-private partnerships.

To analyze the effect of fluid on visual acuity in cases of Type 3 macular neovascularization.This multicentric, retrospective cohort study included eyes with treatment-naïve Type 3 macular neovascularization. Analysis of fluid in different compartments was performed. Group A included eyes with isolated intraretinal fluid, whereas Group B included eyes with intraretinal fluid in conjunction with subretinal fluid and/or sub retinal pigment epithelial fluid.Eyes in Group A (31, 55.3%) had better best-corrected visual acuity of 20/50 snellen equivalent (0.42 ± 0.31 logarithm of the minimum angle of resolution) at baseline and 20/50 snellen equivalent (0.40 ± 0.28 logarithm of the minimum angle of resolution) at complete resolution compared with Group B with visual acuity of 20/80 snellen equivalent (0.64 ± 0.35 logarithm of the minimum angle of resolution) (P = 0.0181) at baseline and 20/100 snellen equivalent (0.70 ± 0.40 logarithm of the minimum angle of resolution) (P = 0.0021) at complete resolution. Subfoveal atrophy was more in Group B (82.6% 19/23) at complete resolution in comparison to Group A (16/31, 51.6%). Eyes in Group B needed more anti-vascular endothelial growth factor injections (10.3 ± 9.0) for complete resolution compared with Group A (5.7 ± 4.8).Intraretinal fluid may be associated with good visual acuity in Type 3 macular neovascularization in contrast to other forms of neovascular age related macular degeneration. Furthermore, intraretinal fluid in isolation may need fewer injections and could probably be associated with less subfoveal atrophy.

Inherited retinal diseases (IRDs) are a heterogenous group of orphan eye diseases that typically result from monogenic mutations and are considered attractive targets for gene-based therapeutics. Following the approval of an IRD gene replacement therapy for Leber’s congenital amaurosis due to RPE65 mutations, there has been an intensive international research effort to identify the optimal gene therapy approaches for a range of IRDs and many are now undergoing clinical trials. In this review we explore therapeutic challenges posed by IRDs and review current and future approaches that may be applicable to different subsets of IRD mutations. Emphasis is placed on five distinct approaches to gene-based therapy that have potential to treat the full spectrum of IRDs: 1) gene replacement using adeno-associated virus (AAV) and nonviral delivery vectors, 2) genome editing via the CRISPR/Cas9 system, 3) RNA editing by endogenous and exogenous ADAR, 4) mRNA targeting with antisense oligonucleotides for gene knockdown and splicing modification, and 5) optogenetic approaches that aim to replace the function of native retinal photoreceptors by engineering other retinal cell types to become capable of phototransduction.

Acquired retinal diseases such as age-related macular degeneration and diabetic retinopathy rank among the leading causes of blindness and visual loss worldwide. Effective treatments for these conditions are available, but often have a high treatment burden, and poor compliance can lead to disappointing real-world outcomes. Development of new treatment strategies that provide more durable treatment effects could help to address some of these unmet needs. Gene-based therapeutics, pioneered for the treatment of monogenic inherited retinal disease, are being actively investigated as new treatments for acquired retinal disease. There are significant advantages to the application of gene-based therapeutics in acquired retinal disease, including the presence of established therapeutic targets and common pathophysiologic pathways between diseases, the lack of genotype-specificity required, and the larger potential treatment population per therapy. Different gene-based therapeutic strategies have been attempted, including gene augmentation therapy to induce in vivo expression of therapeutic molecules, and gene editing to knock down genes encoding specific mediators in disease pathways. We highlight the opportunities and unmet clinical needs in acquired retinal disease, review the progress made thus far with current therapeutic strategies and surgical delivery techniques, and discuss limitations and future directions in the field.