Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

KESTREL and KITE Phase 3 Studies: 100-Week Results With Brolucizumab in Patients With Diabetic Macular Edema.

PURPOSE: To report the 100-week outcomes from the KESTREL and KITE trials. DESIGN: Two phase 3, double-masked, active-controlled, randomized trials. METHODS: Patients with diabetic macular edema (DME) were randomized 1:1:1 to brolucizumab 3 mg/6 mg (BRO3/BRO6) or aflibercept 2 mg (AFL) in KESTREL (N = 566) or 1:1 to BRO6 or AFL in KITE (N = 360). BRO3/BRO6 arms received 5 loading doses every 6 weeks (q6w) followed by q12w dosing, with an option to adjust to q8w at predefined disease activity assessment visits. In KITE, at week 72, based on the disease stability assessment, treatment intervals could be extended by 4 weeks in the BRO6 arm. AFL arms received 5 monthly loading doses followed by fixed q8w dosing. RESULTS: At week 100, change from baseline in BCVA (letters) was +8.8 for BRO6 and +10.6 for AFL in KESTREL; and +10.9 for BRO6 and +8.4 for AFL in KITE. In both studies, fewer BRO6 subjects had intraretinal fluid and/or subretinal fluid than AFL subjects. Results were achieved with 32.9% (KESTREL) and 47.5% (KITE) of BRO6 subjects maintained on q12w and q12w/q16w dosing, respectively. Intraocular inflammation rates for BRO6 vs AFL were 4.2% vs 1.1% (KESTREL) and 2.2% vs 1.7% (KITE), of which retinal vasculitis rates were 0.5% vs 0% in KESTREL, with no cases in KITE. Retinal vascular occlusion rates were 1.6% vs 0.5% (KESTREL) and 0.6% in both treatment arms in KITE. CONCLUSIONS: Results show the long-term efficacy and durability of brolucizumab in improving visual and anatomical outcomes in DME; the overall safety profile of brolucizumab remained unchanged through year 2.

IMPACT OF RETINAL FLUID-FREE MONTHS ON OUTCOMES IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Treatment Agnostic Analysis of the HAWK and HARRIER Studies.

PURPOSE: To assess the effect of the total number of fluid-free months after loading on visual and anatomical outcomes in neovascular age-related macular degeneration patients receiving anti-vascular endothelial growth factor therapy. METHODS: This post hoc analysis pooled patient-level data from the brolucizumab 6 mg (n = 718) and aflibercept 2 mg (n = 715) arms of the HAWK and HARRIER randomized clinical trials. Based on data from Weeks 12 to 96, patients were assigned to one of five categories based on fluid-free visits (FFVs; the total number of monthly visits at which they were observed to be without retinal fluid). Three definitions of "fluid-free" were explored based on the location of the fluid observed. RESULTS: Patients allocated to Categories 4 (15-21 FFV) and 5 (22 FFV, always dry) consistently had the best visual and anatomical outcomes at Week 96, whereas patients allocated to Categories 1 (0 FFV, never dry) and 2 (1-7 FFV) consistently had the worst visual and anatomical outcomes. Variability in retinal thickness over time was lowest in Categories 4 and 5. CONCLUSION: Absence of retinal fluid at more visits after loading has a positive association with visual and anatomic outcomes in neovascular age-related macular degeneration patients, regardless of fluid type.

Associations between age-related macular degeneration and sleep dysfunction: A systematic review.

BACKGROUND: Age-related macular degeneration, a prevalent degenerative retinal disease, is associated with non-visual and psychosocial impairments that may affect sleep. In this systematic review, we evaluated associations between age-related macular degeneration (AMD) and sleep, highlighted knowledge gaps and provided evidence-based recommendations to clinicians to enable holistic management of AMD patients. METHODS: We searched PubMed, Embase and the Cochrane Central registries for papers published before May 2022. Non-English, qualitative studies and grey literature were excluded. Studies evaluating the association between AMD and sleep (including sleep disorders like insomnia and sleep apnea), and vice versa, were included. The quality of shortlisted studies was evaluated using the Newcastle Ottawa Scale. RESULTS: Six (two case-control studies, three longitudinal cohort studies and one cross-sectional study) of 551 studies were included in this review. Four studies found that AMD was associated with increased rates of sleep apnea and poorer reported sleep quality, while five studies showed that patients with sleep apnea or insomnia were at higher risk of developing AMD. Associations between self-reported sleep quantity and AMD were conflicting. No study evaluated the relationship between AMD and sleep using objective sleep assessment tools. CONCLUSION: Only a limited number of studies investigated associations between AMD and sleep. These studies suggest a bidirectional relationship between AMD and sleep dysfunction yet disagree on the relationship between sleep quantity and the likelihood of AMD. Additional studies, using objective characterisation of sleep in patients with AMD are required to confirm these findings.

Effects of primary glaucoma on sleep quality and daytime sleepiness of patients residing at an equatorial latitude.

AIM: To investigate the impact of primary glaucoma on sleep quality and daytime sleepiness of patients. METHODS: Prospective cross-sectional study with consecutive sampling in South-East Asian population was performed. Validated questionnaires: the Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were administered prospectively. Subjects with non-glaucomatous optic neuropathy or concomitant retinal pathology were excluded. Glaucoma severity was based on HVF 24-2 perimetry. Binocular single vision was represented based on the better eye. Frequency of and predictive factors for poor sleep quality and excessive daytime sleepiness were compared. RESULTS: A total of 79 primary open angle glaucoma (POAG), 27 primary angle-closure glaucoma (PACG) patients, and 89 controls were recruited. PACG patients had higher median PSQI scores (P=0.004) and poorer sleep quality (P<0.001). Compared to controls, PACG patients were 3.34 times more likely to have poor sleep quality (P=0.008), which remained significant after adjustment for demographics (P=0.016) and predictive variables (P=0.013). PACG patients have poorer sleep quality when visual acuity (VA) was 6/15 or worse (P=0.009). Univariate and multivariate analysis of predictive variables for poor sleep quality and daytime sleepiness did not find statistical significance. CONCLUSION: PACG patients have poorer sleep quality but not daytime sleepiness. This is important in South-East Asian population with heavy disease burden. Evaluations on sleep disturbances can be considered to provide more holistic care.

Diabetic Macular Edema Management in Asian Population: Expert Panel Consensus Guidelines.

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.

A longitudinal study of choroidal changes following cataract surgery in patients with diabetes.

OBJECTIVE: To study the structural changes in the choroid of diabetic patients following cataract surgery, using choroidal vascularity index and choroidal thickness. METHODS: A prospective case-control study was conducted in 18 diabetic and 18 non-diabetic patients undergoing cataract surgery (phacoemulsification) in one eye. Enhanced depth imaging optical coherence tomography images were obtained before and after surgery. Niblack's image binarization of images was performed to derive the choroidal vascularity index. Independent sample T-test compared the differences of choroidal vascularity index and choroidal thickness between diabetic and non-diabetic patients. RESULTS: The baseline choroidal vascularity index was significantly lower in diabetic patients for both operated (mean difference vs non-diabetic: 0.0184, 95% CI: 0.004-0.0324, p = 0.012) and non-operated (mean difference vs non-diabetic: 0.0145, 95% CI: 0.003-0.0256, p = 0.012) eyes. Choroidal thickness increased following cataract surgery (diabetes: mean difference = 12.4, 95% CI: 0.70-24.0, adjusted p = 0.036; non-diabetic: mean difference = 21.0, 95% CI: 4.39-37.6, adjusted p = 0.011). CONCLUSION: Diabetic patients have reduced choroidal vascularity index than non-diabetic patients, suggestive of possible reduction in choroidal vascularity in diabetes. Choroidal thickness increased following cataract surgery in both diabetic and non-diabetic patients.

Automatic Detection of Preferred Retinal Locus (PRL) for Low Vision Rehabilitation using Oculometrics Analysis.

Low vision rehabilitation is an important step towards individuals with Age-related macular degeneration (AMD) regaining useful functional vision and quality of life. One of the key steps in low vision rehabilitation is the determination of the preferred retinal locus (PRL). Currently, localization of PRL is performed manually though the guidance of a low vision therapist and the process is highly time-consuming, labour-intensive and subjective. In this paper, we present an automated system to objectively and accurately locate an individual's PRL with the aid of gaze tracking technology. We also propose a graph-based method for false fixation detection to improve the system robustness. We validated the reliability of the system by using eye tracking technology to simulate central vision loss on people with normal vision. Experimental results show the potential use of eye tracking in detecting PRL for low vision rehabilitation.

Computer-aided diagnosis of glaucoma using fundus images: A review.

BACKGROUND AND OBJECTIVES: Glaucoma is an eye condition which leads to permanent blindness when the disease progresses to an advanced stage. It occurs due to inappropriate intraocular pressure within the eye, resulting in damage to the optic nerve. Glaucoma does not exhibit any symptoms in its nascent stage and thus, it is important to diagnose early to prevent blindness. Fundus photography is widely used by ophthalmologists to assist in diagnosis of glaucoma and is cost-effective. METHODS: The morphological features of the disc that is characteristic of glaucoma are clearly seen in the fundus images. However, manual inspection of the acquired fundus images may be prone to inter-observer variation. Therefore, a computer-aided detection (CAD) system is proposed to make an accurate, reliable and fast diagnosis of glaucoma based on the optic nerve features of fundus imaging. In this paper, we reviewed existing techniques to automatically diagnose glaucoma. RESULTS: The use of CAD is very effective in the diagnosis of glaucoma and can assist the clinicians to alleviate their workload significantly. We have also discussed the advantages of employing state-of-art techniques, including deep learning (DL), when developing the automated system. The DL methods are effective in glaucoma diagnosis. CONCLUSIONS: Novel DL algorithms with big data availability are required to develop a reliable CAD system. Such techniques can be employed to diagnose other eye diseases accurately.

Human pharyngeal microbiota in age-related macular degeneration.

BACKGROUND: While the aetiology of age-related macular degeneration (AMD)-a major blinding disease-remains unknown, the disease is strongly associated with variants in the complement factor H (CFH) gene. CFH variants also confer susceptibility to invasive infection with several bacterial colonizers of the nasopharyngeal mucosa. This shared susceptibility locus implicates complement deregulation as a common disease mechanism, and suggests the possibility that microbial interactions with host complement may trigger AMD. In this study, we address this possibility by testing the hypothesis that AMD is associated with specific microbial colonization of the human nasopharynx. RESULTS: High-throughput Illumina sequencing of the V3-V6 region of the microbial 16S ribosomal RNA gene was used to comprehensively and accurately describe the human pharyngeal microbiome, at genus level, in 245 AMD patients and 386 controls. Based on mean and differential microbial abundance analyses, we determined an overview of the pharyngeal microbiota, as well as candidate genera (Prevotella and Gemella) suggesting an association towards AMD health and disease conditions. CONCLUSIONS: Utilizing an extensive study population from Singapore, our results provided an accurate description of the pharyngeal microbiota profiles in AMD health and disease conditions. Through identification of candidate genera that are different between conditions, we provide preliminary evidence for the existence of microbial triggers for AMD. Ethical approval for this study was obtained through the Singapore Health Clinical Institutional Review Board, reference numbers R799/63/2010 and 2010/585/A.

Pulse waveform analysis on temporal changes in ocular blood flow due to caffeine intake: a comparative study between habitual and non-habitual groups.

PURPOSE: To evaluate and compare the temporal changes in pulse waveform parameters of ocular blood flow (OBF) between non-habitual and habitual groups due to caffeine intake. METHOD: This study was conducted on 19 healthy subjects (non-habitual 8; habitual 11), non-smoking and between 21 and 30 years of age. Using laser speckle flowgraphy (LSFG), three areas of optical nerve head were analyzed which are vessel, tissue, and overall, each with ten pulse waveform parameters, namely mean blur rate (MBR), fluctuation, skew, blowout score (BOS), blowout time (BOT), rising rate, falling rate, flow acceleration index (FAI), acceleration time index (ATI), and resistive index (RI). Two-way mixed ANOVA was used to determine the difference between every two groups where p < 0.05 is considered significant. RESULT: There were significant differences between the two groups in several ocular pulse waveform parameters, namely MBR (overall, vessel, tissue), BOT (overall), rising rate (overall), and falling rate (vessel), all with p < 0.05. In addition, the ocular pulse waveform parameters, i.e., MBR (overall), skew (tissue), and BOT (tissue) showed significant temporal changes within the non-habitual group, but not within the habitual group. The temporal changes in parameters MBR (vessel, tissue), skew (overall, vessel), BOT (overall, vessel), rising rate (overall), falling rate (overall, vessel), and FAI (tissue) were significant for both groups (habitual and non-habitual) in response to caffeine intake. CONCLUSION: The experiment results demonstrated caffeine does modulate OBF significantly and response differently in non-habitual and habitual groups. Among all ten parameters, MBR and BOT were identified as the suitable biomarkers to differentiate between the two groups.

A bilayer photoreceptor-retinal tissue model with gradient cell density design: A study of microvalve-based bioprinting.

ARPE-19 and Y79 cells were precisely and effectively delivered to form an in vitro retinal tissue model via 3D cell bioprinting technology. The samples were characterized by cell viability assay, haematoxylin and eosin and immunofluorescent staining, scanning electrical microscopy and confocal microscopy, and so forth. The bioprinted ARPE-19 cells formed a high-quality cell monolayer in 14 days. Manually seeded ARPE-19 cells were poorly controlled during and after cell seeding, and they aggregated to form uneven cell layer. The Y79 cells were subsequently bioprinted on the ARPE-19 cell monolayer to form 2 distinctive patterns. The microvalve-based bioprinting is efficient and accurate to build the in vitro tissue models with the potential to provide similar pathological responses and mechanism to human diseases, to mimic the phenotypic endpoints that are comparable with clinical studies, and to provide a realistic prediction of clinical efficacy.

Tissue engineering of retina and Bruch's membrane: a review of cells, materials and processes.

The biological, structural and functional configuration of Bruch's membrane (BM) is significantly relevant to age-related macular degeneration (AMD) and other chorioretinal diseases, and AMD is one of the leading causes of blindness in the elderly worldwide. The configuration may worsen along with the ageing of retinal pigment epithelium and BM that finally leads to AMD. Thus, the scaffold-based tissue-engineered retina provides an innovative alternative for retinal tissue repair. The cell and material requirements for retinal repair are discussed including cell sheet engineering, decellularised membrane and tissue-engineered membranes. Further, the challenges and potential in realising a whole tissue model construct for retinal regeneration are highlighted herein. This review article provides a framework for future development of tissue-engineered retina as a preclinical model and possible treatments for AMD.

Automated retinal health diagnosis using pyramid histogram of visual words and Fisher vector techniques.

Untreated age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma may lead to irreversible vision loss. Hence, it is essential to have regular eye screening to detect these eye diseases at an early stage and to offer treatment where appropriate. One of the simplest, non-invasive and cost-effective techniques to screen the eyes is by using fundus photo imaging. But, the manual evaluation of fundus images is tedious and challenging. Further, the diagnosis made by ophthalmologists may be subjective. Therefore, an objective and novel algorithm using the pyramid histogram of visual words (PHOW) and Fisher vectors is proposed for the classification of fundus images into their respective eye conditions (normal, AMD, DR, and glaucoma). The proposed algorithm extracts features which are represented as words. These features are built and encoded into a Fisher vector for classification using random forest classifier. This proposed algorithm is validated with both blindfold and ten-fold cross-validation techniques. An accuracy of 90.06% is achieved with the blindfold method, and highest accuracy of 96.79% is obtained with ten-fold cross-validation. The highest classification performance of our system shows the potential of deploying it in polyclinics to assist healthcare professionals in their initial diagnosis of the eye. Our developed system can reduce the workload of ophthalmologists significantly.

Automatic visual impairment detection system for age-related eye diseases through gaze analysis.

Visual impairment associated with Age-related Macular Degeneration (AMD) often results in a central scotoma which is an alteration in the central vision, leading to distortion or loss of vision. Current methods for assessing visual performance such as Amsler grid and Microperimetry are typically manual and have limitations as an indicator of visual field. In this paper, we present an automated system for detecting visual impairment through gaze tracking (AVIGA). Two types of assessments namely, Impulse Stimuli Response (ISR) test and Pursuit Stimuli Response (PSR) test were implemented in AVIGA system. A Support Vector Regression (SVR)-based approach is applied on the assessment results to differentiate the severity of visual impairment. The results show that AVIGA system is well-correlated to visual acuity test (VA) and performs better in identifying presence of visual impairments in eyes, compared to Microperimetry.

Detecting impaired vision caused by AMD from gaze data.

Age Related Macular Degeneration (AMD) is the third leading cause of blindness and the first one in the elderly. AMD usually causes central blindness due to loss of photoreceptor cell . In this paper, we propose to detect AMD caused vision impairment from gaze data. Compared with the current methods, e.g., Amsler grid, Microperimetry and Preferential Hyperacuity Perimetry, to detect vision impairments, the proposed method has several advantages. 1) It does not require the patient to stare at a fixed position throughout the test. 2) It does not require the patient to orally or manually report / mark out the vision impairment. 3) It is easy to operate thus a trained nurse is capable of operating the test. We collect gaze data while the patient is performing fixation and smooth pursuit. Features describing the gaze properties are extracted and SVM with linear kernel is trained to detect AMD impaired vision. To implement the proposed method, we collected gaze data of 74 eyes of 57 patients, who are diagnosed as AMD patient by clinicians. Nidek Microperimetry is adopted as gold standard. 57 eyes with normal vision and 17 eyes with impaired vision (blind at more than half test points in Nidek test) are used for test. The result verifies the effectiveness of detecting vision impairment from gaze data.

The Impact of Switching Anti-Vascular Endothelial Growth Factor Therapy in the Management of Exudative Age-Related Macular Degeneration.

Switching of anti-vascular endothelial growth factor (VEGF) therapy in the management of poorly responsive exudative age-related macular degeneration (AMD) has had suggested benefits in individual reports that have yet to be consolidated. In this retrospective review, 24 studies published between 2009 and 2014 were identified. Reasons for switching included tachyphylaxis, health insurance coverage, cost issues, and nonresponse or inadequate response. Nine studies had data that could be used for comparison between studies. Median follow-up was 10.6 months (range: 4.2 months to 21.8 months). Mean baseline visual acuity (VA) ranged from 0.42 logMar to 0.94 logMar (standard deviation [SD] range: 0.05 logMar to 0.50 logMar) and mean VA on final follow-up ranged from 0.38 logMar to 0.78 logMar (SD range: 0.08 logMar to 0.50 logMar). Five of nine studies reported no statistically significant change in vision, and five of nine studies reported a statistically significant improvement in central retinal thickness. This review found that switching anti-VEGF did not confer significant improvement of VA, although it provided some anatomical improvement. Pertinent considerations for evaluating response following anti-VEGF therapy are also presented in this review. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:859-869.].

HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization.

Background: Dyslipidemia, particularly high-density lipoprotein cholesterol (HDL-C), has recently been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss. However, epidemiological studies have yielded conflicting results. Methods: We investigated the causal role of plasma lipid levels in AMD in multiethnic populations comprising 16 144 advanced AMD cases and 17 832 controls of European descent, together with 2219 cases and 5275 controls of Asian descent, using Mendelian randomization in three models. Model 1 is a conventional meta-analysis which does not account for pleiotropy of instrumental variable (IV) effects. Model 2 is a univariate, inverse variance weighted regression analysis that accounts for potential unbalanced pleiotropy using MR-Egger method. Finally, Model 3 is a multivariate regression analysis that addresses pleiotropy by MR-Egger method and by adjusting for effects on other lipid traits. Results: A 1 standard deviation (SD) higher HDL-cholesterol level was associated with an odds ratio (OR) for AMD of 1.17 (95% confidence interval: 1.07-1.29) in Europeans (P = 6.88 × 10-4) and of 1.58 (1.24-2.00) in Asians (P = 2.92 × 10-4) in Model 3. The corresponding OR estimates were 1.30 (1.09-1.55) in Europeans (P = 3.18 × 10-3) and 1.42 (1.11-1.80) in Asians (P = 4.42 × 10-3) in Model 1, and 1.21 (1.11-1.31) in Europeans (P = 3.12 × 10-5) and 1.51 (1.20-1.91) in Asians (P = 7.61 × 10-4) in Model 2. Conversely, neither LDL-C (Europeans: OR = 0.96, P = 0.272; Asians: OR = 1.02, P = 0.874; Model 3) nor triglyceride levels (Europeans: OR = 0.91, P = 0.102; Asians: OR = 1.06, P = 0.613) were associated with AMD. We also assessed the association between lipid levels and polypoidal choroidal vasculopathy (PCV) in Asians, a subtype of AMD, and found a similar trend for association of PCV with HDL-C levels. Conclusions: Our study shows that high levels of plasma HDL-C are causally associated with an increased risk for advanced AMD in European and Asian populations, implying that strategies reducing HDL-C levels may be useful to prevent and treat AMD.

The effect of intravitreal injections on dry eye, and proposed management strategies.

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents has become a commonly used treatment method for a number of ophthalmic conditions, including age-related macular degeneration. Although anti-VEGF therapy has shown promising results for many patients, there are several aspects of its application that have not been thoroughly investigated. One of these is the development and/or escalation of concurrent dry eye syndrome. Many patients undergoing treatment are already predisposed to dry eye disease due to their age and overall ocular health. As dry eye can have a substantial impact on quality of life, it has become increasingly apparent that the clinical signs and symptoms should be closely monitored and aggressively managed. This will allow for the optimization of patient comfort and visual potential. Here, we discuss the reasons why dry eye may develop during the course of repeated ocular anti-VEGF therapy, highlighting the key concerns about current practices and proposing possible solutions to improve the outcome for the patients.

Shared genetic variants for polypoidal choroidal vasculopathy and typical neovascular age-related macular degeneration in East Asians.

Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD) more frequently seen in East Asians, has both common and distinct clinical manifestations with typical neovascular AMD (tAMD). We aim to examine the extent to which common genetic variants are shared between these two subtypes. We performed the meta-analysis of association in a total of 1062 PCV patients, 1157 tAMD patients and 5275 controls of East Asian descent from the Genetics of AMD in Asians Consortium at the 34 known AMD loci. A total of eight loci were significantly associated with PCV, including age-related maculopathy susceptibility 2 (ARMS2)-HtrA serine peptidase 1 (HTRA1), complement factor H (CFH), C2-CFB-SKIV2L, CETP, VEGFA, ADAMTS9-AS2 and TGFBR1 (P<5 × 10-4) from the single-nucleotide polymorphism-based test and COL4A3 from the gene-based tests (Pgene=2.02 × 10-4). PCV and tAMD are genetically highly correlated (rg=0.69, P=4.68 × 10-3), with AMD known loci accounting for up to 36% variation. Weaker association for PCV was observed at ARMS2-HTRA1 (Pdif=4.39 × 10-4) and KMT2E-SRPK2(Pdif=4.43 × 10-3), compared with tAMD. Variants at CFH, CETP and VEGFA exhibited different association signals in East Asians, in contrast to those in European individuals. Our data suggest a substantially shared genetic susceptibility for PCV and tAMD, while also highlight the unique associations for PCV, which is useful in understanding the pathogenesis of PCV.