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Purpose: Helicobacter pylori (HP), which colonizes exclusively in the gastrointestinal tract, has been reported to dysregulate the immune response and gives rise to several extra-gastrointestinal autoimmune disorders. However, the relationship between HP and immune-mediated ocular diseases remains ambiguous. This study aims to clarify the association between immune-mediated ocular diseases and HP infection, as well as the impact of HP treatment on the incidence of immune-mediated ocular diseases., Methods: This is a retrospective population-based study using National Health Insurance Research Database in Taiwan. Patients with newly diagnosed peptic ulcer disease or HP infection between 2009 and 2015 were identified as HP group and compared to the non-HP group with one-to-one exact matching. Moreover, the incident risk of immune-mediated ocular diseases and its two subgroups (ocular surface and orbital inflammation group, intraocular inflammation group) were compared in HP patients with or without treatment., Results: A total of 1,030,119 subjects in the non-HP group and 1,030,119 patients in the HP group were enrolled. The incidence rate of immune-mediated ocular diseases was significantly higher in the HP group (95% confidence interval (CI): 2.534-2.547). The incident rate ratio was significantly higher in HP with treatment than without treatment (HR: 1.654, 95% CI: 1.641-1.668). The Cox proportional hazards regression model demonstrated a significantly increased HR of immune-mediated ocular diseases in HP treated group (HR: 2.265, 95% CI: 2.024-2.534) and less increased HR in HP non-treated group (HR: 1.427, 95% CI: 1.273-1.598) when comparing to non-HP group. Subgroup analysis demonstrated a significantly higher incidence rate of ocular surface and orbital inflammation as well as intraocular inflammation in the HP group., Conclusion: This study illustrated a higher incidence of immune-mediated ocular diseases in HP infection, and a heightened risk following HP eradication.

Uveitis remains one of the leading causes of blindness worldwide, with different etiologies requiring separate approaches to treatment. For over a decade, oral, topical, and local injection of corticosteroids as well as systemic conventional disease-modifying antirheumatic drugs (DMARDs) have remained the most effective treatment for noninfectious uveitis (NIU). Systemic administration of antitumor necrosis factor-α and other biological DMARDs have been used for treating cases that responded inadequately to conventional treatments. Unfortunately, some refractory patients still suffer from frequent attacks despite the combination of multiple treatments. Recently, there has been promising evidence for Janus kinase (JAK) inhibitors as the next-generation therapy for NIU. The JAK/signal transducers and activators of the transcription (STAT) signaling pathway mediate the downstream events involved in immune fitness, tissue repair, inflammation, apoptosis, and adipogenesis by binding various ligands, such as cytokines, growth hormones, and growth factors. The mutation or loss of JAK/STAT components is implicated in autoimmune diseases, thus inhibition of such pathways has been an important area of research in therapeutic development. 1 In this review, we provide a comprehensive overview of the efficacy and safety of JAK inhibitors for the management of NIU, with evidence from current trials and case reports.

Purpose: To offer consensus on the utilization of corticosteroids (CS) for treating non-infectious uveitis in the context of clinical practice in Taiwan. This entails examining the different administration methods, their advantages and disadvantages, and considering alternative treatments according to the prevailing evidence and health policies., Methods: Ten ophthalmologists and one rheumatologist convened on December 11, 2022, to review and discuss literature on the topic. The databases explored were the Central Cochrane library, EMBASE, Medline, PUBMED, and Web of Science using relevant keywords. The search spanned from January 1996 to June 2023. After the initial results of the literature review were presented, open voting determined the final statements, with a statement being accepted if it secured more than 70% agreement. This consensus was then presented at significant meetings for further discussions before the final version was established., Results: A flow chart and nine statements emerged from the deliberations. They address the importance of CS in uveitis management, guidelines for using topical CS, indications for both periocular or intravitreal and systemic therapies, and tapering and discontinuation methods for both topical and systemic CS., Conclusion: While CS are a cornerstone for non-infectious uveitis treatment, their administration requires careful consideration, depending on the clinical situation and the specific type of uveitis. The consensus generated from this article provides a guideline for practitioners in Taiwan, taking into account local health policies and the latest research on the subject. It emphasizes the significance of strategic tapering, the potential for alternative therapies, and the importance of patient-centric care.

A recent resurgence in the incidence of syphilis has sparked a new interest in this old disease. Syphilitic uveitis remains a challenging disease, among the variable syphilis infections, due to the diagnostic complexity and the wide clinical manifestations. Here, we provide recommendations regarding clinical manifestations, diagnosis, and treatment for patients with syphilitic uveitis in Taiwan based on an expert meeting and consensus from experienced uveitis specialists., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

We presented the development of a consensus guideline for managing juvenile idiopathic arthritis-associated uveitis (JIAU) in Taiwan, considering regional differences in manifestation and epidemiology. The Taiwan Ocular Inflammation Society (TOIS) committee formulated this guideline using a modified Delphi approach with two panel meetings. Recommendations were based on a comprehensive evidence-based literature review and expert clinical experiences, and were graded according to the Oxford Centre for Evidence-Based Medicine's "Levels of Evidence" guideline (March 2009). The TOIS consensus guideline consists of 10 recommendations in four categories: screening and diagnosis, treatment, complications, and monitoring, covering a total of 27 items. These recommendations received over 75% agreement from the panelists. Early diagnosis and a coordinated referral system between ophthalmologists and pediatric rheumatologists are crucial to prevent irreversible visual impairment in children with JIAU. However, achieving a balance between disease activity and medication use remains a key challenge in JIAU management, necessitating further clinical studies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Anterior uveitis is the most common anatomical type of uveitis. Patients with noninfectious anterior uveitis may develop various ocular complications and eventually visual impairment. Appropriately differentiating the etiologies can help clinicians to predict the outcome, arrange clinical follow-up, and decide the treatment or prevention strategy. Adequate treatment and effective prevention strategies can reduce the frequency of recurrence and the risk of developing complications. Human leukocyte antigen (HLA)-B27 is the most common positive finding in patients with noninfectious AAU in many countries including Taiwan., Purpose: To report a consensus from experienced uveitis specialists and rheumatologists was made in Taiwan., Methods: A panel of nine ophthalmologists from nine different referral centers with expertise in the management of uveitis and an experienced rheumatologist was held on January 16, 2022. A comprehensive literature review was performed. Differential diagnoses for etiologies, general treatments, and prevention strategies were discussed. Each statement in the consensus was made only if more than 70% of the experts agreed., Results: A flow chart and seven statements regarding the differential diagnoses for etiologies, treatments and preventions, and co-management with rheumatologists were included in the consensus., Conclusions: This article discusses the general diagnosis, treatment, and prevention of noninfectious acute anterior uveitis, with or without HLA-B27, in adults for general ophthalmologists to improve overall outcomes of these patients.

Clinical practices on acute post-operative and endogenous endophthalmitis (EnE) are highly variable among clinicians due to a lack of up-to-date, high-quality evidential support. An expert consensus is thus much needed. A panel consisting of ten retinal specialists in Taiwan was organized. They evaluated relevant literature and developed key questions regarding acute post-operative and EnE that are cardinal for practice but yet to have conclusive evidence. The panel then attempted to reach consensus on all the key questions accordingly. There were eight key questions proposed and their respective consensus statements were summarized as follows: Gram staining and culture are still the standard procedures for the diagnosis of endophthalmitis. Vitrectomy is recommended to be performed earlier than the timing proposed by the Endophthalmitis Vitrectomy Study (EVS). Routine intracameral antibiotic injection for post-cataract surgery endophthalmitis prophylaxis is not recommended because of potential compounding error hazards and a lack of support from high-quality studies. Routine fundus examination is recommended for all patients with pyogenic liver abscess. In EnE, vitrectomy is recommended if diffused and dense vitritis is present, or if the disease progresses. These consensus statements may work as handy guidance or reference for clinical practices of acute post-operative and EnE., (© 2023. The Author(s).)

Rhegmatogenous retinal detachment (RRD) is a significant cause of vision loss and requires appropriate surgical intervention. There are several approaches available, including observation, laser demarcation, pneumatic retinopexy, scleral buckling, and pars plana vitrectomy, which are chosen based on patient condition, surgeon experience, and national health insurance policies. Despite the various options, there is still no consensus on the optimal intervention. To address this, the Taiwan Retina Society assembled an expert committee with 11 experienced retina specialists to review the current evidence and develop a guideline with seven recommendations for managing RRD patients. Additionally, a survey was conducted with six questions to assess treatment patterns in Taiwan, which included input from the expert committee and an open poll at the 2023 Congress of the Taiwan Retina Society. This report provides a comprehensive summary of the current knowledge and expert consensus on the treatment of RRD, discussing the characteristics of current approaches and providing an overview of current treatment patterns in Taiwan. These findings aim to provide ophthalmologists with the best possible treatment for RRD., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

In this study, we reported the patterns, epidemiology, and clinical features of anterior uveitis (AU) in Taiwan, an area of Eastern Asia. This prospective, cross-sectional case series study was performed to identify patients with AU at two tertiary medical centers (Kaohsiung Chang Gung Memorial Hospital and Kaohsiung Veterans General Hospital) located at the southern Taiwan between December 1, 2018, and March 31, 2020. The clinical diagnoses, ocular presentations, and laboratory data, including the results of the aqueous polymerase chain reaction tests, were investigated in these patients. A total of 112 patients, with a mean age of 48.9 years, were included. Most patients (87.5%) presented with unilateral eye disease, with 30 cases of ocular hypertension at the first presentation (27%). The most common clinical diagnoses were idiopathic AU (37.5%), human leukocyte antigen (HLA)-B27-associated acute AU (25.0%), and herpetic AU (18.8%). Among patients with herpetic AU, cytomegalovirus (CMV) was the most common pathogen (17/21, 81%). Compared to HLA-B27-associated acute AU, CMV-related AU was mostly observed in patients that were older in age, exhibited higher intraocular pressure, more keratic precipitates, greater iris atrophy, and more pseudophakia, but was least reported in those with posterior synechiae. This prospective study identified the pattern and clinical features of AU in southern Taiwan., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Wei-Yu Chiang et al.)

Background: Remote areas of Taiwan lack routine and specialized ophthalmology services. This study aimed to analyze feasibility of teleophthalmology service for diseases diagnosis and referral in remote areas of Taiwan. Methods: A retrospective study of medical records from 11 remote teleophthalmology clinics in the Taitung area of Taiwan was conducted from May 2020 to December 2021. Vision and intraocular pressure were checked. Ophthalmic imaging was performed by local trained nurses using a hand-held ophthalmoscope and slit lamp biomicroscope. The images were transmitted by telemedicine system to a medical center. Consultation was conducted via face-to-face real-time video calls. Ophthalmologists in the medical center provided diagnosis and treatment advice based on the real-time images and interactive history taking via the telemedicine system. All the images and data were collected and well-reviewed by ophthalmologists in the medical center, and disease prevalence and referral were analyzed for the program. A small-scale satisfaction questionnaire survey was conducted for efficacy evaluation of the program. Results: A total of 1,401 medical records from 1,094 patients were collected and screened. Patients' ages ranged from 9 months to 94 years, with a mean age of 57.27 (standard deviation ± 20.47) years. The most frequent ophthalmologic diagnosis was dry eye disease (20.2%), followed by conjunctivitis (12.4%). Among 322 patients with underlying diseases of diabetes mellitus, 59 patients (18.3%) were diagnosed with diabetic retinopathy. Major diagnosis was made in 102 patients (7.3%) and referral to hospital for further management was suggested. This program had high overall satisfaction score of 89% (mean 4.43 ± 0.52 points) in satisfaction questionnaire survey. Conclusion: Teleophthalmology provides an alternative tool for ocular disease diagnosis and screening for patients in remote areas, especially during the COVID-19 pandemic. This service helps to detect major but undiagnosed diseases and promotes health care accessibility and availability in remote areas that lack specialists.

Chronic hyperglycemia involves persistent high-glucose exposure and correlates with retinal degeneration. It causes various diseases, including diabetic retinopathy (DR), a major cause of adult vision loss. Most in vitro studies have investigated the damaging short-term effects of high glucose exposure on retinal pigment epithelial (RPE) cells. DR is also a severe complication of diabetes. In this study, we established a model with prolonged high-glucose exposure (15 and 75 mM exogenous glucose for two months) to mimic RPE tissue pathophysiology in patients with hyperglycemia. Prolonged high-glucose exposure attenuated glucose uptake and clonogenicity in ARPE-19 cells. It also significantly increased reactive oxygen species levels and decreased antioxidant protein (superoxide dismutase 2) levels in RPE cells, possibly causing oxidative stress and DNA damage and impairing proliferation. Western blotting showed that autophagic stress, endoplasmic reticulum stress, and genotoxic stress were induced by prolonged high-glucose exposure in RPE cells. Despite a moderate apoptotic cell population detected using the Annexin V-staining assay, the increases in the senescence-associated proteins p53 and p21 and SA-β-gal-positive cells suggest that prolonged high-glucose exposure dominantly sensitized RPE cells to premature senescence. Comprehensive next-generation sequencing suggested that upregulation of oxidative stress and DNA damage-associated pathways contributed to stress-induced premature senescence of ARPE-19 cells. Our findings elucidate the pathophysiology of hyperglycemia-associated retinal diseases and should benefit the future development of preventive drugs. Prolonged high-glucose exposure downregulates glucose uptake and oxidative stress by increasing reactive oxygen species (ROS) production through regulation of superoxide dismutase 2 (SOD2) expression. Autophagic stress, ER stress, and DNA damage stress (genotoxic stress) are also induced by prolonged high-glucose exposure in RPE cells. Consequently, multiple stresses induce the upregulation of the senescence-associated proteins p53 and p21. Although both apoptosis and premature senescence contribute to high glucose exposure-induced anti-proliferation of RPE cells, the present work shows that premature senescence rather than apoptosis is the dominant cause of RPE degeneration, eventually leading to the pathogenesis of DR., (© 2023. L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.)

Cytomegalovirus (CMV) uveitis, a type of herpetic uveitis, is a major cause of infectious uveitis. Anterior and posterior CMV uveitis have diverse clinical presentations and treatment modalities. Based on expert consensus in Taiwan, this article provides suggestions regarding clinical manifestations, diagnosis, and treatment strategies for CMV uveitis based on clinical practice experience in Taiwan. CMV uveitis may have a distinct clinical presentation. Polymerase chain reaction (PCR) is an essential diagnostic tool to confirm a diagnosis. Antiviral therapy is the mainstay of treatment. Different agents, routes, and other supplemental treatments have been summarized and discussed in this article. Early diagnosis and appropriate treatment of CMV uveitis are crucial to avoid irreversible complications and vision loss. This consensus provides practical guidelines for ophthalmologists in Taiwan., Competing Interests: Conflicts of interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This retrospective case-control study aimed to investigate associations between disease severity of Alzheimer's dementia (AD) and macular thickness. Data of patients with AD who were under medication (n = 192) between 2013 and 2020, as well as an age- and sex-matched control group (n = 200) with normal cognitive function, were included. AD patients were divided into subgroups according to scores of the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Macular thickness was analyzed via the Early Treatment Diabetic Retinopathy Study (ETDRS) grid map. AD patients had significant reductions in full macula layers, including inner circle, outer inferior area, and outer nasal area of the macula. Similar retinal thinning was noted in ganglion cells and inner plexiform layers. Advanced AD patients (MMSE score < 18 or CDR ≥ 1) showed more advanced reduction of macular thickness than the AD group (CDR = 0.5 or MMSE ≥ 18), indicating that severe cognitive impairment was associated with thinner macular thickness. Advanced AD is associated with significant macula thinning in full retina and inner plexiform layers, especially at the inner circle of the macula. Macular thickness may be a useful biomarker of AD disease severity. Retinal imaging may be a non-invasive, low-cost surrogate for AD., Competing Interests: The authors declare no conflicts of interest.

In recent years, optical coherence tomography (OCT) biomarkers for specific retinal diseases have been found to be associated with treatment outcome and disease recurrence. The main purposes of this study were to identify OCT biomarkers for myopic choroidal neovascularization (mCNV) treated with intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF). OCT features in 43 eyes of 39 patients with mCNV treated with anti-VEGF with at least 1 year of follow-up were retrospectively analyzed. Eyes with subretinal hyperreflective material (SHM) in baseline spectral-domain OCT (SD-OCT) had significantly more visual improvement than eyes without SHM at month 6 (p = 0.007) and had a trend of more visual improvement than eyes without SHM (p = 0.058) at month 12. Eyes with subretinal fluid (SRF) at baseline had significantly more central retinal thickness (CRT) decrease than patients without SRF at month 6 and 12 (p = 0.012 and 0.006 respectively). In univariate regression analysis, dome-shaped macula (DSM), SRF in baseline OCT image and fuzzy border of mCNV when entering pro re nata (PRN) injection protocol tended to have higher risk of disease recurrence in 1 year (odds ratio: 14.86 (p = 0.003), 3.75 (p = 0.049) and 22.92 (p < 0.001) respectively). However, they were not significant in multivariate regression analysis. OCT biomarkers at baseline could provide prognostic information for mCNV management., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Purpose: This study aims to conduct a narrative review about the current role of vitreoretinal surgery in the management of infectious and non-infectious uveitis., Methods: This review was performed based on a search of the PubMed database or on relevant published papers according to our current knowledge., Results: A total of 91 articles were identified in the literature review. With the advance of microincision vitrectomy surgery (MIVS), pars plana vitrectomy (PPV) has gained increasing popularity in the management of infectious and non-infectious uveitis. For diagnostic purposes, larger amounts of sample can be obtained by MIVS than traditional vitreous aspiration using needles. For treatment purposes, PPV removes vitreous opacities, decreases inflammatory cytokines and mediators of inflammation, and tackles related complications, including hypotony, epiretinal membrane, macular holes, and retinal detachment. Achieving optimum control of inflammation prior to surgery is important for surgical interventions for non-emergent therapeutic indications and complications of uveitis. Peri-operative inflammation management is essential for decreasing the risk of surgical intervention. An overall complication rate of 42-54% was reported with cataract to be the leading cause of complications., Conclusion: Most reports affirm the role of PPV in the management of infectious and non-infectious uveitis, although the quality of data remains limited by a lack of applying standardized reporting outcomes, limitations in study design, and a paucity of prospective data., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Age-related macular degeneration (AMD) is a disease of retinal pigment epithelium (RPE) cells. We have previously demonstrated that blue light can damage RPE cells and their underlying mechanisms. We found that hexahydrocurcumin (HHC), a metabolite of curcumin, had better retinal protection than curcumin. However, the involved mechanisms remain unclear., Methods: By exposing ARPE-19 human RPE cells and mouse primary RPE cells to blue light, the intracellular mechanisms of HHC in cells were investigated, including the proliferation of RPE cells and the effects of HHC on activating intracellular protective mechanisms and related factors. Next-generation sequencing (NGS) RNA sequencing revealed the underlying mechanisms involved in the induction and regulation of HHC treatment following blue light exposure., Results: HHC promoted autophagy by enhancing autophagic flux, reduced oxidative stress and endoplasmic reticulum (ER) stress, and effectively reversed blue light-induced cell death. RNA sequencing-based bioinformatics approaches comprehensively analyze HHC-mediated cellular processes., Conclusion: Our findings elucidate the mechanisms of HHC against blue light damage in RPE cells and are beneficial for the development of natural metabolite-based preventive drugs or functional foods., Competing Interests: Conflicts of Interest The authors declare that there are no conflicts of interest., (Copyright © 2022. Published by Elsevier GmbH.)

Purpose: In this study, we describe our experience of sympathetic ophthalmia (SO) at a tertiary referral center in Taiwan., Materials and Methods: We retrospectively analyzed records of patients diagnosed with SO from January 2011 to December 2020., Results: We collected data of 15 patients diagnosed with SO (eight males, seven females). Six patients developed SO after ocular penetrating trauma, and nine developed SO after ocular surgery, including seven with vitrectomy, one with penetrating keratoplasty, and one with cataract surgery. Penetrating ocular trauma was the primary cause of SO in the first 5 years (four of six cases), but the proportion was much lower in the last 5 years (two of nine cases). The interval between trigger events and SO ranged from 0.2 to 120 months. Nine patients received oral steroids alone, five patients received methylprednisolone pulse therapy followed by oral steroids, and immunosuppressants were added in four cases. Visual acuity of sympathetic eyes and exciting eyes improved after treatment. The initial visual acuity of sympathetic eyes in trauma related and ocular surgery related revealed no significant difference, but the final visual acuity of sympathetic eyes was better in ocular surgery-related cases than in the trauma-related cases (mean ± standard deviation, 1.01 ± 1.33 versus 0.49 ± 0.68 logarithm of the minimum angle of resolution, P = 0.021)., Conclusions: With the increased number of eye surgeries performed in recent years, eye surgery has emerged as the dominant etiology of SO in our 10-year study. Early detection and proper treatment help to maintain vision in most of the SO patients., Competing Interests: The authors declare that there are no conflicts of interests of this paper., (Copyright: © 2023 Taiwan J Ophthalmol.)

Uveitis is a sight-threatening disease that can be associated with many different etiologies. Successful treatment of uveitis relies on accurate diagnosis and prompt efficient therapy. History taking, physical and ocular examinations, systemic evaluations, and response to treatment provide crucial information to differentiate possible etiologies involved in the pathophysiology of intraocular inflammation. This article provides recommendations for a step-wise approach to patients with uveitis in Taiwan based on an expert meeting and consensus. Systemic evaluations for uveitis should be performed step-by-step and include investigation of patients' general systemic conditions, ruling out infectious etiologies, and obtaining evidential biomarkers to diagnose a specific disease entity., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest related to the subject matter or materials discussed in this article., (Copyright © 2022. Published by Elsevier B.V.)

Background: Patients with psoriatic arthritis (PsA) may develop uveitis, a potentially serious ocular complication. PsA-related uveitis may result in significant morbidity and even vision loss if underdiagnosed or under-treated. We presented a case with long-standing recurrent uveitis and retinal vasculitis successfully managed by fortified systemic immunomodulators for systemic PsA., Case Presentation: A 47-year-old woman was referred under the impression of acute anterior uveitis in her right eye in recent one month. Ocular examinations showed panuveitis in both eyes with intense vitreous opacity in her right eye. Fundus fluorescence angiography revealed retinal vasculitis in both eyes. Systemic surveys excluded the possibility of infection but showed an elevated inflammation marker. With intensive immunosuppressive treatment, inflammation resolved and the vision improved., Conclusion: Our case highlights not only the importance of intensified systemic therapy in treating PsA-related uveitis but the importance of multidisciplinary collaboration. Recurrent uveitis may be an indicator of disease activity prior to other inflammatory markers., (© 2022. The Author(s).)

Background: Optimal regimen using intravitreal aflibercept injections for diabetic macular edema (DME) in clinical practice remains to be elucidated. The purpose of this study is to evaluate a treat-and-extend (TAE) approach using intravitreal aflibercept in participants with center-involved DME., Methods: A 52-week open-label, prospective, multicenter, interventional study was conducted between August 2015 and November 2017 in Taiwan. Adults with diabetes mellitus and center-involved DME who have best-corrected visual acuity (BCVA) of 73 to 24 Early Treatment Diabetic Retinopathy Study letters and central retinal thickness (CRT) >300 μm were included. Participants received five monthly loading doses of 2 mg intravitreal aflibercept, followed by a TAE regimen with a four-week increment/decrement interval over 48 weeks; the maximum interval was 12 weeks. Main outcomes included changes in BCVA and CRT from baseline to week 52, additional anatomical outcomes, and treatment burden parameters., Results: Forty-five participants with mean (SD) age of 63.7 (8.3) years were analyzed. At baseline, mean (SD) BCVA and CRT were 58.3 (11.9) letters and 434.4 (116.8) μm, respectively. Changes from baseline in BCVA and CRT were +8.3 (9.3) letters and -138.2 (150.0) μm (both p < 0.001) at week 52, respectively. In addition, 22% (10/45) of patients gained ≥15 letters, 14% (6/44) of participants achieved ≥2-level improvement in diabetic retinopathy severity, and 51% (23/45) demonstrated dry retina at week 52 compared with 13% (6/45) at baseline. In total, 87% (39/45) of patients reached disease stability, entering TAE at week 20. Subsequently, 89% (40/45) of patients reached maximum interval at week 52. Mean (SD) number of injections was 7.7 (1.5) over a period of 52 weeks., Conclusion: This straightforward and practical TAE regimen using intravitreal aflibercept injections resulted in favorable clinical outcomes with minimal treatment burden for DME at week 52., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

The management of neovascular age-related macular degeneration (nAMD) has taken a major stride forward with the advent of anti-VEGF agents. The treat-and-extend (T&E) approach is a refined management strategy, tailoring to the individual patient's disease course and treatment outcome. To provide guidance to implementing anti-VEGF T&E regimens for nAMD in resource-limited health care systems, an advisory board was held to discuss and generate expert consensus, based on local and international guidelines, current evidence, as well as local experience and reimbursement policies. In the experts' opinion, treatment of nAMD should aim to maximize and maintain visual acuity benefits while minimizing treatment burden. Based on current evidence, treatment could be initiated with 3 consecutive monthly injections. After the initial period, treatment interval may be extended by 2 or 4 weeks each time for the qualified patients (i.e. no BCVA loss ≥5 ETDRS letters and dry retina), and a maximum interval of 16 weeks is permitted. For patients meeting the shortening criteria (i.e. any increased fluid with BCVA loss ≥5 ETDRS letters, or presence of new macular hemorrhage or new neovascularization), the treatment interval should be reduced by 2 or 4 weeks each time, with a minimal interval of 4 weeks. Discontinuation of anti-VEGF may be considered for those who have received 2-3 consecutive injections spaced 16 weeks apart and present with stable disease. For these individuals, regular monitoring (e.g. 3-4 months) is recommended and monthly injections should be reinstated upon signs of disease recurrence., (© 2022. The Author(s).)

Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss. The present consensus provides suggestions on diagnosis, evaluation, treatment, and follow-up strategies for nAMD from a panel of 11 practicing ophthalmologists. The experts suggest that the baseline visit for nAMD management should include a comprehensive ophthalmologic examination via a multimodal approach consisting of visual and anatomical evaluation. Patients diagnosed with nAMD should be subjected to treatment with the goal of maintaining visual function while diminishing anatomical disease activity and minimizing treatment burden. Currently, anti-VEGF therapy is the main treatment strategy for nAMD, and evaluation involving comprehensive ophthalmologic examination within 1 month of completion of the loading phase comprising three monthly injections is recommended to guide subsequent management. Either a treat-and-extend or pro re nata regimen can be considered for the maintenance phase of anti-VEGF therapy, and the regimen should be chosen and adjusted according to disease activity, reimbursement criteria, financial burden, and patient preferences. In the event of inactive nAMD or poor treatment outcomes, after thorough evaluation and patient education, anti-VEGF therapy may be stopped. The consensus provides practical nAMD management guidelines for ophthalmologists and fellow healthcare professionals., Competing Interests: Declaration of competing interest None of the authors have any affiliations with or involvement in any organization or entity with any financial interest (such as educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

We aim to investigate the role of medication adherence history in treatment needed diabetic retinopathy (TNDR). We conducted a retrospective nested case-control study using 3 population-based databases in Taiwan. The major one was the 2-million-sample longitudinal health and welfare population-based database from 1997 to 2017, a nationally representative random sample of National Health Insurance Administration enrolled beneficiaries in 2010 (LHID2010). The national death registry and national cancer registry were also checked to verify the information. The outcome was defined as the TNDR. The Medication possession ratio (MPR) was defined as the ratio of total days of diabetes mellitus (DM) medication supply divided by total observation days. MPR ≥ 80% was proposed as good medication adherence. The association of MPR and the TNDR was analyzed. Other potential confounders and MPR ratio were also evaluated. A total of (n = 44,628) patients were enrolled. Younger aged, male sex and patients with less chronic illness complexity or less diabetes complication severity tend to have poorer medication adherence. Those with severe comorbidity or participating pay-for-performance program (P4P) revealed better adherence. No matter what the characteristics are, patients with good MPR showed a significantly lower likelihood of leading to TNDR after adjustment with other factors. The protection effect was consistent for up to 5 years. Good medication adherence significantly prevents treatment needed diabetic retinopathy. Hence, it is important to promote DM medication adherence to prevent risks of diabetic retinopathy progression, especially those who opt to have low medication adherence., (© 2021. The Author(s).)

Under metabolic stress conditions such as hypoxia and glucose deprivation, an increase in the AMP:ATP ratio activates the AMP-activated protein kinase (AMPK) pathway, resulting in the modulation of cellular metabolism. Metformin, which is widely prescribed for type 2 diabetes mellitus (T2DM) patients, regulates blood sugar by inhibiting hepatic gluconeogenesis and promoting insulin sensitivity to facilitate glucose uptake by cells. At the molecular level, the most well-known mechanism of metformin-mediated cytoprotection is AMPK pathway activation, which modulates metabolism and protects cells from degradation or pathogenic changes, such as those related to aging and diabetic retinopathy (DR). Recently, it has been revealed that metformin acts via AMPK- and non-AMPK-mediated pathways to exert effects beyond those related to diabetes treatment that might prevent aging and ameliorate DR. This review focuses on new insights into the anticancer effects of metformin and its potential modulation of several novel types of nonapoptotic cell death, including ferroptosis, pyroptosis, and necroptosis. In addition, the antimetastatic and immunosuppressive effects of metformin and its hypothesized mechanism are also discussed, highlighting promising cancer prevention strategies for the future.

Purpose: To investigate the association of autophagy-related gene expression with age-related macular degeneration (AMD)., Methods: Patients with AMD were recruited for analysis by conjunctival impression cytology. mRNA was assessed by real-time polymerase chain reaction (RT-PCR) to evaluate whether the expression of 26 autophagy-related genes (ATGs) was correlated with AMD. Further studies on cell viability and autophagic flux in response to oxidative stress by H2O2 were performed in human retinal pigment epithelial (RPE) cell lines based on the results of impression cytology., Results: Both the neovascular AMD (nAMD) and polypoidal choroidal vasculopathy (PCV) groups had significantly higher mRNA levels of gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1) and microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) than the control group, but there was no significant difference between these two groups. Age difference existed only in the AMD group. GABARAPL1 and MAP1LC3B mRNA expression increased significantly after acute oxidative stress in adult retinal pigment epithelial (ARPE-19) cells. Cell viability significantly increased and decreased in the cells harboring GABARAPL1 expression vector and silenced with siRNA against GABARAPL1, respectively, during short-term oxidative stress, whereas viability increased in the GABARAPL1-silenced cells after long-term oxidative stress. Silencing GABARAPL1 itself caused a reduction in autophagic flux under both short and long-term oxidative stress., Conclusion: Our study showed the possibility of assessing autophagy-related gene expression by conjunctival impression cytology. GABARAPL1 was significantly higher in AMD. Although an in vitro study showed an initial protective effect of autophagy, a cell viability study revealed the possibility of a harmful effect after long-term oxidative injury. The underlying mechanism or critical factors require further investigation.

Age-related macular degeneration (AMD) is the progressive degeneration of the retinal pigment epithelium (RPE), retina, and choriocapillaris among elderly individuals and is the leading cause of blindness worldwide. Thus, a better understanding of the underlying mechanisms in retinal tissue activated by blue light exposure is important for developing novel treatment and intervention strategies. In this study, blue-light-emitting diodes with a wavelength of 440 nm were applied to RPE cells at a dose of 3.7 ± 0.75 mW/cm 2 for 24 h. ARPE-19 cells were used to investigate the underlying mechanism induced by blue light exposure. A trypan blue exclusion assay was used for the cell viability determination. Flow cytometry was used for apoptosis rate detection and autophagy analysis. An immunofluorescence microscopy analysis was used to investigate cellular oxidative stress and DNA damage using DCFDA fluorescence staining and an anti-γH2AX antibody. Blue light exposure of zebrafish larvae was established to investigate the effect on retinal tissue development in vivo. To further demonstrate the comprehensive effect of blue light on ARPE-19 cells, next-generation sequencing (NGS) was performed for an ingenuity pathway analysis (IPA) to reveal additional related mechanisms. The results showed that blue light exposure caused a decrease in cell proliferation and an increase in apoptosis in ARPE-19 cells in a time-dependent manner. Oxidative stress increased during the early stage of 2 h of exposure and activated DNA damage in ARPE-19 cells after 8 h. Furthermore, autophagy was activated in response to blue light exposure at 24-48 h. The zebrafish larvae model showed the unfavorable effect of blue light in prohibiting retinal tissue development. The RNA-Seq results confirmed that blue light induced cell death and participated in tissue growth inhibition and maturation. The current study reveals the mechanisms by which blue light induces cell death in a time-dependent manner. Moreover, both the in vivo and NGS data uncovered blue light's effect on retinal tissue development, suggesting that exposing children to blue light could be relatively dangerous. These results could benefit the development of preventive strategies utilizing herbal medicine-based treatments for eye diseases or degeneration in the future.

Abstract: Uveitic macular edema is a significant cause of visual impairment in most uveitis types. Treatment options of uveitis have advanced remarkably in recent years. Up to now, corticosteroids remain the mainstay of treatment. Nonsteroidal immunomodulators, and recently the biologic agents, which can reinforce efficacy and enable discontinuation or reduction of steroids to maintenance doses, are becoming increasingly popular in the management of uveitic macular edema. Several medications can be used in intraocular delivery and more and more sustained releasing implants are being developed. This review will briefly focus on the review of local therapy for the management of cystoid macular edema in uveitis, as many of these novel approaches are currently being evaluated in clinical trials., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Purpose: To investigate the prognostic factors and visual outcomes for patients with epiretinal membrane after pars plana vitrectomy and possible interactions between multiple factors., Methods: A retrospective chart review of adult patients with epiretinal membrane treated with pars plana vitrectomy performed by a single surgeon between February 1, 2015, and January 31, 2017 was conducted. The surgical procedures included standard 25-gauge vitrectomy with peeling of the epiretinal membrane and internal limiting membrane (ILM). Factors including age, sex, vision, intraocular pressure (IOP), lens status, and baseline optical coherence tomography angiography were analyzed to determine any association with visual outcomes. IOP and lens status were evaluated at every visit point and were used for analysis., Results: Visual changes after pars plana vitrectomy in patients with epiretinal membrane were significantly associated with time, lens status, baseline ellipsoid zone integrity, baseline vision, baseline parafoveal vessel density of superficial capillary plexus (SPVD), and IOP. Further investigation using Johnson-Neyman analysis revealed that vision improved over time, especially in pseudophakic eyes. High IOP at baseline or during follow-up was identified as a significant factor associated with limited visual improvement., Conclusion: Our study showed that vision improved over time after vitrectomy for patients with epiretinal membrane. The surgical outcomes are more stable in pseudophakic eyes, and vision improved after cataract extraction in phakic eyes. IOP should be managed and monitored closely to optimize surgical and visual outcomes in patients.

Purpose of Review: Ocular sarcoidosis is one of the most common causes of uveitis worldwide. The diagnosis and treatment of patients with ocular sarcoidosis remains challenging in some cases. It is important for clinicians to keep up to date with new diagnostic and treatment tools for this disease., Recent Findings: The International Workshop on Ocular Sarcoidosis diagnostic criteria were first proposed in 2009 and revised in 2017. The new criteria contained two parts: ocular presentation and systemic investigation. The diagnostic value of liver enzymes was reduced in the new criteria, whereas the value placed of lymphopenia and the CD4/CD8 ratio in bronchoalveolar lavage fluid were increased. Despite not being included in the criteria, recent studies have also highlighted the diagnostic value of serum soluble interleukin-2 receptors. Recent ophthalmologic imaging also provides useful insights for the differential diagnosis.Many new treatments for ocular sarcoidosis have been developed in recent years. The introduction of biological immunomodulatory agents for uveitis treatment represents a big improvement. Antitumor necrosis factor-alpha antibodies, including adalimumab, have been proven to be effective for treating ocular sarcoidosis. Many studies have also suggested that other biological agents could be effective and well tolerated. Newer intravitreal dexamethasone and fluocinolone implants have been developed. Patients treated with these implants have experienced good and sustained control of their intraocular inflammation., Summary: Diagnosis and treatment options for ocular sarcoidosis have changed over time. However, challenges still exist in some difficult patients. Future studies should focus on finding more sensitive biomarkers and developing more effective immunomodulatory treatments with longer efficacy and less side effects.

Diabetic macular edema (DME) is the most common cause of vision loss among patients with diabetes mellitus (DM), rendering it an important growing challenge in ophthalmology. In the past decades, the management strategies for DME had a few paradigm shifts, and the advent of an expanding number of anti-vascular endothelial growth factor (VEGF) agents also calls for an in-depth examination of the currently available evidence. This article was composed with the intention to provide recommendations for practicing clinicians to improve the management and, through it the outcomes of DME. Drawing from current guideline recommendations, clinical trial findings and local clinical experiences, these consensus recommendations for the management of DME were formed by an expert panel through iterations of discussion and voting. First, the treatment goal of DME is to achieve best visual outcome with edema improvement while minimizing treatment burden. Second, anti-VEGF therapy should be considered as the first-line treatment for patients with center-involving DME causing vision loss. Baseline visual acuity (VA) and central subfield thickness (CST) should be taken into consideration when choosing anti-VEGF agents. Third, early intensive anti-VEGF therapy (at least 3 monthly doses) is important for better patients' VA and anatomical improvement. In non-responders who have already been treated with 3-5 injections of anti-VEGF agents, it is reasonable to switch to other modalities, such as steroids. Finally, for the follow-up phase, fixed or individualized dosing should be considered based on VA and OCT.

Purpose: To investigate the outcomes of primary full-thickness macular hole (MH) after surgical intervention with tailored internal limiting membrane (ILM) flap technique., Methods: Patients were reviewed for their clinical characteristics and surgical outcomes. The technique included incomplete circular peeling of the perifoveal ILM which was then trimmed according to the size of the MH. Fluid-gas exchange was done without further manipulation., Results: Nineteen eyes of 19 patients were included. The patients were in average 61 years old (range 41-83) and had an average follow-up period of 11.0 months. At baseline visit, minimal linear diameter of the MH was 311.6 μm (range 80-768). After a single surgery, the MH closed in all cases with improvement of mean visual acuity (from 0.9 to 0.4 logarithm of the minimum angle of resolution units, p < 0.0001, Wilcoxon signed-rank test). At the final visit, 15 (78.9%) eyes achieved a visual acuity ≥ 20/40. Outer retinal gliosis was found to be associated with less favorable postoperative visual acuity. Factors related to the formation of outer retinal gliosis were worse preoperative visual acuity and a large MH with a diameter > 400 μm., Conclusion: Tailored ILM flap technique is an effective method for favorable anatomical and visual outcomes for treatment of primary MH.

Purpose: The objective of the study was to investigate possible factors influencing gas fill after microincision vitrectomy surgery (MIVS) combined with fluid-gas exchange., Materials and Methods: This was a retrospective chart review of patients who underwent MIVS combined with fluid-gas exchange (20% C 3 F 8 ) from February 2017 to December 2017., Results: Sixty-one eyes of 58 patients were identified. The mean age was 59.97 ± 9.65 years. The mean gas fill percentage was 76.28% ± 14.29% on day 1, 65.49% ±13.65% on day 3, 60.03% ± 14.53% on day 4, and 43.9% ± 20.88% on day 7 postoperatively. Compared to phakic eyes, eyes that were pseudophakic prior to surgery had a lower gas fill on days 1-3, but the difference did not reach significance on day 3. Eyes that underwent phacovitrectomy had a significantly lower gas fill on days 1-3 than eyes that did not., Conclusion: Postoperative pseudophakic status is associated with lower gas fill after MIVS. Adjusted gas fill should be considered in these cases., Competing Interests: The authors declare that there are no conflicts of interests of this paper., (Copyright: © 2020 Taiwan J Ophthalmol.)

Purpose: To evaluate the effect of autophagy inducers on damage caused by vital dye in adult human RPE (ARPE) cells and in a rat model., Methods: ARPE-19 cells were exposed to ICG or BBG (0.05 mg/ml) with rapamycin (200 nM) or metformin (2 mM) for 30 min and treated with or without 20 μM chloroquine (CQ) to identify the protein levels of LC3 and SQSTM1 by immunoblotting. In vivo study was performed by injecting 10 μl 0.05% ICG and 0.25% BBG into the subretinal space of the rat eyes, and/or co-treated them with metformin and rapamycin. The retinas were used to determine autophagy with the LC3-II level and apoptosis with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) assay., Results: In this study, both ICG and BBG inhibited autophagy flux in adult human retinal pigment epithelium cells (ARPE-19), whereas only ICG consistently reduced autophagy in the retina of rats. Moreover, rapamycin and metformin induced autophagic flux in ARPE-19 cells and increased the LC3-II level in retinal tissues exposed to vital dyes. Both ICG and BBG increased apoptosis in the retina of rats. However, both rapamycin and metformin induced autophagy and reduced the apoptosis caused by vital dyes., Conclusion: Taken together, these results suggest that rapamycin and metformin may diminish vital dye-induced retinal damage in vivo through activation of autophagy.

Purpose: To evaluate changes in the microcirculation of various retinal layers and choroid following successful repair of macula-off rhegmatogenous retinal detachment (RRD) using optical coherence tomography angiography (OCTA)., Methods: Twenty-eight patients (28 eyes) who underwent successful repair of macula-off RRD were prospectively investigated. Differences in OCTA characteristics between retinal detachment (RD) and fellow eyes were compared. Quantitative measurements of the retinal capillary and choriocapillary associated with the preoperative and intraoperative factors were analyzed., Results: The mean vessel and parafoveal vessel densities were significantly lower in the superficial retinal capillary plexus (SCP) and deep retinal capillary plexus (DCP) in the RD eyes than the fellow eyes. Presence of preoperative intraretinal separation in the RD eyes was significantly associated with both an enlarged foveal avascular zone (P = 0.022) and a lower DCP vessel density (P = 0.031) postoperatively. Eyes with a scleral buckle alone had a greater postoperative subfoveal choroidal thickness (P = 0.037). Eyes undergoing vitrectomy alone had a higher postoperative vessel density in the choriocapillaris (P = 0.035). Eyes undergoing a vitrectomy and scleral buckle had a lower SCP (P = 0.031) and DCP (P = 0.035) vessel density postoperatively., Conclusions: Macula-off RRD may cause not only retinal structural damage but also decreased retinal perfusion even after successful anatomical repair. Our findings suggested that RD eyes had a significantly lower vessel density than fellow eyes after surgery. The combined procedure might result in a lower vessel density, as compared with a scleral buckle or vitrectomy alone.

Age-related macular degeneration (AMD) is an ocular disease with retinal degeneration. Retinal pigment epithelium (RPE) degeneration is mainly caused by long-term oxidative stress. Kinase activity could be either protective or detrimental to cells during oxidative stress; however, few reports have described the role of kinases in oxidative stress. In this study, high-throughput screening of kinome siRNA library revealed that erb-b2 receptor tyrosine-protein kinase 2 (ERBB2) knockdown reduced reactive oxygen species (ROS) production in ARPE-19 cells during oxidative stress. Silencing ERBB2 caused an elevation in microtubule associated protein light chain C3-II (MAP1LC3B-II/I) conversion and sequesterone (SQSTM)1 protein level. ERBB2 deprivation largely caused an increase in autophagy-regulating protease (ATG4B) expression, a protease that negatively recycles MAP1LC3-II at the fusion step between the autophagosome and lysosome, suggesting ERBB2 might modulate ATG4B for autophagy induction in oxidative stress-stimulated ARPE-19 cells. ERBB2 knockdown also caused an accumulation of nuclear factor erythroid 2-related factor 2 (NRF2) and enhanced its transcriptional activity. In addition, ERBB2 ablation or treatment with autophagy inhibitors reduced oxidative-induced cytotoxic effects in ARPE-19 cells. Furthermore, ERBB2 silencing had little or no additive effects in ATG5/7-deficient cells. Taken together, our results suggest that ERBB2 may play an important role in modulating autophagic RPE cell death during oxidative stress, and ERBB2 may be a potential target in AMD prevention., Competing Interests: The authors have declared that no competing interests exist.

Purpose : To investigate the prevalence and characteristics of ocular manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in patients treated at a tertiary referral center in Taiwan during a time of highly active antiretroviral therapy (HAART) Materials and Methods : A retrospective cohort study in Taiwan was performed between January 2006 and July 2016. Ocular examination and systemic information were recorded from the HIV-infected patients. Results : 1242 patients with HIV/AIDS were identified. Ninety patients had ophthalmic records, and HIV-related ocular manifestations were reported in 57 patients. The most prevalent ocular manifestations were cytomegalovirus (CMV) retinitis, ocular syphilis, and HIV microvasculopathy. Mean CD4 count was significantly lower in patients with HIV-related ocular manifestations compared to those without. Conclusion : We found that lower CD4 count, especially <200 cells/μL, was a significant factor for detecting HIV-related ocular manifestations. Comprehensive ophthalmic screening in high-risk group is helpful for early diagnosis and prompt treatment of sight-threatening ocular complications.

Aim: To assess the effectiveness and safety of ranibizumab 0.5 mg in Taiwanese patients with polypoidal choroidal vasculopathy (PCV) by performing a retrospective exploratory subgroup analysis of the REAL study., Methods: REAL was a 12-month, observational, prospective, non-interventional phase IV post-marketing surveillance study conducted at 9 centers in Taiwan. The study collected data as part of the routine patient visits from the medical records of patients with neovascular age-related macular degeneration treated with ranibizumab 0.5 mg according to local standard medical practice and local label and/or reimbursement guidelines. The presence of PCV at baseline was determined using indocyanine green angiography., Results: At baseline, PCV was diagnosed in 64 of the 303 enrolled patients (21.1%). Of these, 41 patients (64.1%) had received prior treatment; 15 (23.4%) patients had received ranibizumab. The intent-to-treat population included 58 patients; 47 (80%) who received ranibizumab and 11 (20%) who received ranibizumab plus photodynamic therapy (PDT; 9 patients received once, 2 patients received twice). Bevacizumab was used as a concomitant medication in a similar percentage of patients who received ranibizumab (43%, n =20) or ranibizumab plus PDT (45%, n =5). In patients who received ranibizumab, visual acuity (VA) at baseline was 50.1±12.9 Early Treatment Diabetic Retinopathy Study letters, and the gain at month 12 was 1.1±17.8 letters. In patients who received ranibizumab plus PDT, VA at baseline was 51.4±15.9 letters, and there was a marked gain in VA at month 12 (14.0±9.2 letters, P =0.0009). In the intent-to-treat population, the reduction in central retinal subfield thickness from baseline at month 12 was 69.6±122.6 µm (baseline: 310.8±109.8 µm, P =0.0004). The safety results were consistent with the well-characterized safety profile of ranibizumab., Conclusion: In real-world settings, ranibizumab 0.5 mg treatment for 12mo results in maintenance of VA and reduction in central retinal subfield thickness in Taiwanese patients with PCV. Improvements in VA are observed in patients who received ranibizumab plus PDT. There are no new safety findings.

Objectives: To characterize diabetic macular edema (DME) treatment patterns in Taiwan and examine their impact on health care resource utilization and visual and anatomic outcomes., Methods: Retrospective, observational cohort study of longitudinal data from medical records of five hospital ophthalmology clinics. Patients with type 2 diabetes and DME who received ≥1 laser treatment or pharmacotherapy (intravitreal/subtenon corticosteroids and/or intravitreal anti-vascular endothelial growth factor [VEGF] agents) between January 2012 and December 2013 (index period) and attended ≥1 follow-up visit after the first treatment during that period were identified (prevalent population, N=431). In addition, a subset that received no anti-VEGFs before 2012 (anti-VEGF-naïve population, N=77) was analyzed. Outcome measures were change in DME treatment distribution between January 2009 and December 2014 and health care resource utilization over up to 3 years from the first DME treatment received in the index period (prevalent population), mean number of anti-VEGF injections and change from baseline in visual acuity and central macular thickness over 12 months (anti-VEGF-naïve population)., Results: Between 2009 and 2014, laser treatment use declined, overall use of anti-VEGFs increased, and bevacizumab use decreased proportionately as ranibizumab use increased. Patients receiving corticosteroids and anti-VEGFs in the first 6 months post-index had greater health care resource utilization than those treated with laser, corticosteroids, or anti-VEGF alone ( P <0.0001, cross-cohort comparison). Among anti-VEGF-naïve patients, 69% received one to four anti-VEGF injections in the first year post-index. Overall, visual acuity improvement from baseline was minimal at 1 year (0.4 letters, observed data; 0.1 letters, last observation carried forward), and modest central macular thickness reduction (28 µm [last observation carried forward]) was detected., Conclusion: In Taiwanese clinics, DME treatment patterns have shifted from use of laser to anti-VEGFs (with higher health care resource utilization); however, few patients receive anti-VEGF injections at the frequency reported in landmark trials, consistent with poorer visual outcomes. Effective alternative treatments with lower treatment burden should be considered., Competing Interests: Disclosure CKC, HKK, CYT, and TCL report no competing interests. SJS is a speaker for Allergan, Novartis, and Bayer, and has received research support from Allergan and Novartis. SJC has received grant/research support from Novartis, Bayer, and Allergan; honoraria/consulting fees/reimbursement for travel expenses from Novartis and Bayer; and is a member of an advisory panel, standing committee, and board of directors for Novartis and Bayer. MA is an employee of Datalytics Pty Ltd and a statistical consultant for Allergan, Novartis, and Bayer. HC is an employee of Allergan Singapore Pte. Ltd. JT was an employee of Allergan Singapore Pte. Ltd at the time this study was conducted. The authors report no other conflicts of interest in this work.

Choroidal neovascularization (CNV) is a key pathological feature of several leading causes of vision loss including neovascular age-related macular degeneration. Here, we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation, migration of endothelial cells, and vascular sprouting from rat aortic ring explants. In a rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10 μg and 20 μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10 μg/mL and 20 μg/mL of CAD27 instilled, respectively). Retinal function was unaffected, as measured using electroretinography in both groups receiving interareal injection or topical applications of CAD27 for at least fourteen days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in diseases such as neovascular age-related macular degeneration.

Purpose: To investigate optical coherence tomography (OCT) characteristics in diabetic macular edema (DME) over time and after treatment., Patients and Methods: OCT morphological features in DME eyes treated with ranibizumab with at least 1 year of follow-up were retrospectively analyzed., Results: Thirty-five eyes were included. From baseline to Month 12, mean visual gain was 7.2±13.6 letters and mean central retinal thickness reduction was 61.9±121.8 μm. Fovea-involving ellipsoid zone (EZ) disruption was significantly associated with final vision of <70 letters. Subretinal fluid at baseline was present only in eyes naïve to previous intravitreal pharmacotherapy and was related to better visual gain and fewer injections. Treatment-naïve eyes had shorter DME duration and less EZ damage., Conclusion: DME characteristics on OCT may change over time or after treatment. Subretinal fluid may be associated with earlier change and less EZ damage in DME., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Pay-for-Performance programs have shown improvement in indicators monitoring adequacy and target achievement in diabetic care. However, less is known regarding the impact of this program on the occurrence and long-term effects of diabetic retinopathy. The objective of this study was to determine the effect of pay-for-performance program on the development of treatment needed for diabetic retinopathy in type 2 diabetes patients., Methods: We conducted a nationwide retrospective cohort study with a matching design using the Taiwan National Health Insurance Research Database from 2000 to 2012. The outcome was defined as the treatment needed diabetic retinopathy. We matched Pay-for-Performance and non-Pay-for-Performance groups for age, gender, year diabetes was diagnosed and study enrollment, and duration of follow-up., Results: A total of 9311 patients entered the study cohort, of whom 2157 were registered in the Pay-for-Performance group and 7154 matched in the non-Pay-for-Performance group. The incidence of treatment needed diabetic retinopathy was not significantly different in two groups. However, the incidence of treatment needed diabetic retinopathy was significantly different if restricted the non-Pay-for-Performance group who had at least 1 eye examination or optical coherence tomography within 1 year (adjusted hazard ratio, 0.78; 95% confidence interval, 0.64-0.94)., Conclusions: Pay-for-Performance is valuable in preventing the development of treatment needed diabetic retinopathy, which could be attributed to the routine eye examination required in the Pay-for-Performance program. We could improve our diabetic care by promoting eye health education and patient awareness on the importance of regular examinations.