Use of corticosteroids in non-infectious uveitis - expert consensus in Taiwan.

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.

Diagnosis and treatment of syphilitic uveitis: Taiwan experts consensus.

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.

Taiwan ocular inflammation society consensus recommendations for the management of juvenile idiopathic arthritis-associated uveitis.

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.

Diagnosis, Treatment, and Prevention of Noninfectious Acute Anterior Uveitis with or without Human Leukocyte Antigen B27 in Adults - Expert Consensus in Taiwan.

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.

Literature- and Experience-Based Consensus for Acute Post-operative Endophthalmitis and Endogenous Endophthalmitis in Taiwan.

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.

Guidelines and treatment patterns for primary rhegmatogenous retinal detachments: Expert consensus and survey in Taiwan Retina Society.

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.

Changing etiology of sympathetic ophthalmia: A 10-year study from a tertiary referral center in Taiwan.

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.

A Prospective Study of Clinical Features of Anterior Uveitis in Taiwan.

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.

Prolonged Exposure to High Glucose Induces Premature Senescence Through Oxidative Stress and Autophagy in Retinal Pigment Epithelial Cells.

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-ß-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.

Optical Coherence Tomography Assessment of Macular Thickness in Alzheimer's Dementia with Different Neuropsychological Severities.

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.

Diagnosis and Treatment of Tubercular Uveitis in Taiwan - Consensus of Expert Panels.

There is currently a lack of guidelines with regard to tubercular uveitis (TBU) management in Taiwan. We therefore propose an evidence-based consensus on the management for TBU. The Taiwan Ocular Inflammation Society conducted a meeting that included nine ophthalmologist and one infection disease expert that focused on three broad areas of (1) nomenclature for TBU, (2) assessment and diagnosis for TBU, and (3) treatment of TBU. Brief literature review on TBU diagnosis and management was conducted that informed this panel meeting in order to make decisions on each consensus statements. In terms of our results, a consensus statements and recommendations for the diagnosis and management of TBU were developed. This consensus statement provides an algorithmic approach toward diagnosing and managing TBU. These statements are meant to enhance but not replace individual clinician-patient interactions and to facilitate real-world clinical practice improvement in terms of TBU patients care.

Feasibility Analysis of Teleophthalmology Diagnosis and Referral in Remote Areas of Taiwan.

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.

Cytomegalovirus Uveitis: Taiwan expert consensus.

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.

Optical coherence tomography biomarkers for myopic choroidal neovascularization treated with anti-vascular endothelial growth factor.

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.

Retinal protective effect of curcumin metabolite hexahydrocurcumin against blue light-induced RPE damage.

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.

Vitreoretinal surgery in the management of infectious and non-infectious uveitis - a narrative review.

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.

Step-wise diagnostic approach for patients with uveitis - Experts consensus in Taiwan.

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.

Cooperation with rheumatologists on intensive systemic treatment for psoriatic arthritis-related panuveitis with retinal vasculitis: a case report.

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.

One-year outcomes of the treat-and-extend regimen using aflibercept for the treatment of diabetic macular edema.

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.