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.

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.

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.

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.

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.

Optimal approaches and criteria to treat-and-extend regimen implementation for Neovascular age-related macular degeneration: experts consensus in Taiwan.

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.

Management of neovascular age-related macular degeneration: Taiwan expert consensus.

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.

New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway.

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.

The Role of Oxidative Stress and Autophagy in Blue-Light-Induced Damage to the Retinal Pigment Epithelium in Zebrafish In Vitro and In Vivo.

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/cm2 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.

An update on the diagnosis and management of ocular sarcoidosis.

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.

Intraocular pressure might play a role in the surgical management of patients with epiretinal membrane.

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.

Tailored internal limiting membrane flap technique for primary macular hole.

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.

Metformin and rapamycin protect cells from vital dye-induced damage in retinal pigment epithelial cells and in vivo.

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.

Imaging analysis with optical coherence tomography angiography after primary repair of macula-off rhegmatogenous retinal detachment.

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.

Pay for performance program reduces treatment needed diabetic retinopathy - a nationwide matched cohort study in Taiwan.

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.

Choroidal Neovascularization Secondary to Intense Pulsed Light Injury.

The authors report a 26-year-old medical device saleswoman developing choroidal neovascularization after injury by intense pulsed light with detection and monitoring by optical coherence tomography angiography and treatment with intravitreal injection of ranibizumab. This is the first intense pulsed light-related choroidal neovascularization case, which reminds the importance of using appropriate eye protection throughout the course of treatment for all individuals present in the therapy room.

Inhibition of Experimental Choroidal Neovascularization by a Novel Peptide Derived from Calreticulin Anti-Angiogenic Domain.

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.

Early Response to Ranibizumab Is Associated with 12-Month Outcome in Diabetic Macular Edema after Prior Macular Laser Therapy.

PURPOSE: To evaluate the efficacy of ranibizumab in persistent or recurrent diabetic macular edema (DME) after previous laser therapy. METHODS: This prospective, interventional study consisted of a 3-month period of scheduled ranibizumab treatment followed by a 9-month period of pro re nata treatment. RESULTS: A total of 21 eyes (18 patients) were included. Both best corrected visual acuity and central retinal thickness had statistically significantly improved from baseline at month 12 (p < 0.001). The mean number of injections within these 12 months was 7.8 ± 2.6 (range 3-11). The visual change at month 12 did not vary by more than 5 letters from the response observed at week 12. CONCLUSIONS: Our study showed a beneficial effect from ranibizumab in DME patients previously treated with macular laser therapy. The response at week 12 was sustained up to 1 year. A suboptimal early visual response may predict a long-term suboptimal response and help identify patients who would benefit from an alternative regimen.

Review of Janus Kinase Inhibitors as Therapies for Noninfectious Uveitis.

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.