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Purpose: To assess the clinical relevance of pathophysiology-based biomarkers, specifically serum C1q and whole blood interferon gene signature score (IGSS), in ocular tuberculosis (OTB) diagnosis by conducting an integrative analysis of clinical presentations and treatment response., Methods: This retrospective cohort study analysed data from 70 patients with suspected OTB at a tertiary care uveitis practice in Indonesia. Serum C1q levels and whole blood IGSS were quantified. Patients were categorized into four quadrants based on their biomarker profiles: quadrant 1 (high C1q & low IGSS), quadrant 2 (high C1q & high IGSS), quadrant 3 (low C1q & high IGSS), and quadrant 4 (low C1q & low IGSS). Characteristics of clinical presentations, work-up results, and treatment outcomes were explored according to the predefined quadrants., Results: We identified that the majority of OTB patients diagnosed with concurrent active pulmonary TB were in quadrant 1, 2, or 3 (20/23, 87.0%). Twenty-seven patients (27/47, 57.4%) with clinically undifferentiated uveitis were in quadrant 4 ( p  < 0.001). Among patients in quadrants 1, 2, and 3, completion of a full course of antitubercular treatment (ATT) was associated with a lower number of patients showing persistence or recurrence of ocular inflammation compared to those who were not fully treated with ATT (14.3% vs 85.7%, p  = 0.001)., Conclusions: Based on the analysis of clinical features and treatment outcomes, patients with elevated levels of either or both serum C1q and whole blood IGSS may reflect active TB disease in the eye, necessitating full ATT management.

Purpose: To describe and compare clinical features, treatment approaches, and treatment outcomes of ocular tuberculosis (OTB) patients in the Netherlands, a low tuberculosis (TB)-endemic country, and Indonesia, a high TB-endemic country. We also aimed to identify predictors of treatment outcomes., Methods: A medical chart review of 339 OTB patients ( n  = 93 from the Netherlands and n  = 246 from Indonesia) was performed. The primary outcome was response to treatment, whether with or without anti-tubercular treatment, after six months of treatment initiation (good versus poor responders)., Results: Indonesian OTB patients displayed a higher prevalence of chest radiograph findings indicative of TB infection ( p  < 0.001) and concurrent active systemic TB ( p  = 0.011). Indonesian cohort exhibited a more acute and severe disease profile, including uveitis duration ≤ 3 months ( p  < 0.001), blindness ( p  < 0.001), anterior chamber (AC) cells ≥ 2+ ( p  < 0.001), and posterior synechiae ( p  < 0.001). Overall proportions of good responders to treatment were 67.6% in the Netherlands and 71.5% in Indonesia. Presence of AC cell ≥ 2+ (adjusted odds ratio (aOR): 2.12, 95% CI: 1.09-4.14), choroidal lesions other than serpiginous-like choroiditis (SLC) or tuberculoma (aOR: 4.47, 95% CI: 1.18-16.90), and retinal vasculitis (aOR: 2.32, 95% CI: 1.10-4.90) at baseline were predictors for poor response to treatment., Conclusions: Despite a more severe initial clinical presentation in the Indonesian cohort, the overall treatment outcomes of OTB was comparable in both cohorts. Three baseline clinical features were identified as predictors of treatment outcomes.

Infectious uveitis is a major global cause of vision impairment. Despite the eye's immune privilege, afforded by the blood-ocular barrier that restricts microbial entry, several pathogens such as bacteria, viruses, fungi, and parasites can still infiltrate and cause ocular infections and complications. Clinicians often encounter significant challenges in treating infectious uveitis due to limited or ineffective treatment options. Modern molecular techniques and imaging can aid in diagnosing and assessing intraocular infections. Various antimicrobial therapies exist, spanning topical and systemic treatments, but these are constrained by issues like drug concentration, penetration, effective duration, toxicity, and side effects. Treatment approaches also differ based on the infection's etiology. This review provides recent updates on antimicrobial therapies from a clinical perspective, covering topical, systemic, and regional treatments for infectious uveitis.

Aims: To assess the risk of uveitis relapse in ocular tuberculosis (OTB) following clinical inactivity, to analyse clinical factors associated with relapses and to describe the management strategies for relapses., Methods: A retrospective study was conducted on a 10-year patient registry of patients with OTB diagnosed at Erasmus MC in Rotterdam, The Netherlands. Time-to-relapse of uveitis was evaluated with Kaplan-Meier curve and risk factors for relapses were analysed., Results: 93 OTB cases were identified, of which 75 patients achieved clinical inactivity following treatment. The median time to achieve uveitis inactivity was 3.97 months. During a median follow-up of 20.7 months (Q1-Q3: 5.2-81.2) after clinical inactivity, uveitis relapse occurred in 25 of these 75 patients (33.3%). Patients who were considered poor treatment responders for their initial uveitis episode had a significantly higher risk of relapse after achieving clinical inactivity than good responders (adjusted HR=3.84, 95% CI: 1.28 to 11.51). 13 of the 25 relapsed patients experienced multiple uveitis relapse episodes, accounting for 78 eye-relapse episodes during the entire observation period. Over half (46 out of 78, 59.0%) of these episodes were anterior uveitis. A significant number of uveitis relapse episodes (31 episodes, 39.7%) were effectively managed with topical corticosteroids., Conclusions: Our results suggest that approximately one-third of patients with OTB will experience relapse after achieving clinical inactivity. The initial disease course and poor response to treatment predict the likelihood of relapse in the long-term follow-up. Topical corticosteroids were particularly effective in relapse presenting as anterior uveitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Vitamin D plays a critical role in immunomodulation, and its deficiency is implicated in the pathogenesis of several autoimmune diseases. Nevertheless, its relationship with non-infectious uveitis (NIU), an inflammatory ocular disorder, remains inconclusive., Methods: A systematic search was conducted in three databases from database inception until May 8, 2023, to investigate the potential relationship between vitamin D deficiency and NIU. We included observational studies reporting the measurement of vitamin D levels in patients with NIU and healthy controls without restriction of language or date of publication. Three pairs of authors independently screened the title and abstracts for potential eligibility and then in full text. A third author resolved disagreements. Three pairs of independent reviewers abstracted the data from the fully reviewed records and evaluated the risk of bias. We followed The MOOSE and PRISMA guidelines. Random effects meta-analyses were used for primary analysis. Studies not included in the meta-analysis were summarized descriptively. This review was registered in PROSPERO: CRD42022308105., Findings: Of 933 records screened, 11 studies were included, and five were meta-analyzed, encompassing 354 cases and 5728 controls (mean participant age ranging from 7.1 to 58.9 years). Patients with vitamin D deficiency exhibited an Odds Ratio of 2.04 (95% CI = 1.55-2.68, P < 0.00001) for developing NIU compared to controls. Overall, potential sources of bias were low across most studies., Interpretation: Our findings suggest that vitamin D may play an essential role in the pathophysiology of NIU. While the included studies demonstrated generally low potential bias, additional rigorous prospective studies are necessary to confirm these findings and further elucidate the underlying mechanisms involved. Vitamin D supplementation could represent a possible therapeutic strategy for preventing or managing NIU if substantiated. Clinicians should consider screening for and addressing vitamin D deficiency in patients with or at risk for NIU., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Aims: To present current expert practice patterns and to formulate a consensus for the management of HSV and VZV AU by uveitis specialists worldwide., Methods: A two-round online modified Delphi survey with masking of the study team was conducted. Responses were collected from 76 international uveitis experts from 21 countries. Current practices in the diagnosis and treatment of HSV and VZV AU were identified. A working group (The Infectious Uveitis Treatment Algorithm Network [TITAN]) developed data into consensus guidelines. Consensus is defined as a particular response towards a specific question meeting ≥75% of agreement or IQR ≤ 1 when a Likert scale is used., Results: Unilaterality, increased intraocular pressure (IOP), decreased corneal sensation and diffuse or sectoral iris atrophy are quite specific for HSV or VZV AU from consensus opinion. Sectoral iris atrophy is characteristic of HSV AU. Treatment initiation is highly variable, but most experts preferred valacyclovir owing to simpler dosing. Topical corticosteroids and beta-blockers should be used if necessary. Resolution of inflammation and normalisation of IOP are clinical endpoints., Conclusions: Consensus was reached on several aspects of diagnosis, choice of initial treatment, and treatment endpoints for HSV and VZV AU. Treatment duration and management of recurrences varied between experts., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Acute retinal necrosis is a progressive intraocular inflammatory syndrome characterized by diffuse necrotizing retinitis that can lead to a poor visual outcome, mainly from retinal detachment. The antiviral treatment approach for acute retinal necrosis varies as there are no established guidelines. We summarize the outcomes of acute retinal necrosis with available antiviral treatments. Electronic searches were conducted in PubMed/MEDLINE, EMBASE, Scopus, and Google Scholar for interventional and observational studies. Meta-analysis was performed to evaluate the pooled proportion of the predefined selected outcomes. This study was registered in PROSPERO (CRD42022320987). Thirty-four studies with a total of 963 participants and 1,090 eyes were included in the final analysis. The estimated varicella-zoster virus and herpes simplex virus polymerase chain reaction-positive cases were 63% (95% CI: 55-71%) and 35% (95% CI: 28-42%), respectively. The 3 main antiviral treatment approaches identified were oral antivirals alone, intravenous antivirals alone, and a combination of systemic (oral or intravenous) and intravitreal antivirals. The overall pooled estimated proportions of visual acuity improvement, recurrence, and retinal detachment were 37% (95% CI: 27-47%), 14% (95% CI: 8-21%), and 43% (95% CI: 38-50%), respectively. Patients treated with systemic and intravitreal antivirals showed a trend towards better visual outcomes than those treated with systemic antivirals (oral or intravenous) alone, even though this analysis was not statistically significant (test for subgroup differences P = 0.83)., Competing Interests: Declaration of Competing Interest All authors: None., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To present current practice patterns in the diagnosis and management of Cytomegalovirus anterior uveitis (CMV AU) by uveitis experts worldwide., Methods: A two-round modified Delphi survey with masking of the study team was performed. Based on experience and expertise, 100 international uveitis specialists from 21 countries were invited to participate in the survey. Variation in the diagnostic approaches and preferred management of CMV AU was captured using an online survey platform., Results: Seventy-five experts completed both surveys. Fifty-five of the 75 experts (73.3%) would always perform diagnostic aqueous tap in suspected CMV AU cases. Consensus was achieved for starting topical antiviral treatment (85% of experts). About half of the experts (48%) would only commence systemic antiviral treatment for severe, prolonged, or atypical presentation. The preferred specific route was ganciclovir gel 0.15% for topical treatment (selected by 70% of experts) and oral valganciclovir for systemic treatment (78% of experts). The majority of experts (77%) would commence treatment with topical corticosteroid four times daily for one to two weeks along with antiviral coverage, with subsequent adjustment depending on the clinical response. Prednisolone acetate 1% was the drug of choice (opted by 70% of experts). Long-term maintenance treatment (up to 12 months) can be considered for chronic course of inflammation (88% of experts) and those with at least 2 episodes of CMV AU within a year (75-88% of experts)., Conclusions: Preferred management practices for CMV AU vary widely. Further research is necessary to refine diagnosis and management and provide higher-level evidence., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Introduction: There is a scarcity of long-term follow-up data and management strategies for recurrent uveitis in tubercular uveitis (TBU), especially in cases extending beyond 10 years after the completion of initial antitubercular treatment (ATT)., Methods: This retrospective study involved five TBU patients who were initially treated with a combination of four-drug ATT for 6 months, and the five of them had more than 10 years of follow-up after uveitis resolution upon ATT completion. We describe the occurrence of recurrent uveitis and present our approach to managing these recurrent episodes., Results: Recurrent uveitis and cystoid macular edema (CME) developed in three out of five included TBU patients with a median of 18 years (range 13-20 years) of follow-up. The anatomical sites of the recurrences were anterior, intermediate, and pan-uveitis. The recurrent episodes varied from 6 years to 15 years after ATT completion. Systemic or local corticosteroids/immunosuppressants successfully resolved all recurrent episodes, but one was also treated with the combination of isoniazid monotherapy again. Two patients needed anti-tumor necrosis factor-α therapy., Conclusion: Long-term monitoring of TBU patients after ATT completion is warranted. Further well-designed studies with larger sample sizes are required to better estimate the risk of recurrences, investigate the underlying mechanism of recurrences, and identify biomarkers that predict who is at risk for recurrences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Putera, van Daele, ten Berge, Dik, La Distia Nora, van Hagen and Rombach.)

Anterior uveitis is the most common type of uveitis worldwide. The etiologies of anterior uveitis can be divided into infectious and non-infectious (idiopathic, autoimmune, autoinflammatory, trauma, and others). The viral pathogens most commonly associated with infectious anterior uveitis include Herpes Simplex Virus, Varicella-Zoster Virus, Cytomegalovirus, and Rubella Virus. Other emerging causes of viral anterior uveitis are West Nile Virus, Human-Immunodeficiency Virus, Epstein-Barr Virus, Parechovirus, Dengue Virus, Chikungunya Virus, and Human Herpesvirus type 6,7, and 8. Early recognition allows prompt management and mitigates its potential ocular complications. This article provides an updated literature review of the epidemiology, clinical manifestations, diagnostic tools, and treatment options for viral anterior uveitis.

In the current literature, clinical registry cohorts related to ocular inflammation are few and far between, and there are none involving multi-continental international data. Many existing registries comprise administrative databases, data related to specific uveitic diseases, or are designed to address a particular clinical problem. The existing data, although useful and serving their intended purposes, are segmented and may not be sufficiently robust to design prognostication tools or draw epidemiological conclusions in the field of uveitis and ocular inflammation. To solve this, we have developed the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) Clinical Registry. OASIS collects prospective and retrospective data on patients with all types of ocular inflammatory conditions from centers all around the world. It is a primarily web-based platform with alternative offline modes of access. A comprehensive set of clinical data ranging from demographics, past medical history, clinical presentation, working diagnosis to visual outcomes are collected over a range of time points. Additionally, clinical images such as optical coherence tomography, fundus fluorescein angiography and indocyanine green angiography studies may be uploaded. Through the capturing of diverse, well-structured, and clinically meaningful data in a simplified and consistent fashion, OASIS will deliver a comprehensive and well organized data set ripe for data analysis. The applications of the registry are numerous, and include performing epidemiological analysis, monitoring drug side effects, and studying treatment safety efficacy. Furthermore, the data compiled in OASIS will be used to develop new classification and diagnostic systems, as well as treatment and prognostication guidelines for uveitis., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Introduction: Accurate diagnosis and timely management are vital for favorable uveitis outcomes. Artificial Intelligence (AI) holds promise in medical decision-making, particularly in ophthalmology. Yet, the diagnostic precision and management advice from AI-based uveitis chatbots lack assessment., Methods: We appraised diagnostic accuracy and management suggestions of an AI-based chatbot, ChatGPT, versus five uveitis-trained ophthalmologists, using 25 standard cases aligned with new Uveitis Nomenclature guidelines. Participants predicted likely diagnoses, two differentials, and next management steps. Comparative success rates were computed., Results: Ophthalmologists excelled (60-92%) in likely diagnosis, exceeding AI (60%). Considering fully and partially accurate diagnoses, ophthalmologists achieved 76-100% success; AI attained 72%. Despite an 8% AI improvement, its overall performance lagged. Ophthalmologists and AI agreed on diagnosis in 48% cases, with 91.6% exhibiting concurrence in management plans., Conclusions: The study underscores AI chatbots' potential in uveitis diagnosis and management, indicating their value in reducing diagnostic errors. Further research is essential to enhance AI chatbot precision in diagnosis and recommendations.

Introduction: Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide, affecting individuals acrossdifferent age groups. The key to reducing vision loss includes prompt diagnosis and treatment. However, despite the prevalence of ocular toxoplasmosis, there has been little consensus regarding its pathophysiology,clinical features, diagnosis, and especially management., Methods: The data sources were literature reviews, including Pub Med and Medline databases. Search terms included toxoplasmosis, retinitis, vasculitis, vitritis, uveitis alone or in combination with, serum, aqueous, vitreous eye, ocular and review., Results: In this review paper, we have sought to provide an overview of the pathophysiology, epidemiology, and clinical features of the disease, both based on current literature and our own clinical experience. We have also discussed the use of serology, ocular fluid, and ophthalmic investigations that could further facilitate the diagnosis of ocular toxoplasmosis.Different management strategies have been reported worldwide, including newer approaches such as local therapy., Conclusion: A better understanding of critical aspects of ocular toxoplasmosis will hopefully lead to reduced morbidity, including blindness associated with this condition.

Tubercular uveitis (TB-uveitis) remains a conundrum in the uveitis field, which is mainly related to the diverse clinical phenotypes of TB-uveitis. Moreover, it remains difficult to differentiate whether Mycobacterium tuberculosis (Mtb) is present in the ocular tissues, elicits a heightened immune response without Mtb invasion in ocular tissues, or even induces an anti-retinal autoimmune response. Gaps in the immuno-pathological knowledge of TB-uveitis likely delay timely diagnosis and appropriate management. In the last decade, the immunopathophysiology of TB-uveitis and its clinical management, including experts' consensus to treat or not to treat certain conditions with anti-tubercular treatment (ATT), have been extensively investigated. In the meantime, research on TB treatment, in general, is shifting more toward host-directed therapies (HDT). Given the complexities of the host-Mtb interaction, enhancement of the host immune response is expected to boost the effectiveness of ATT and help overcome the rising burden of drug-resistant Mtb strains in the population. This review will summarize the current knowledge on the immunopathophysiology of TB-uveitis and recent advances in treatment modalities and outcomes of TB-uveitis, capturing results gathered from high- and low-burden TB countries with ATT as the mainstay of treatment. Moreover, we outline the recent progress of HDT development in the pulmonary TB field and discuss the possibility of its applicability to TB-uveitis. The concept of HDT might help direct future development of efficacious therapy for TB-uveitis, although more in-depth research on the immunoregulation of this disease is still necessary., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tuberculosis is an airborne disease caused by Mycobacterium tuberculosis (Mtb) and can manifest both pulmonary and extrapulmonary disease, including ocular tuberculosis (OTB). Accurate diagnosis and swift optimal treatment initiation for OTB is faced by many challenges combined with the lack of standardized treatment regimens this results in uncertain OTB outcomes. The purpose of this study is to summarize existing diagnostic approaches and recently discovered biomarkers that may contribute to establishing OTB diagnosis, choice of anti-tubercular therapy (ATT) regimen, and treatment monitoring. The keywords ocular tuberculosis, tuberculosis, Mycobacterium , biomarkers, molecular diagnosis, multi-omics, proteomics, genomics, transcriptomics, metabolomics, T-lymphocytes profiling were searched on PubMed and MEDLINE databases. Articles and books published with at least one of the keywords were included and screened for relevance. There was no time limit for study inclusion. More emphasis was placed on recent publications that contributed new information about the pathogenesis, diagnosis, or treatment of OTB. We excluded abstracts and articles that were not written in the English language. References cited within the identified articles were used to further supplement the search. We found 10 studies evaluating the sensitivity and specificity of interferon-gamma release assay (IGRA), and 6 studies evaluating that of tuberculin skin test (TST) in OTB patients. IGRA (Sp = 71-100%, Se = 36-100%) achieves overall better sensitivity and specificity than TST (Sp = 51.1-85.7%; Se = 70.9-98.5%). For nuclear acid amplification tests (NAAT), we found 7 studies on uniplex polymerase chain reaction (PCR) with different Mtb targets, 7 studies on DNA-based multiplex PCR, 1 study on mRNA-based multiplex PCR, 4 studies on loop-mediated isothermal amplification (LAMP) assay with different Mtb targets, 3 studies on GeneXpert assay, 1 study on GeneXpert Ultra assay and 1 study for MTBDRplus assay for OTB. Specificity is overall improved but sensitivity is highly variable for NAATs (excluding uniplex PCR, Sp = 50-100%; Se = 10.5-98%) as compared to IGRA. We also found 3 transcriptomic studies, 6 proteomic studies, 2 studies on stimulation assays, 1 study on intraocular protein analysis and 1 study on T-lymphocyte profiling in OTB patients. All except 1 study evaluated novel, previously undiscovered biomarkers. Only 1 study has been externally validated by a large independent cohort. Future theranostic marker discovery by a multi-omics approach is essential to deepen pathophysiological understanding of OTB. Combined these might result in swift, optimal and personalized treatment regimens to modulate the heterogeneous mechanisms of OTB. Eventually, these studies could improve the current cumbersome diagnosis and management of OTB., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: Wound healing and fibrosis modulation are considered pivotal for the long-term outcome of strabismus surgery. Nonsteroidal anti-inflammatory drugs, including diclofenac sodium, are inflammation suppressive drugs that may modulate wound healing, including postoperative inflammation. This study aimed to compare the effect of oral and 0.1% topical diclofenac sodium on short-term inflammation and α -smooth muscle actin ( α -SMA) expression at the tendon-scleral attachment site following strabismus surgery in an experimental rabbit model., Methods: Superior rectus recession was performed in 12 eyes of six New Zealand rabbits. Rabbits were divided into three groups: oral diclofenac 2 × 5 mg/kg for three days (group A), 0.1% diclofenac sodium eye drops 3 times/day for three days (group B), and controls (group C). On postoperative day 14, enucleation was performed. Macroscopic adhesion score, microscopic adhesion score, percentage of postoperative inflammation area (Masson's trichrome staining), and α -SMA (immunohistochemistry staining) were assessed. Data analysis was performed using a semi-quantitative and quantitative assessment with ImageJ. All groups were compared with reciprocal staining intensity (RSI) values to measure α -SMA expression., Results: All groups showed no difference in macroscopic ( p  = 0.13) and microscopic adhesion scores ( p  = 0.28). The percentage of postoperative inflammation area in group B (12.44% (8.63-18.29)) was significantly lower than group A (26.76% (21.38-37.56) p  = 0.03) and group C (27.80% (16.42-36.28), p  = 0.04). Comparative RSI analysis found that group B had a significantly lower α -SMA expression than group C (174.08 ± 21.78 vs 212.58 ± 12.06, p  = 0.04)., Conclusion: The results suggest that compared to oral, the administration of topical diclofenac showed a more significant reduction of short-term postoperative inflammation and α -SMA expression at the tendon-scleral attachment site following strabismus surgery.

We quantitatively evaluated the efficacy of antitubercular therapy (ATT) in tubercular uveitis (TBU) patients. Main outcome measures include inflammation recurrence, inflammation reduction, complete resolution of inflammation, improved visual acuity (VA), ability to taper corticosteroids to < 10 mg/day without inflammatory progression, and use of adjunctive immunosuppressants while on ATT. This review is prospectively registered in PROSPERO (CRD42020206845). Forty-nine studies reporting data for 4,017 TBU patients were included. In comparative studies, the odds ratio (OR) of inflammatory recurrence was 0.33 (95%CI:0.19-0.60) for TBU patients treated with ATT±corticosteroid versus no ATT. For TBU patients treated with ATT±corticosteroid, the pooled absolute incidences of inflammatory recurrence, inflammatory reduction, complete resolution of inflammation, and visual acuity improvement were 13% (n=310/2,216; 95%CI:9-18), 81% (n=217/276; 95%CI: 62-95), 83% (n=1,167/1,812; 95%CI: 77-89), and 65% (n=347/542; 95%CI:51-78), respectively. Corticosteroids were tapered to <10 mg/day without inflammatory progression in 91% (n=326/395; 95%CI:78-99) of patients, 9% (n=121/1,376; 95%CI:6-13) of whom were administered concomitant immunosuppressive agents alongside ATT. We conclude that treatment of TBU with ATT±corticosteroid is associated with a high level of control or improvement of inflammation. More prospective studies with detailed reporting of ATT regimens, patient subgroups, and outcomes are required to better evaluate ATT effectiveness., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To assess the clinical value of aqueous humor real-time polymerase chain reaction (RT-PCR) and serological antibody tests among uveitis patients in Indonesian cohort., Methods: In this prospective cohort study, single-plex RT-PCR analysis of aqueous samples from 86 new uveitis patients was performed to detect Mycobacterium tuberculosis , Toxoplasmosis gondii , cytomegalovirus, herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, and rubella virus. Specific serological antibodies for suspected pathogens were also obtained. Comparison of PCR and serological antibodies with the initial and final diagnosis were presented., Results: The diagnostic positivity of aqueous RT-PCR in our cohort was 20% (17/86). The rate of infection as final etiological classification was higher after RT-PCR was performed (45 patients, 52%) compared to initial diagnosis based on clinical presentation alone (38 patients, 44%). In particular, the RT-PCR positivity among patients with infection as the final etiological classification was 33.33% (15/45). A significant difference in the IgG but not IgM toxoplasma value among those with ocular toxoplasmosis as the final diagnosis compared to the other etiologies were observed (3953 (IQR 2707-19562) IU/mL vs 428 (IQR 82-1807) IU/mL; p < 0.0001)., Conclusion: RT-PCR analysis of aqueous fluid from uveitis patients helped confirm a third of infectious uveitis cases in Indonesia. In ocular toxoplasmosis, high IgG but not IgM antibody value might help differentiate those with other etiology., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior uveitis may delay adequate treatment and affect outcomes. We sought to review systemically the overall clinical characteristics and compare treatment outcomes in CMV anterior uveitis and endotheliitis. A literature search was performed, and studies describing clinical characteristics, treatment regimens, and outcomes that included more than 5 treated eyes were included. In these 23 studies, acute CMV anterior uveitis commonly presented with high intraocular pressure (95.31%, 95% CI 90.45-98.60) and mild anterior chamber inflammation (cells >2+ = 3.18%, 95% CI 0.21-0.54). About two-thirds of CMV endotheliitis cases presented with high intraocular pressure and coin-shaped corneal lesions. Acute CMV anterior uveitis showed good clinical response to topical 0.15% ganciclovir (GCV) gel or oral valganciclovir (VGCV) (90%, 95% CI 74-100% and 95%, 95% CI 88-100%, respectively). For chronic CMV anterior uveitis, both topical GCV and oral VGCV yielded comparable results. Topical 0.5-2% GCV or a combination of topical and oral VGCV for CMV endotheliitis both resulted in good clinical response. Recurrence of inflammation was common after cessation of maintenance therapy. Overall, topical GCV resulted in an optimal outcome for CMV anterior uveitis. Escalated concentration and frequency of usage are needed for chronic CMV anterior uveitis and endotheliitis. Adequate induction and maintenance phases of anti-CMV treatment seem necessary to prevent recurrences., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To investigate the utility of nonroutine polymerase chain reaction analysis of intraocular fluid to guide the diagnosis of infectious uveitis., Patients and Methods: A retrospective cohort study was conducted by reviewing medical record data from intraocular fluid samples of uveitis patients who underwent single-plex real-time polymerase chain reaction analysis at the Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Kirana Eye Hospital between January 2014 and December 2018., Results: The positivity rate of nonroutine polymerase chain reaction analysis was 17.2%. The vitreous sample tended to show a higher positive outcome (28.6%) than the aqueous sample (16.2%), even though the outcome was not statistically significant. Mycobacterium tuberculosis and Toxoplasma gondii were the most frequently observed microorganisms in the polymerase chain reaction analysis among uveitis patients in our setting. The duration of symptoms, type of sample fluid (aqueous/vitreous), or presence of anterior chamber cells ≥2 were not significantly associated with polymerase chain reaction positivity (p > 0.05)., Conclusion: Nonroutine polymerase chain reaction analysis of intraocular fluid among a cohort of Indonesian patients demonstrated low positivity. The sensitivity and specificity of nonroutine single-plex polymerase chain reaction could not be estimated due to limitations such as lost to follow-up patients and incomplete monitoring data. The use of multiplex polymerase chain reaction in the future may be beneficial in our setting., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Putera et al.)

Background: Polymerase chain reaction (PCR) is currently considered the method of choice for diagnosing ocular tuberculosis. However, the sensitivity and specificity of PCR using ocular samples remain uncertain. Our meta-analysis aimed to review the diagnostic accuracy of PCR testing in confirming ocular tuberculosis, with responses to antitubercular therapy (ATT) as reference indices., Methods: A systematic literature search of the PubMed, EBSCOHost, Scopus, and Google Scholar databases was performed using the standardized PRISMA guideline. Observational studies reporting both PCR MTb positivity and ATT response were included. Meta-analysis was performed to estimate the pooled positivity rate, sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratios (DOR), and summary receiver operating curves (SROC)., Results: The pooled positivity rate for PCR MTb was 0.55 (95% CI 0.44-0.67). The overall sensitivity and specificity were 88% (95% CI 83-92) and 71% (95% CI 60-80), respectively. The pooled DOR was 12.15 (95% CI 5.55-26.62). The area under the SROC was 0.83., Conclusions: The diagnostic accuracy of PCR Mtb is not sufficient for use as a benchmark for ocular TB diagnosis routinely based on ATT response. A negative result may help avoid prescribing unnecessary ATT in dilemmatic cases., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To review and critically appraise the ocular manifestation and the presence of SARS-CoV-2 through PCR positivity from ocular samples in COVID-19-related patients. Moreover, to evaluate the time and severity association of ocular manifestation to systemic disease of COVID-19., Methods and Analysis: A systematic literature search from PubMed, ScienceDirect and Google Scholar databases was performed using standardised Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Selected keywords were related to COVID-19, ocular manifestation and PCR testing of SARS-CoV-2. Studies were assessed for their validity, and the data were extracted by two independent reviewers. Observational, case series and case report studies were included if they met the selection criteria. Meta-analysis was performed to estimate the pooled prevalence of ocular manifestations and PCR positivity from tears., Results: Thirty-one articles were qualitatively reviewed, and 14 studies were included in the meta-analysis. The pooled prevalence of ocular manifestation among COVID-19-related patients was 0.05 (95% CI 0.02% to 0.08). The overall PCR from tears samples positivity rate from COVID-19-related patients presenting with ocular manifestation was 0.38 (95% CI 0.14% to 0.65). Ocular manifestation could precede systemic manifestation in about 0.28 (95% CI 0.05% to 0.58) of COVID-19-related patients with ocular manifestations. Besides, ocular manifestation was not associated with a severe form of COVID-19., Conclusion: Although the overall number of ocular manifestation and SARS-CoV-2 PCR positivity rate from ocular samples was very low, around a quarter of COVID-19-related patients with ocular manifestation presented their ocular manifestation earlier than the systemic manifestation regardless of the severity. Interestingly, SARS-CoV-2 PCR was positive from one-third of ocular samples, which could potentially be the source of infection to the respiratory tract and the environment, although the infectivity is yet to be determined., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Health definition consists of three domains namely, physical, mental, and social health that should be prioritized in delivering healthcare. The emergence of chronic diseases in aging populations has been a barrier to the realization of a healthier society. The value-based healthcare concept seems in line with the true health objective: increasing value. Value is created from health outcomes which matter to patients relative to the cost of achieving those outcomes. The health outcomes should include all domains of health in a full cycle of care. To implement value-based healthcare, transformations need to be done by both health providers and patients: establishing true health outcomes, strengthening primary care, building integrated health systems, implementing appropriate health payment schemes that promote value and reduce moral hazards, enabling health information technology, and creating a policy that fits well with a community., Competing Interests: The authors have declared that no competing interests exist.

Health definition consists three domains, namely physicial, mental and social health, that should be prioritized in delivering healthcare. The emergence of chronic diseases in the aging populations has been a barrier to the realization of healthier society. The value-based healthcare concept seems in line with the true health objectives: increasing value. Value is created from health outcomes which matter to patient relative to cost of achieving those outcomes. The health outcomes should include all domain of health in a full cycle of care. To implement value-based healthcare, transformations need to be done by both health providers and patients: establishing true health outcomes, strenghtening primary care, buidling integrated health system, implementing appropriate health payment scheme that promote value and reduce moral hazards, enabling health information technology, and policy that fits well with community., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2017, Putera et al.)

Introduction: The aim of this study was to identify the preference of Indonesian medical students to work in rural areas, to enroll in the (PTT; which means 'temporary employment') program, and to identify factors that influence their choice of a preferred future practice area. Under the PTT program, doctors are obliged to work as temporary staff on a contract basis for a certain period in a rural area of Indonesia., Methods: The study design was cross-sectional and a total sampling method was used. The subjects were year 4 and 5 medical students from the Faculty of Medicine at Universitas Indonesia and had already been exposed to clinical practice rotations within their education program. Students rated the importance of 21 factors influencing their future workplace preference using a questionnaire with a five-point Likert scale., Results: A total of 310 students (83.3%) responded to the questionnaire. The authors found that 27 out of 310 (8.71%) subjects wanted to work in rural areas, while 128 out of 264 (48.5%) students who chose other than rural areas wanted to enroll in the PTT program. A previous experience of living in rural areas seemed to be the only factor favouring students' choice to have future practice in rural areas (adjusted odds ratio (OR) 3.20, 95% confidence interval (CI) 1.27-8.08, =0.01). Factors that influenced respondents to say they didn't intend to practice rurally were the influence of spouse (adjusted OR 0.38, 95%CI 0.16-0.89, =0.03), and the opportunities for career advancement (adjusted OR 0.28, 95%CI 0.11-0.73, =0.009). The choice of enrollment in the PTT program was positively associated with opportunity for an academic career (adjusted OR 2.39, 95%CI 1.27-4.50, =0.007) and negatively associated with proximity to family/friends (adjusted OR 0.38, 95%CI 0.22-0.65, 0.001)., Conclusions: Only 8.7% of the students were interested in rural areas for their future practice location. Multiple factors were associated with students' interest to choose a career in rural areas later, after graduation from medical school.

Background: Despite the high efficacy of tuberculosis (TB) drug regiments, one of the barriers in the TB control program is the non-compliance to treatment. Morbidity, mortality, and risk to become resistant to drugs are emerging among defaulters. Thus, the aim of this study is to identify the factors, especially knowledge and perceptions of TB and association with treatment default among patients treated in primary care settings, East Nusa Tenggara., Methods: This study was part of a bigger cohort community-based controlled trial study. The subjects were newly diagnosed pulmonary TB patients from four districts in East Nusa Tenggara. Knowledge, perception of TB, and other related factors were assessed prior to the treatment. Patients who interrupted the treatment in two consecutive months were classified as defaulters, as World Health Organization stated. Odds ratio (OR) looking for factors associated with becoming defaulter was analyzed., Results: A total of 300 patients were recruited for this study. At the end of the treatment, 255 patients (85%) completed the treatment without interruption from regular visit. In univariate analysis, none of the socio-demographic factors attributed to treatment default yet lack of knowledge and incorrect perception of TB prior therapy (OR 2.49 1.30-4.79 95% CI, p = 0.006; OR 5.40 2.64-11.04 95% CI, p < 0.001, respectively). In multivariate analysis, only incorrect perception of TB showed significant association with treatment default (OR 4.75 2.30-9.86 95% CI)., Conclusions: Assessing the knowledge and perception of TB prior to the treatment in newly pulmonary TB patients is important as both of them were known as risk factor for treatment default. Education and counseling may be required to improve patients' compliance to treatment.

Introduction: Bacille Calmette-Guerin (BCG) vaccination remains a routine immunization in primary care in tuberculosis (TB)-endemic areas, though several studies found that its efficacy was inconclusive. Natural resistance-asociated machrophage protein 1 (NRAMP1) polymorphism has been shown to result in higher susceptibility to TB. Information on genetic susceptibility in populations will be useful in planning the application of the BCG vaccine. The present study explored BCG efficacy in a rural Timor population with specific NRAMP1 polymorphism in a TB-endemic region of eastern Indonesia., Methodology: A case-control study with 64 newly diagnosed pulmonary TB patients and 65 healthy controls was performed. BCG scars were examined by a physician. NRAMP1 polymorphism was evaluated using molecular methods., Results: Half of the subjects (65; 50.4%) had a clear presenting BCG scar on the upper arm, suggesting a successful BCG vaccination. Among the subjects, D543N NRAMP1 polymorphism, history of contact with TB patients, and not having a clear BCG scar on the upper arm tended to be significantly association with active TB. The significant differences were more profound when subjects were divided based on presenting BCG scar. Subjects without clear BCG scars had significant association with developing TB disease (p = 0.014). In multivariate analysis, history of previous contact with TB patients and unclear presenting BCG scar were associated with active TB (OR 9.2; 2.0-43.8 95% CI, OR 4.8; 2.1-11.0 95% CI, respectively)., Conclusions: BCG vaccination in our population was effective for TB protection, especially in highly endemic areas of TB, regardless genetic susceptibility.

Aim: to know the relationship between salted fish consumption and nasopharyngeal carcinoma (NPC)., Methods: we searched for the articles from PubMed® and ScienceDirect® based on our clinical question. After filtered with our in- and exclusion criteria, we had six articles about this topic, all of them were case-control studies. All articles were then critically appraised for their validity, importance, and applicability., Results: there was no consistent relationship between salted fish consumption and NPC. Worth to note that those studies wo showed the firm relationship were conducted in Southern China, where the incidence of NPC was extremely high and related to specific Chineese-style salted fish consumption., Conclusion: there was an inconsistent relationship between salted fish consumption and NPC.