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Ikhwanuliman Putera,1,2 Mei Riasanti,1 Lukman Edwar,1 Made Susiyanti,1 Ratna Sitompul,1 Yulia Aziza,1 Priscilla Jessica,1 Andriansjah Rukmana,3 Andi Yasmon,3 Rina La Distia Nora1,2,4 1Department of Ophthalmology, Faculty of MedicineUniversitas Indonesia – Cipto Mangunkusumo Kirana Eye Hospital, Jakarta, Indonesia; 2Department of Immunology, Erasmus Medical Center, Rotterdam, the Netherlands; 3Department of Microbiology, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia; 4University of Indonesia Hospital (RSUI), Depok, West Java, IndonesiaCorrespondence: Rina La Distia Nora, Department of Ophthalmology, Faculty of Medicine Universitas Indonesia – Cipto Mangunkusumo Kirana Eye Hospital, Jl. Kimia No. 8, Menteng, Central Jakarta, Jakarta, 10320, Indonesia, Tel +62811198910, Email rina.ladistia@ui.ac.idPurpose: 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.Keywords: aqueous humor, vitreous humor, infection, ocular inflammation, Mycobacterium tuberculosis, epidemiology

Introduction: Olfactory dysfunction is prevalent among individuals with chronic kidney disease (CKD), with prevalence escalating alongside disease severity. The uremic toxin we observed in this study is Indoxyl sulfate (IS), a potent uremic toxin that markedly accumulates in the plasma of patients with chronic insufficiency. Olfactory damage may occur in the setting of neuronal damage due to renal failure., Materials and Methods: 27 patients, a total sample in this study with diagnosed chronic kidney disease within stage 5 on regular hemodialysis, were examined for indoxyl sulfate levels in blood plasma and then examined for their olfactory function using the Sniffin' Sticks test. A correlation analysis was conducted between indoxyl sulfate levels and olfactory function test results in patients with CKD., Results: The Pearson correlation test revealed a strong, significant negative correlation between indoxyl sulfate levels and olfactory function (r = -0.613; p = 0.001). Additionally, correlations were found between indoxyl sulfate levels and each component of olfactory function: threshold value (r = -0.408; p = 0.035), discrimination (r = -0.807; p = 0.001), and identification (r = -0.703; p = 0.001)., Conclusion: Olfactory function is compromised in individuals with chronic renal disease and correlates with the level of accumulation of the uremic toxin indoxyl sulfate., (©2025 Mashhad University of Medical Sciences.)

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.

Cytomegalovirus retinitis (CMVR) is a significant cause of blindness in patients with advanced acquired immunodeficiency syndrome (AIDS). There are no established guidelines for its treatment, resulting in varied antiviral approaches. We pooled data from 59 studies (4501 patients) to evaluate treatment variations and outcomes (CRD42022321088). Overall pooled estimates showed visual acuity improvement at 18 % (95 % CI: 7-41 %), inflammation resolution at 90 % (95 % CI: 81-95 %), retinal detachment at 11 % (95 % CI: 8-14 %), and recurrence at 19 % (95 % CI: 11-31 %). The main antiviral treatment approaches identified were: (1) intravenous antivirals alone in 33 studies, (2) intravitreal antivirals alone in 26 studies, (3) oral antivirals alone in 3 studies, and (4) a combination of systemic (oral or intravenous[IV]) and intravitreal antivirals in 7 studies, with varying schemes and durations. Ganciclovir was the predominant antiviral, with intravenous administration being the most reported (in 23 studies), followed by intravitreal administration (in 20 studies). While visual acuity improvement was comparable, inflammation resolution tended to be higher with intravitreal than with IV antivirals, though not statistically significant (88 %, 95 % CI: 69-96 % vs 75 %, 95 % CI: 35-94 %, p = 0.38). Retinitis progression rate for IV ganciclovir was lower than for those without ganciclovir. Inflammation recurrence was significantly lower in antiretroviral (ART)-treated compared to non-ART-treated HIV/AIDS patients (10 % (95 % CI: 4-20 %) vs 33 % (95 % CI: 19-50 %), p < 0.01). Neutropenia, particularly with ganciclovir, was the most reported adverse effect (up to 50 %)., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To provide the long-term outcome of patients with end-stage severe ocular surface disease (OSD) consecutively treated with cultivated oral mucosal epithelial transplantation (COMET) followed by limbal-rigid contact lens (CL)-wear therapy., Design: Retrospective cohort., Methods: In 23 eyes of 18 patients with severe OSD who underwent COMET surgery between 2002 and 2019 and who were followed with limbal-rigid CL-wear therapy for at least 1 year postoperative, patient demographics, best-corrected visual acuity (BCVA, logMAR), Ocular Surface Grading Scores (OSGS), surgical indication and adverse events were reviewed. Primary and secondary outcomes were BCVA and OSGS changes at baseline and final examination, respectively., Results: This study involved 16 patients with Stevens-Johnson syndrome and 2 patients with mucous membrane pemphigoid (mean age: 59±15 years). The indications for COMET were as follows: corneal reconstruction for vision improvement (10 eyes (43.5%)), corneal reconstruction for persistent epithelial defect (4 eyes (17.4%)) and conjunctival (fornix) reconstruction for symblepharon release (9 eyes (39.1%)). The mean duration of CL-wear postsurgery was 6.4±3.9 years (range: 1.4 to 13.3 years). The mean BCVA at baseline and at final follow-up was logMAR 1.9±0.5 and 1.3±0.7, respectively (p<0.05). Compared with those at baseline, the OSGSs for symblepharon and upper and lower fornix shortening showed significant improvement at each follow-up time point post treatment initiation. No serious intraoperative or postoperative adverse events were observed., Conclusion: In patients afflicted with severe OSD, COMET combined with limbal-rigid CL-wear therapy postsurgery was found effective for vision improvement and ocular surface stabilisation., 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.)

Objective: The objective of this study is to determine the validity and reliability of the red filter meibography by smartphone compared with infrared in assessing meibomian gland drop-out., Methods and Analysis: An analytical cross-sectional study was done with a total of 35 subjects (68 eyes) with suspected MGD based on symptoms and lid morphological abnormalities. Meibomian glands were photographed using two smartphones (Samsung S9 and iPhone XR) on a slit-lamp with added red filter. Images were assessed subjectively using meiboscore by the two raters and drop-out percentages were assessed by ImageJ., Results: There was no agreement in meiboscore and a minimal level of agreement in drop-out percentages between red filter meibography and infrared. Inter-rater reliability showed no agreement between two raters. Intra-rater reliability demonstrated weak agreement in rater 1 and no agreement in rater 2., Conclusion: Validity of the red filter meibography technique by smartphones is not yet satisfactory in evaluating drop-out. Further improvement on qualities of images must be done and research on subjective assessment was deemed necessary due to poor results of intrarater and inter-rater reliability., 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.)

Purpose: To evaluate the correlation between dry eye symptoms and coronavirus disease 2019 (COVID-19) infection and to assess the real-time reverse transcription-polymerase chain reaction (RT‒PCR) of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) from the conjunctival swab., Methods: A prospective observational case series study was conducted of all suspected and confirmed COVID-19 patients from Dr. Cipto Mangunkusumo Hospital (RSCM) and the Universitas Indonesia Hospital (RSUI). On the first day of the visit (day 0), systemic clinical symptoms and naso-oropharyngeal (NO) RT‒PCR results will classify all subjects as non-, suspected, or confirmed (mild, moderate, and severe) COVID-19. In all patients, we determined the dry eye symptoms based on the Ocular Surface Disease Index (OSDI) and followed up 7(day 7) and 14 days (day 14) after the first visit. When it was technically possible, we also examined the objective dry eye measurements: tear meniscus height (TMH), noninvasive Keratograph® break-up time (NIKBUT), and ocular redness. Additionally, we took conjunctival swab samples for SARS-CoV-2 RT-PCR in all patients., Results: The OSDI scores for 157 patients decreased across days 0, 7, and 14 (median (interquartile range): 2.3 (0-8), 0 (0-3), and 0 (0-0), p value < 0.0001 (D0 vs D14). The moderate-severe COVID-19 group had a higher OSDI score than the other groups at median D0 (15.6 vs 0-2.3), p value < 0.0001 and this pattern was consistently seen at follow-up D7 and D14. However, dry eye complaints were not correlated with the three objective dry eye measurements in mild-moderate COVID-19 patients. NO RT‒PCR results were positive in 32 (20.4%) patients, namely, 13 and 19 moderate-severe and mild COVID-19 patients, respectively. Positive RT‒PCR results were observed in 7/157 (4.5%) conjunctival swab samples from 1 in non-COVID-19 group and 6 in mild group., Conclusion: In the early phase of infection, COVID-19 patients experience dry eye symptoms, which have no correlation with objective dry eye measurements. SARS-CoV-2 in conjunctival swab samples can be detected in patients with normal-to-mild COVID-19, which shows the risk of ocular transmission., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Rina La Distia Nora reports financial support was provided by Indonesia Endowment Fund for Education (Lembaga Pengelola Dana Pendidikan) with grant number RISPRO/MAN/COVID/B1/1/16/113/2020 and Design and Development Prototype Grant (Program Pendanaan Perancangan dan Pengembangan Purwarupa/P5) special assignment from Rector Universitas Indonesia with assignment number 722/SK/R/UI/2020. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

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.)

Background: Infectious keratitis (IK) is a sight-threatening condition requiring immediate definite treatment. The need for prompt treatment heavily depends on timely diagnosis. The diagnosis of IK, however, is challenged by the drawbacks of the current "gold standard." The poorly differentiated clinical features, the possibility of low microbial culture yield, and the duration for culture are the culprits of delayed IK treatment. Deep learning (DL) is a recent artificial intelligence (AI) advancement that has been demonstrated to be highly promising in making automated diagnosis in IK with high accuracy. However, its exact accuracy is not yet elucidated. This article is the first systematic review and meta-analysis that aims to assess the accuracy of available DL models to correctly classify IK based on etiology compared to the current gold standards., Methods: A systematic search was carried out in PubMed, Google Scholars, Proquest, ScienceDirect, Cochrane and Scopus. The used keywords are: "Keratitis," "Corneal ulcer," "Corneal diseases," "Corneal lesions," "Artificial intelligence," "Deep learning," and "Machine learning." Studies including slit lamp photography of the cornea and validity study on DL performance were considered. The primary outcomes reviewed were the accuracy and classification capability of the AI machine learning/DL algorithm. We analyzed the extracted data with the MetaXL 5.2 Software., Results: A total of eleven articles from 2002 to 2022 were included with a total dataset of 34,070 images. All studies used convolutional neural networks (CNNs), with ResNet and DenseNet models being the most used models across studies. Most AI models outperform the human counterparts with a pooled area under the curve (AUC) of 0.851 and accuracy of 96.6% in differentiating IK vs. non-IK and pooled AUC 0.895 and accuracy of 64.38% for classifying bacterial keratitis (BK) vs. fungal keratitis (FK)., Conclusion: This study demonstrated that DL algorithms have high potential in diagnosing and classifying IK with accuracy that, if not better, is comparable to trained corneal experts. However, various factors, such as the unique architecture of DL model, the problem with overfitting, image quality of the datasets, and the complex nature of IK itself, still hamper the universal applicability of DL in daily clinical practice., Competing Interests: AS was employed by the company Siemens Healthineers. The remaining 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 Sarayar, Lestari, Setio and Sitompul.)

Background: Diabetic retinopathy (DR) is an emerging cause of visual impairment and blindness and is often detected in the irreversible stage. General practitioners (GPs) play an essential role in the prevention of DR through diabetes control, early detection of retinal changes, and timely referral to ophthalmologists. This study aimed to determine the knowledge, attitude, and practice (KAP) towards DR screening among GPs in the district primary health centres (PHCs) in Jakarta, Indonesia., Methods: A cross-sectional study was conducted between April 2021 and February 2022 in 17 randomly selected district PHCs. A validated online questionnaire was then distributed. Good knowledge was defined when the correct response rate was > 75%, positive attitude was indicated when desired attitudes were found in more than half of the items (> 50%), and good practice was defined when more than half of the practice items (> 50%) were performed., Results: A total of 92 GPs, with a response rate of 60.1%, completed the questionnaire. Seventy-nine respondents (85.9%) were female with a median (range) age of 32 (24-58) years. Among the respondents, 82 (89.1%) had good knowledge and all showed positive attitude on DR screening. However, only four (4.3%) demonstrated good practices. We found a weak positive correlation (r s = 0.298, p = 0.004) between attitude and practices., Conclusion: GPs in Jakarta showed good knowledge and positive attitude on DR screening. However, they did not show good practice. There was a positive correlation between attitude and practice., (© 2023. The Author(s).)

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.)

To investigate the efficacy of Wharton's jelly mesenchymal stem cells (WJSCs) and their conditioned medium (CM) for corneal nerve regeneration in rats with diabetic keratopathy. Streptozotocin (STZ)-induced male diabetic (DM) rats (250-300 g) were divided into four groups (n=7/group): Control, DM, DM with WJSCs (DM+WJ), and DM with CM treatment (DM+CM). DM+WJ and DM+CM group received WJSCs or CM, respectively, topically with eye drops. Corneal sensibility, corneal epithelial layer integrity, histology, expression of GAP-43 and TUBB3 on mRNA level and their immunohistochemical expression were examined after two weeks of treatment. There were changes in corneal sensibility and corneal integrity between normal control and diabetic groups with/without WJSC or CM injection. Total central corneal thickness was significantly higher in DM+CM (249.81 ± 43.85 μm) than in control (174.72 ± 44.12 μm, P=0.004) and DM groups (190.15 ± 9.63 μm, P=0.03). GAP-43 mRNA expression levels of DM+WJ and DM+CM groups were higher compared with DM and control groups. TUBB3 mRNA level was increased after CM (P=0.047), but not after WJSCs treatment (P=1.00). GAP-43 and TUBB3 immunohistochemical expression of nerve fibers along the epithelial layer significantly increased in DM+WJ and DM+CM compared with DM group. Our findings showed that WJSCs and their CM improved corneal nerve regeneration in rats with diabetic keratopathy.

Purpose: To highlight the role of atopobiosis and dysbiosis in the pathomechanism of autoimmune uveitis, therefore supporting fecal microbiota transplant (FMT) and probiotics as potential targeted-treatment for uveitis., Methods: This review synthesized literatures upon the relation between gut microbiota, autoimmune uveitis, FMT, and probiotics, published from January 2001 to March 2021 and indexed in PubMed, Google Scholar, CrossRef., Results: The basis of the gut-eye axis revolves around occurrences of molecular mimicry, increase in pro-inflammatory cytokines, gut epithelial barrier disruption, and translocation of microbes to distant sites. In patients with autoimmune uveitis, an increase of gut Fusobacterium and Enterobacterium were found. With current knowledge of aforementioned mechanisms, studies modifying the gut microbiome and restoring the physiologic gut barrier has been the main focus for pathomechanism-based therapy. In mice models, FMT and probiotics targeting repopulation of gut microbiota has shown significant improvement in clinical manifestations of uveitis. Consequently, a better understanding in the homeostasis of gut microbiome along with their role in the gut-eye axis is needed to develop practical targeted treatment., Conclusion: Current preliminary studies are promising in establishing a causative gut-eye axis relationship and the possibility of conducting FMT and probiotics as targeted treatment to mitigate autoimmune uveitis, to shorten disease duration, and to prevent further complications., Competing Interests: There are no conflicts of interest., (Copyright © 2021 Gunardi 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.)

Purpose: To assess the safety and tissue response of a polymethyl methacrylate (PMMA) glaucoma drainage device (GDD) in the rabbit eye., Methods: Specially constructed PMMA GDD devices were implanted into rabbit eyes and evaluated histopathologically following euthanasia on days 5, 30, and 60 after implantation surgery. Hematoxylin-eosin, Masson's trichrome, and periodic acid-Schiff were used to stain tissue specimens dissected from the surgical site. Inflammatory cell count and capsule thickness measurements were performed., Results: Three rabbits were sacrificed on day 5, 3 on day 30, and 4 on day 60. Macrophage and lymphocyte counts increased from day 5 to day 30 then decreased ( P = 0.0000) with greater counts seen in the superior regions. At day 30, a fibrous capsule had formed around the plate area. Fibroblast counts increased significantly between day 5 to day 30 and again to day 60 ( P = 0.001) with greatest numbers anteriorly. The inferior capsule thickness at day 60 was 243 µm (standard deviation, 120; 95% confidence interval: 53-433). The superior capsule thickness was 388 µm (standard deviation, 136; 95% confidence interval: 172-604). No adverse reactions were seen., Conclusions: Histopathologically, the inflammatory response toward this PMMA glaucoma drainage device was comparable to other reported GDDs. No accentuated response or adverse event was seen suggesting that PMMA may be useful as a GDD material., Translational Relevance: An affordable, locally built GDD is needed in Indonesia because of the high prevalence of severe glaucoma. This rabbit study is a significant step toward justifying the use of PMMA as a GDD material. PMMA is cheap and easily manufactured and sterilized in developing economies., Competing Interests: Disclosure: V.D. Oktariana Asrory, None; R. Sitompul, None; W. Artini, None; S. Estuningsih, None; D. Noviana, None; W.H. Morgan, None, (Copyright 2020 The Authors.)

HIV patients responding to antiretroviral therapy (ART) have a high burden of cytomegalovirus (CMV) and display accelerated cardiovascular change assessed systemically. We assessed the effects of HIV, ART and CMV on retinal artery calibers (RAC), as a non-invasive measure of vasculopathy in HIV patients beginning ART. We analysed 79 HIV patients beginning ART in Jakarta, Indonesia, with a median (range) age of 31 (19-48) years. RAC was assessed using Image J software from fundus photos of both eyes, before ART (V0) and after 3-12 months (V3-V12). CMV DNA and antibodies were assessed. Systemic vascular pathology was assessed by carotid intima media thickness (cIMT). Multivariable models assessed which variables best predicted RAC values at V12. HIV patients had narrower retinal arteries and higher levels of CMV antibodies than healthy controls. RAC decreased over 12 months of ART ( p  < .0001). Right RAC correlated with CMV IE-1 antibody, while the left RAC at V3 correlated with cIMT. Multivariable models linked RAC at V12 with detectable HIV RNA at V12 and declared use of alcoholic drinks, while a smoking habit was protective. Decreases in RAC in HIV patients responding to ART suggest progressive microvascular change distinct from changes assessed in large vessels. Correlations with CMV IE-1 antibodies suggest the decline in RAC may be accelerated by frequent reactivations of CMV. This may be a feature of severe HIV disease before ART, confirmed by associations with high baseline HIV RNA in multivariable models. Links with alcohol consumption and smoking testify to a complex pattern of modifiable risk factors.

A strategic multilateral dialogue related to biosecurity risks in Southeast Asia, established in 2014, now includes participants from Singapore, Malaysia, Indonesia, Thailand, Philippines, and the United States. This dialogue is conducted at the nonministerial level, enabling participants to engage without the constraints of operating in their official capacities. Participants reflect on mechanisms to detect, mitigate, and respond to biosecurity risks and highlight biosecurity issues for national leadership. Participants have also identified factors to improve regional and global biosecurity, including improved engagement and collaboration across relevant ministries and agencies, sustainable funding for biosecurity programs, enhanced information sharing for communicable diseases, and increased engagement in international biosecurity forums.

Indonesia is a rapidly growing middle-income country with 262 million inhabitants from more than 300 ethnic and 730 language groups spread over 17 744 islands, and presents unique challenges for health systems and universal health coverage (UHC). From 1960 to 2001, the centralised health system of Indonesia made gains as medical care infrastructure grew from virtually no primary health centres to 20 900 centres. Life expectancy improved from 48 to 69 years, infant mortality decreased from 76 deaths per 1000 livebirths to 23 per 1000, and the total fertility rate decreased from 5·61 to 2·11. However, gains across the country were starkly uneven with major health gaps, such as the stagnant maternal mortality of around 300 deaths per 100 000 livebirths, and minimal change in neonatal mortality. The centralised one size fits all approach did not address the complexity and diversity in population density and dispersion across islands, diets, diseases, local living styles, health beliefs, human development, and community participation. Decentralisation of governance to 354 districts in 2001, and currently 514 districts, further increased health system heterogeneity and exacerbated equity gaps. The novel UHC system introduced in 2014 focused on accommodating diversity with flexible and adaptive implementation features and quick evidence-driven decisions based on changing needs. The UHC system grew rapidly and covers 203 million people, the largest single-payer scheme in the world, and has improved health equity and service access. With early success, challenges have emerged, such as the so-called missing-middle group, a term used to designate the smaller number of people who have enrolled in UHC in wealth quintiles Q2-Q3 than in other quintiles, and the low UHC coverage of children from birth to age 4 years. Moreover, high costs for non-communicable diseases warrant new features for prevention and promotion of healthy lifestyles, and investment in a robust integrated digital health-information system for front-line health workers is crucial for impact and sustainability. This Review describes the innovative UHC initiative of Indonesia along with the future roadmap required to meet sustainable development goals by 2030., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

QuantiFERON-Gold TB (QFT)-positive patients with undetermined cause of uveitis are problematic in terms of whether to diagnose and treat them for tuberculosis (TB). Here, we investigated whether peripheral blood expression of type 1 interferon (IFN)-inducible genes may be of use to stratify QFT-positive patients with uveitis into groups of high versus low risk of having active TB-associated uveitis. We recruited all new uveitis patients in Cipto Mangunkusumo Hospital, Jakarta, Indonesia for one year. We included 12 patients with uveitis and clinically diagnosed active pulmonary TB, 58 QFT-positive patients with uveitis of unknown cause, 10 newly diagnosed sputum-positive active pulmonary TB patients without uveitis and 23 QFT-negative healthy controls. Expression of 35 type 1 IFN-inducible genes was measured in peripheral blood cells from active pulmonary TB patients without uveitis and healthy controls. Differentially expressed genes were identified and used for further clustering analyses of the uveitis groups. A type-1 IFN gene signature score was calculated and the optimal cut-off value for this score to differentiate active pulmonary TB from healthy controls was determined and applied to QFT-positive patients with uveitis of unknown cause. Ten type 1 IFN-inducible genes were differentially expressed between active pulmonary TB and healthy controls. Expression of these 10 genes in QFT-positive patients with uveitis of unknown cause revealed three groups: 1); patients resembling active pulmonary TB, 2); patients resembling healthy controls, and 3); patients displaying an in-between gene expression pattern. A type 1 IFN gene signature score ≥5.61 displayed high sensitivity (100%) and specificity (91%) for identification of active TB. Application of this score to QFT-positive patients with uveitis of unknown cause yielded two groups with expected different likelihood (high vs. low) of having active-TB uveitis, and therefore may be useful in clinical management decisions., Competing Interests: The authors have declared that no competing interests exist.

Intraocular lens (IOL) dislocation is a rare complication of cataract extraction requiring prompt surgery. This case report aims to raise awareness of such cases and the importance of post-surgery follow-up. A 58-year-old female patient was found with anterior IOL dislocation a week after phacoemulsification surgery in her right eye. Visual acuity of the right eye was 1/60 with ciliary injection and IOL dislocation to the anterior chamber of the right eye. The patient underwent surgery of the right eye and the IOL haptic was found to be broken. In this case report, the factors affecting IOL dislocation are axis length, broken IOL haptic, and patient activity that increased intraocular pressure. Cataract extraction surgery, although common, needs to be conducted carefully, and it is important for ophthalmologists and general practitioners to detect this condition, especially in rural areas where facilities are limited, as IOL dislocation could occur and requires immediate treatment to achieve a better result.

Ocular trauma occurring in children often leads to visual impairment or blindness when it is not properly managed. This often occurs in underdeveloped regions with difficult access to professional care at local health facilities. We report a case of post-trauma corneal staphyloma in an underdeveloped region of eastern Indonesia to illustrate the importance of proper management of ocular trauma in areas lacking such expertise and where patients have difficulty accessing even basic health care. During a community health outreach in Southwest Sumba, eastern Indonesia in May 2017, a 7-year-old boy presented with white protrusion of the left eye of 3 years' duration following an event of sharp trauma. The patient lived in an inaccessible and impoverished area. Upon contemporary examination, visual acuity of the left eye was 1/300 while that of the right eye was 6/6. Anterior examination revealed corneal staphyloma of the left eye, and its posterior segment could not be evaluated. The patient was transported to an eye care center in Jakarta, receiving a stock prosthesis implant while awaiting a corneal evisceration procedure with dermofat graft. Ocular trauma is one of the most common causes of visual impairment in children. This case illustrates the consequences of inadequate post-trauma management and the importance of prevention of infection.

Diabetes mellitus (DM) is a complex and chronic metabolic disorder leading to many complications. One of the most common complications of DM is diabetic neuropathy. There are many studies exploring corneal sensitivity as a potential marker of diabetic neuropathy. This review aims to explore association between corneal sensitivity and diabetic neuropathy. In diabetic neuropathy, corneal sensitivity is impaired due to low level of corneal nerve trophic factors, impaired sensory nerve fibers, and lost communication of dendtritic cell. In diabetic patients, this condition can be assessed by several techniques, such as Cochet Bonnet aesthesiometry, non-contact corneal aesthesiometry, and confocal microscopy. Few promising therapeutic targets for impaired corneal sensitivity include stem cell and growth factor therapy that can be used to prevent complication in patient with diabetic neurotrophic keratopathy. Impaired corneal sensitivity serve as a potential marker of diabetic neuropathy. Doctors, opthalmologists and internists, should anticipate the possibility of observing the following changes in diabetic patients with neuropathy by using corneal sensitivity assessment test.

We conducted a survey of ocular diseases among HIV/AIDS outpatients in Jakarta, Indonesia. This cross sectional study was conducted among 311 HIV/ AIDS patients presenting to three referral hospitals in Jakarta, Indonesia from September 2008 to May 2009. All subjects underwent ophthalmological examination, including visual acuity, intraocular pressure, eye movement, Schirmer's test and anterior and posterior segment evaluation. Most subjects (86%) were aged 20-40 years; and 77% were male. Intravenous drug use was the most common risk factor (48.9%) for HIV infection. At the time of enrollment, 85% of subjects were receiving anti-retroviral therapy (ART); the median CD4+ T cell count prior to ART was 56 (0-757) cells/microl. The most common ocular manifestations were dry eye syndrome (54%), followed by toxoplasma retinochoroiditis (8.4%) and cytomegalovirus (CMV) retinitis (5.8%). Risk factors associated with ocular diseases were late HIV clinical stage (OR = 4.35 for clinical stage 4 vs 1; p = 0.001), co-infection (OR = 2.67 for 2 co-infections vs no co-infection; p = 0.009) and low CD4+ T cell count prior to ART (< 50 cells/microl vs > or = 200 cells/microl; p = 0.003). The CD4+ count at the first visit (p = 0.041) and clinical stage (p = 0.049) were associated with dry eyes. This study shows dry eyes were the most prevalent ocular disease among HIV/ AIDS patients in Jakarta. HIV clinical stage 3 or 4, co-infection with tuberculosis and hepatitis C infection and a CD4+ T cell count of <50 cells/microl were risk factors for ocular disease in HIV/AIDS patients.

Purpose: To evaluate the efficacy of topical levofloxacin 0.5% in treating levofloxacin-resistant Pseudomonas aeruginosa-induced keratitis., Design: Longitudinal study., Methods: The study was conducted in 21 New Zealand White rabbits whose corneas were inoculated with 0.1 mL of 1000 colony-forming units of levofloxacin-resistant P. aeruginosa. After 24 hours, the rabbits were randomized into 3 groups: 9 were treated with levofloxacin 0.5%, 6 were treated with ceftazidime 50 mg/mL, and 6 were treated with a placebo. The rabbits were given a loading dose once every 5 minutes in the first hour and continued to receive a dose once an hour in the next 11 hours. Afterward, 3 rabbits treated with levofloxacin were killed. Their corneas were examined for levofloxacin concentration. The remaining rabbits continued to receive 6 regular doses for 4 more days, each of which was administered at a 2-hour interval. Levofloxacin concentration was examined. Treatment efficacy was evaluated based on 4 clinical characteristics: corneal infiltrate, conjunctival edema, conjunctival injection, and discharge., Results: All clinical characteristics, except conjunctival edema, improved significantly in rabbits treated with either levofloxacin or ceftazidime, compared to the placebo group. At the last follow-up (120 hours), all clinical characteristics improved significantly in both treatment groups. Mean corneal levofloxacin concentration in the treatment groups was 6.25 (0.32) μg/g, which declined significantly to a mean of 2.15 (1.23) μg/g after another 120 hours., Conclusions: Topical levofloxacin 0.5% improved the clinical characteristics of keratitis induced by levofloxacin-resistant P. aeruginosa. Such improvement could be attributed to a high concentration of levofloxacin that was above the minimum inhibitory level.

Purpose: To describe corneal sensitivity changes caused by different incision methods-manual small-incision cataract surgery (manual SICS) and phacoemulsification-and their influence on tear film quantity and quality., Methods: This was a prospective observational study conducted in 30 subjects undergoing manual SICS or phacoemulsification. Corneal sensitivity was assessed before and 1, 7, and 15 days after surgery by Cochet-Bonnet esthesiometer. Tear meniscus, noninvasive breakup time, lipid pattern, and Schirmer test results were evaluated. Patient symptoms were reviewed based on the Ocular Surface Disease Index., Results: In the group undergoing phacoemulsification, corneal sensitivity decreased at the incision site and at other sites on days 1, 7, and 15 after surgery, whereas in the group undergoing manual SICS, no change in corneal sensitivity was noted. Between-group difference in corneal sensitivity was significant on days 1, 7, and 15. Aqueous production significantly (P = 0.016) increased on the first day in both groups and returned to presurgery level on day 15. Tear film quality decreased on day 1 only in the group undergoing manual SICS (P = 0.035). Tear meniscus and tear lipid profile showed no change in either group. Patient symptoms significantly increased on day 1 in both groups, and the difference between the 2 groups was significant on day 15 (P = 0.044)., Conclusions: Compared with manual SICS, temporal-side incision in phacoemulsification decreased corneal sensitivity in the incision site and other sites until day 15 and changes in tear film quantity and patient symptoms only on day 1.

Aim: To evaluate correlation between blood glucose control, corneal sensitivity and lacrimal secretion in type 2 DM with peripheral neuropathy., Methods: A cross sectional study has been conducted in 20 type DM with peripheral neuropathy and 20 without peripheral neuropathy at the Department of Internal Medicine and Ophthalmology, Ciptomangunkusumo Hospital, Faculty of Medicine University of Indonesia, from August through November 2002. All subject underwent a comprehensive medical examination, including esthesiometer Semmes-Weinstein 10 g, HbA1c, Schirmer test, and corneal sensitivity measurements., Results: The mean corneal sensitivity was significantly lower in diabetic patients with neuropathy (p=0.000). HbA1(c) was related to corneal sensitivity (p=0.016)., Conclusion: In type 2 DM with peripheral neuropathy, corneal sensitivity was demonstrated to be significantly decrease, all of which seems to be due to the status of blood glucose control.