Dry eye symptoms are prevalent in moderate-severe COVID-19, while SARS-COV-2 presence is higher in mild COVID-19: Possible ocular transmission risk of COVID-19.

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.

Antiviral treatment for acute retinal necrosis: A systematic review and meta-analysis.

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).

Safety of intracameral injection of levofloxacin 0.5% eye drops single dose 0.6 ml preservative free on rabbit eye.

Background: This was an experimental, parallel, and randomized study to evaluate the safety of single intracameral injection of 0.6 ml 0.5% preservative-free levofloxacin eye drops on rabbit eye. Methods: In total, 24 eyes of 12 New Zealand white rabbits were divided into three groups. The first group (LFX) was treated with 0.1 ml intracameral injection of levofloxacin 0.5% eye drops of 0.6 ml preservative-free (n = 6), the second group (CRAV) was treated with 0.1 ml intracameral injection of levofloxacin 0.5% eye drops 5 ml commercially available eye drops preservative-free (n = 6), and the third group (BSS) were treated with 0.1 ml intracameral injection of balanced salt solution (n = 12). All groups received a single dose. The clinical evaluation was performed on the 1 st, 3 rd, 5 th, and 7 th day after injection. Each eye was enucleated on the 7 th day and underwent a histopathology examination. Results: The clinical scores among the three groups did not show any significant difference on days 1 st, 2 nd, 3 rd, and 7 th (p>0.05). The only ones noted in clinical scores were mild corneal opacity, mild cells, and flares in the anterior chamber. The histopathology score demonstrated no statistically significant difference between the three groups (p>0.05). Vacuolization of corneal endothelial cells was noted in all groups but was not statistically significant. Conclusions: A single intracameral injection of 0.6 ml 0.5% preservative-free levofloxacin eye drops was safe for rabbit eye, according to clinical and histopathology scores, similar to levofloxacin 0.5% eye drops in 5 ml bottle preservative free.

Comparison of Culture Results between Specimens from Corneal Scraping with Microhomogenization and Corneal Swab in Moderate and Severe Bacterial Corneal Ulcers.

The purpose of this study was to compare the bacterial culture results from corneal infiltrate specimens collected using two different methods, corneal scraping followed by microhomogenization and corneal swab. This is a comparative crosssectional study, with 18 participants undergoing corneal specimen collection using each of the 2 sampling techniques. The results from the scraping and swab methods were separated and then compared using data analysis. The proportion of Gram stain results that matched the culture results for the scraping-microhomogenization technique was 6/13 (46.2%), and the proportion of Gram stain results that matched the culture results for the swab technique was 5/13 (38.5%) (McNemar test P value, 1.000; P > 0.05). The proportion of positive cultures obtained using the scraping-microhomogenization technique was 13/18 (72.2%), and the proportion of positive cultures obtained using the swab technique was 9/18 (50%) (McNemar test P value, 0.219; P > 0.05). The Kappa suitability test value for comparison of the scraping-microhomogenization technique to the corneal swab was 0.333. The specimens collected by corneal scraping followed by microhomogenization had a higher positive bacterial culture rate than those collected by corneal swab, but the results were not statistically significant. IMPORTANCE This study aimed to compare the culture results between scraping specimens with microhomogenization and corneal smears in patients with moderate to severe bacterial corneal ulcers. This study could be a guideline for treating bacterial corneal ulcers.

The impact of aqueous humor polymerase chain reaction and serological test results for establishing infectious uveitis diagnosis: An Indonesian experience.

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.

A case of aseptic bilateral cavernous sinus thrombosis following a recent inactivated SARS-CoV-2 vaccination.

This case report aims to describe the first report of bilateral aseptic cavernous sinus thrombosis (CST) with a recent history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. A 50-year-old woman presented with bilateral proptosis, decreased vision, and ophthalmoplegia 16 days following CoronaVac® vaccine. The visual acuity of the left eye was 20/150, while the right eye was no light perception with a hyperemic optic nerve head. She had a history of hyperthyroidism and currently on warfarin consumption. Laboratory results depicted elevated free T4, free T3, international normalized ratio, and low protein S and C. Magnetic resonance imaging showed bilateral CST, and high-dose methylprednisolone along with fondaparinux was given. The symptoms were significantly resolved, with the visual acuity of the left eye being improved to 20/20 but not the right eye. Bilateral CST has not been previously reported following inactivated SARS-CoV-2 vaccination. The underlying systemic conditions should be taken into consideration for the possibility of the inactivated SARS-CoV-2 vaccine-related event.

Azithromycin concentration in rabbits' plasma and posterior segment of the eyes following oral drug administration: a dose-finding study for the application in ocular toxoplasmosis.

INTRODUCTION: Azithromycin has been used as an ocular toxoplasmosis alternative treatment due to its pharmacokinetic profiles. However, sufficient concentrations to promote toxoplasmosis eradication is still unknown. This study was aimed to evaluate azithromycin levels in rabbits after three regimens equivalent to human doses for ocular toxoplasmosis. METHODS: Three groups of New Zealand albino rabbits were given one of the following: azithromycin at 26 mg/kg BW daily (Group 1), 26 mg/kg BW every two days (Group 2), and 50 mg/kg BW once weekly (Group 3) for 14 days. Plasma and ocular azithromycin concentrations were examined. RESULTS: Following 14 days, median ratio of plasma maximum azithromycin concentration to the minimum inhibitory concentration for Toxoplasma gondii (C-max/MIC) for Group 1, and 2 were 51.29, 5.33, while Group 3 was undetected. The median azithromycin concentration in the retina-choroid was higher than the MIC in Group 1 (1356.0 ng/ml) and Group 2 (189.0 ng/ml), but not in Group 3. CONCLUSION: Azithromycin administered orally at the dose of 26 mg/kg BW daily or 26 mg/kg BW every two days resulted a sufficient criteria of C-max/MIC as well as retina-choroid concentration needed for its parasiticidal activity. However, well-conducted clinical trial is warranted to support its therapeutic potential in ocular toxoplasmosis.

The Utility of Nonroutine Intraocular Fluid Polymerase Chain Reaction for Uveitis in Indonesia.

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.

Delivering a modified continuous objective structured clinical examination for ophthalmology residents through a hybrid online method.

Since coronavirus disease 2019 was declared a global pandemic by the World Health Organization, it has become a challenging situation to continue medical education, including in Indonesia. The situation prohibited face-to-face (direct) educational activities in clinical settings, therefore also postponing examinations involving especially procedural skills. Adaptations were urgently needed to maintain the delivery of high-stake examinations to sustain the number of ophthalmology graduates and the continuation of eye health service. Objective structured clinical examination (OSCE) has been one of our widely used method to assess clinical competencies for ophthalmology residents, and is the one method that involves gatherings, close contact of examiners, examinees and patients, therefore the most difficult to adjust. Pandemic challenges brought technical changes in our delivering the OSCE to online, maximizing digital platforms of meetings, while still concerned to guarding the safety of candidates, patients and staffs. OSCE scenarios were also made as timely efficient as possible by changing continuous station models to a cascade one. The purpose of this article is to document our experience in conducting a feasible and reproducible OSCE in this pandemic era filled with limitations.

A TNF Block Genotype may Influence CMV Retinitis in HIV Patients without Affecting Systemic Viral Replication.

BACKGROUND: A conserved TNF block haplotype marked by the minor alleles of rs1800629 (TNFA-308*A) and rs9281523 [BAT1(intron 10)*C] has been linked with several immunopathological conditions and with rapid progression of HIV disease. Reported associations with cytomegalovirus (CMV) retinitis in HIV patients before or during early antiretroviral therapy (ART) may therefore reflect greater replication of CMV in advanced HIV disease or an immunopathological response to CMV in the retina. OBJECTIVE: As all Indonesian HIV patients display high levels of CMV replication, we evaluated whether TNF block genotypes alter markers of their burden of CMV and/or associate with retinitis. METHODS: We assessed 79 consecutive HIV patients beginning ART, 25 HIV patients with a history of CMV-retinitis and 63 healthy adults. HIV RNA, CD4 T-cell counts, CMV-reactive antibody and CMV DNA were measured and alleles of TNFA-308, BAT1(intron 10) and TNFA-1031 (rs1799964) were determined. RESULTS: TNFA-308 and BAT1(intron 10) were in complete linkage disequilibrium. Patients carrying minor alleles at both loci had higher levels of CMV-reactive antibody after one month on ART (p=0.01), but not at other time points spanning 1 year on ART. 50% of patients had detectable CMV DNA before ART, irrespective of TNF block genotypes. However, the TNFA-308*A/- BAT1(intron 10)*C haplotype was more common in CMV-retinitis patients than other patients or healthy controls (p<0.01). CONCLUSION: The TNFA-308*A/BAT1(intron 10)*C haplotype appears to affect CMV-induced pathology rather than CMV replication.

Therapeutic response time of topical voriconazole 1% and intrastromal voriconazole 0.05% versus topical natamycin 5% monotherapy in Fusarium keratitis in rabbit.

BACKGROUND: Fungal keratitis can be more difficult to treat than bacterial keratitis with worse outcomes. OBJECTIVE: To evaluate the therapeutic response time of topical voriconazole combined with intrastromal voriconazole, and topical natamycin on Fusarium keratitis. METHODS: The stroma of corneas of twelve New Zealand White rabbits was inoculated with Fusarium sp spores. Seven days after inoculation, they were divided into 2 groups randomly. Group A was treated with topical natamycin 5% for 21 days. Group B was treated with intrastromal voriconazole 0.05% single injection at the beginning of treatment, continued with topical voriconazole 1% for 21 days. Clinical evaluations for epithelial defect size and clinical scores in each group were performed on 1st, 3rd, 7th, 10th, 14th and 21st days after treatment. Mycological examinations were performed before and after the treatment. RESULTS: After treatment, there was no statistically significant difference between natamycin and voriconazole in reducing epithelial defect size at first, second or third week after treatment (P = .15; P = .39; and P = .90). The clinical scores on both groups also showed no statistically significant differences at first, second and third weeks after treatment (P = .24; P = .09; and P = .32). Qualitative mycological evaluation before and after the treatment showed no statistically significant difference in KOH examination (P = 1; P = 1) and culture in Sabouraud dextrose agar (P = 1; P = 1). CONCLUSION: Intrastromal voriconazole injection combined with topical voriconazole seems to give similar response time but not earlier in improving clinical presentation of Fusarium keratitis as topical natamycin.

Toxoplasma gondii SAG2 type III in an atypical presentation of ocular toxoplasmosis in Indonesia.

OBJECTIVE: This study aimed to perform genotyping of Toxoplasma gondii strain or variant causing atypical toxoplasmic uveitis in Indonesian patients. METHODS: Ocular fluid samples originating from 46 uveitis patients with non-specific ocular manifestations were analysed for Toxoplasma infection by PCR of the B1 locus. The clonal type was determined by amplification, sequencing and phylogenetic analysis of SAG2 and GRA6 loci in B1-positive samples. Clinical data were obtained from the medical records. RESULTS: Pan uveitis was the most frequent manifestation (65.2%) and mostly unilateral (76.1%). PCR of the B1 locus identified eight positive subjects (12.5%); six had panuveitis and two of these had diabetes mellitus. Phylogenetic analysis with maximum likelihood of the SAG2 locus in the B1-positive samples resulted in Toxoplasma gondii SAG2 type III allele. No positive result was obtained from the PCR of GRA6 locus. CONCLUSION: Toxoplasma gondii SAG2-type III allele was identified in an atypical presentation of toxoplasmic uveitis in Indonesia.

Factors Affecting the Health of Retinal Vessels in Human Immunodeficiency Virus Patients Beginning Anti-Retroviral Therapy.

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.

Characterization of Natural Killer Cells in HIV Patients Beginning Therapy with a High Burden of Cytomegalovirus.

BACKGROUND: Active infections with cytomegalovirus (CMV) increase NK cell expression of the inhibitory receptor LIR-1 and the activating receptor NKG2C in transplant recipients. However, the effects of CMV on NK cells are different in HIV patients stable on antiretroviral therapy (ART) and have not been analyzed in young HIV patients beginning ART. METHODOLOGY: We followed a cohort of 78 Indonesian HIV patients beginning ART. CMV antibodies were measured in plasma before ART (baseline), and after 1, 3, 6, and 12 months. CMV DNA was sought in blood granulocytes at baseline by quantitative PCR assay and a deletion in the NKG2C gene was identified by PCR. NK cell profiles were monitored by flow cytometry in 19 patients stratified by the presence of CMV DNA. Healthy controls (n = 17) were assessed once. RESULTS: All 78 patients were CMV seropositive and 41 had detectable CMV DNA. CMV DNA+ patients had higher proportions of total NK cells and CD16+ NK cells at baseline, but similar expression of LIR-1 and NKp30 on NK cells on ART. However, levels of CMV antibody were inversely related to median LIR-1 expression on NK cells. A dramatic elevation in cells expressing NKG2C was restricted to CMV DNA+ patients heterozygous for the NKG2C deletion. Patients with High NKG2C expression had lower levels of CMV antibodies. CONCLUSION: A subpopulation of NK cells expressing NKG2C was induced by CMV replication in HIV patients heterozygous for a deletion in this gene. Individuals with an abundant NKG2C+ and LIR-1+ NK cells displayed lower levels of CMV reactive antibody.

Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: A tool to stratify a high versus low risk of active tuberculosis?

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.

Ocular diseases among HIV/AIDS patients in Jakarta, Indonesia.

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.