Ocular Tuberculosis Diagnosis Through Biomarkers: Clinical Relevance of Serum C1q and Whole Blood Interferon Gene Signature Score.

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.

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.

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.

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.