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.

Current application of intense pulsed light for the management of dry eye disease: A systematic review and meta-analysis.

This review explored intense pulsed light (IPL) as an alternative treatment for dry eye disease (DED) symptom relief by correcting tear-film homeostasis. A systematic search was performed in March 2022 on five databases (Medline, Embase, SCOPUS, ProQuest, and EBSCO). Studies were extracted for the following outcomes of interest: standard patient evaluation of eye dryness questionnaire (SPEED), ocular surface disease index (OSDI), tear break-up time (TBUT), and corneal fluorescein staining (CFS). All studies published up to March 2022 were reviewed. Cochrane risk of bias tool (RoB 2) was used to screen studies for risk of bias where appropriate. A meta-analysis was done to quantify any reported quantitative data. Thirteen studies were included in this study. A total of 931 individuals and 1454 numbers of eyes were reviewed in this meta-analysis. Among studies that explored and reported the effect of IPL in individuals with DED, TBUT and OSDI improved significantly post intervention, with a standardized mean difference (SMD) of 1.02 [95% CI 0.41-1.64] and 0.28 [95% CI 0.04-0.52], respectively. CFS and SPEED scores, however, showed no statistically significant difference, with an SMD of 0.22 [95% CI -0.19 to 0.64] and 0.28 [95% CI -0.11 to 0.66], respectively. In conclusion, current evidence indicates IPL as a possible adjunctive treatment in individuals with DED in an otherwise limited treatment option. Further studies through more extensive trials are needed to validate this finding and elucidate its mechanism.

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).

Strategic combination of cultivated oral mucosal epithelial transplantation and postoperative limbal-rigid contact lens-wear for end-stage ocular surface disease: a retrospective cohort study.

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.

Strengthening of the barrier function in human telomerase reverse transcription (hTERT) immortalized corneal and conjunctival epithelium by double-stranded RNA.

To investigate the response to polyinosinic:polycytidylic acid [poly(I:C)], a double-stranded RNA Toll-like receptor 3 agonist that mimics viral infection, in the barrier function of two established human telomerase reverse transcriptase-immortalized cell lines, termed HCLE for the human corneal-limbal epithelial line and HCjE for the human conjunctival-epithelial line. In this study, HCLE and HCjE cells were used to evaluate the underlying mechanism of epithelial-cell barrier function regulation. Briefly, HCLE and HCjE cells were first cultured on 12-well Transwell® (Corning®) filter-plates, and reverse transcription-polymerase chain reaction, western blotting, and immunohistochemical examinations were then performed to assess tight junction (TJ)-related protein expression and cellular distribution. Next, the barrier function of the cells was measured via transepithelial electrical resistance (TEER) and paracellular molecular flux. The cells were then stimulated with poly(I:C) and the TEER and TJ-related protein expressions were analyzed. Similar to that in in vivo epithelium, the expression of claudin (CLDN) subtypes CLDN-1, -4, and -7 was observed in the HCLE and HCjE cells, and the barrier function in the HCLE cells was tighter than that in the HCjE cells. Post stimulation with poly(I:C), TEER of the HCLE and HCjE cells increased in a dose- and time-dependent manner, the production of TJ-related protein mRNA and CLDN-4 protein were elevated, and the barrier function of the HCLE and HCjE cells increased, thus possibly indicating that the increased barrier function is a defense mechanism against viral infection.

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.

Limbal-Rigid Contact Lens Wear for the Treatment of Ocular Surface Disorders: A Review.

ABSTRACT: Recently, the prescription of large-diameter rigid gas-permeable contact lenses (CLs), also known as "scleral lenses," "corneoscleral lenses," and "limbal-rigid CLs," is on the rise for the treatment of both moderate and severe ocular surface disorders (OSDs). Compared with scleral lenses, the diameter of limbal-rigid CLs is generally smaller, that is, a diameter ranging from 13.0 to 14.0 mm, and they are designed so that the peripheral edge bears on the limbus. The Suncon Kyoto-CS (Sun Contact Lens Co., Ltd.) is a novel limbal-rigid CL design with multistep curves on the peripheral edge for easy tear exchange during blinking that removes debris and prevents lens clouding or fogging, thus allowing patients to enjoy a longer daily duration of CL wear. In severe OSD cases, limbal-rigid CL wear after surgery is a noninvasive therapeutic approach that can neutralize corneal irregularities, decrease dry eye symptoms, prevent the progression or recurrence of symblepharon, and improve the patient's visual acuity and overall quality of life. Thus, surgeries such as amniotic membrane transplantation and cultivated oral mucosal epithelial transplantation, as well as limbal-rigid CL wear, which is noninvasive, are valuable and effective treatment strategies that can now be applied for the management of patients afflicted with severe OSDs.

Toxicity of Amphotericin B in Rabbit Corneal Epithelial Cells Stored in Optisol™-GS: Corneal Epithelial Cell Morphology and Migration.

PURPOSE: To evaluate the toxicity of Amphotericin B (AmB) in Optisol™-GS Corneal Storage Media (Bausch & Lomb) on corneal epithelial cell (CEC) morphology and migration ability. METHODS: Sclerocorneal strips were removed from male Japanese white rabbits, and then stored at 4 °C in Optisol™-GS containing 0 µg/ml of AmB (control group) and 2.5, 5, 25, and 50 µg/ml of AmB (AmB groups; four eyes per group). After 7 days of storage, CEC morphology was evaluated by hematoxylin-eosin staining, immunohistochemical staining (ZO-1), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Moreover, to evaluate CEC migration ability, three corneal blocks (6-8 × 3 mm each) from one preserved cornea were cultured for 24 h, and the area of CEC migration (2 mm at the central region) onto the stromal surface was then measured. RESULTS: At 5, 25, and 50 µg/ml of AmB, deformation and vacuolation of CECs were observed in all preserved corneas. ZO-1 expression was significantly reduced in corneas preserved at AmB concentrations of 25 and 50 µg/ml. TUNEL Labeling Index was significantly increased at AmB concentrations of ≥5 µg/ml. CEC migration was inhibited in a dose-dependent manner at AmB concentrations of 25 and 50 µg/ml compared to the control group. CONCLUSIONS: The addition of AmB to Optisol™-GS can be toxic to CECs and inhibit their migration at a concentration of ≥5 µg/ml. AmB at a concentration of 2.5 µg/ml can be considered safe for the preservation of donor corneal tissue used in corneal epithelial transplantation surgery.

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.

Challenges in the management of bilateral eyelid closure in Stevens-Johnson Syndrome.

Purpose: To describe the challenges of surgically treating Stevens-Johnson syndrome (SJS) cases with bilateral eyelid closure, a serious ocular sequela. Observations: This study involved two 69-year-old females, with subacute-stage SJS (Case 1 and Case 2), and a 37-year-old male with chronic-stage SJS (Case 3). Case 1 had undergone simultaneous bilateral symblepharon lysis at 4-months post SJS onset, and her logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (VA) (BCVA) improved from 2.8 (both eyes) to 0.7 OD and 0.4 OS. Cases 2 and 3 underwent symblepharon lysis with intraoperative use of mitomycin C (MMC) and amniotic membrane transplantation (AMT) at 9 months (OD) and 11 months (OS) (Case 2) and at 31 years (OD) (Case 3) post SJS onset. At 3-months postoperative, Case 3 underwent cultivated oral mucosal epithelial sheet transplantation (COMET). In both cases, BCVA (logMAR) improved with the postoperative use of limbal-rigid contact lenses (CLs); i.e., from 2.8 to 0.5 OD and 1.2 OS (Case 2) and from 2.8 to 1.1 OD (Case 3). In all 5 treated eyes, eyelid opening and VA were maintained through final follow-up. Conclusion and importance: In severe bilateral symblepharon cases, it can be difficult to predict postoperative outcomes, as proper surgical treatment is often delayed. In SJS cases with bilateral eyelid closure, the surgical intervention strategy of AMT and COMET, combined with limbal-rigid CL wear post surgery, can result in improved vision, and symblepharon surgery might be easier and possibly result in a better prognosis when performed at the early phase.

Pterygium excision with modified bare sclera technique combined with mitomycin C.

PURPOSE: Numerous surgical methods, with varying rates of recurrence, have been applied for the treatment of pterygium. Adjuvant mitomycin C (MMC) application has shown promising results in the prevention of recurrence. Here we propose and describe modified bare sclera technique combined with the intraoperative application of MMC for pterygium excision. STUDY DESIGN: Retrospective study. METHODS: Primary pterygium patients who underwent pterygium excision via the bare sclera combined with 0.04% MMC technique from January 2014 to December 2016 were reviewed. In all patients, the subconjunctival pterygium strand was exposed and then sufficiently excised in combination with the safe use of MMC; i.e., the prevention of MMC dilution and diffusion to surrounding tissue. Surgical complications, recurrence rates, and recurrence onset were recorded. RESULTS: This study involved 32 primary pterygium eyes (grade T1 = 22 eyes; 68.7%). The mean postoperative follow-up period was 26.4 ± 14.5 months (range: 12-60 months). MMC was applied for 1-3 min. The mean complete epithelialization was 12.6 ± 7.6 days and no surgical complications were observed. In 1 patient with double-head primary pterygium, recurrence occurred at 15-months postoperative. CONCLUSIONS: The modified bare sclera technique combined with MMC application was found to be safe, effective, and presents good cosmetic appearance for the treatment of primary pterygium when safety points are strictly applied.

Microorganism detection and contamination rate of donor eyes in Japan.

PURPOSE: To evaluate the microorganism detection and contamination rate of donor eyes. STUDY DESIGN: Retrospective study. METHODS: In this retrospective study, we reviewed all donor cornea data collected from Kyoto Prefectural University of Medicine (KPUM) Eye Bank, Kyoto, Japan from April 2015 to June 2018, including microbiologic data obtained from conjunctival swabs and preservation medium and findings of postoperative infection from the medical records. RESULTS: During the study period, 77 eyes from 44 deceased individuals (mean age at time of death: 75 ± 17.3 years [range, 30-102 years]) were donated to the KPUM Eye Bank after being harvested using standard safety precautions and disinfection procedures. In 49 of the 77 eyes (63.6%), the conjunctival-swab culture revealed microorganisms, with the 3 most commonly detected being methicillin-resistant Staphylococcus epidermidis (MRSE), methicillin-sensitive S aureus (MSSA), and methicillin-resistant S aureus (MRSA). The data revealed positive microorganism detection in only 4 (5.2%) of the 77 donor-cornea storage-medium cultures. Positive microorganism detection was found in all the age groups, with no statistical difference between the groups (P > .05). In the eyes enucleated ≥ 2.5 h postmortem, a higher positive microorganism detection occurred (P = .03). During the postoperative follow-up period, there was no record of corneal infection. CONCLUSIONS: The preenucleation conjunctival-swab-culture findings revealed that the rate of positive microorganism detection was similar for advanced-age and younger-age donors and that a shorter elapsed time from donor death to postmortem enucleation resulted in less donor-microorganism contamination.

Safety of retrocorneal plaque aspiration for managing fungal keratitis.

PURPOSE: To evaluate the safety of retrocorneal plaque aspiration in patients with fungal keratitis. STUDY DESIGN: Retrospective study. METHODS: A retrospective case series of fungal keratitis seen at Kyoto Prefectural University of Medicine between November 2013 and September 2018. Patients with retrocorneal plaque who underwent retrocorneal plaque aspiration for the diagnosis and treatment of fungal keratitis were included. The retrocorneal plaques were either aspirated using a tuberculin syringe with a 27-gauge blunt needle or were directly pulled out using a forceps. The anterior chamber was carefully washed out using bimanual irrigation and aspiration (I/A). Diagnosis accuracy and treatment safety were evaluated. RESULTS: Five eyes of five patients aged 68.4 ± 13.0 years old (range: 45-81 years) were included. Three of the five patients (60%) were positive for fungus obtained from corneal scrapings. Retrocorneal plaque aspiration improved the diagnosis accuracy to five out of five patients (100%), including two cases positive to Fungiflora Y® staining. Three of the five patients (60%) had good response rapidly after retrocorneal plaque aspiration, and two patients received therapeutic keratoplasty. All cases were finally stabilized without severe complications. CONCLUSION: Retrocorneal plaque aspiration may be useful for the precise diagnosis of fungal keratitis.

Efficacy of Intravitreal Levofloxacin 0.5% Ophthalmic Solution in Treating Pseudomonas Aeruginosa Endophthalmitis on a Rabbit Model.

PURPOSE: To evaluate the efficacy of intravitreal levofloxacin 0.5% ophthalmic solution as treatment of Pseudomonas aeruginosa endophthalmitis in a rabbit model. DESIGN: This is a parallel randomized experimental study. METHODS: Twenty-six New Zealand white rabbits were enrolled. P. aeruginosa was inoculated intravitreally on the right eyes of all rabbits, which were further categorized into 2 groups, the treatment group (Group A) receiving 0.1 mL intravitreal injection levofloxacin 0.5% 24 hours after inoculation and the control group (Group B), which had 0.1 mL intravitreal aqua destilata (placebo). Clinical observation of the eyes in each group was performed on the first until the sixth day after the inoculation using clinical grading scale. On the sixth day, the eyes were examined for microbiological and histopathologic evaluations. RESULTS: The total clinical grading scores of each group were similar 24 hours after P. aeruginosa inoculation (P > 0.05). The total clinical grading scores of Group A on the sixth day and the difference in total clinical scores on the first and the sixth day were shown to be significantly lower than that of Group B (P < 0.05). Microbiological analysis revealed that there was a lower bacterial count in Group A (mean = 1.18 ± 0.93 logCFU/0.1 mL) compared with Group B (mean = 4.09 ± 1.51 logCFU/0.1 mL), and the histopathologic scores of both groups were also significantly different (P < 0.05). CONCLUSIONS: Intravitreal levofloxacin 0.5% ophthalmic solution at 0.1 mL dose appeared to be effective in treating P. aeruginosa endophthalmitis in rabbits.