Evaluation of adjuvant role of topical cyclosporine 1% in acute Stevens-Johnson syndrome: a randomised control trial.

PURPOSE: To evaluate the role of topical cyclosporine A 1% (CsA) as an adjuvant therapy in patients with acute Stevens-Johnson syndrome (SJS). METHODS: This is a randomised controlled trial in which 44 patients (88 eyes) with acute SJS, presenting within 3 months from the onset of the disease, were enrolled and randomised. Group A (n=44 eyes) patients received treatment with topical CsA 1% along with standard therapy consisting of topical corticosteroids, antibiotics and lubricants. Group B (n=44 eyes) patients received topical saline drops in combination with standard therapy. Various ocular surface parameters were assessed at baseline and the 6-month follow-up. RESULTS: The mean age of patients (years) was 23.9±15.1 in the CsA group and 26.0±18.7 in the control group (p=0.6840). The mean time from disease onset to presentation (days) was 17.0±14.0 and 12.9±11.3 in CsA and control groups, respectively (p=0.1568). At presentation, the mean grades of severity scores of various parameters were comparable. At 6 months, both groups showed a significant improvement in the mean severity grades of conjunctival hyperaemia (A, p=0.001; B, p=0.0001), mucocutaneous junction involvement (A, p=0.001; B, p=0.0001) and meibomian gland involvement (A, p=0.0471; B, p=0.006). Compared with baseline, the grades of corneal keratinisation (baseline, 0.48±0.7; 6 months, 1.02±0.8; p=0.0015) and neovascularisation (baseline, 1.07±1.2; 6 months, 1.57±1.0; p=0.0412) worsened after 6 months of CsA therapy. Intergroup comparison of grades of various parameters however did not reveal any significant difference at 6 months. CONCLUSIONS: Adjuvant treatment with topical CsA is not superior to standard therapy, in cases of acute SJS.

Prognostic significance of matrix metalloproteinase 9 in COMET operated chronic ocular Stevens-Johnson syndrome.

PURPOSE: Molecular pathogenesis underlying persistent ocular surface inflammation in chronic Stevens-Johnson syndrome (SJS) still remains largely unexplored. The present study investigates the expression of matrix metalloproteinase 2 (MMP2), MMP3, MMP9, MMP11 and TIMP1 (tissue inhibittor of matrix metalloproteinase 1) in pannus tissues of chronic ocular SJS undergoing cultivated oral mucosal epithelial transplantation (COMET) and their prognostic relevance. METHODS: In this prospective study, 45 eyes with chronic SJS underwent COMET for visual and anatomical rehabilitation. Preoperative and postoperative clinical parameters were documented. MMP2, MMP3, MMP9, MMP11 and TIMP1 expression were assessed using immunohistochemistry and quantitative real time PCR. Inflammadry MMP9 assay was performed at 1-year follow-up. Kaplan-Meier curves and Cox proportional hazard models were used to correlate protein expression with clinicopathological parameters and COMET graft survival outcomes. RESULTS: MMP9 and MMP11 positivity was seen in both pannus epithelia (48% and 55%, respectively) and in stromal layer (57% and 33%, respectively) while MMP2 and MMP3 showed only pannus epithelial positivity in 35% and 51% cases, respectively. High MMP9 stromal expression was significantly associated with preoperative corneal keratinisation (p=0.011), conjunctival hyperaemia (p=0.014), symblepharon (p=0.028). High MMP9 and MMP3 epithelial expression were found to be independent risk factors for poor best-corrected visual acuity (BCVA) outcomes post-COMET (p=0.022 and p=0.048). Multivariate analysis revealed MMP9 to be the best prognostic marker (p=0.050). CONCLUSION: Our findings suggest that differential expression of MMPs and TIMP1 is seen in SJS in chronic stage. Emergence of MMP9 as a poor prognostic predictor of BCVA post COMET and postoperative MMP9 immunoassay positivity could be a useful tool in further studies to understand the unresolved ocular surface inflammation seen in SJS.

Syphilis in the era of re-emergence: A 6-year retrospective study from a tertiary care center in South India.

Background: During the last several years, we have observed a rise in the number of patients with syphilis in our center. Aims: To find out the trends in the presentation of syphilis to our clinic over a 6-year period and to analyze the clinicoepidemiological features of those patients. Settings and Design: A retrospective chart review. Subjects and Methods: We analyzed the case records of all cases of syphilis registered in our sexually transmitted infection (STI) clinic from October 1, 2012, to September 30, 2018. Syphilis was diagnosed based on clinical or serological evidence. We also evaluated these patients for any concomitant STI, including hepatitis B, hepatitis C, and HIV. Statistical Analysis Used: The data were analyzed using SPSS software (version 20). Chi-square test was done for comparing categorical data, and P < 0.05 was considered statistically significant. Results: During the study period, 215 patients with STI attended our clinic. Of these, 66 (31%) patients had acquired syphilis. Among them, 3 (4.5%) had primary syphilis, 23 (34.8%) had secondary syphilis, and 40 (60.6%) had latent syphilis. Fifteen (22.7%) patients had concomitant HIV infection. A statistically significant rise in the number of cases of syphilis compared with other STIs was noted in the latter half of the study period (P = 0.001). Among the 50 males with acquired syphilis, 29 (58%) were men having sex with men (MSM), including 19 bisexual persons. Among the five antenatal cases, two were detected very late in pregnancy. Conclusions: We observed a marked increase in the number of cases of syphilis during the latter half of the study period. Primary and secondary syphilis were more frequent among MSM, suggesting a need to strengthen targeted intervention programs among them. More rigorous antenatal screening is necessary to prevent congenital syphilis.

Comparison of High Resolution Ultrasonography with Clinical Examination in the Assessment of Peripheral Nerve Involvement in Leprosy.

CONTEXT: Assessment of peripheral nerves in leprosy by clinical methods is subject to considerable inter-observer variability. High resolution ultrasonography (HRUS) can assess peripheral nerves more objectively. AIMS: To compare the findings of peripheral nerve involvement in newly diagnosed cases of leprosy by clinical and sonological methods. SETTINGS AND DESIGN: Cross sectional study in a tertiary care teaching hospital. SUBJECTS AND METHODS: Four pairs of peripheral nerves of 40 newly diagnosed patients with leprosy were examined clinically and by HRUS. STATISTICAL ANALYSIS USED: Agreement between clinical examination and HRUS using kappa statistic; sensitivity; specificity; and predictive values. RESULTS: Of the 320 nerves examined, 71 (22.18%) were abnormal clinically and 63 (19.7%) sonologically. Sonological abnormalities were increased cross sectional area (n = 63; 100%), hypoechogenicity with loss of fascicular architecture (n = 46; 73%) and increased vascularity (n = 35; 55.6%). There was moderate agreement (Cohen's K = 0.59) between clinical and sonological findings. HRUS findings were abnormal in 18 (7.2%) nerves that were clinically normal. HRUS was normal in 26 (36.6%) nerves which were clinically abnormal. Sensitivity of HRUS compared to clinical examination was 63%; specificity 92.7%; positive predictive value 71.4%; and negative predictive value 89.9%. Increased cross sectional area agreed with clinical findings the most. CONCLUSIONS: HRUS has low sensitivity (63%) and high specificity (92.7%) to identify abnormal peripheral nerves in leprosy, compared to clinical examination. It could detect abnormality of some (n = 18, 7.2%) clinically normal nerves, but showed normal findings of some nerves (n = 26, 36.6%), which were considered clinically abnormal.

Outcomes of Cultivated Oral Mucosal Epithelial Transplantation in Eyes With Chronic Stevens-Johnson Syndrome Sequelae.

PURPOSE: To study the outcomes of cultivated oral mucosal epithelial transplantation (COMET) in eyes with chronic Stevens-Johnson syndrome (SJS) sequelae. DESIGN: Prospective interventional case series. METHODS: Forty-five eyes of 41 patients with chronic SJS sequelae were recruited and evaluated from 2013 to 2017 in an institutional setting. All patients underwent COMET, with an aim of fornix reconstruction and visual rehabilitation. Change in corrected distance visual acuity (CDVA), severity scores of various ocular surface parameters, and the occurrence of complications were documented during a follow up period of 2 years. Attainment and maintenance of a stable ocular surface, as assessed by change in the ocular surface severity scores was the primary outcome measure, while change in CDVA was the secondary outcome measure. RESULTS: The mean preoperative CDVA was 2.7± 0.5 logMAR, which improved to 1.5± 0.7 logMAR and 1.49± 0.98 postoperatively, at 1- and 2-year follow-up visit. Overall, 82.2% eyes (37/45) had improvement in visual acuity, 13.3% (6/45) experienced no change, whereas 2 eyes (4.4%) had worsening of visual acuity. The total ocular surface severity scores improved from a mean preoperative value of 29.1± 9.7 to 18.7± 7.2 postoperatively, at 2-year follow-up. Two eyes developed persistent epithelial defects, with progression to corneal melting requiring keratoplasty. CONCLUSIONS: COMET allows successful and sustained restoration of ocular surface anatomy with functional improvement, in eyes with chronic sequelae of SJS.

Microbial Keratitis in Stevens-Johnson Syndrome: A Prospective Study.

PURPOSE: To evaluate the microbiological profile and outcome in cases with infective keratitis in Stevens-Johnson syndrome (SJS). METHODS: Eighty-three eyes of 68 patients with SJS presenting with microbial keratitis were recruited and managed with standard antimicrobial therapy. RESULTS: Microbial keratitis developed in 34% of patients with SJS (83 eyes, 68 patients) over a period of 5 years. Four eyes (4.8%) had a history of concurrent topical steroid use at the onset of keratitis. Mean baseline best-corrected visual acuity was 1.8 ± 0.9 logMAR units. The site of corneal ulceration was central in 52 eyes (62.6%), paracentral in 17 eyes (20.5%), and peripheral in 14 eyes (16.8%). The mean ulcer area was 3.9 ± 2.7 mm. Approximately 15 of 24 (62.5%) culture-positive eyes had bacterial infection, most of which (80%) were caused by Gram-positive bacteria. Polymicrobial infection was noted in 7 of 24 eyes (29.1%). Although 57 of 83 (68.6%) eyes healed with medical therapy, 26 of 83 (31.3%) eyes had corneal perforation and were managed with cyanoacrylate glue application (30.7%) or therapeutic keratoplasty (69.3%). Systemic infection as an inciting factor of SJS and an early presentation for keratitis were the major risk factors associated with corneal perforation. Large mean ulcer size, paracentral ulcers, and punctal involvement were associated with a good visual outcome. CONCLUSIONS: Infective keratitis in SJS is common, and unlike routine cases, surgical intervention is often required. However, the antibiotic sensitivity pattern suggests that resistance is not that high.

Multistep Grading System for Evaluation of Chronic Ocular Sequelae in Patients With Stevens-Johnson Syndrome.

PURPOSE: To propose a new scoring system for grading of chronic ocular sequelae in Stevens-Johnson syndrome (SJS). DESIGN: Reliability and validity analysis. METHODS: Participants: Four hundred eyes of 200 patients with chronic ocular SJS/toxic epidermal necrolysis (TEN) were included in the study. SETTINGS: Single-center, tertiary eye care referral center. PROCEDURE: All patients with SJS/TEN with chronic (more than 1 year) ocular sequelae were recruited for the study. Corneal, eyelid, and conjunctival signs were evaluated and given scores ranging from 0 to 5 depending on the increasing severity. Twelve signs (6 corneal, 3 conjunctival, and 3 eyelid) were evaluated to obtain the total severity score for each eye. Based on the corrected distance visual acuity (CDVA) and total score, each eye was graded using receiver operating characteristic (ROC) analysis. MAIN OUTCOME MEASURES: Correlation of CDVA with the severity score determined on the basis of 12 corneal, eyelid, and conjunctival signs. RESULTS: Mean age was 24.09 ± 10.9 years. The most common inciting agent for SJS was oral medications (85%). The scores of 12 ocular surface parameters correlated significantly with CDVA (P < .001). ROC analysis revealed 4 grades of total severity score of 0-11 (stage 0), 12-16 (stage 1), 17-22 (stage 2), and 23-53 (stage 3). The total severity score correlated significantly with logMAR visual acuity grades with an agreement of 60.7% using Cohen's kappa analysis (kappa coefficient = 0.420 ± 0.03). The most common stage of total severity score was stage 3 in 49% of eyes (196/400), followed by stage 0 (107/400, 26.7%). CONCLUSIONS: The multistep scoring system of chronic ocular features in SJS/TEN sequelae is a useful tool to grade all levels of severity. This may help to evaluate the efficacy of the surgical intervention by comparing preoperative with postoperative ocular grades.

Corneal Ectasia in Stevens-Johnson Syndrome: A Sequela of Chronic Disease.

PURPOSE: To describe corneal ectasia in cases of chronic Stevens-Johnson syndrome (SJS). DESIGN: Prospective observational study. METHODS: Setting: Institutional. PATIENTS: Fifteen consecutive cases of chronic SJS. MAIN OUTCOME MEASURES: Best-corrected distance visual acuity (BCDVA), maximum corneal curvature (Kmax), anterior elevation, posterior elevation, thinnest pachymetry, and Sotozono severity score. RESULTS: Thirty eyes of 15 patients were included. Corneal tomography using Scheimpflug technology (Pentacam-HR, Oculus GmbH) was performed. Nine eyes were excluded owing to poor-quality scans. The median age was 26 years. The median time from onset of disease to assessment for corneal ectasia was 7 years. The median BCDVA was 0.8 logMAR units at presentation. The median Sotozono severity score was 11. Corneal ectasia (Kmax > 48 diopters [D]) was noted in 76.2% of eyes. The mean Kmax was 58.37 ± 14.89 D. On Belin/Ambrosio enhanced ectasia display the median front and back elevation was 42 µm (10-176 µm) and 267 µm (15-2392 µm), respectively. The mean pachymetry was 377.76 ± 165.05 µm (133-448 µm). The point of maximum ectasia was peripheral in 57.1%, both central and peripheral in 19.1%, and central in 23.8% of eyes. On Spearman correlation analysis, deterioration in BCDVA (R = 0.759, P < .001) and increase in Kmax (R = 0.589, P = .005) was associated with higher disease severity (Sotozono grading). CONCLUSION: Corneal ectasia is a common but often missed entity in cases of chronic SJS that may be a cause for poor visual acuity in these cases. All cases of SJS must be evaluated for corneal ectasia, especially when the visual acuity is disproportionate to the disease severity.

New surgical approach in cases of cataract with ocular Stevens-Johnson syndrome.

We describe the intraoperative difficulties encountered in cases of ocular Stevens-Johnson syndrome as a result of a poor ocular surface, the presence of symblepharon, and varying degrees of corneal opacity with secondary poor visibility of anterior segment structures. Modifications to the standard phacoemulsification technique enabled safe and successful completion of the surgery in these cases. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Conjunctival Microbial Flora in Ocular Stevens-Johnson Syndrome Sequelae Patients at a Tertiary Eye Care Center.

PURPOSE: To evaluate the conjunctival microbial flora in cases of ocular Stevens-Johnson Syndrome (SJS) in a tertiary eye care center. METHODS: This prospective study comprised 176 eyes of 88 patients with ocular SJS compared with 124 eyes of normal subjects. The conjunctival swabs were collected and sent for microbiological analysis for bacterial isolation and antibiotic sensitivity examination. The type of bacteria isolated and its antibiotic sensitivity pattern were studied. RESULTS: Of 176 eyes, 104 (59%) had positive cultures for bacteria in cases of SJS and 16 (12.9%) had positive culture in the control group, the difference being statistically significant (P = 0.001). In the SJS group, 14 different types of bacterial isolates were identified. The most common isolate was coagulase-negative staphylococci (CNS) (30/104, 28.8%) followed by Corynebacteria species (35/104, 33.6%) and Staphylococcus aureus (19/104, 18.2%). More than 1 bacteria were isolated in 7 eyes (6.7%). Most of the isolates showed resistance to ciprofloxacin with no resistance to gatifloxacin and moxifloxacin. In the control group, only 2 bacteria were isolated, which included CNS (14/16, 87.5%) and Streptococcus pneumoniae (2/16, 12.5%). CNS showed resistance to ciprofloxacin, and S. pneumoniae was resistant to tobramycin and gentamycin. CONCLUSIONS: Ocular SJS is associated with alteration of the normal microbial flora residing in the conjunctival sac. The study of which is vital in cases of infection in these eyes with compromised ocular surface. Mixed flora are seen more often in cases of ocular SJS as compared with controls.