Mohammed Hasnat Ali

Cultivated Limbal Epithelial Transplantation in Children With Ocular Surface Burns

IMPORTANCE Although several reports are available on the use of conventional and cultured limbal epithelium using various substrates in the treatment of limbal stem cell deficiency (LSCD), the patient populations studied have been largely adults. Thus, to our knowledge, the outcomes of this procedure exclusively in a pediatric population have not been reported previously. OBJECTIVE To report the outcomes of autologous ex vivo cultivated limbal epithelial transplantation (CLET) in pediatric patients with LSCD after ocular burns. DESIGN AND SETTING A retrospective, interventional case series of patients treated at the L. V. Prasad Eye Institute, Hyderabad, India. PARTICIPANTS Children up to 15 years with LSCD secondary to chemical or thermal injury who underwent CLET from April 1, 2001, through June 31, 2010, with a follow-up of at least 1 year, were included in the study. INTERVENTION After a limbal biopsy specimen obtained from a healthy area of the limbus, the limbal epithelial cells were cultured on a denuded human amniotic membrane substrate using a xeno-free explant culture technique. A monolayer of cultivated epithelial cells along with the amniotic membrane was transplanted on the patients affected eye after pannus excision. In cases of failure, the same procedure was repeated. MAIN OUTCOMES AND MEASURES Ocular surface stability and visual improvement were the primary and secondary outcome measures, respectively. Success was defined as a stable corneal epithelium without conjunctivalization. Eyes with conjunctivalization and persistent epithelial defects were classified as failures. RESULTS Of the 107 eyes of 107 patients included in this study, 73 eyes (68.2%) underwent 1 and 34 eyes (31.8%) underwent 2 autologous CLET procedures. At a mean follow-up of 3.4 years, 50 eyes (46.7%) achieved completely epithelialized, avascular, and stable ocular surfaces. At the final visit, 58 eyes (54.2%) had improvement in visual acuity of 0.2 or more logMAR units. CONCLUSIONS Autologous CLET was successful in restoring the ocular surface and improving vision in almost half of the children blinded by ocular burns.

Re-appraisal of topical 1% voriconazole and 5% natamycin in the treatment of fungal keratitis in a randomised trial

Purpose To compare the efficacy of topical 1% voriconazole vs 5% natamycin for the treatment of fungal keratitis. Methods In a prospective, double-masked, randomised, controlled, registered clinical trial, 118 patients with fungal keratitis were treated using identical dosage schedule with either voriconazole (58) or natamycin (60) as inpatients for 7 days and followed up weekly. The outcome measures were percentage of patients with healed or resolving ulcer and final visual acuity at last follow-up (primary) and on day 7 (secondary) in each group. Results More patients (p=0.005) on natamycin (50/56, 89.2%) had healed or resolving ulcer compared with voriconazole (34/51, 66.6%) at last follow-up. The improvement in vision was marginally greater in patients in the natamycin group compared with the voriconazole group at day 7 (p=0.04) and significantly greater at final visit (p=0.01). In univariate analysis, drug, age and mean size of corneal infiltrate and epithelial defect had a significant effect on the final visual outcome. In multivariate analysis, the effect of drug (voriconazole vs natamycin, adjusted coefficient 0.27 (−0.04 to 0.57), p=0.09) was marginal while the effect of age and epithelial defect was significant (p<0.001 for both). In the group treated with natamycin, the final visual acuity was significantly better (p=0.005, Wilcoxon signed-rank test) in patients with Fusarium keratitis but not with Aspergillus keratitis (p=0.714, paired t test). Conclusions When compared with voriconazole, natamycin was more effective in the treatment of fungal keratitis, especially Fusarium keratitis. Trial registration number: Clinical Trial Registry India (2010/091/003041).

Autologous simple limbal epithelial transplantation for unilateral limbal stem cell deficiency: multicentre results

Purpose To report outcomes of autologous simple limbal epithelial transplantation (SLET) performed for unilateral limbal stem cell deficiency (LSCD) at multiple centres worldwide. Methods In this retrospective, multicentre, interventional case series, records of patients who had undergone autologous SLET for unilateral LSCD, with a minimum of 6 months of follow-up, were reviewed. The primary outcome measure was clinical success, defined as a completely epithelised, avascular corneal surface. Kaplan–Meier survival curves were constructed and survival probability was calculated. A Cox proportional hazards analysis was done to assess association of preoperative characteristics with risk of failure. Secondary outcome measures included the percentage of eyes achieving visual acuity of 20/200 or better, percentage of eyes gaining two or more Snellen lines and complications encountered. Results 68 eyes of 68 patients underwent autologous SLET, performed across eight centres in three countries. Clinical success was achieved in 57 cases (83.8%). With a median follow-up of 12 months, survival probability exceeded 80%. Presence of symblepharon (HR 5.8) and simultaneous keratoplasty (HR 10.8) were found to be significantly associated with a risk of failure. 44 eyes (64.7%) achieved a visual acuity of 20/200 or better, and 44 eyes (64.7%) gained two or more Snellen lines. Focal recurrences of pannus were noted in 21 eyes (36.8%) with clinical success. Conclusion Autologous SLET is an effective and safe modality for treatment of unilateral LSCD. Clinical success rates and visual acuity improvement are equal to or better than those reported with earlier techniques.

Comparison of augmented superior rectus transposition with medial rectus recession for surgical management of esotropic Duane retraction syndrome.

BACKGROUND Medial rectus recession (MRc) and vertical rectus transpositions are procedures used to treat esotropic Duane retraction syndrome. Recently superior rectus transposition (SRT) combined with MRc has also been shown to improve primary alignment and abduction. The purpose of this study is to compare the results of augmented (ie, with scleral fixation) SRT with or without MRc with either unilateral or bilateral MRc for treatment of esotropic Duane syndrome. METHODS The medical records of patients who underwent surgery for esotropic Duane syndrome between May 2007 and February 2013 were retrospectively reviewed. Success was defined as alignment within 8(Δ) of orthotropia and abnormal head posture of <5°. RESULTS There were 8 patients in the SRT group (6 of whom had additional ipsilateral MRc) and 13 in the MRc group (6 unilateral and 7 bilateral). In the SRT group, the mean preoperative deviation was 20(Δ) of esotropia; the mean postoperative deviation, 3(Δ). In the MRc group, the mean preoperative deviation was 24(Δ) of esotropia; the mean postoperative deviation, 4(Δ). The success rate was 87% in the SRT group; 77%, in MRc group (P = 0.98). Mean abduction limitation improved from -3.6 to -2.4 units in the SRT group and from -3.6 to -3.3 units in the MRc group (P = 0.003). Induced vertical deviation or subjective torsion was not seen. Three patients in each group developed adduction limitation postoperatively. CONCLUSIONS Although both the procedures successfully correct esotropia in Duane syndrome, SRT with or without MRc has the additional advantage of improving abduction.

OPTIC NERVE INFILTRATION BY RETINOBLASTOMA: Predictive Clinical Features and Outcome.

Purpose: To identify the clinical features predictive of any optic nerve infiltration and postlaminar optic nerve infiltration by retinoblastoma on histopathology and to report the outcome (metastasis and death) in these patients. Methods: Retrospective study. Results: Of the 403 patients who underwent primary enucleation for retinoblastoma, 196 patients had optic nerve tumor infiltration (Group 1) and 207 patients had no evidence of optic nerve tumor infiltration (Group 2). Group 1 included patients with prelaminar (n = 47; 24%), laminar (n = 74; 38%), and postlaminar tumor infiltration with or without involving optic nerve transection (n = 74; 38%). Comparing Group 1 and Group 2, the patients in Group 1 had prolonged duration of symptoms (>6 months) (16% vs. 8%; P = 0.02) and were associated with no vision at presentation (23% vs. 10%; P = 0.01), higher rates of secondary glaucoma (42% vs. 12%; P < 0.0001), iris neovascularization (39% vs. 23%; P < 0.001), and larger tumors (mean tumor thickness, 12.8 mm vs. 12 mm; P = 0.0001). There was a higher prevalence of metastasis in Group 1 than in Group 2 (4% vs. 0%; P = 0.006). On multivariate analysis, clinical features predictive of any optic nerve tumor infiltration secondary glaucoma (hazard ratio = 5.38; P < 0.001) and those predictive of postlaminar optic nerve tumor infiltration included iris neovascularization (hazard ratio = 2.66; P = 0.001) and secondary glaucoma (hazard ratio = 3.13; P < 0.001). Conclusion: In this study, clinical features predictive of any optic nerve tumor infiltration included secondary glaucoma and those predictive of postlaminar optic nerve tumor infiltration included iris neovascularization and secondary glaucoma. Despite adjuvant treatment in those with postlaminar optic nerve tumor infiltration, metastasis occurred in 8% of patients.

Genotype-Phenotype Correlations in CYP1B1-Associated Primary Congenital Glaucoma Patients Representing Two Large Cohorts from India and Brazil.

Background Primary congenital glaucoma (PCG), occurs due to the developmental defects in the trabecular meshwork and anterior chamber angle in children. PCG exhibits genetic heterogeneity and the CYP1B1 gene has been widely implicated worldwide. Despite the diverse mutation spectra, the clinical implications of these mutations are yet unclear. The present study attempted to delineate the clinical profile of PCG in the background of CYP1B1 mutations from a large cohort of 901 subjects from India (n=601) and Brazil (n=300). Methods Genotype-phenotype correlations was undertaken on clinically well characterized PCG cases from India (n=301) and Brazil (n=150) to assess the contributions of CYP1B1 mutation on a set of demographic and clinical parameters. The demographic (gender, and history of consanguinity) and quantitative clinical (presenting intraocular pressure [IOP] and corneal diameter [CD]) parameters were considered as binary and continuous variables, respectively, for PCG patients in the background of the overall mutation spectra and also with respect to the prevalent mutations in India (R368H) and Brazil (4340delG). All these variables were fitted in a multivariate logistic regression model using the Akaike Information Criterion (AIC) to estimate the adjusted odds ratio (OR) using the R software (version 2.14.1). Results The overall mutation spectrum were similar across the Indian and Brazilian PCG cases, despite significantly higher number of homozygous mutations in the former (p=0.024) and compound heterozygous mutations in the later (p=0.012). A wide allelic heterogeneity was observed and only 6 mutations were infrequently shared between these two populations. The adjusted ORs for the binary (demographic) and continuous (clinical) variables did not indicate any susceptibility to the observed mutations (p>0.05). Conclusions The present study demonstrated a lack of genotype-phenotype correlation of the demographic and clinical traits to CYP1B1 mutations in PCG at presentation. However, the susceptibility of these mutations to the long-term progression of these traits are yet to be deciphered.

Efficacy of conjunctival resection with cyanoacrylate glue application in preventing recurrences of Mooren's ulcer

Aim To evaluate the role of conjunctival resection along with cyanoacrylate glue and bandage contact lens application in preventing recurrences and arresting progression in cases of Moorens ulcer. Method This retrospective interventional case series included cases of Moorens ulcer that underwent conjunctival resection with cyanoacrylate glue and bandage contact lens application between 2011 and 2014. Systemic immunosuppression was initiated depending on the laterality and severity of disease. The primary outcome measures were clinical quiescence and recurrence-free survival. Kaplan–Meier plots were constructed and survival analysis done using the R software environment for statistical analysis. Secondary outcome measures were needed for systemic immunosuppression, change in best-corrected visual acuity and complications encountered. Results We evaluated 16 eyes of 12 patients who presented to us during the study period. The mean follow-up duration was 9.6 months. All eyes achieved clinical quiescence with a median recurrence-free survival of 141 days. The Kaplan–Meier survival curve showed probability of recurrence-free survival to be 42.5% at 1 year, which further dropped down to 21.3% at 2 years. All patients with recurrence (seven eyes of four patients) required systemic immunosuppression. Conclusions Conjunctival resection and cyanoacrylate glue application are not effective in avoiding recurrences and halting the disease progression in cases of Moorens ulcer. Systemic immunosuppression remains the mainstay of therapy.

Dysbiosis in the Gut Bacterial Microbiome of Patients with Uveitis, an Inflammatory Disease of the Eye

Uveitis (UVT), an inflammatory disease of the eye significantly contributes to vision impairment and blindness. Uveitis is associated with systemic infectious and autoimmune diseases, but in most cases, the aetiology remains unidentified. Dysbiosis in the gut microbiome has been implicated in autoimmune diseases, inflammatory diseases, cancers and mental disorders. In a mice model of autoimmune UVT, it was observed that manipulating the gut microbiome reduces the inflammation and disease severity. Further, alterations in the bacterial gut microbiome and their metabolites were reported in UVT patients from a Chinese cohort. Hence, it is worth comparing the bacterial gut microbiome of UVT patients with that of healthy controls (HC) to ascertain whether dysbiosis of the gut microbiome has implications in UVT. Our analyses showed reduced diversity of several anti-inflammatory organisms including Faecalibacterium, Bacteroides, Lachnospira, Ruminococcus and members of Lachnospiraceae and Ruminococcaceae families, and enrichment of Prevotella (proinflammatory) and Streptococcus (pathogenic) OTUs in UVT microbiomes compared to HC. In addition, decrease in probiotic and antibacterial organisms was observed in UVT compared to HC microbiomes. Heatmap and PCoA plots also indicated significant variations in the microbiomes of UVT versus HC. This is the first study demonstrating dysbiosis in the gut bacterial communities of UVT patients in an Indian cohort and suggests a role of the gut microbiome in the pathophysiology of UVT.

Choroidal Infiltration by Retinoblastoma: Predictive Clinical Features and Outcome

PURPOSE To identify the clinical features predictive of choroidal infiltration by retinoblastoma on histopathology and to report the outcome in these patients. METHODS Retrospective study. RESULTS Of the 403 patients who underwent primary enucleation for retinoblastoma, 113 patients had choroidal tumor infiltration and 290 patients had no choroidal tumor infiltration. There was a higher incidence of metastasis and related death in the choroidal tumor infiltration group compared to the no choroidal tumor infiltration group (4% vs 1%; P = .02). On multivariate analysis, the clinical features predictive of histopathologic massive choroidal infiltration included prolonged duration of symptoms for more than 6 months (hazard ratio [HR] = 3.04; P = .001) and secondary glaucoma (HR = 2.24; P = .005). CONCLUSIONS In this study, the patients with retinoblastoma with prolonged duration of symptoms (> 6 months) had a three-fold greater risk and those with secondary glaucoma at presentation had a two-fold greater risk of massive choroidal tumor infiltration. [J Pediatr Ophthalmol Strabismus. 2016;53(6):349-356.].

Elevated cytokine levels in vitreous as biomarkers of disease severity in infectious endophthalmitis

Purpose To investigate the immunopathogenesis of endophthalmitis, and determine if cytokine profiles could serve as biomarkers of disease severity in infectious endophthalmitis. Materials and methods Vitreous samples of 46 patients clinically diagnosed as endophthalmitis (of which 25 were culture positive) and 20 non-infectious controls from patients with Retinal Detachment (RD) or diabetic retinopathy were included in the study. The cytokine and chemokine expression patterns of 40 immune mediators including 6 antiinflammatory cytokines, 15 proinflammatory cytokines, 9 Growth factors and 10 proinflammatory chemokines in the vitreous were were analyzed by multiplex cytokine immunoassay. In addition, significant immune mediators were correlated with initial and final visual acuity (VA). Results Our results demonstrated elevated expression of 16 mediators such as GCSF, GRO, IFN-γ, IL-1α, IL-1β, IL-1 RA, IL-6, IL-8, IP-10, MCP-1, MCP-3, MIP-1α, IL-1β, TGF-α, TNF-α in patients with culture positive endophthalmitis. Cytokine profile expression significantly differed between patients with proven endophthalmitis and the non-infectious controls in heat map analysis. PCoA plot indicated five mediators (IL-1RA, IL-6, IL-8, GRO, G-CSF) as biomarkers that could be Independent Predictors of Disease especially in culture negative cases. Correlation of cytokines with VA revealed strong association between the initial VA and intraocular levels of TGF-α, IL-1β and IL-8 but there was no correlation with the severity or visual outcome of infection. Conclusion In comparison to non-infectious ocular conditions, the pathogenesis of infectious endophthalmitis correlates with increased expression levels of IL-1RA, IL-6, IL-8, GRO, G-CSF. Understanding cytokine profiles in culture negative endophthalmitis patients could aid in therapy in non-responders to empirical antibiotic therapy.