Srikant K. Sahu

Diagnosis and treatment outcome of mycotic keratitis at a tertiary eye care center in eastern India.

BackgroundMycotic keratitis is an important cause of corneal blindness world over including India. Geographical location and climate are known to influence the profile of fungal diseases. While there are several reports on mycotic keratitis from southern India, comprehensive clinico-microbiological reports from eastern India are few. The reported prevalence of mycotic keratitis are 36.7%,36.3%,25.6%,7.3% in southern, western, north- eastern and northern India respectively. This study reports the epidemiological characteristics, microbiological diagnosis and treatment outcome of mycotic keratitis at a tertiary eye care center in eastern India.MethodsA retrospective review of medical and microbiology records was done for all patients with laboratory proven fungal keratitis.ResultsBetween July 2006 and December 2009, 997 patients were clinically diagnosed as microbial keratitis. While no organisms were found in 25.4% (253/997) corneal samples, 23.4% (233/997) were bacterial, 26.4% (264/997) were fungal (45 cases mixed with bacteria), 1.4% (14/997) were Acanthamoeba with or without bacteria and 23.4% (233/997) were microsporidial with or without bacteria. Two hundred fifteen of 264 (81.4%, 215/264) samples grew fungus in culture while 49 corneal scrapings were positive for fungal elements only in direct microscopy. Clinical diagnosis of fungal keratitis was made in 186 of 264 (70.5%) cases. The microscopic detection of fungal elements was achieved by 10% potassium hydroxide with 0.1% calcoflour white stain in 94.8%(238/251) cases. Aspergillus species (27.9%, 60/215) and Fusarium species (23.2%, 50/215) were the major fungal isolates. Concomitant bacterial infection was seen in 45 (17.1%, 45/264) cases of mycotic keratitis. Clinical outcome of healed scar was achieved in 94 (35.6%, 94/264) cases. Fifty two patients (19.7%, 52/264) required therapeutic PK, 9 (3.4%, 9/264) went for evisceration, 18.9% (50/264) received glue application with bandage contact lens (BCL) for impending perforation, 6.1% (16/264) were unchanged and 16.3% (43/264) were lost to follow up. Poor prognosis like PK (40/52, 75.9%, p < 0.001) and BCL (30/50, 60%, p < 0.001) was seen in significantly larger number of patients with late presentation (> 10 days).ConclusionsThe relative prevalence of mycotic keratitis in eastern India is lower than southern, western and north-eastern India but higher than northern India, however, Aspergillus and Fusarium are the predominant genera associated with fungal keratitis across India. The response to medical treatment is poor in patients with late presentation.

Reevaluating intracameral cefuroxime as a prophylaxis against endophthalmitis after cataract surgery in India.

Purpose To determine whether an intracameral injection of cefuroxime sodium at the conclusion of cataract surgery lowers the incidence of acute‐onset postoperative endophthalmitis. Setting Tertiary eye care center, Bhubaneswar, India. Design Prospective comparative interventional cohort study. Methods Under a uniform protocol, cataract surgery with posterior chamber intraocular lens (PC IOL) implantation was performed from September 27, 2006, to July 31, 2010 (Group 1). All eyes were evaluated 1 day, 7 days, and 5 weeks ± 1 (SD) postoperatively. Treatment of eyes suspected to have developed infectious endophthalmitis was managed by retina–vitreous surgeons. From August 1, 2010, to August 31, 2012, the same surgeons performed cataract surgery with PC IOL implantation in another group of eyes, in which they administered intracameral cefuroxime prophylaxis (Group 2). All other protocols of postoperative care and microbiological investigation of the vitreous samples were similar. The rate of clinical and culture‐positive endophthalmitis was compared between the 2 study groups: eyes without intracameral cefuroxime (Group 1) and eyes with intracameral cefuroxime (Group 2). Results The incidence of clinical endophthalmitis in Group 1 (0.155% [12/7756 eyes]) and in Group 2 (0.108% [8/7366 eyes]) was not significantly different (P = .57). The culture positivity rate in Group 1 (0.09 % [7 eyes]) and in Group 2 (0.04% [3 eyes]) was also not significantly different (P = .38). In the treatment without intracameral cefuroxime, there was a minimal, statistically insignificant increase in postoperative acute endophthalmitis (odds ratio, 1.42; 95% confidence interval, 0.53‐4.02; P = .506). Conclusion There is not strong evidence to support use of intracameral cefuroxime to reduce the rate of acute endophthalmitis after cataract surgery; however, the marginal benefit might justify its use. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Natamycin in the treatment of keratomycosis: Correlation of treatment outcome and in vitro susceptibility of fungal isolates

In this study, 60 fungal isolates from 60 patients with fungal keratitis were tested in vitro for their susceptibility to natamycin and the mean minimum inhibitory concentrations of natamycin (MICn) were correlated with clinical outcome. The mean MICn for various groups of fungi from patients with either early (<10 days) or late (≥10 days) presentation was correlated with the outcome. Aspergillus flavus showed resistance to natamycin with a high mean MICn (>16 μg/ml). While the clinical response in all patients with early A. flavus keratitis was good it was poor in late cases (5/8 patients, 62.5%). Fusarium species, Acremonium species and dematiaceous fungi were sensitive with low mean MICn (Fusarium: 5.7-7.2 μg/ml, Acremonium: 5.7-6.8 μg/ml, dematiaceous: (1.6-4 μg/ml). However, 46.6% (7/15) patients in Fusarium and 57.1% (4/7) in Acremonium group needed keratoplasty. We conclude that despite susceptibility of most fungal species causing keratitis to natamycin, the treatment outcome is poor in advanced fungal keratitis.

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).

Clinical Trial of 0.02% Polyhexamethylene Biguanide Versus Placebo in the Treatment of Microsporidial Keratoconjunctivitis

PURPOSE To evaluate the efficacy of 0.02% polyhexamethylene biguanide (PHMB) in the treatment of keratoconjunctivitis caused by microsporidia. DESIGN Prospective, double-masked, randomized, placebo-controlled clinical trial. METHODS One hundred forty-five patients in a single-center, institutional setting were recruited. Patients with superficial keratoconjunctivitis and corneal scrapings with positive results for microsporidial spores were included. Patients with any known allergy to PHMB, and clinically suspected bacterial, viral, or fungal infection were excluded from the study. One hundred forty-five patients were treated at 4-hour intervals with either topical 0.02% PHMB (n = 72) or placebo (n = 73). The patients were followed-up on day 3 +/- 1, day 7 +/- 1, and weekly thereafter, until complete resolution of the corneal lesions. Patients with deterioration of clinical symptoms and signs were removed from the study and were treated with PHMB. Main outcome measures included resolution time, cure time, and final visual outcome. RESULTS Resolution time was defined as the amount of time until disappearance of corneal epithelial infiltrates. Cure time was defined as the interval until absence of conjunctival congestion, corneal epithelial lesion, and superficial punctate keratitis. Baseline characteristics showed no relevant difference between the groups. The mean resolution time was 4.9 +/- 2.2 days and 4.6 +/- 2.3 days in the PHMB and placebo groups, respectively (P = .49). The mean time for cure was 13.5 +/- 6.6 days and 9.4 +/- 5.1 days in PHMB and placebo groups, respectively (P = .004). There was no significant difference in the final visual outcome between the groups (P = .10). No serious adverse effects were noted. CONCLUSIONS Treatment of microsporidial keratoconjunctivitis with PHMB does not offer any significant advantage over placebo, suggesting self-limiting nature of the disease.

Diagnosis, clinical features and treatment outcome of microsporidial keratoconjunctivitis

Aim To report the clinical and microbiological profile of patients with microsporidial keratoconjunctivitis in a tertiary eye care centre in India. Methods A retrospective analysis of medical records of all cases of microbiologically confirmed microsporidial keratoconjunctivitis, who presented between March 2007 and October 2010, was done. In a single-centre, institutional setting, 278 eyes of 277 apparently healthy patients were analysed. Results The mean age was 36±14 years (range 6–80). The mean duration of symptoms was 7.7±6.2 days (range 1–60). Keratic precipitates were present in 20.1% patients. A superficial scar was present in 39.2% patients. Majority (26.6%) of the patients reported in the month of August. Microscopic examination of corneal scraping, using potassium hydroxide with calcofluor white and Gram stain, demonstrated microsporidial spores in 98.9% and 89.7% cases, respectively. Patients received either topical 0.02% polyhexamethylene biguanide or lubricants. The mean time for resolution was 6.0±2.9 days (range 2–18). Final visual acuity was ≥20/30 in 75.1% cases. Conclusions Microsporidial keratoconjunctivitis is common in India. It is seasonal, can occur in healthy individuals and can be diagnosed using simple microbiological methods. Treatment outcome is generally satisfactory.

Pythium insidiosum keratitis: clinical profile and role of DNA sequencing and zoospore formation in diagnosis.

Purpose: To report the molecular and microbiological diagnosis and clinical profile of 13 patients with Pythium insidiosum keratitis. Methods: Phase 1 of the study consisted of DNA sequencing of the ITS region of the rDNA of 162 stocked morphologically unidentified nonconsecutive fungal isolates from corneal scraping of patients with keratitis (2010–2012). Blast and phylogenetic analyses of the sequences showed 9 to be P. insidiosum. A retrospective review of archived photographs of colony and direct microscopy of corneal scrapings and clinical records of the cases were performed. Phase 2 began in 2014, in which a simple method of zoospore formation was used for fungal colonies resembling those of P. insidiosum followed by DNA sequencing. Results: The prevalence of P. insidiosum among unidentified fungal isolates from keratitis was 9/162 (5.5%) in phase 1. In phase 2, 4/102 cases (3.9%) of fungal keratitis were identified as P. insidiosum (January–February, 2014). Phylogenetic analysis of all 13 fungal isolates confirmed the identification of P. insidiosum. Corneal infiltrates exhibited hyphate edges, tentacle-like extensions, and dot-like infiltrates surrounding the main infiltrate. Response to topical 5% natamycin eye drops with or without oral antifungals was poor (penetrating keratoplasty: 9 and evisceration: 2) with a mean follow-up period of 82 days. Conclusions: P. insidiosum keratitis needs to be considered in the differential diagnosis of severe fungal keratitis. It can be identified using the zoospore formation method and confirmed by ITS DNA sequencing. Lack of response to currently used antifungal drugs calls for evaluation of newer drugs for medical therapy and consideration for early penetrating keratoplasty.

Is inclusion of Sabouraud dextrose agar essential for the laboratory diagnosis of fungal keratitis

Purpose: To determine whether the inclusion of Sabouraud dextrose agar (SDA) is essential in the diagnosis of fungal keratitis. Materials and Methods: Corneal scrapings of 141 patients with microbial keratitis were smeared and cultured. Sheep blood agar (BA), chocolate agar (CA), SDA, non-nutrient agar (NNA) with Escherichia coli overlay, and brain heart infusion broth (BHI) were evaluated for time taken for growth and cost. The media were also evaluated experimentally for rate of growth and time taken for identification. Results: Twenty-six of 39 patients positive for fungus in corneal scrapings by microscopy were culture-positive. Fungus grew on BA in 22/39, on CA in 18/39, on SDA in 17/39, on NNA in 17/39, and on BHI in 13/39 cases. Growth on SDA was higher in ulcers with larger infiltrate (6/18 versus 9/13, P = 0.04). Estimated saving with inclusion of only BA/CA was Rs. 600 per patient. Performance of all media was similar in in vitro experiment although the characteristic spores and color were seen earlier on SDA. Conclusion: Fungal keratitis can be reliably confirmed on BA or CA, which support growth of both bacteria and fungus.

Clinico-Microbiological Profile and Treatment Outcome of Infectious Scleritis: Experience from a Tertiary Eye Care Center of India

Medical and microbiology records of seventeen patients (17 eyes), diagnosed as scleritis of infectious origin were reviewed; to study clinical features, predisposing risk factors, microbiologic profile and treatment outcome of infectious scleritis. The mean patient age was 52.3 ± 19.75 years. Twelve patients (70.6%) had history of trauma/prior surgery. Isolated organisms included Staphylococcus species (spp) (n = 5), Fungus (n = 4), Nocardia spp (n = 3), two each of atypical Mycobacterium spp and Streptococcus pneumoniae and one Pseudomonas aeruginosa. Treatment included intensive topical antimicrobial in all eyes and systemic medication in 15 (88.2%) patients; surgical exploration was needed for 13 (76.5%) patients and scleral patch graft was done in four (23.5%) patients. Lesions resolved in all patients and none required evisceration. The presenting log MAR visual acuity of 1.77 ± 1.40 and improved to 0.99 ± 0.91. (P ≤ 0.039) after treatment with a mean follow up of 22.57 ± 19.53 weeks. A microbiological confirmation, appropriate medical and/or surgical intervention has a good tectonic and visual outcome.

Fungal periorbital necrotizing fasciitis in an immunocompetent adult.

A 55-year-old man presented with profound swelling of the upper face and fever with a history of preceding insect bite. He was nonalcoholic and immunocompetent. Orbital CT showed a predominantly preseptal soft-tissue swelling. Empiric treatment with broad-spectrum antibiotics resulted in partial response. Surgical debridement and microbiologic evaluation of the necrotic tissue were performed. Gram stain showed budding yeast cells. Candida and Aspergillus spp. grew in culture after 48 hours. The patient received oral fluconazole, 200 mg once a day for 8 weeks. Complete resolution was documented at 16 weeks. In tropical regions, Candida and Aspergillus spp. may cause periorbital necrotizing fasciitis in immunocompetent adults.