Muthiah Srinivasan

Corneal blindness: a global perspective

Diseases affecting the cornea are a major cause of blindness worldwide, second only to cataract in overall importance. The epidemiology of corneal blindness is complicated and encompasses a wide variety of infectious and inflammatory eye diseses that cause corneal scarring, which ultimately leads to functional blindness. In addition, the prevalence of corneal disease varies from country to country and even from one population to another. While cataract is responsible for nearly 20 million of the 45 million blind people in the world, the next major cause is trachoma which blinds 4.9 million individuals, mainly as a result of corneal scarring and vascularization. Ocular trauma and corneal ulceration are significant causes of corneal blindness that are often underreported but may be responsible for 1.5-2.0 million new cases of monocular blindness every year. Causes of childhood blindness (about 1.5 million worldwide with 5 million visually disabled) include xerophthalmia (350,000 cases annually), ophthalmia neonatorum, and less frequently seen ocular diseases such as herpes simplex virus infections and vernal keratoconjunctivitis. Even though the control of onchocerciasis and leprosy are public health success stories, these diseases are still significant causes of blindness--affecting a quarter of a million individuals each. Traditional eye medicines have also been implicated as a major risk factor in the current epidemic of corneal ulceration in developing countries. Because of the difficulty of treating corneal blindness once it has occurred, public health prevention programmes are the most cost-effective means of decreasing the global burden of corneal blindness.

Epidemiology and aetiological diagnosis of corneal ulceration in Madurai, south India

AIMS/BACKGROUND To determine the epidemiological characteristics and risk factors predisposing to corneal ulceration in Madurai, south India, and to identify the specific pathogenic organisms responsible for infection. METHODS All patients with suspected infectious central corneal ulceration presenting to the ocular microbiology and cornea service at Aravind Eye Hospital, Madurai, from 1 January to 31 March 1994 were evaluated. Sociodemographic data and information pertaining to risk factors were recorded, all patients were examined, and corneal cultures and scrapings were performed. RESULTS In the 3 month period 434 patients with central corneal ulceration were evaluated. A history of previous corneal injury was present in 284 patients (65.4%). Cornea cultures were positive in 297 patients (68.4%). Of those individuals with positive cultures 140 (47.1%) had pure bacterial infections, 139 (46.8%) had pure fungal infections, 15 (5.1%) had mixed bacteria and fungi, and three (1.0%) grew pure cultures ofAcanthamoeba. The most common bacterial pathogen isolated was Streptococcus pneumoniae, representing 44.3% of all positive bacterial cultures, followed by Pseudomonas spp (14.4%). The most common fungal pathogen isolated was Fusariumspp, representing 47.1% of all positive fungal cultures, followed by Aspergillus spp (16.1%). CONCLUSIONS Central corneal ulceration is a common problem in south India and most often occurs after a superficial corneal injury with organic material. Bacterial and fungal infections occur in equal numbers with Streptococcus pneumoniaeaccounting for the majority of bacterial ulcers and Fusariumspp responsible for most of the fungal infections. These findings have important public health implications for the treatment and prevention of corneal ulceration in the developing world.

Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endothelial dystrophy (CHED2)

Congenital hereditary endothelial dystrophy (CHED) is a heritable, bilateral corneal dystrophy characterized by corneal opacification and nystagmus. We describe seven different mutations in the SLC4A11 gene in ten families with autosomal recessive CHED. Mutations in SLC4A11, which encodes a membrane-bound sodium-borate cotransporter, cause loss of function of the protein either by blocking its membrane targeting or nonsense-mediated decay.

Microbial Keratitis in South India: Influence of Risk Factors, Climate, and Geographical Variation

Purpose: To determine the influence of risk factors, climate, and geographical variation on the microbial keratitis in South India. Methods: A retrospective analysis of all clinically diagnosed infective keratitis presenting between September 1999 and August 2002 was performed. A standardised form was filled out for each patient, documenting sociodemographic features and information pertaining to risk factors. Corneal scrapes were collected and subjected to culture and microscopy. Results: A total of 3,183 consecutive patients with infective keratitis were evaluated, of which 1,043 (32.77%) were found to be of bacterial aetiology, 1,095 (34.4%) were fungal, 33 (1.04%) were Acanthamoeba, 76 (2.39%) were both fungal and bacterial, and the remaining 936 (29.41%) were found to be culture negative. The predominant bacterial and fungal pathogens isolated were Streptococcus pneumoniae (35.95%) and Fusarium spp. (41.92%), respectively. Most of the patients (66.84%) with fungal keratitis were between 21 and 50 years old, and 60.21% of the patients with bacterial keratitis were older than 50 (p < 0.0001) (95% CI: 5.19–7.19). A majority of patients (64.75%) with fungal keratitis were agricultural workers (p < 0.0001) [odds ratio (OR): 1.4; 95% CI: 1.19–1.61], whereas bacterial keratitis occurred more commonly (57.62%) in nonagricultural workers (p < 0.0001) (OR: 2.88; 95% CI: 2.47–3.36). Corneal injury was identified in 2,256 (70.88%) patients, and it accounted for 92.15% in fungal keratitis (p < 0.0001) (OR: 7.7; 95% CI: 6.12–9.85) and 100% in Acanthamoeba keratitis. Injuries due to vegetative matter (61.28%) were identified as a significant cause for fungal keratitis (p < 0.0001) (OR: 23.6; 95% CI: 19.07–29.3) and due to mud (84.85%) for Acanthamoeba keratitis (p < 0.0001) (OR: 26.01; 95% CI: 3.3–6.7). Coexisting ocular diseases predisposing to bacterial keratitis accounted for 68.17% (p < 0.0001) (OR: 33.99; 95% CI: 27.37–42.21). The incidence of fungal keratitis was higher between June and September, and bacterial keratitis was less during this period. Conclusion: The risk of agricultural predominance and vegetative corneal injury in fungal keratitis and associated ocular diseases in bacterial keratitis increase susceptibility to corneal infection. A hot, windy climate makes fungal keratitis more frequent in tropical zones, whereas bacterial keratitis is independent of seasonal variation and frequent in temperate zones. Microbial pathogens show geographical variation in their prevalence. Thus, the spectrum of microbial keratitis varies with geographical location influenced by the local climate and occupational risk factors.

Corneal ulceration in the developing world--a silent epidemic.

Anyone who has spent time in Asia or Africa can invariably recall a vivid image of a blind beggar, sometimes an elderly person but frequently a child with opaque corneas, haunting the bazaars and marketplaces of cities and villages. The spectre is so common that it almost passes unnoticed, but these individuals who are bilaterally blind represent only a small fraction of the millions who suffer monocular blindness as a result of corneal trauma and subsequent microbial keratitis. With the global figure of blindness rapidly approaching 40 million, attention naturally is focused on cataract, which is responsible for 50% or more of all visual disability, and trachoma which is still an enormous public health problem affecting 500 million people worldwide and responsible for 25% of all bilaterally blind individuals.1 Xerophthalmia, onchocerciasis, and glaucoma account for several millions more of the 85% of the world’s blind individuals who live in developing countries in Asia and Africa.2 While corneal blindness in the developing world has traditionally been attributed to trachoma, xerophthalmia, …

Incidence of corneal ulceration in Madurai District, South India

OBJECTIVE To determine the incidence of corneal ulceration in Madurai District, South India. DESIGN Retrospective incidence study. SETTING General community. PATIENTS All patients who reside in Madurai District and presented to an ophthalmologist in 1993 with corneal ulceration. MAIN OUTCOME MEASURE Cases of corneal ulceration. RESULTS 1148 cases of corneal ulceration were recorded in the medical records of those ophthalmologists who maintained records. Based upon the recorded number of cases, the annual incidence per 10,000 population was 3.4. The ratio of male to female patients was 1.6:1.0. When the estimated number of cases from those without records was added to the total number of recorded cases the annual incidence was 11.3 per 10,000 population. CONCLUSION Corneal ulceration is a common occurrence in South India. While the true incidence of this problem is impossible to determine because of the lack of medical records, we believe our estimation of the incidence to be close to the true incidence in this community.

Comparison of natamycin and voriconazole for the treatment of fungal keratitis.

OBJECTIVE To conduct a therapeutic exploratory clinical trial comparing clinical outcomes of treatment with topical natamycin vs topical voriconazole for fungal keratitis. METHODS The multicenter, double-masked, clinical trial included 120 patients with fungal keratitis at Aravind Eye Hospital in India who were randomized to receive either topical natamycin or topical voriconazole and either had repeated scraping of the epithelium or not. MAIN OUTCOME MEASURES The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months. Other outcomes included scar size, perforations, and a subanalysis of BSCVA at 3 months in patients with an enrollment visual acuity of 20/40 to 20/400. RESULTS Compared with those who received natamycin, voriconazole-treated patients had an approximately 1-line improvement in BSCVA at 3 months after adjusting for scraping in a multivariate regression model but the difference was not statistically significant (P = .29). Scar size at 3 months was slightly greater with voriconazole after adjusting for scraping (P = .48). Corneal perforations in the voriconazole group (10 of 60 patients) were not significantly different than in the natamycin-treated group (9 of 60 patients) (P >.99). Scraping was associated with worse BSCVA at 3 months after adjusting for drug (P = .06). Patients with baseline BSCVA of 20/40 to 20/400 showed a trend toward a 2-line improvement in visual acuity with voriconazole (P = .07). CONCLUSIONS Overall, there were no significant differences in visual acuity, scar size, and perforations between voriconazole- and natamycin-treated patients. There was a trend toward scraping being associated with worse outcomes. Application to Clinical Practice The benefit seen with voriconazole in the subgroup of patients with baseline visual acuity of 20/40 to 20/400 needs to be validated in a confirmatory clinical trial. Trial Registration clinicaltrials.gov Identifier: NCT00557362.

Corticosteroids for Bacterial Keratitis: The Steroids for Corneal Ulcers Trial (SCUT)

OBJECTIVE To determine whether there is a benefit in clinical outcomes with the use of topical corticosteroids as adjunctive therapy in the treatment of bacterial corneal ulcers. METHODS Randomized, placebo-controlled, double-masked, multicenter clinical trial comparing prednisolone sodium phosphate, 1.0%, to placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and received topical moxifloxacin for at least 48 hours before randomization. MAIN OUTCOME MEASURES The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months from enrollment. Secondary outcomes included infiltrate/scar size, reepithelialization, and corneal perforation. RESULTS Between September 1, 2006, and February 22, 2010, 1769 patients were screened for the trial and 500 patients were enrolled. No significant difference was observed in the 3-month BSCVA (-0.009 logarithm of the minimum angle of resolution [logMAR]; 95% CI, -0.085 to 0.068; P = .82), infiltrate/scar size (P = .40), time to reepithelialization (P = .44), or corneal perforation (P > .99). A significant effect of corticosteroids was observed in subgroups of baseline BSCVA (P = .03) and ulcer location (P = .04). At 3 months, patients with vision of counting fingers or worse at baseline had 0.17 logMAR better visual acuity with corticosteroids (95% CI, -0.31 to -0.02; P = .03) compared with placebo, and patients with ulcers that were completely central at baseline had 0.20 logMAR better visual acuity with corticosteroids (-0.37 to -0.04; P = .02). CONCLUSIONS We found no overall difference in 3-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers. APPLICATION TO CLINICAL PRACTICE Adjunctive topical corticosteroid use does not improve 3-month vision in patients with bacterial corneal ulcers. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00324168.

The Antioxidants in Prevention of Cataracts Study: effects of antioxidant supplements on cataract progression in South India.

Aim: To determine if antioxidant supplements (β carotene and vitamins C and E) can decrease the progression of cataract in rural South India. Methods: The Antioxidants in Prevention of Cataracts (APC) Study was a 5 year, randomised, triple masked, placebo controlled, field based clinical trial to assess the ability of interventional antioxidant supplements to slow cataract progression. The primary outcome variable was change in nuclear opalescence over time. Secondary outcome variables were cortical and posterior subcapsular opacities and nuclear colour changes; best corrected visual acuity change; myopic shift; and failure of treatment. Annual examinations were performed for each subject by three examiners, in a masked fashion. Multivariate modelling using a general estimating equation was used for analysis of results, correcting for multiple measurements over time. Results: Initial enrolment was 798 subjects. Treatment groups were comparable at baseline. There was high compliance with follow up and study medications. There was progression in cataracts. There was no significant difference between placebo and active treatment groups for either the primary or secondary outcome variables. Conclusion: Antioxidant supplementation with β carotene, vitamins C and E did not affect cataract progression in a population with a high prevalence of cataract whose diet is generally deficient in antioxidants.

Microbiological diagnosis of infective keratitis: comparative evaluation of direct microscopy and culture results

Aims: To determine the sensitivity, specificity and predictive values of potassium hydroxide (KOH) wet mount, Gram stain, Giemsa stain and Kinyoun’s acid-fast stain in the diagnosis of infective keratitis. Methods: A retrospective analysis of all patients with clinically diagnosed infective keratitis presenting between September 1999 and September 2002 was carried out. Corneal scrapes were taken and subjected to direct microscopy and culture. Results: 3298 eyes of 3295 consecutive patients with infective keratitis were evaluated, of which 1138 (34.51%) eyes had fungal growth alone, 1069 (32.41%) had bacterial growth alone, 33 (1%) had Acanthamoeba growth alone, 83 (2.5%) had mixed microbial growth and the remaining 975 (29.56%) had no growth. The sensitivity of KOH wet mount was higher (99.3%; 95% confidence interval (CI) 98.6 to 99.6) in the detection of fungi, 100% (95% CI 90.4 to 100) in the detection of Nocardia and 91.4% (95% CI 75.8 to 97) in the detection of Acanthamoeba) than that of Gram-stained smears (89.2% (95% CI 87.3 to 90.8) in fungi, 87% (95% CI 73.0 to 94.6) in Nocardia and 60% (95% CI 42.2 to 75.6) in the detection of Acanthamoeba) in the detection of fungi, Nocardia and Acanthamoeba. 1764 of 3295 (53.54%) patients presented more than 7 days after onset of illness and 84.69% of the eyes had corneal ulcers with size >2 mm in diameter. Positivities of KOH (44.46%; p<0.001) and Gram-stained smears (77.37%; p<0.001) were found to be higher among eyes with larger ulcers (>2 mm) than among eyes with smaller ulcers (<2 mm). Conclusion: KOH smear is of greater diagnostic value in the management of infective keratitis, and it is recommended in all clinics without exception for establishing timely treatment.