American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort.

OBJECTIVE: We propose new classification criteria for Sjögren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS. METHODS: Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sjögren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American­European Consensus Group (AECG) criteria, a model-based "gold standard"obtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development. RESULTS: Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications. CONCLUSION: These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.

Corticosteroids for bacterial corneal ulcers.

AIMS: The aim of the study was to conduct a preliminary clinical trial to assess whether adjunctive topical corticosteroids improve outcomes in bacterial keratitis and, if no difference was found, to determine the feasibility and sample size necessary for conducting a larger trial to answer this question. METHODS: In this single centre, double-masked clinical trial, 42 patients with culture-confirmed bacterial keratitis at Aravind Eye Hospital in India were randomised to receive either topical prednisolone phosphate or placebo. All patients received topical moxifloxacin. The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months, adjusting for enrolment BSCVA and arm. Other pre-specified outcomes included re-epithelialisation time, infiltrate/scar size and adverse events. RESULTS: Compared with placebo, patients in the steroid group re-epithelialised more slowly (hazard ratio 0.47, 95% CI 0.23 to 0.94). There was no significant difference in BSCVA or infiltrate/scar size at 3 weeks or 3 months. To have 80% power to detect a two-line difference in acuity, 360 cases would be required. CONCLUSIONS: Although corticosteroid treatment resulted in a statistically significant delay in re-epithelialisation, this did not translate to a significant difference in visual acuity, infiltrate/scar size or adverse events. To assess the effect of steroids on acuity, a larger trial is warranted and feasible.

Mooren''s ulcer following extracapsular cataract extraction.

PURPOSE: Prior cataract surgery is a recognized risk factor for the development of Mooren''s ulcer, but the demographic and clinical features of a large cohort of such patients have not been described. METHODS: The authors performed a retrospective review of demographic and clinical data from 14 eyes in 13 patients who developed Mooren's ulcer following extracapsular cataract extraction at Aravind Eye Hospital in Madurai, South India. RESULTS: Eight (62%) of the 13 patients were men and 5 (39%) were women. The median age in our population was 65 years, with a range of 45 to 85 years. The median number of months from surgery to the onset of Mooren's ulcer was 19, with a range of 4 to 156 months. Of the 14 eyes with prior cataract surgery, the location of the ulcer was at or contiguous with the wound in 10 eyes (71%), which was 2.5 times more likely than other circumlimbal locations, and only one patient (8%) had bilateral disease. CONCLUSIONS: Mooren''s ulcer may occur following extracapsular cataract extraction and when it does it is most likely to be unilateral and contiguous with the wound. These findings support the notion that exposure of normally concealed corneal antigens may contribute to the pathogenesis of Mooren''s ulcer in some patients.

Corneal ulceration in south-east Asia III: prevention of fungal keratitis at the village level in south India using topical antibiotics.

AIM: To determine whether topical antifungal prophylaxis distributed by paid village health workers (VHWs) in south India is necessary after corneal abrasion to prevent fungal keratitis in a population where half of the ulcers are fungal. METHODS: Two panchayaths (village administrative units in Madurai district with a combined population of 48 039 were followed prospectively for 18 months by 15 VHWs who were trained to identify post-traumatic corneal abrasions. Patients fulfilling the eligibility criteria were randomised into two groups and treated with either 1% chloramphenicol and 1% clotrimazole ointment or 1% chloramphenicol and a placebo ointment three times a day for 3 days. Patients, doctors and VHWs were blinded to treatment. RESULTS: During the 18-month period, 1365 people reported to VHWs with ocular injuries, of whom 374 with corneal abrasions were eligible for treatment. Of these, 368 (98.5%) abrasions healed without complications. Two patients had mild localised allergic reactions to the ointment, two dropped out and two patients in the placebo group developed microscopic culture-negative corneal stromal infiltrates that healed in 1 week with natamycin drops. CONCLUSIONS: Both fungal and bacterial ulcers that occur after traumatic corneal abrasions seem to be effectively prevented in a village setting using only antibiotic prophylaxis.

Corneal ulceration in South East Asia. II: a strategy for the prevention of fungal keratitis at the village level in Burma.

AIM: To prove that topical antifungal and antibiotic prophylaxis distributed by grass roots village health workers (VHWs) in Burma is an effective public health intervention for the prevention of post-traumatic microbial keratitis in a population where the majority of ulcers are fungal. METHODS: Three villages in Bago District with a combined population of 16,987 were selected for the study. This defined population was followed prospectively for 12 months by 15 VHWs who were trained to identify post-traumatic corneal abrasions with fluorescein dye and a blue torch and to administer 1% chloramphenicol and 1% clotrimazole ointment three times a day for 3 days to the eyes of individuals who fulfilled the eligibility criteria. RESULTS: During the 12 month period 273 individuals reported to VHWs with an ocular injury and 126 were found to have a corneal abrasion. All 126 were treated with 1% chloramphenicol and 1% clotrimazole ointment three times a day for 3 days, and all healed without sequelae. CONCLUSIONS: Both fungal and bacterial ulcers that occur following traumatic corneal abrasions can be effectively prevented in a village setting by using relatively simple measures that local volunteer public health workers can easily be taught to employ.

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

AIM: To determine if antioxidant supplements (beta 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 beta 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.

Corneal ulceration in South East Asia. I: a model for the prevention of bacterial ulcers at the village level in rural Bhutan.

AIM: To prove that antibiotic distribution by grassroots volunteer village health workers (VVHWs) in Bhutan is an effective and efficient public health intervention for the prevention of post-traumatic corneal ulceration. METHODS: 55 villages in two districts in Bhutan were selected for the study. A defined population of 10 139 individuals was followed prospectively for 18 months by 31 VVHWs who were trained to identify post-traumatic corneal abrasions with fluorescein dye and a blue torch and to administer 1% chloramphenicol ointment three times a day for 3 days to the eyes of individuals who fulfilled the eligibility criteria. RESULTS: During the 18 month period 135 individuals reported to VVHWs with an ocular injury and 115 were found to have a corneal abrasion. All 115 were treated with 1% chloramphenicol ointment three times a day for 3 days and all healed without sequelae CONCLUSIONS: Corneal ulcers that occur following traumatic corneal abrasions can be effectively prevented, even in the setting of isolated rural conditions such as those that exist in villages in Bhutan, by using relatively simple preventative measures that local VVHWs can easily be taught to employ.

Topical ocular antibiotics induce bacterial resistance at extraocular sites.

AIM: To compare the prevalence of antibiotic resistance found in nasopharyngeal Streptococcus pneumoniae between villages treated with topical tetracycline or systemic azithromycin as part of a trachoma control programme. METHODS: All children aged 1-10 years were offered either single dose oral azithromycin treatment (20 mg/kg) or a course of topical 1% tetracycline ointment, depending on the area. Treatment was given annually for 3 years. Six months after the third annual treatment in each village, children were surveyed for nasopharyngeal carriage of S pneumoniae and resistance was determined using broth dilution MIC technique. Children in two additional villages, which had not yet been treated, were also surveyed. RESULTS: Nasopharyngeal carriage of S pneumoniae was similar in the tetracycline treated, azithromycin treated, and untreated areas (p=0.57). However, resistance to tetracycline and azithromycin was distributed differently between the three areas (p=0.004). The village treated with topical tetracycline had a higher prevalence of tetracycline resistance than the other villages (p=0.010), while the oral azithromycin treated village had a higher prevalence of macrolide resistance than the other villages (p=0.014). CONCLUSIONS: Annual mass treatment with oral azithromycin may alter the prevalence of drug resistant S pneumoniae in a community. Surprisingly, topical tetracycline may also increase nasopharyngeal pneumococcal resistance. Topical antibiotics may have an effect on extraocular bacterial resistance.

Lamivudine is not effective in primary Sjögren's syndrome.

BACKGROUND: Retroviral infection has been implicated in the pathogenesis of primary Sjögren's syndrome. OBJECTIVE: To examine the efficacy of the reverse transcriptase inhibitor lamivudine in patients with this syndrome. METHODS: 16 patients with primary Sjögren's syndrome were randomised to receive either lamivudine 150 mg twice daily or placebo for three months. Measures of lacrimal and salivary function, including minor salivary gland biopsies, were obtained before and after treatment. RESULTS: Treatment with lamivudine did not result in significant improvement in the primary outcome measure of unstimulated whole salivary flow or other secondary measures, including minor salivary gland biopsy focus scores. CONCLUSION: Lamivudine is not effective in patients with primary Sjögren's syndrome, suggesting either that a retroviral aetiology is not present or that it may be important only in early disease.

Pesky trachoma suspect finally caught.

AIM: Face seeking flies have long been thought to transmit Chlamydia trachomatis, the causative agent of trachoma, but this has never been proven. The four criteria proposed by Barnett, previously used to incriminate other arthropods suspected of transmitting disease, were examined. One of these criteria remains unmet: the repeated demonstration of the presence of C trachomatis on flies. The authors used polymerase chain reaction (PCR) to look for the presence of C trachomatis DNA on flies in the Gurage Zone of Ethiopia. METHODS: Using sticky paper, one fly was collected from the face of each of 103 children aged 1-10 years. The piece of fly paper to which the fly was attached was cut out, followed by the collection of an empty piece from an arbitrary area of the fly paper, which served as control. Roche Amplicor PCR kits were used to detect C trachomatis DNA. RESULTS: Evidence of C trachomatis by PCR was found on 15 of 103 flies versus 0 of 103 controls (p = 0.0001). CONCLUSION: These results meet the final criterion needed to incriminate flies as a vector of trachoma. However, interventional studies will be needed to show the importance of fly control.

Community treatment with azithromycin for trachoma is not associated with antibiotic resistance in Streptococcus pneumoniae at 1 year.

AIMS: To determine if macrolide resistant Streptococcus pneumoniae will be a major concern in areas that receive annual mass azithromycin distributions for trachoma. METHODS: A cross sectional survey was conducted of nasopharyngeal S pneumoniae isolates for susceptibility to azithromycin 1 year after administering a single dose of azithromycin to treat trachoma in a village in Nepal. RESULTS: S pneumoniae was isolated from 50 (86%) of 57 nasopharyngeal cultures and no resistance to azithromycin was detected. CONCLUSION: The authors were unable to demonstrate that mass azithromycin therapy for trachoma produced macrolide resistant S pneumoniae that persists until the next scheduled annual treatment.

Biotypes and serotypes of Haemophilus influenzae ocular isolates.

AIM: To determine which subtypes of Haemophilus influenzae are most commonly associated with ocular disease, and whether the site of ocular H influenzae infection is correlated with specific subtypes of the organism. METHODS: The biotypes and serotypes of ocular H influenzae isolates collected at the Francis I Proctor Foundation between March 1989 and January 2000 were examined. A total of 62 ocular isolates were retrieved from frozen storage and plated on chocolate agar. Biotypes were assigned based upon the ability of the isolates to produce indole, urease, and ornithine decarboxylase. Capsular subtypes a-f were determined by slide agglutination using commercially available subtype specific antisera. Identified biotypes and serotypes were then analysed with regard to site of infection. RESULTS: Patient age ranged from 1 to 92 years with a median age of 45 years. 38 (61%) of the isolates were biotype II, 23 (37%) were biotype III, and one (2%) was biotype VII. All of the isolates were non-encapsulated and thus serologically non-typable. H influenzae biotype II was found in 28 of 48 (58%) conjunctivitis cases, five of eight (63%) keratitis cases, and two of two (100%) endophthalmitis cases. Biotype III was found in 20 of 48 (42%) conjunctivitis cases, two of eight (25%) keratitis cases, and a single case of dacryocystitis. Biotype VII was associated with one of eight (13%) keratitis cases. CONCLUSION: Most ocular H influenzae isolates appear to be serologically non-typable strains from biotypes II and III, less virulent subtypes that frequently colonise the nasopharynx. In addition, the site of ocular H influenzae infections appears to be largely independent of species subtype.

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.