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.

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.

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.

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.

Haemophilus influenzae associated scleritis.

AIMS: To describe the clinical course and treatment of Haemophilus influenzae associated scleritis. METHODS: Retrospective case series. RESULTS: Three patients developed scleritis associated with ocular H influenzae infection. Past medical history, review of systems, and laboratory testing for underlying collagen vascular disorders were negative in two patients. One patient had arthritis associated with an antinuclear antibody titre of 1:160 and a Westergren erythrocyte sedimentation rate of 83 mm in the first hour. Each patient had ocular surgery more than 6 months before developing scleritis. Two had cataract extraction and one had strabismus surgery. Nodular abscesses associated with areas of scleral necrosis were present in each case. Culture of these abscesses revealed H influenzae in all patients. Treatments included topical, subconjunctival, and systemic antibiotics. Scleral inflammation resolved and visual acuity improved in each case. CONCLUSION: H influenzae infection may be associated with scleritis. Accurate diagnosis and treatment may preserve ocular integrity and good visual acuity.

Mooren ulcer in South India: serology and clinical risk factors.

PURPOSE: To investigate the rate of undiagnosed rheumatologic diseases and hepatitis C infection among patients with the clinical diagnosis of Mooren ulcer seen at Aravind Eye Hospital, Madurai, South India. METHODS: Twenty-one patients with the clinical diagnosis of Mooren ulcer and 44 control patients underwent a complete ophthalmic history and examination, as well as serologic testing for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies. RESULTS: There were no statistically significant differences in the rates of seropositivity for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies between patients with Mooren ulcer and control patients. Two patients with Mooren ulcer and four control patients were found to have a rheumatoid factor titer of greater than 1:20. One of the control patients, but none of the patients with Mooren ulcer, was found to have serologic evidence of hepatitis C infection. A history of corneal trauma, surgery, or infection was reported by 68% of patients with Mooren ulcer, compared with 20% of control patients (P < .001). Among patients with Mooren ulcer, bilateral disease occurred in 37% of patients, visual acuity was reduced to light perception in 15% of eyes, and perforation occurred in 19% of eyes. CONCLUSIONS: Nineteen (90%) of 21 patients with the clinical diagnosis of Mooren ulcer were found to have no evidence of an underlying rheumatologic disease by history, examination, or serologic testing, and none was seropositive for hepatitis C. However, patients with Mooren ulcer were more likely than control patients to report a history of corneal trauma, surgery, or infection.

Tear lysozyme activity in frozen Schirmer strips and salivary gland biopsy as parameters of lacrimal gland function.

PURPOSE: The lysozyme concentration in human tears is an important parameter for tear gland function. The decline of lysozyme in tears reflects lacrimal gland destruction. In Sjögren's patients, lacrimal gland destruction parallels labial salivary gland destruction. The objective of this study was to determine whether human tear lysozyme that was frozen on Schirmer strips at -20 degrees C for several years maintained activity and whether there was a linear relation with inflammatory changes in labial salivary glands. METHODS: A total of 200 frozen Schirmer strips were processed. They were collected from 20 randomly selected patients each year of five consecutive years, all attending the UCSF Sjögren's Clinic. The tear lysozyme in the Schirmer strips was measured by a colorimetric assay. The average lysozyme concentration each year was calculated and compared. One third of the patients underwent labial salivary gland biopsy. The correlation was calculated between the tear lysozyme concentration and the lymphocytic focus scores in biopsy specimens. RESULTS: No significant difference of average lysozyme concentration in the Schirmer strips was found when the five different years of collection were compared. The linear relation between the tear lysozyme concentrations and the focus score in labial salivary gland biopsies showed a coefficient of r = -0.41. The linear relation between other diagnostic measurements, like Schirmer test, tear breakup time, or rose bengal staining pattern, and the focus score was lower. CONCLUSIONS: Human tear lysozyme in Schirmer strips can be stored at -20 degrees C for at least five years. There is little difference in lysozyme activity of frozen compared to unfrozen specimens. The lysozyme concentration in tears correlates better with the lymphocytic focus score in labial salivary gland biopsy than does clinical assessment and is therefore a parameter for the actual degree of tear gland destruction.

The Francis I. Proctor Foundation: the first fifty years.

September 15, 1997 marked the golden anniversary of the Francis I. Proctor Foundation, which was established in affiliation with the University of California in San Francisco. Over 50 years, 182 fellows from 27 countries have been trained in programs focusing on the study of infectious and inflammatory eye disease, and the prevention of blindness worldwide. Many of the people and events that have contributed to the success of the Proctor Foundation are presented in this brief essay.

Sarcoidosis Mimicking Sjögren's Syndrome: Histopathologic Observations.

The clinical manifestations of Sjõgren's syndrome (SS) and sarcoidosis can be identical. Of the 1600 patients whom we have evaluated for dryness of the mouth and eyes, 300 proved to have SS and 5 had sarcoidosis. The patients with sarcoidosis had combinations of salivary gland enlargement, elevated antinuclear antibody titers, reduced salivary flow rates, and keratoconjunctivitis sicca, findings typically associated with SS. Finding non-caseating granulomas in a labial salivary gland biopsy specimen may be the only way to definitively differentiate these two disorders.

Nocardia scleritis.

PURPOSE: To describe a case of Nocardia scleritis, an unusual ocular infection. METHODS: Case report and review of pertinent literature. RESULTS: An 83-year-old man with leukocytoclastic vasculitis was initially examined for infectious necrotizing scleritis after explantation of an extruded scleral buckle. The patient was successfully treated with sulfonamides. CONCLUSIONS: Nocardia asteroides may cause infectious scleritis in the absence of cataract surgery or trauma. Treatment with sulfonamides can result in a satisfactory outcome.

Cataract progression in India.

AIMS: The study was undertaken to test the feasibility of using the LOCS III cataract grading scale in the field and to determine the rate of cataract progression over a 1 year period of time. METHODS: For 150 subjects between the ages of 33 and 55 who attended the refraction clinic at Aravind Eye Hospital in Madurai, India, lens abnormalities were graded at the slit lamp using the LOCS III scale. One year later, 99 of the subjects were re-evaluated by the same methodology to assess the amount of lens change. RESULTS: Interrater reliability was high. A change of 0.5 or more in lens colour, cortical, nuclear, or posterior subcapsular cataract was observed in at least one eye of 54% of the subjects. CONCLUSION: The LOCS III grading scale is a feasible method for measuring lens changes in the field with the slit lamp. Cataract progression in India is rapid enough to permit intervention studies to be performed with relatively small numbers of subjects over a short period of time (that is, 600 subjects for 2 years).

Antibiotic supplementation of intraocular irrigating solutions. An in vitro model of antibacterial action.

PURPOSE: The addition of antibiotics to infusion solutions for cataract surgery is becoming increasingly popular. The authors developed an in vitro model to evaluate antibacterial effects of this use of antibiotics. METHODS: Clinical isolates and/or reference strains of the following organisms were examined: coagulase-negative Staphylococcus spp, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus viridans, Streptococcus spp, Enterococcus spp, Proprionibacterium acnes, Moraxella nonliquifaciens, and Pseudomonas aeruginosa. Standardized suspensions of each organism were incubated with a control solution (Balanced Salt Solution) or Balanced Salt Solution containing the following antibiotics: vancomycin (20 micrograms/ml) or gentamicin (8 micrograms/ml) or gentamicin and vancomycin combined (8 and 20 micrograms/ml, respectively). Suspensions were incubated for 30, 60, and 120 minutes at room temperature. Samples were centrifuged, and the organisms were washed with Balanced Salt Solution before quantitative culturing. Each organism also was incubated for 48 hours in Mueller-Hinton broth with the same antibiotic concentrations. RESULTS: Most of the organisms were not affected by exposure to the antibiotics for up to 140 minutes. P. aeruginosa and M. nonliquifaciens were exceptions, decreasing in colony numbers even with 30 minutes of exposure. Several Staphylococcus spp yielded variable results. All organisms demonstrated nearly complete inhibition of growth when exposed for an extended time to the appropriate antibiotic in broth. CONCLUSIONS: Exposure to antibiotics for a short period of time, such as during intraocular surgery, generally has no effect on organisms commonly responsible for endophthalmitis. The use of antibiotics in this manner should be critically reassessed until further study.

Corneal subepithelial infiltrate recurrence sine adenovirus.

Corneal subepithelial infiltrates are a known complication of adenoviral conjunctivitis. In this article, we present a case of a 32-year-old man who developed these classic infiltrates after a well-documented adenoviral conjunctivitis. What is unique about this case is that the infiltrates recurred 8 months later after an upper respiratory infection without any clinical or laboratory evidence of a viral conjunctivitis. The possible confounding variable of corticosteroid withdrawal being responsible for the recurrence is highly unlikely because he had not used topical corticosteroids for almost 4 months.

Risk factors for age-related cataracts.

Cataracts, the world's leading cause of blindness, are an enormous public health problem in both developing and industrialized countries. Identifying the risk factors responsible for cataract formation is a difficult and complicated problem because a realistic causal model in cataract formation would not be a simple linear sufficient cause paradigm (e.g., one exposure-one cataract type). A more complex model depicting each risk factor as a component cause, or part of a sufficient cause such as the sufficient/component cause model proposed by Rothman (62), is a more realistic way to summarize how multiple risk factors act in cataract etiology. Moreover, even this model has shortcomings, especially in explaining cataract etiology. It ignores the obvious importance of time to cataract formation and the way different component causes may act on different etiologic branches of cataract formation, e.g., nuclear sclerosis, posterior subcapsular cataracts, and mixed. Despite the complexity in identifying cataract risk factors, attempting to do so provides new hope in dealing with the morbidity, mortality, and cost of this disease. The evidence is overwhelming that age, trauma, and intraocular inflammation are important cataract risks. However, these exposures either are inevitable or are not major contributors to the population attributable risk. On the basis of both coherence and predictive performance, undernutrition is an important risk factor that can be altered. However, work still needs to be done in two areas related to this risk. First, regarding individuals in developing nations, the question must be asked about which nutrients (or lack thereof) are the culprits. The epidemiologic evidence that antioxidants are the missing nutrients is far from overwhelming. For developed nations, the obvious question still to be answered is whether the results of the Linxian Cataract Studies (11) and the India-US Case-Control Study (12) can be generalized to industrial nations. To help answer this question, an intervention study sponsored by the National Institutes of Health is now underway (K. Kupfer, Director, National Eye Institute of the USA, Bethesda, Maryland, personal communication, 1993). Ultraviolet radiation, especially ultraviolet B radiation, is an important risk for cortical cataracts, and one study (27) has even demonstrated a dose-response relation. However, the public health implication of this finding is not clear. Isolating the risk of ultraviolet B radiation exposure as a cause of cortical cataracts (and, in general, not of other types) indicates that the risk is small on a public health scale. This is because cortical cataracts are well tolerated and frequently require no treatment at all. The evidence that links ultraviolet B radiation to other cataract types comes mainly from ecologic studies and needs to be verified by analytic studies that are specifically designed to study the association. The strength of the association, consistency of studies, coherence, and biologic plausibility all indicate that both systemic and topical steroids are significant risk factors for the formation of posterior subcapsular cataracts. Given that most people are not chronic steroid users, the population attributable risk is low; however, the relative risk of those unfortunate enough to require chronic steroid use is high. The evidence is accumulating that cataracts can be added to the list of illnesses that are at least partially attributed to smoking. Although consistency among studies has not been obtained, this is certainly a plausible cause, and dose-response relations have been demonstrated (53). At this point, nuclear sclerosis is the most important cataract type associated with smoking. More work needs to be done to assess the role of smoking on other cataract types and to assess the risk of those who stop smoking. Retrospective studies that examine diabetes as a risk for cataracts are almost inevitably marred by hte selection bia

Association of patterns of labial salivary gland inflammation with keratoconjunctivitis sicca. Analysis of 618 patients with suspected Sjögren's syndrome.

OBJECTIVE: To determine the association between patterns of inflammation in labial salivary glands (LSG) and the ocular component of Sjögren's syndrome (SS). METHODS: We classified LSG biopsy specimens from 618 patients with suspected SS as showing focal lymphocytic sialadenitis (FLS), other chronic sialadenitis (CS), or other diagnoses. We then determined the association of the other component of primary SS, keratoconjunctivitis sicca (KCS), with FLS, CS, parotid flow rate, and xerostomia. RESULTS: FLS, rather than CS, was associated with a diagnosis of KCS (chi 2 = 191, P < 0.0001). The severity of KCS correlated directly with the severity of FLS (r = 0.52, P < 0.0001), but not of CS, and correlated inversely with parotid flow rate in those patients who had FLS (r = -0.29), but not in those who had CS (r = -0.03). Xerostomia was marginally associated with KCS (chi 2 = 5, P = 0.02). CONCLUSION: The stronger KCS association found in patients whose LSG biopsies show FLS makes FLS the best criterion presently available for diagnosing the salivary component of SS. CS is a common feature of labial salivary glands but is neither associated with SS nor an end stage of primary SS. Histopathologic examination of salivary tissue is currently essential for diagnosing primary SS as well as secondary SS in which KCS is lacking, especially cases to be included in studies of SS.

Anhidrosis (hypohidrosis) in Sjögren's syndrome.

There has been a relative lack of literature on the association of hypohidrosis in Sjögren's syndrome with any lesion having specific histologic findings. We looked at a recent case presentation of a 55-year-old man with complaints of dry mouth and dry eyes, becoming easily overheated in direct sunlight, and having difficulty in perspiring. Physical examination showed fissuring and atrophy of the tongue and angular cheilitis. A punch biopsy of the skin showed a moderate number of eccrine gland and ductal structures in the lower reticular dermis, each surrounded by a dense cellular infiltrate of plasma and lymphocytic cells. Our patient also had a markedly decreased sweating response to methacholine. In reviewing the literature as far back as 1951 and on the basis of findings in our present case study, we conclude that it seems probable that the severity of the skin disease is an important determining factor in predicting whether the sweat gland lesion does exist.