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CONTEXT: The World Health Organization recommends mass antibiotic distributions in its strategy to eliminate blinding trachoma as a public health concern. Some hypothesize that a single distribution is sufficient to control the ocular strains of chlamydia that cause trachoma. Others believe infection will inevitably return and periodic treatments or other measures are essential. OBJECTIVE: To determine whether ocular chlamydial infection returns to the community up to 24 months after a single mass antibiotic distribution in a hyperendemic region of Ethiopia. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study conducted March 2003 to March 2005 in the Gurage Zone of Ethiopia. Eight randomly selected villages were assessed for ocular chlamydial infection. Fifteen untreated villages were randomly chosen at 12 months to allow assessment of a secular trend. INTERVENTION: A single dose of oral azithromycin was offered to all residents of the 8 selected villages who were aged 1 year or older. MAIN OUTCOME MEASURE: Prevalence of ocular chlamydial infection in all children aged 1 to 5 years from each intervention village prior to treatment and 2, 6, 12, 18, and 24 months after mass antibiotic treatment, and also in untreated villages enrolled at 12 months. RESULTS: Five hundred fifteen children were examined for ocular chlamydial infection at baseline. For the follow-up examinations, the mean participation rate was 83%. The mean prevalence of infection in children aged 1 to 5 years decreased from 43.5% (95% confidence interval [CI], 35.0%-52.0%) to 5.1% (95% CI, 1.1%-9.2%) after treatment. On average, infection returned gradually over 24 months to 11.3% (95% CI, 4.5%-18.1%; P = .001). In 7 of 8 villages, infection was higher at 24 months than at 2 months. In the remaining village, no infection could be identified at any point after treatment. Villages enrolled at 12 months had significantly fewer infections than those enrolled 12 months earlier, suggesting a secular trend (P

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.

Purpose To compare the microbiological yield of corneal ulcer cultures established by direct inoculation of culture media vs indirect inoculation by means of transport medium (Amies without charcoal). Design Single masked, prospective clinical trial. Methods Scrapings were obtained for Gram and potassium hydroxide (KOH) stains from eyes with presumed infectious keratitis and cultured by direct plating onto standard media. Samples were also held in transport media (Amies without charcoal) at room temperature and then plated after 4 and 24 hours. Yields from direct plating vs cultures by means of transport media were compared. Results Of 100 consecutive eyes examined with presumed infectious keratitis, Gram or KOH stain revealed a bacterial or fungal agent in 69 cases (69%). Of these, 26 were bacterial and 43 fungal. Twenty-two bacterial infections produced positive cultures by direct plating, and all produced the same organism with Amies medium after 4 and 24 hours, respectively. For 43 fungal infections identified by KOH stain, 29 (67%) yielded a positive result after 4 hours in Amies transport medium and 27 (63%) after 24 hours in Amies medium. A total of three cases (7%) that showed fungal infection on KOH stain but did not yield organisms by direct plating did so after inoculation with Amies transport medium. For all comparisons, there was no difference in recovery rates by means of transport medium compared with direct plating (McNemar exact P > .05). Conclusions In the clinical setting, Amies transport medium may be a useful alternative to direct inoculation onto blood agar for the laboratory evaluation of infectious keratitis.

Mass antibiotic administrations for ocular chlamydial infection play a key role in the World Health Organization's trachoma control program. Mathematical models suggest that it is possible to eliminate trachoma locally with repeat mass treatment, depending on the coverage level of the population, frequency of mass treatments, and rate that infection returns into a community after each mass treatment. Precise estimates of this latter parameter have never been reported.To determine the rate at which chlamydial infection returns to a population after mass treatment and to estimate the treatment frequency required for elimination of ocular chlamydia from a community.Longitudinal cohort study of 24 randomly selected villages from the Gurage Zone in Ethiopia conducted February 2003 to October 2003. A total of 1332 children aged 1 to 5 years were monitored for prevalence of ocular chlamydial infection pretreatment and 2 and 6 months posttreatment.All individuals older than 1 year were eligible for single-dose oral azithromycin treatment. Pregnant women were offered tetracycline eye ointment.Prevalence of ocular chlamydial infection, measured by polymerase chain reaction, in children aged 1 to 5 years, in each of 24 villages at each time point was used to estimate the rate of return of infection and the treatment frequency necessary for elimination.The prevalence of infection was 56.3% pretreatment (95% confidence interval [CI], 47.5%-65.1%), 6.7% 2 months posttreatment (95% CI, 4.2%-9.2%), and 11.0% 6 months posttreatment (95% CI, 7.3%-14.7%). Infection returned after treatment at an exponential rate of 12.3% per month (95% CI, 4.6%-19.9% per month). The minimum treatment frequency necessary for elimination was calculated to be once every 11.6 months (95% CI, 7.2-30.9 months), given a coverage level of 80%. Thus, biannual treatment, already being performed in some areas, was estimated to be more than frequent enough to eventually eliminate infection.The rate at which ocular chlamydial infection returns to a community after mass treatment suggests that elimination of infection in a hyperendemic area is feasible with biannual mass antibiotic administrations and attainable coverage levels.

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.

Objective: We analyzed laboratory results from corneal ulcers seen from 1976 to 1999 at the Francis I. Proctor Foundation, a referral center in San Francisco, to determine the relative frequencies of pathogens and to analyze for trends in frequencies of the most common pathogens. The results were compared with a previous study of corneal ulcers seen from 1948 to 1976 at the same institution. Methods: Ulcers presenting to the Proctor Foundation were Gram stained and cultured using standard techniques. Herpetic corneal ulcers were excluded from the study. Results: Organisms were isolated from 427 ulcers, 38% of all cases. Two hundred seventy-eight (59%) isolates were gram-positive bacteria, 145 (31%) gram-negative bacteria, 16 (3%) Acanthamoeba spp., and 36 (8%) fungi. Staphylococcus aureus was the most common organism, composing 20% of all isolates, followed by viridans group streptococci (12%), Streptococcus pneumoniae (11%), Pseudomonas aeruginosa (6%), Moraxella spp. (5%), and Serratia marcescens (4%). Over the 24-year study period the proportion of positive cultures decreased and the incidence of S. marcescens increased significantly. Comparing the period of 1948–1976 to 1976–1999, the frequency of S. pneumoniae and P. aeruginosa decreased, and that of S. marcescens increased significantly. Conclusion: The common pathogens associated with corneal ulcers have changed over the past 50 years in Northern California, with S. pneumoniae and P. aeruginosa being isolated relatively less often and S. marcescens being isolated with increasing frequency. The decrease in isolation of organisms over the 1976–1999 period may have resulted from increasing empiric antibiotic treatment by referring ophthalmologists.

Azithromycin is highly effective against trachoma, but the practical difficulties of community-wide distribution often leave many individuals untreated. We demonstrate, after mass azithromycin treatment of a population in Ethiopia, an indirect protective effect that occurred among untreated children who resided in villages in which most individuals had been treated. Similarities with the indirect protection within a treated community (i.e., "herd protection") that has been observed in vaccination programs are discussed.

The common wisdom is that a trachoma program cannot eliminate ocular chlamydia from a community, just reduce infection to a level where there would be minimal blindness. We describe the success of multiple mass antibiotic treatments, demonstrating that complete elimination of infection may be an attainable goal in an area with modest disease.

Leprosy is one of the oldest scourges of humankind. Accurate portrayals of the disease in Chinese medical treatises date from 400 bc, and classic descriptions in ancient Indian literature occur even earlier.1 In our western tradition the fear and loathing directed towards the disease come directly from the bible. Leprosy was the “disease of the soul”, the “punishment for sin”. By the dawn of the Middle Ages the leper had become the universal symbol of persecution, the diseased and disenfranchised outcast of Western society.2 Even though the prevalence of leprosy steadily declined in Western Europe after a peak in the 14th century, it became epidemic in other parts of the world, especially in Asia, Africa, and South America. Until the introduction of dapsone in the 1940s there was no effective treatment for leprosy, and infected individuals were routinely isolated and segregated from all contact with society. In some areas of the world this approach continued until well into the 1980s, even after a number of highly effective antileprosy drugs had been developed. Today the prevalence of this ancient disease is …

BACKGROUND/AIMS—The World Health Organisation has recommended repeated mass treatment of children in trachoma endemic areas with oral azithromycin. While chlamydia, the causative agent of trachoma, remains universally sensitive to azithromycin, there is concern that large scale programmes may alter the bacterial flora and induce resistance in streptococcal species. In this study the effect of a single dose of azithromcyin on the prevalence, species distribution, and resistance of conjunctival bacterial flora was determined. METHODS—Baseline and 14 day follow up bacterial cultures were taken from the conjunctivae of 121 children who reside in a trachoma endemic area of Nepal. 91 children were treated with azithromycin at baseline and 31 children received deferred treatment at the 14 day follow up. RESULTS—Although the prevalence of bacterial pathogens decreased significantly with azithromycin treatment, a significant change in the distribution of specific bacterial pathogens could not be demonstrated. Streptococcal resistance to azithromycin was found significantly more frequently after treatment. No change in the prevalence, distribution, or resistance pattern was found in the untreated control group. CONCLUSION—Repeated mass treatment of trachoma endemic areas with oral azithromycin will have an effect on bacterial flora. However, further work needs to be done to determine if this will have any clinical relevance.

PURPOSE: To describe a case of a bilateral scleral pit in a patient with systemic sclerosis. METHODS: Case report. RESULTS: A bilateral scleral pit with surrounding scleral ischemia overlying the pars plana was noted in a 72-year-old woman with known systemic sclerosis. CONCLUSIONS: Scleral pits should be added to the list of ocular findings associated with systemic sclerosis.

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.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.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.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.

Tear lysozyme and tear lactoferrin are enzymes synthesized by the lacrimal gland. Their concentration in human tears reflects tear gland function. Tear gland dysfunction can lead to ocular surface disease. We developed a colorimetric lysozyme assay. The objective of this study was to determine the diagnostic power and the clinical application of this assay that allows rapid and precise quantification of tear lysozyme.Tear specimens of 120 eyes (30 Sjögren's patients and 30 controls) were collected using standardized filter paper discs. Tear lysozyme concentration was determined using p-nitrophenyl penta-N-acetyl-beta-chitopentaoside as substrate in the colorimetric assay. The results were compared to clinical findings and to two commonly used tests, the Micrococcus agar diffusion assay for tear lysozyme and the tear lactoferrin immunodiffusion assay.The colorimetric assay showed a good dose-response relationship. The use of the assay as a method of diagnosing aqueous tear deficiency, using the clinical findings and the medical history as gold standard, demonstrated 85% sensitivity and 92% specificity. The results of the colorimetric assay when compared with the Micrococcus agar diffusion assay showed a linear relationship of r=0.77; when compared with the lactoferrin immunoassay r=0.73.The colorimetric assay is simple to perform and does not require sophisticated laboratory equipment and personnel. Results can be precisely quantified within one hour after tear collection. The diagnostic power of the test is comparable to previously reported assays for lysozyme and lactoferrin and will be useful in the diagnosis of ocular surface disease.

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. Keywords: necrosis; scleritis; Haemophilus influenzae

Purpose To compare polymerase chain reaction (PCR) results to presumptive clinical diagnosis in patients with vitritis. Design Retrospective review of PCR laboratory records from vitreous samples. Methods Fifty consecutive laboratory records of vitreous samples sent for PCR testing were reviewed. Three reviewers with uveitis training ranked the clinical suspicion of a specific diagnosis using a classification system (scale of 1 to 4) and were masked to the PCR results. Results The degree of clinical suspicion of a particular diagnosis was significantly associated with a positive PCR result ( P = .048). Higher clinical suspicion was significantly more associated with a positive PCR result compared with cases with lower clinical suspicion ( P = .01). Conclusions If the clinical suspicion of a specific diagnosis is low, the PCR for any infectious etiology is unlikely to be positive.

Purpose To report treatment of a patient with acquired immunodeficiency syndrome (AIDS) and ocular and paranasal sinus microsporidial infection. METHOD: Case report. Results A patient with AIDS and ocular microsporidial infection experienced resolution of ocular symptoms with topical fumagillin, but symptoms recurred upon cessation of therapy. Paranasal sinus microsporidial infection was diagnosed. The patient received sequential systemic treatment with itraconazole followed by albendazole. Sinus symptoms resolved with albendazole. He remained symptom-free with a normal examination 17 months after concluding therapy. Conclusions Although fumagillin and itraconazole may have played a role, systemic albendazole appears to be responsible for clinical resolution of microsporidial infection.

Editor,—Postoperative bacterial endophthalmitis is an uncommon but potentially blinding complication of intraocular surgery.1 Most postoperative endophthalmitis results from Gram positive organisms,2 although Gram negative organisms are now recognised to constitute from 15 to 30% of cases in some series.3 This stated, few cases of Morganella morganii (formerly known as Proteus ) postoperative endophthalmitis have been reported, and all but one3 have had poor visual outcomes.2-6 We now describe a patient who developed M morganii endophthalmitis following uncomplicated extracapsular cataract extraction, and in whom early, aggressive treatment resulted in good initial visual recovery. ### CASE REPORT A 68-year-old Filipino woman with well controlled adult onset diabetes mellitus underwent uncomplicated extracapsular cataract extraction by phacoemulsification followed by placement of a posterior chamber intraocular lens. The skin and eye were prepared with povidone-iodine preoperatively. The patient failed to return for follow up for 3 days, at which time she presented with hand movement vision, marked corneal oedema, and a 4+ anterior chamber cell and flare with hypopyon (Hogan, Kimura, and Thygeson grading7). The intraocular pressure was normal. The fundus was not visible but ultrasound failed to demonstrate vitritis. The diagnosis of early postoperative endophthalmitis was made, and anterior chamber and vitreous aspirates were taken for Gram stain and culture. The patient was then treated with: (1) intravitreal vancomycin (1 mg/0.1 ml), ceftazidime (2.25 mg/0.1 ml), and dexamethasone (0.4 mg/0.1 ml); (2) subconjunctival vancomycin (25 mg/0.5 …

Pseudogerontoxon is a lesion that resembles a small segment of arcus senilis or gerontoxon and is seen in many individuals with limbal vernal or atopic keratoconjunctivitis. It is an important clinical finding because pseudogerontoxon is often times the only clinical evidence of previous allergic eye disease. To the authors' knowledge, pseudogerontoxon has only rarely been mentioned, and has never been pictured, in the peer-reviewed literature. Three examples are presented of this important clinical entity.

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

There is hope that trachoma will be the first major bacterial disease eliminated by a worldwide effort A few minutes spent searching Medline reveals some interesting trends: while the total number of scientific publications has exploded over the past 35 years, the number of papers incorporating the keyword “trachoma” has actually decreased (Fig 1A). The number of reviews of trachoma, however, has increased (Fig 1B). Is this a sign that the study of trachoma has matured—that effective treatments are well known and that the only challenge left is to implement them? Many recent editorials have indeed suggested that a wide variety of treatments are effective.1–6 In fact, studies suggest that trachoma is disappearing even in the absence of a programme specifically targeting the disease.7–10 Is the war against trachoma, or at least the scientific part, finally over? The past decade has witnessed numerous advances in chlamydia research: the chlamydial genome has been sequenced,11 diagnosis with sensitive nucleic acid amplification tests has become routine,12–14 and randomised clinical trials have purported to demonstrate the efficacy of behavioural,15 pharmacological,16 and even entymological17 control measures in reducing the prevalence of trachoma. A course of three doses of oral azithromycin administered to all members of a community was shown to be as effective as a 6 week course of topical tetracycline.18 This is important because compliance with oral azithromycin is clearly far superior. Another trial suggested that an …

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.

PURPOSE. The purpose of this study was to determine whether clinical signs of infectious keratitis can be used to identify the causative organism. METHODS. Eighty photographs of eyes with culture-proven bacterial keratitis or smear-proven fungal keratitis were randomly selected from 2 clinical trials. Fifteen cornea specialists from the F. I. Proctor Foundation and the Aravind Eye Care System assessed the photographs for prespecified clinical signs of keratitis, and they identified the most likely causative organism. RESULTS. Clinicians were able to correctly distinguish bacterial from fungal etiology 66% of the time (P < 0.001). The Gram stain, genus, and species were accurately predicted 46%, 25%, and 10% of the time, respectively. The presence of an irregular/ feathery border was associated with fungal keratitis, whereas a wreath infiltrate or an epithelial plaque was associated with bacterial keratitis. CONCLUSIONS. Cornea specialists correctly differentiated bacterial from fungal keratitis more often than chance, but in fewer than 70% of cases. More specific categorization led to less successful clinical distinction. Although certain clinical signs of infectious keratitis may be associated with a bacterial or fungal etiology, this study highlights the importance of obtaining appropriate microbiological testing during the initial clinical encounter. (ClinicalTrials.gov number, NCT00324168.) (Invest Ophthalmol Vis Sci. 2012;53:1787‐1791) DOI:10.1167/iovs.11-8478

The Schirmer test is commonly used to evaluate aqueous tear production in suspected dry eyes. Tear lysozyme concentration can be measured directly from tear samples collected on standard Schirmer test strips using an agar disk diffusion technique. In conjunction with results from other diagnostic measurements, such as tear breakup time (TBUT), rose bengal staining pattern, and labial salivary gland cytology, a classification system has been proposed to group patients into categories of severe, moderate, and mild disease. The standardized method for measuring tear lysozyme requires that specimens be incubated within 24 hours of collection on an agar plate flooded with M. lysodeikticus. This is not always feasible, nor practical, in a large referral center. The Schirmer measurement, rose bengal staining pattern, and TBUT can be determined immediately during the clinical encounter. The analysis of tear lysozyme is more cumbersome and lysozyme measurement is not always necessary to make a diagnosis of Sjogrens syndrome in our patients. We routinely freeze all Schirmer strips collected from patients referred to the UCSF Sjogren’s Clinic if the specimens are not immediately analyzed for lysozyme content. Over the past 15 years, this has allowed us to accumulate more than 600 Schirmer strip specimens with associated clinical and histopathological data. To our knowledge, there are no studies investigating the activity of lysozyme frozen on Schirmer strips for more than 24 hours. The purpose of this study was to determine whether human tear lysozyme that was frozen on Schirmer strips for greater than one year maintained activity and could be used to to contribute clinically useful information for future retrospective studies.

Sjogren’s syndrome is an infrequent but extremely symptomatic condition which occurs primarily in postmenopausal females. The classic triad of dry eyes, dry mouth, and an associated autoimmune disease is not always clinically apparent and the diagnosis of the syndrome becomes problematic [1], Clinical diagnosis usually depends on a strong positive history for keratoconjunctivitis sicca (KCS) and on typical signs including Rose Bengal staining, fluorescein staining, and tear breakup time (TBUT) [2]. Ocular findings may be correlated with oral symptoms of xerostomia and documented by decreased parotid flow rate (PFR) [3], as well as by rheumatologie evaluation and correspondingly abnormal serologic tests (SS-A, SS-B, ANA, and Rheumatoid Factor) [4], Even though several ocular tests, including tear osmolarity, cellulose acetate impression cytology and tear fluorescein dilution tests have been proposed as the “gold standard” for diagnosing Sjogren’s syndrome, we propose that labial salivary gland (LSG) biopsy should be considered as the basic standard by which all other diagnostic criteria are compared.

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.

Context Treatment recommendations assume that repeated mass antibiotic distributions can control, but not eradicate or even locally eliminate, the ocular strains of chlamydia that cause trachoma. Elimination may be an important end point because of concern that infection will return to communities that have lost immunity to chlamydia after antibiotics are discontinued. Objective To determine whether biannual treatment can eliminate ocular chlamydial infection from preschool children and to compare results with the World Health Organization–recommended annual treatment. Design, Setting, and Participants A cluster-randomized clinical trial of biannual vs annual mass azithromycin administrations to all residents of 16 rural villages in the Gurage Zone, Ethiopia, from March 2003 to April 2005. Interventions At scheduled treatments, all individuals aged 1 year or older were offered a single dose of oral azithromycin either annually or biannually. Main Outcome Measure Village prevalence of ocular chlamydial infection and presence of elimination at 24 months in preschool children determined by polymerase chain reaction, correcting for baseline prevalence. Antibiotic treatments were performed after sample collections. Results Overall, 14 897 of 16 403 eligible individuals (90.8%) received their scheduled treatment. In the villages in which residents were treated annually, the prevalence of infection in preschool children was reduced from a mean of 42.6% (range, 14.7%-56.4%) to 6.8% (range, 0.0%-22.0%) at 24 months. In the villages in which residents were treated biannually, infection was reduced from 31.6% pretreatment (range, 6.1%-48.6%) to 0.9% (range, 0.0%-4.8%) at 24 months. Biannual treatment was associated with a lower prevalence at 24 months (P = .03, adjusting for baseline prevalence). At 24 months, no infection could be identified in 6 of 8 of those treated biannually and in 1 of 8 of those treated annually (P = .049, adjusting for baseline prevalence). Conclusion Local elimination of ocular chlamydial infection appears feasible even in the most severely affected areas, although it may require biannual mass antibiotic distributions at a high coverage level. Trial Registration clinicaltrials.gov Identifier: NCT00221364

Background The World Health Organization recommends periodic mass antibiotic distributions to reduce the ocular strains of chlamydia that cause trachoma, the world's leading cause of infectious blindness. Their stated goal is to control infection, not to completely eliminate it. A single mass distribution can dramatically reduce the prevalence of infection. However, if infection is not eliminated in every individual in the community, it may gradually return back into the community, so often repeated treatments are necessary. Since public health groups are reluctant to distribute antibiotics indefinitely, we are still in need of a proven long-term rationale. Here we use mathematical models to demonstrate that repeated antibiotic distributions can eliminate infection in a reasonable time period. Methods We fit parameters of a stochastic epidemiological transmission model to data collected before and 6 months after a mass antibiotic distribution in a region of Ethiopia that is one of the most severely affected areas in the world. We validate the model by comparing our predicted results to Ethiopian data which was collected biannually for two years past the initial mass antibiotic distribution. We use the model to simulate the effect of different treatment programs in terms of local elimination of infection. Results Simulations show that the average prevalence of infection across all villages progressively decreases after each treatment, as long as the frequency and coverage of antibiotics are high enough. Infection can be eliminated in more villages with each round of treatment. However, in the communities where infection is not eliminated, it returns to the same average level, forming the same stationary distribution. This phenomenon is also seen in subsequent epidemiological data from Ethiopia. Simulations suggest that a biannual treatment plan implemented for 5 years will lead to elimination in 95% of all villages. Conclusion Local elimination from a community is theoretically possible, even in the most severely infected communities. However, elimination from larger areas may require repeated biannual treatments and prevention of re-introduction from outside to treated areas.

Health care in the United States is in a crisis. At present, rising costs account for 13% of the gross national product making health care the third largest industry in the country, and there is no end in sight as costs spiral out of control.1 For years we have been admonished as healthcare providers to control costs by improving productivity and flexibility, by adopting new appropriate technologies, and by using competitive market strategies to squeeze the fat out of the healthcare system. All of these innovations, it was assumed, would allow healthcare providers to continue to deliver high quality care while eventually cutting costs to the bone.2The promise of managed care as the big fix for US healthcare problems has not been realised. An analysis of managed care plan performance from 37 recently published peer reviewed studies reveals …

Eduardo C. Alfonso, MD; Jorge Cantu-Dibildox, MD; Wuqaas M. Munir, MD; Darlene Miller, DHSc, MPH; Terrence P. O’Brien, MD; Carol L. Karp, MD; Sonia H. Yoo, MD; Richard K. Forster, MD; William W. Culbertson, MD; Kendall Donaldson, MD; Jill Rodila, MD; Yunhee Lee, MDObjective: To describe the clinical presentation and course of patients who developed keratitis due to Fusarium while wearing nontherapeutic soft contact lenses.Methods: A retrospective review of microbiologic records from January 1, 2004, through April 15, 2006, was performed, identifying all patients with corneal ulceration and a culture positive for Fusarium species. Medical records of 34 patients were reviewed for clinical characteristics, treatment regimens, and microbiologic features.Results: The most common antimicrobial medications administered prior to Fusarium diagnosis were antibacterials in 31 of 34 patients. No distinct preponderance of any one brand of either contact lens or solution was identified. The microbiologic cultures found Fusarium oxysporum in 20 cases, Fusarium solani in 3 cases, Fusarium species not further identifiable in 10 cases, and no growth in 1 case. Patients with a delayed onset of treatment had a tendency for prolonged treatment until cure.Conclusions: Fusarium has previously been an unusual organism in the etiology of infectious keratitis in the setting of nontherapeutic soft contact lens wear. A delay in proper diagnosis and intervention may contribute to a prolonged treatment course. The microbial spectrum of contact lens–related keratitis may be evolving with higher participation of Fusarium species compared with prior reports.

Even though endophthalmitis is a rare complication of cataract surgery (recent studies report an incidence of 0.12% in the USA1 and 0.17% in Denmark2 ) its treatment continues to be a frustrating problem leading frequently to disastrous visual results. In this issue of the BJO (p 719) Okhravi et al assess the effect of a standard treatment protocol on the visual outcome of patients who have been diagnosed as having presumed bacterial endophthalmitis following intraocular surgery or penetrating ocular trauma. This protocol utilises early aggressive treatment with a standard regimen of high dose broad spectrum intraocular and systemic antibiotics. It also assesses the sensitivity of the organisms isolated to the specific antibiotics employed. In spite of aggressive and appropriate broad spectrum antibiotic therapy the final visual outcome was poor, with 55% of postsurgical and 40% of post-traumatic cases achieving a final visual acuity of 6/60 or less. Why is the treatment of endophthalmitis still such an exercise in frustration? Are we somehow missing the point as clinicians, or is intraocular infection a problem in which a successful cure will always remain beyond our grasp? One difficulty is that …

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, …

To describe a case of Nocardia scleritis, an unusual ocular infection.Case report and review of pertinent literature.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.Nocardia asteroides may cause infectious scleritis in the absence of cataract surgery or trauma. Treatment with sulfonamides can result in a satisfactory outcome.

Context Mass antibiotic administrations for ocular chlamydial infection play a key role in the World Health Organization’s trachoma control program. Mathematical models suggest that it is possible to eliminate trachoma locally with repeat mass treatment, depending on the coverage level of the population, frequency of mass treatments, and rate that infection returns into a community after each mass treatment. Precise estimates of this latter parameter have never been reported. Objective To determine the rate at which chlamydial infection returns to a population after mass treatment and to estimate the treatment frequency required for elimination of ocular chlamydia from a community.

Objective To further characterize the role of the carbohydrate sulfotransferase( CHST6 ) gene in macular corneal dystrophy (MCD) through identification of causative mutations in a cohort of affected patients from southern India. Methods Genomic DNA was extracted from buccal epithelium of 75 patients (51 families) with MCD, 33 unaffected relatives, and 48 healthy volunteers. The coding region of the CHST6 gene was evaluated by means of polymerase chain reaction amplification and direct sequencing. Subtyping of MCD into types I and II was performed by measuring serum levels of antigenic keratan sulfate. Results Seventy patients were classified as having type I MCD, and 5 patients as having type II MCD. Analysis of the CHST6 coding region in patients with type I MCD identified 11 homozygous missense mutations(Leu22Arg, His42Tyr, Arg50Cys, Arg50Leu, Ser53Leu, Arg97Pro, Cys102Tyr, Arg127Cys, Arg205Gln, His249Pro, and Glu274Lys), 2 compound heterozygous missense mutations(Arg93His and Ala206Thr), 5 homozygous deletion mutations (del CG707-708, del C890, del A1237, del1748-1770, and del ORF), and 2 homozygous replacement mutations(ACCTAC 1273 GGT, and GCG 1304 AT). One patient with type II MCD was heterozygous for the C890 deletion mutation, whereas 4 possessed no CHST6 coding region mutations. Conclusion A variety of previously unreported mutations in the coding region of the CHST6 gene are associated with type I MCD in a cohort of patients in southern India. Clinical Relevance An improved understanding of the genetic basis of MCD allows for earlier, more accurate diagnosis of affected individuals, and may provide the foundation for the development of novel disease treatments.

Purpose. To determine whether there are quantitative or qualitative differences in the ocular flora of patients with acquired immunodeficiency syndrome (AIDS) compared with human immunodeficiency virus (HlV)-negative patients. Methods. Forty patients with AIDS and 42 HIV-negative controls were sex a

PURPOSE To determine whether microorganisms are able to survive in a solution of 50 mg/ml of 5-fluorouracil (5-FU) and, therefore, whether there is a risk of vial contamination with multiple use. METHODS Ten common nosocomial pathogens were tested. Minimal inhibitory concentrations (MICs) of 5-FU were determined for each organism. Organisms were then inoculated into 1 ml of 5-FU (50 mg/ml) and, after timed periods of exposure, were plated onto blood agar and incubated at 37 degrees C. Plates were checked daily for the presence or absence of growth. RESULTS The MICs of Klebsiella pneumoniae and Pseudomonas cepacia were within one log unit of the 10 mg/ml concentration of 5-FU used by some clinics. After incubation in 5-FU for 1 h, all species survived; after 24 h of exposure, five of the 10 species-Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, K. pneumoniae, and Proteus mirabilis-were still viable. CONCLUSION 5-FU has limited bactericidal activity, and there is a risk of contamination if 5-FU vials are used in multiple dose fashion.

Although Streptococcus pneumoniae is usually extremely sensitive to penicillin, recent reports in the nonophthalmic literature indicate a rise in the prevalence of penicillin-resistant pneumococci. We report a case of penicillin-resistant S. pneumoniae keratitis in a 51-year-old woman with severe rheumatoid arthritis. This report is only the second such case in the ophthalmic literature and may indicate the emergence of penicillin-resistant strains of S. pneumoniae as ocular pathogens.

We treated two sporadic cases of postoperative endophthalmitis caused by rapidly growing (Runyon's group IV) mycobacteria. Both involved intraocular lenses, one a secondary implant after intracapsular cataract extraction ( Mycobacterium chelonae subspecies abscessus ) and the other a primary posterior chamber lens implantation after extracapsular cataract extraction (pigment-producing member group IV). Signs of inflammation were judged severe enough to warrant diagnostic and therapeutic intervention during the fourth postoperative week in both cases. In both eyes the organism seemed to be eradicated by intravitreal amikacin in combination with vitrectomy, as well as topical, subconjunctival, and, in one case, systemic antibiotic therapy.