Durga S. Borkar

Incidence and Prevalence of Uveitis: Results From the Pacific Ocular Inflammation Study

IMPORTANCE Uveitis is responsible for a significant proportion of legal blindness in the United States. Currently, there are few population-based reports characterizing the epidemiology of uveitis. OBJECTIVE To ascertain the incidence and prevalence of uveitis in a Hawaiian population and compare these estimates with those from prior population-based studies. DESIGN Retrospective, population-based cohort study conducted from January 1, 2006, to December 31, 2007. SETTING Kaiser Permanente Hawaii, a multispecialty managed care organization serving approximately 15% of the general Hawaiian population with locations throughout the Hawaiian islands. PARTICIPANTS All patients enrolled in the Kaiser Permanente Hawaii health plan during the study (N = 217,061). MAIN OUTCOMES AND MEASURES Clinical diagnosis of uveitis, either incident or prevalent, during the study determined by an initial search of the electronic medical record database of Kaiser Permanente Hawaii for uveitis-associated International Classification of Diseases, Ninth Revision diagnosis codes and subsequently confirmed through individual record review by a uveitis specialist. RESULTS Of 217,061 eligible patients, 872 were identified using International Classification of Diseases, Ninth Revision codes and 224 cases of uveitis were confirmed. The overall uveitis incidence rate was 24.9 cases per 100,000 person-years. The annual prevalence rates for 2006 and 2007 were 57.5 and 58.0 per 100,000 persons, respectively. No difference in incidence rate was found by sex (P = .63), but female patients had a higher prevalence (P = .008). Incidence and prevalence increased with older age (P < .001 for incidence and prevalence). Pacific Islanders had a lower prevalence rate than non-Pacific Islanders (2006: P = .09, 2007: P = .04), while white individuals had a higher prevalence rate than nonwhite individuals (2006: P = .07, 2007: P = .01). CONCLUSIONS AND RELEVANCE The incidence and prevalence of uveitis in this population were much lower than in the Northern California Epidemiology of Uveitis Study, but similar to the Northwest Veterans Affairs Study. The results of this study highlight incidence and prevalence estimates in a new population and provide novel comparisons by race. These differences by race raise questions regarding the effects of genetic and environmental influences on the pathophysiology of uveitis.

Incidence of Herpes Zoster Ophthalmicus: Results from the Pacific Ocular Inflammation Study

PURPOSE To provide a population-based estimate of the incidence of herpes zoster ophthalmicus (HZO) with comparisons across racial, sex, and age groups, as well as to estimate the frequency of postherpetic neuralgia (PHN). DESIGN Retrospective, population-based cohort study. PARTICIPANTS All patients enrolled in the Kaiser Permanente Hawaii health plan during the study period (N = 217 061). METHODS All patient encounters between January 1, 2006, and December 31, 2007, in the electronic medical record of Kaiser Permanente Hawaii were queried for International Classification of Diseases, 9th edition (ICD-9) codes corresponding to HZO. Charts were reviewed to confirm a diagnosis of HZO and to collect information about specific ocular manifestations. Demographic data and information on PHN were collected electronically. Incidence rates were calculated per 100 000 person-years for the entire population and for age-, sex-, and race-specific subgroups. MAIN OUTCOME MEASURES Clinical diagnosis of HZO during the study period. RESULTS A total of 134 cases of HZO were identified in this population of 217 061 people. The overall incidence was 30.9 per 100 000 person-years (95% confidence interval [CI], 25.9-36.6). The incidence rate for the population aged ≥65 years was 104.6 per 100 000 person-years (95% CI, 79.0-135.9), approximately 5 times the remainder of the population (P < 0.001). The most common manifestation of HZO was dermatitis, followed by keratitis and conjunctivitis. The incidence of HZO for Pacific Islanders was 19.0 per 100 000 person-years (95% CI, 12.4-28.3), which was significantly lower than the rate for non-Pacific Islanders (P = 0.007). Twenty-one percent of patients with HZO developed PHN. Older age and HZO with keratitis, conjunctivitis, or uveitis were found to be risk factors for PHN. CONCLUSIONS This study provides a population-based estimate of HZO and highlights differences across various age and racial groups. It also suggests that demographic characteristics may be useful in determining the risk of developing HZO.

Acanthamoeba, fungal, and bacterial keratitis: a comparison of risk factors and clinical features.

PURPOSE To determine risk factors and clinical signs that may differentiate between bacterial, fungal, and acanthamoeba keratitis among patients presenting with presumed infectious keratitis. DESIGN Hospital-based cross-sectional study. METHODS We examined the medical records of 115 patients with laboratory-proven bacterial keratitis, 115 patients with laboratory-proven fungal keratitis, and 115 patients with laboratory-proven acanthamoeba keratitis seen at Aravind Eye Hospital, Madurai, India, from 2006-2011. Risk factors and clinical features of the 3 organisms were compared using multinomial logistic regression. RESULTS Of 95 patients with bacterial keratitis, 103 patients with fungal keratitis, and 93 patients with acanthamoeba keratitis who had medical records available for review, 287 (99%) did not wear contact lenses. Differentiating features were more common for acanthamoeba keratitis than for bacterial or fungal keratitis. Compared to patients with bacterial or fungal keratitis, patients with acanthamoeba keratitis were more likely to be younger and to have a longer duration of symptoms, and to have a ring infiltrate or disease confined to the epithelium. CONCLUSIONS Risk factors and clinical examination findings can be useful for differentiating acanthamoeba keratitis from bacterial and fungal keratitis.

Association between Cytotoxic and Invasive Pseudomonas aeruginosa and Clinical Outcomes in Bacterial Keratitis

OBJECTIVES To determine whether cytotoxic and invasive Pseudomonas aeruginosa strains differentially influence clinical presentation, outcomes, or therapeutic response in bacterial keratitis. METHODS Pseudomonas aeruginosa isolates from the National Eye Institute-funded Steroids for Corneal Ulcers Trial were subtyped as cytotoxic or invasive strains. The main outcome measure compared between the 2 subtypes was change in visual acuity at 3 months using Huber robust regression, adjusting for topical corticosteroid treatment. RESULTS Of 101 confirmed P aeruginosa isolates from the Steroids for Corneal Ulcers Trial, 74 had a classically cytotoxic or invasive genotype. While corneal ulcers caused by genotypically invasive P aeruginosa strains were associated at presentation with significantly better visual acuity than corneal ulcers caused by genotypically cytotoxic P aeruginosa strains when adjusting for the effect of ulcer location (P= .008), invasive ulcers had improved significantly less than cytotoxic ulcers at 3 months (0.35; 95% CI, 0.04-0.66 logMAR; P= .03 [3.5-line difference]). Compared with topical moxifloxacin alone, adjunctive treatment with topical corticosteroids was associated with significantly more improvement in visual acuity in the invasive subgroup (P= .04) but was associated with less improvement in visual acuity in the cytotoxic subgroup (P= .07). CONCLUSIONS Rational profiling of differentially expressed virulence determinants (eg, cytotoxicity and invasiveness for P aeruginosa) could be used as a tool for decision making in the management of infections to optimize outcomes.

Association Between Atopy and Herpetic Eye Disease: Results From the Pacific Ocular Inflammation Study

IMPORTANCE Immune dysregulation in patients with atopy has been hypothesized to increase susceptibility to viral infections. Herpetic eye disease (due to herpes simplex and herpes zoster) is a significant cause of visual impairment, and data on an association between this sight-threatening disease and atopy are limited. OBJECTIVE To assess the association between atopy and herpetic eye disease, including herpes simplex virus (HSV) ocular disease and herpes zoster ophthalmicus (HZO). DESIGN, SETTING, AND PARTICIPANTS Retrospective, population-based case-control study from January 1, 2006, through December 31, 2007, at Kaiser Permanente Hawaii, a multispecialty managed care organization serving approximately 15% of the general Hawaiian population. Participants were 217,061 patients enrolled in the Kaiser Permanente Hawaii health plan during the study period. MAIN OUTCOMES AND MEASURES Clinical diagnosis of HSV ocular disease or HZO during the study period determined by an initial search of the electronic medical record of Kaiser Permanente Hawaii and then confirmed through individual medical record review by a uveitis and cornea fellowship-trained ophthalmologist. Atopic disease status was determined based on International Classification of Diseases, Ninth Revision codes for patients with HSV ocular disease or HZO and 2 control groups, each randomly selected at a 4:1 ratio of controls to cases. RESULTS One hundred fourteen patients with HSV ocular disease and 137 patients with HZO were identified. Using the age- and sex-matched controls, patients who had atopy had a 2.6-fold (95% CI, 1.6-4.2; P < .001) higher odds of having HSV ocular disease compared with patients who did not have atopy. Similarly, patients with atopy had a 1.8-fold (95% CI, 1.2-2.8; P = .01) increased odds of having HZO. Patients with 2 or more atopic conditions had an 8.9-fold (95% CI, 3.5-22.6; P < .001) higher odds of having HSV ocular disease and a 2.9-fold (95% CI, 1.1-7.7; P = .04) higher odds of having HZO. CONCLUSIONS AND RELEVANCE The association between atopy and herpetic eye disease may be explained by various factors, including immunologic dysfunction in patients with atopy. Clinically, these results could help support the diagnosis of herpetic eye disease in these patients.

Emerging Moxifloxacin Resistance in Pseudomonas aeruginosa Keratitis Isolates in South India

ABSTRACT Purpose: To describe temporal trends in Pseudomonas aeruginosa resistance to moxifloxacin in keratitis isolates from South India. Methods: The Steroids for Corneal Ulcers Trial (SCUT) was a randomized, double-masked, placebo-controlled trial assessing outcomes in patients with culture positive bacterial corneal ulcers randomized to receive prednisolone phosphate or placebo. All patients received moxifloxacin, and susceptibility to moxifloxacin was measured at baseline using Etest. We investigated trends in moxifloxacin susceptibility of P. aeruginosa during 2007, 2008, and 2009 isolated in SCUT in South India. Results: There were 89 P. aeruginosa isolates during 2007, 2008, and 2009 in SCUT that were eligible for this study. There was an increase in the proportion of resistant isolates from 19% in 2007 to 52% in 2009 (p = 0.02, χ2 test for trend). Logistic regression showed that there was a 2-fold increase in odds of resistance per 1 year increase during the study period (odds ratio 2.16, 95% confidence interval 1.09–4.26, p = 0.027). Conclusions: We found a sharp increase in the proportion of isolates that were resistant to moxifloxacin from 2007 to 2009. Further work needs to be done to characterize the nature of this increase.

Association between Smoking and Uveitis: Results from the Pacific Ocular Inflammation Study

PURPOSE To assess whether cigarette smoking is associated with the development of uveitis in a population-based setting. DESIGN Retrospective, population-based, case-control study. PARTICIPANTS Patients aged ≥ 18 years who were seen at a Kaiser Permanente Hawaii clinic between January 1, 2006, and December 31, 2007. Analysis included 100 confirmed incident uveitis cases, 522 randomly selected controls from the general Kaiser Hawaii population, and 528 randomly selected controls from the Kaiser Hawaii ophthalmology clinic. METHODS International Classification of Diseases, 9th revision (ICD-9), diagnosis codes were used to identify possible uveitis cases. A uveitis fellowship-trained ophthalmologist then conducted individual chart review to confirm case status. Multivariate logistic regression models were used to evaluate the association between smoking and uveitis, adjusting for age, sex, race, and socioeconomic status. MAIN OUTCOME MEASURES Development of uveitis. RESULTS Current smokers had a 1.63 (95% confidence interval [CI], 0.88-3.00; P = 0.12) and 2.33 (95% CI, 1.22-4.45; P = 0.01) times greater odds of developing uveitis compared with those who never smoked using the general and ophthalmology control groups, respectively. The association was even stronger with noninfectious uveitis, which yielded odds ratios of 2.10 (95% CI, 1.10-3.99; P = 0.02) and 2.96 (95% CI, 1.52-5.77; P = 0.001) using the general and ophthalmology control groups, respectively. CONCLUSIONS Cigarette smoking is significantly associated with new-onset uveitis within a population-based setting. The association was stronger for noninfectious uveitis. Given the well-established risks of smoking with regard to other inflammatory disorders, these results reaffirm the importance of encouraging patients to avoid or cease smoking.

Cytotoxic Clinical Isolates of Pseudomonas Aeruginosa Identified During the Steroids for Corneal Ulcers Trial Show Elevated Resistance to Fluoroquinolones

BackgroundTo determine the relationship between type three secretion genotype and fluoroquinolone resistance for P. aeruginosa strains isolated from microbial keratitis during the Steroids for Corneal Ulcers Trial (SCUT) and for two laboratory strains, PA103 and PAO1.MethodsConfirmed P. aeruginosa isolates from the SCUT were divided into exoU(+) or exoU(−). The exoU(+) strains contained the gene encoding ExoU, a powerful phospholipase toxin delivered into host cells by the type three secretion system. Isolates were then assessed for susceptibility to fluoroquinolone, cephalosporin, and aminoglycoside antibiotics using disk diffusion assays. Etest was used to determine the MIC of moxifloxacin and other fluoroquinolones. Laboratory isolates in which the exoU gene was added or deleted were also tested.ResultsA significantly higher proportion of exoU(+) strains were resistant to ciprofloxacin (p = 0.001), gatifloxacin (p = 0.003), and ofloxacin (p = 0.002) compared to exoU(−) isolates. There was no significant difference between exoU(+) or exoU(−) negative isolates with respect to susceptibility to other antibiotics except gentamicin. Infections involving resistant exoU(+) strains trended towards worse clinical outcome. Deletion or acquisition of exoU in laboratory isolates did not affect fluoroquinolone susceptibility.ConclusionsFluoroquinolone susceptibility of P. aeruginosa isolated from the SCUT is consistent with previous studies showing elevated resistance involving exoU encoding (cytotoxic) strains, and suggest worse clinical outcome from infections involving resistant isolates. Determination of exoU expression in clinical isolates of P. aeruginosa may be helpful in directing clinical management of patients with microbial keratitis.

Clinical Characteristics of Scleritis and Episcleritis: Results from the Pacific Ocular Inflammation Study

While episcleritis has been classically described as self-limited, scleritis may require systemic immunosuppression and be more commonly associated with systemic diseases and ocular complications. Prior studies are limited to retrospective case series from tertiary care settings, which may overestimate ocular complications and systemic disease associations due to referral bias. Therefore, there is a need for a population-based study describing the clinical characteristics of scleritis and episcleritis, including associated diagnoses, complications, and treatments. We used Kaiser Permanente Hawaii (KPH) as a source of data. This retrospective cohort study compares clinical characteristics of KPH members with scleritis and episcleritis, and elucidates practice patterns in a general population. To that end, electronic medical records for KPH enrollees (n = 217,061) from January 1, 2006 to December 31, 2007 were searched for International Classification of Diseases, 9th ed., codes corresponding to ocular inflammation as previously described. Clinical diagnoses of scleritis and episcleritis were confirmed by chart review. Associated diagnoses, ocular complications, prescribed medications, and smoking status of scleritis and episcleritis patients were compared using Fisher’s exact test. Patients were followed for 2 years after the study period for the development of associated diagnoses. A p value less than 0.05 was considered statistically significant. STATA 11.0 (StataCorp, TX) was used. Institutional review board/ethics committee approval was obtained. Seventeen scleritis and 93 episcleritis cases were confirmed. Reasons for exclusion have been previously described. A total of 76.5% of scleritis cases and 60.2% of episcleritis cases were female. The median age at diagnosis was 56 years for scleritis (interquartile range [IQR]: 42–60) and 45 years for episcleritis (IQR: 32–54). Clinical characteristics of scleritis and episcleritis varied. The most common associated diagnosis was rheumatoid arthritis, affecting 29.4% of scleritis patients and 0% of episcleritis patients (p50.001). Additionally, there was 1 scleritis patient with inflammatory polyarthropathy and 2 episcleritis patients with psoriasis. In the 2 years after the study period, 1 scleritis patient developed systemic lupus erythematosus and sarcoidosis and 1 episcleritis patient developed psoriasis. Ocular complications and prescribed medications varied among scleritis and episcleritis patients. Ocular complications occurred in 29.4% of scleritis patients and 7.5% of episcleritis patients (p = 0.02, Table 1). Notably, anterior uveitis complicated 11.8% of scleritis cases, compared to 0% of episcleritis cases (p = 0.02). Additionally, scleritis patients were more likely to have been prescribed cycloplegic eyedrops (p = 0.02), systemic immunosuppressants (p50.001), and systemic corticosteroids (p = 0.03). Additionally, 23.5% of scleritis patients and 32.2% of episcleritis patients were smokers (p = 0.58). Our population-based study confirms the burden of rheumatoid arthritis previously described in scleritis patients. Furthermore, our results suggest

Assessment of the Accuracy of Using ICD-9 Codes to Identify Uveitis, Herpes Zoster Ophthalmicus, Scleritis, and Episcleritis

IMPORTANCE With the increased use of data from electronic medical records for research, it is important to validate International Classification of Diseases, Ninth Revision (ICD-9) codes for their respective diagnoses. OBJECTIVE To assess the accuracy of using ICD-9 codes to identify ocular inflammatory diseases. DESIGN, SETTING, AND PARTICIPANTS Retrospective secondary database analysis. The setting was Kaiser Permanente Hawaii, an integrated managed care consortium that serves approximately 15% of the general Hawaiian population. Participants were patients with ICD-9 diagnosis codes that might be associated with a diagnosis of ocular inflammation seen at Kaiser Permanente Hawaii between January 1, 2006, and December 31, 2007. The data collection and analysis took place from January 2011 to August 2015. MAIN OUTCOMES AND MEASURES The main outcome was the positive predictive value (PPV) of ICD-9 codes for identifying specific types of ocular inflammatory disease. The PPVs were calculated by determining the ratio of the confirmed cases found by medical record review to the total number of cases identified by ICD-9 code. RESULTS Of the 873 patients identified by a comprehensive list of ICD-9 codes for ocular inflammatory diseases, 224 cases were confirmed as uveitis after medical record review. Using a set of uveitis-specific codes and eliminating patients with a history of ocular surgery, the overall PPV for uveitis was 61% (95% CI, 56%-66%). The PPVs for individual uveitis codes ranged from 0% to 100%, and 11 uveitis codes had a PPV exceeding 80%. Herpes zoster ophthalmicus and scleritis/episcleritis ICD-9 codes had PPVs of 91% (95% CI, 86%-95%) and 60% (95% CI, 54%-66%), respectively. CONCLUSIONS AND RELEVANCE Our results suggest that using ICD-9 codes alone to capture uveitis and scleritis/episcleritis diagnoses is not sufficient in the Kaiser Permanente Hawaii healthcare system, although there were specific uveitis codes with high PPVs. However, the electronic medical record can reliably be used to identify herpes zoster ophthalmicus cases. Medical record review, as was done in this study, is recommended to elucidate diagnoses for uveitis and scleritis/episcleritis.