Pathogen Surveillance for Acute Infectious Conjunctivitis.

Importance: Acute infectious conjunctivitis is a common ocular condition with major public health consequences. Objective: To assess regional variations and microbial etiologies of acute infectious conjunctivitis to guide treatment. Design, Setting, and Participants: In this cross-sectional study, patients with presumed acute infectious conjunctivitis were enrolled in the study at 5 sites (Honolulu, Hawaii; Los Angeles, San Francisco, and San Diego, California; and Petah-Tikva, Israel) from March 2021 to March 2023. Patients with allergic or toxic conjunctivitis were excluded. Main Outcomes and Measures: Pathogens were identified by unbiased RNA deep sequencing. Results: In all, 52 patients (mean [range] age, 48 [7-80] years; 31 females [60%]) were enrolled at 5 sites (6 patients from Honolulu, 9 from San Diego, 11 from Los Angeles, 13 from San Francisco, and 13 from Petah-Tikva). RNA deep sequencing detected human adenovirus species D in one-quarter of patients (13 of 52). A wide range of pathogens, including human coronavirus 229E, SARS-CoV-2, and herpes simplex virus type 1, was also identified, as well as several bacteria and fungi. Moreover, 62% (32 of 52) of patients presented with purulent discharge, while only 8% (4 of 52) of patients had confirmed bacterial pathogens. Conclusion and Relevance: In this cross-sectional study, pathogens associated with acute infectious conjunctivitis varied between all 5 sites in the US and Israel. Purulent discharge was a common presenting sign in this study, with a low specificity for bacteria-associated conjunctivitis, suggesting that further diagnostic workup may be necessary to inform antibiotic stewardship. Additional research on cost-effectiveness of using RNA deep sequencing is needed to ascertain whether it is better to monitor patients clinically until resolution of disease.

Association Between Thyroid Disease and Uveitis: Results From the Pacific Ocular Inflammation Study.

Importance: Common pathophysiological mechanisms may be responsible for immune dysregulation in both thyroid disease and uveitis. Studies investigating a possible association are limited. Objective: To determine the association between thyroid disease and uveitis. Design, Setting, and Participants: A retrospective, population-based case-control study was conducted from January 1, 2006, to December 31, 2007, among 217 061 members of the Kaiser Permanente Hawaii health system during the study period. A clinical diagnosis of uveitis was determined through a query of the electronic medical record followed by individual medical record review for confirmation by a uveitis specialist. Thyroid disease was determined based on International Classification of Diseases, Ninth Revision, coding. Two control groups were chosen at a 4:1 ratio for comparison with patients with uveitis. A logistic regression analysis was performed with uveitis as the main outcome variable and thyroid disease as the main predictor variable, while adjusting for age, sex, race, smoking status, and history of autoimmune disease. Data analysis was conducted between 2014 and 2016. Main Outcomes and Measures: A diagnosis of thyroid disease among patients with uveitis and respective controls. Results: Of the 224 patients with uveitis (127 women and 97 men; mean [SD] age, 54.1 [17.8] years) identified during the study period, 29 (12.9%) had a diagnosis of thyroid disease, compared with 62 of 896 patients (6.9%) in the control group (P = .01) and 78 of 896 patients (8.7%) in the ophthalmology clinic control group (P = .06). Using the general Kaiser Permanente Hawaii population control group, patients who had thyroid disease had a 1.7-fold (95% CI, 1.03-2.80; P = .04) higher odds of having uveitis compared with patients who did not have thyroid disease when controlling for age, sex, race, smoking status, and autoimmune disease. A similar association was found using the ophthalmology clinic control group (odds ratio, 1.8; 95% CI, 1.1-2.9; P = .02) while adjusting for these factors. Conclusions and Relevance: These findings suggest that a history of thyroid disease has a weak to moderate association with uveitis. Similar autoimmune mechanisms could explain the pathogenesis of both conditions. If future studies corroborate these findings, they may have further clinical implications in the laboratory workup of uveitis.

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.

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.

Association between statin use and uveitis: results from the Pacific Ocular Inflammation study.

PURPOSE: To assess whether there is a protective association between statin use and uveitis diagnosis. DESIGN: Retrospective, population-based case-control study. METHODS: Medical records of all patients in the Kaiser Permanente Hawaii health plan between January 1, 2006 and December 31, 2007 (N = 217 061) were searched electronically for International Classification of Diseases, 9th Revision, diagnosis codes related to uveitis. Chart review was done to confirm incident uveitis diagnosis during the study period. Two control groups were each randomly selected at a 5:1 ratio to cases, and controls were assigned an index date to match their respective case diagnosis date. One control group was selected from the general Kaiser Permanente Hawaii population that had at least 1 healthcare visit during the study period. Another control group was selected from the population of Kaiser Permanente Hawaii members who had at least 1 visit to the ophthalmology clinic during the study period. Statin use was defined as filling a prescription for statin medication in the year prior to the diagnosis or index date based on an electronic search of the Kaiser Permanente Hawaii pharmacy database for Generic Product Identification codes. A conditional logistic regression model with clinical diagnosis of uveitis as the outcome was used to assess the relationship between statin use and uveitis. RESULTS: One hundred eight incident cases of uveitis were identified. Nineteen percent of uveitis patients had used statin medication in the year prior to diagnosis compared to 30% of patients in the general Kaiser population control (P = .03) and 38% of patients in the ophthalmology clinic control (P < .001). Using the general Kaiser population control and adjusting for age, sex, race, and autoimmune diseases, the odds of a statin user developing uveitis were 48% less than the odds of a non-statin user developing uveitis (OR: 0.52, 95% CI: 0.29-0.94, P = .03). Similarly, the odds of developing uveitis were 33% less for statin users compared to non-statin users (OR: 0.67, 95% CI: 0.38-1.19, P = .17) when adjusting for these factors and using the ophthalmology clinic control group. CONCLUSIONS: Statin use may be protective against the development of uveitis. Several anti-inflammatory and immunomodulatory mechanisms may explain this association.

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.

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 scleritis and episcleritis: results from the Pacific Ocular Inflammation Study.

PURPOSE: To ascertain the incidence of scleritis and episcleritis in a Hawaiian population and describe variations by age, sex, and race. DESIGN: Retrospective, population-based cohort study. METHODS: All electronic medical records for enrollees in Kaiser Permanente Hawaii (n = 217,061) from January 1, 2006 to December 31, 2007 were searched for International Classification of Diseases, 9th Edition (ICD-9) codes associated with ocular inflammation. Chart review was conducted to verify a clinical diagnosis of scleritis or episcleritis. Confirmed cases were used to calculate incidence rates per 100,000 person-years. Ninety-five percent confidence intervals (CI) were calculated for each incidence rate, including age-, sex-, and race-specific rates, using bias-corrected Poisson regression. To assess for confounding, a multivariate analysis adjusting for age, sex, and race was also performed. RESULTS: Of 217,061 eligible patients, 17 incident scleritis cases and 93 incident episcleritis cases were confirmed. The overall incidence rates of scleritis and episcleritis were 4.1 (95% CI: 2.6-6.6) and 21.7 (95% CI: 17.7-26.5) cases per 100,000 person-years, respectively. Women were overrepresented among scleritis patients (P = .049). Pacific Islanders were the most underrepresented racial group among cases of scleritis and episcleritis (P = .006, P = .001). Blacks had the highest incidence of scleritis (P = .004). CONCLUSIONS: These results provide a population-based estimate of the incidence of scleritis and episcleritis in a diverse population and highlight differences in patients' demographic characteristics. Differences in incidence by sex and race raise questions about genetic and environmental influences on the development of these conditions.

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.

Eyelid mucous membrane grafts: a histologic study of hard palate, nasal turbinate, and buccal mucosal grafts.

PURPOSE: To histologically evaluate the outcome of mucous membrane grafts to the eyelid. METHODS: Case series of 31 eyes from 24 patients who underwent transplantation of hard palate (25 eyes), buccal (1 eye), or nasal turbinate (5 eyes) mucosa to the posterior eyelid surface. These grafts were biopsied at 0.5 months to 84 months (mean, 20 months) postoperatively. They were examined with light microscopy and compared with either the donor mucosa from the same patient (2 patients) or the typical donor site histology (22 patients). RESULTS: Graft biopsies revealed general epithelial morphology that was quite similar to the respective donor sites in virtually all cases. Six (25%) of 24 hard palate graft biopsies, which were obtained at 8 months to 49 months (mean, 22 months) postoperatively, displayed orthokeratosis alternating with parakeratosis, while 12 (50%) demonstrated parakeratosis alone, and another 6 (25%) showed adjacent regions of parakeratotic and nonkeratinized epithelium. No hard palate grafts showed complete absence of keratinization after transplantation. Other significant findings included loss of goblet cells in nasal turbinate grafts and few submucosal glands remaining in any specimen. CONCLUSIONS: Full-thickness mucosal grafts typically maintain their native epithelial morphology following transplantation to the ocular surface. Submucosal glands usually do not survive transplantation, which could be the result of intentional thinning of the graft at the time of transplantation. Contrary to the opinion that hard palate graft epithelium usually undergoes metaplasia from keratinized to nonkeratinized within 6 months following transplantation to the eye, all hard palate grafts in this study remained orthokeratotic and/or parakeratotic.