Statins do not decrease the risk for wet age-related macular degeneration.

PURPOSE: To investigate the effect of statins on the risk for age-related macular degeneration (AMD) treated with photodynamic therapy (PDT). METHODS: All members in one district of a health maintenance organization in Israel, older than 50 years (n = 139,894), were included. PDT procedures for AMD (775 procedures; 283 patients) and filled statin prescriptions between 1999 and 2002 (471,232 prescriptions; 29,417 patients) were documented. RESULTS: For all age groups, PDT was more prevalent in statin users. Among statin users, the age adjusted proportion of patients undergoing PDT for wet AMD was 0.27% (95% confidence interval (CI): 0.20-0.34%), compared to 0.16% (95% CI: 0.14-0.18%) among non-users (p = 0.002, chi2 test, relative risk = 1.66 (95% CI: 1.29-2.19)). After correction for age, gender, socioeconomic status, place of birth, place of residence, hyperlipidemia, hypertension, ischemic heart disease, diabetes, and congestive heart failure, statins did not have any additional effect on the risk for undergoing PDT for wet AMD. In a case control analysis, statin use in PDT patients was similar to their use by matched controls (odds ratio = 1.0; 95% CI = 0.8-1.3). CONCLUSIONS: This study does not support a beneficial effect of statin use for reducing the risk for wet AMD requiring PDT.

Novel USH2A mutations in Israeli patients with retinitis pigmentosa and Usher syndrome type 2.

OBJECTIVE: To identify USH2A mutations in Israeli patients with autosomal-recessive Usher syndrome type 2 (USH2) and retinitis pigmentosa (RP). METHODS: Patients from 95 families with RP and 4 with USH2 were clinically evaluated. USH2A exons 2-72 were scanned for mutations using single-strand conformation and sequencing analyses. The frequency of novel missense changes was determined in patients and controls using restriction endonucleases. RESULTS: The analysis revealed 3 USH2A mutations, 2 of which are novel, in 2 families with USH2 and a large family (MOL0051) with both USH2 and RP. Compound heterozygotes for 2 null mutations (Thr80fs and Arg737stop) in MOL0051 suffered from USH2 while compound heterozygotes for 1 of the null mutations and a novel missense mutation (Gly4674Arg) had nonsyndromic RP. CONCLUSIONS: Our results support the involvement of USH2A in nonsyndromic RP and we report here of a second, novel, missense mutation in this gene causing autosomal-recessive RP. CLINICAL RELEVANCE: Possible involvement of USH2A should be considered in the molecular genetic evaluation of patients with autosomal-recessive RP. Understanding the mechanism by which different USH2A mutations cause either USH2 or RP may assist in the development of novel therapeutic approaches.

Cataract surgery is associated with a higher rate of photodynamic therapy for age-related macular degeneration.

PURPOSE: To investigate the association between cataract surgery and the rate of photodynamic therapy (PDT) for age-related macular degeneration (AMD). DESIGN: Observational population-based retrospective case-control study. PARTICIPANTS: All members in a district of the largest health maintenance organization (HMO) in Israel > 50 years old on January 1, 2001, who did not terminate their membership through May 31, 2005 (139 894 members). METHODS: All PDT procedures for AMD performed in the study population between January 1, 2001 and May 31, 2005 (283 patients) and all cataract surgeries performed between January 1, 2001 and December 31, 2003 (5913 patients) were documented. We extracted clinical information from the chronic disease registry of the HMO as well as demographic and socioeconomic information. For each patient that underwent cataract surgery, 5 HMO members matched in age, gender, chronic diseases (systemic hypertension, diabetes, hyperlipemia, and ischemic heart disease), place of residence, country of birth and socioeconomic status, who did not undergo cataract surgery, were randomly chosen as controls (n = 29 565). MAIN OUTCOME MEASURES: The rate for undergoing PDT at different time periods after cataract surgery. RESULTS: Fifty (0.85%) cataract patients and 94 control cases (0.32%) underwent PDT after cataract surgery (P<0.0001, chi-square test). A significant rise in PDT rate was noticed in cataract patients compared to controls during the first 6 months after surgery (P = 0.004, chi-square test). Between 6 and 12 months postoperatively, the PDT rates were similar in both groups. However, a more significant rise in PDT rates occurred between 1 and 1.5 years after surgery (P<0.0001, chi-square test). The Kaplan-Meier PDT-free survival curve of cataract patients was significantly worse than that of the controls (P<0.0001, chi-square test; P = 33.7, log-rank test). The hazard ratio for cataract patients compared to controls to undergo PDT after surgery was 2.7 (confidence interval = 2.4-5.7). The most significant factors to reduce the time to PDT were advanced age followed by having had cataract surgery, place of birth, socioeconomic status, and hyperlipidemia (Cox proportional hazards survival regression). CONCLUSIONS: We identified an increased rate of PDT, presumably for subfoveal AMD, 1 to 1.5 years after cataract surgery.

Increased risk for herpetic eye disease in patients with allergic conjunctivitis.

PURPOSE: To evaluate the risk of ocular surface herpetic eye disease (osHED) in allergic eye disease. METHODS: We calculated the risk for osHED in 11,205 patients on antiallergic ocular topical agents compared with 453,069 controls based on filled prescriptions for topical acyclovir between 2001 and 2003. RESULTS: Significantly more allergic patients, of all age groups, received treatment for osHED (p < 0.01). The age and gender adjusted relative risk for allergic patients to suffer an osHED event was 2.31 (95% CI: 1.84-2.90), raising to 3.55 (95% CI: 2.0-6.4) in patients that filled > or = 4 antiallergic prescriptions. CONCLUSIONS: Patients treated for allergic eye disease have an increased risk of osHED.

Risk factors for photodynamic therapy of predominantly classic choroidal neovascularization in age-related macular degeneration.

PURPOSE: To investigate the influence of various risk factors for age-related macular degeneration (AMD) on the rate of undergoing photodynamic therapy (PDT). DESIGN: An observational population based cohort study. SETTINGS: A district of the largest health maintenance organization (HMO) in Israel. STUDY POPULATION: All HMO members in the district, older than 50 years on January 1, 2001, who did not terminate their membership until May 31, 2005 (139,894 members); of those, 283 underwent PDT for AMD during the study period (775 procedures). OBSERVATION PROCEDURES: We extracted information from the chronic disease registry of the HMO as well as demographic information including age, gender, country of birth, place of residency, and social security economic status. MAIN OUTCOME MEASURES: Effect of various risk factors for AMD on the rate of PDT. RESULTS: The age-adjusted proportion of patients requiring PDT was significantly higher in hypertensives (P = .03, chi2 test), in hyperlipidemics (P = .002), in ischemic heart disease patients (P = .002) and among males (P = .03) and Ashkenazi Jews (P = .02). No significant difference in PDT rates was noted in diabetics, congestive heart failure (CHF), and chronic renal failure (CRF) patients. PDT rates were lower in the lower socioeconomic class (P = .002). Logistic regression found a significant effect of age, hyperlipidemia, hypertension, socioeconomic status, and gender on the rate of PDT, while ischemic heart disease (IHD), diabetes, CHF, CRF, place of birth, and place of residence did not contribute significantly to the model. CONCLUSIONS: Advanced age, hypertension, hyperlipidemia, male gender, and socioeconomic status are risk factors for undergoing PDT for predominantly classic neovascular AMD.

Topical beta-blockers are not associated with an increased risk of treatment for depression.

PURPOSE: To investigate the effect of topical beta-blockers on the prevalence of depression among glaucoma patients. DESIGN: Retrospective observational population-based cohort study. PARTICIPANTS: We reviewed the electronic medical records of all the members in a district of the largest health maintenance organization in Israel (Central District of Clalit Health Services) who were older than 20 years (317,469 members). METHODS: We documented all antiglaucoma prescriptions (n = 274,023) and all antidepressant prescriptions (n = 16,948) filled by glaucoma patients in the district between January 1, 2001 and December 31, 2003. We included only those patients who filled at least 6 consecutive antiglaucoma prescriptions at least once every 2 months (n = 6597; 5846 [88.6%] were treated with topical beta-blockers). Depressed patients were defined as patients that filled at least four prescriptions for antidepressants during the study period (n= 810, 12.3% of all glaucoma patients). MAIN OUTCOME MEASURE: Relationship of topical beta-blocker use and prevalence of depression among glaucoma patients. RESULTS: No significant demographic differences were noted between glaucoma patients treated and not treated with topical beta-blockers. Of those treated and not treated with beta-blockers, 12.2% (12.7% after age-adjustment) and 12.7%, respectively, were also receiving drug therapy for depression (P = 0.7, chi-square test). With stratification by age, treatment with topical beta-blockers did not influence the prevalence of depression in any age group. Logistic regression analysis revealed a significant effect of age, place of birth, and gender on the prevalence of depression, but the prevalence of use of topical beta-blockers had no significant effect. CONCLUSIONS: Use of topical beta-blockers by glaucoma patients does not appear to increase the risk of depression in this population.

Herpetic eye disease in diabetic patients.

PURPOSE: To study the incidence of herpetic eye disease (HED) of the ocular surface in diabetics. DESIGN: Observational historical cohort study. SETTING: A district of the largest health maintenance organization in Israel (the Central District of Clalit Health Services). PARTICIPANTS: We reviewed the electronic medical records of all patients older than 50 years (159634 patients) in the district, and of these, 22382 (14.0%) patients had diabetes mellitus. METHODS: All filled prescriptions for acyclovir eye ointment between January 1, 2001 and December 31, 2003 (1483 tubes) and all hemoglobin A1c laboratory tests during 2003 (41910 tests) were documented. An ocular surface HED event was defined when a patient consumed at least 1 tube of topical acyclovir per month, whereas no acyclovir use was documented 3 months before and 3 months after that event. MAIN OUTCOME MEASURES: Incidence of ocular surface HED events in diabetics compared with nondiabetics adjusted for age and gender. RESULTS: After age and gender adjustment, significantly more diabetics had ocular surface HED (5.21 per thousand) compared with nondiabetics (4.27 per thousand; P<0.0001). Stratification by age revealed a significantly higher prevalence of HED in diabetics, aged 60 to 79 years. Recurrent herpetic events occurred during the study period in 25.2% of HED-affected diabetics, and in 16.6% of HED-affected nondiabetics (P = 0.05). Diabetics with poor glycemic control (mean annual hemoglobin A1c > 9%) consumed significantly more ocular acyclovir (P = 0.01). Multivariate analysis revealed this effect to be independent of age, gender, place of birth, or place of residency. CONCLUSIONS: Ocular surface HED is significantly more common among patients with diabetes mellitus. Poor glycemic control correlates with increased consumption of ocular acyclovir in diabetic patients.

Severe blepharoconjunctivitis induced by a peeling mask containing trichloroacetic acid.

PURPOSE: To report a case of severe blepharoconjunctivitis induced by a peeling mask. METHODS: A 32-year-old healthy female was examined one day after undergoing a face-peeling procedure with a mask containing trichloroacetic acid. She complained of severe burning, redness, and epiphora in her left eye that started several hours after the procedure. RESULTS: Her vision was LE 0.2, RE 0.8. Mild upper eyelid edema of the right eye and severe edema of the left eyelids, LE inferior ectropion, and LE blepharoconjunctivitis were noted. The conjunctiva was severely hyperemic with papillary reaction and chemosis. The corneas, anterior chambers, irides, lenses, and posterior segments were normal. The patient was treated with Dexamethasone 0.1% q2h and ocular lubrication. The reaction subsided after 3-4 days. CONCLUSION: Face-peeling masks containing trichloroacetic acid can sometimes severely irritate the eyelids and the ocular surface.

Ultrasonographic tissue characteristics of mushroom-shaped uveal melanoma.

PURPOSE: To evaluate the ultrasonographic tissue characteristics of mushroom-shaped versus dome-shaped uveal melanoma and to compare them with the tumor vasculature. METHODS: We examined clinically and ultrasonically 18 dome-shaped and 11 mushroom-shaped uveal melanomas (29 consecutive patients; mean age 57 years) and compared their normalized A-scan patterns. Using histological sections from a different set of patients (12 dome- and 17 mushroom-shaped tumors), we calculated the percentage of area covered by blood vessels. RESULTS: A-scans of dome-shaped tumors presented low homogeneous reflectivity, whereas the heads of mushroom-shaped tumors had high and irregular reflectivity (p < 0.001). The reflectivity of their bases was low and similar to dome-shaped tumors. The blood vessel area in the histological sections was significantly larger in the heads of mushroom-shaped tumors (0.88 +/- 0.14%), compared both to their bases (0.29 i 0.06%) (p < 0.001) and to dome-shaped tumors (0.07 i 0.03%) (p < 0.0001). CONCLUSIONS: The ultrasonographic pattern suggests vascular congestion in the heads of mushroom-shaped tumors,probably due to strangulated blood vessels in the tumor neck.

Dry eye in diabetic patients.

PURPOSE: To compare the prevalence of keratoconjunctivitis sicca (KCS) in a prospective cohort of 22,382 diabetic patients with that in the general population. DESIGN: Prospective, observational, cohort study. SETTING: A district of israel's largest health maintenance organization. STUDY POPULATION: We followed the electronic medical records of all patients in the district older than 50 years (159,634 patients) between January 1 and December 31, 2003. Of those, 22,382 (14.0%) had diabetes. OBSERVATION PROCEDURE: The proportion of ocular lubrication consumers was compared among diabetic and nondiabetic patients. All HbA1c laboratory tests performed by the diabetic patients were documented (41,910 tests), and glycemic control was correlated with the consumption of ocular lubrication. MAIN OUTCOME MEASURES: Ocular lubrication use by diabetic patients compared with the general population and the relationship between glycemic control and ocular lubrication use. RESULTS: After age and gender adjustment, a significantly higher percentage of diabetic patients (20.6%) received ocular lubrication, compared with nondiabetic patients (13.8%, P < .001). The difference was significant for all age groups and for both sexes (P < .001). A similar significant difference was prominent between diabetic and nondiabetic patients aged 60 to 89 years who were frequent users of ocular lubrication. Ocular lubrication consumption increased with poorer glycemic control (mean annual HbA1c levels). Multivariate analysis revealed this effect to be independent of age, sex, place of birth, or place of residence. CONCLUSIONS: KCS is significantly more common among diabetic patients. Poor glycemic control correlates with increased artificial tear use in diabetic patients.

The effect of combination pharmacotherapy on the prescription trends of glaucoma medications.

PURPOSE: To describe prescription trends within a managed care setting for glaucoma medications and to examine the effect of introduction of Cosopt--a fixed combination of dorzolamide and timolol. PATIENTS AND METHODS: All prescriptions dispensed to any of the 470,350 members of an Israeli health maintenance organization were monthly scanned for patients treated for glaucoma, between January 2000 and May 2003. The monthly mean number of glaucoma patients was 3899 +/- 104 (mean +/- SD). All topical glaucoma prescriptions were documented, and the monthly prescription rate of each medication was calculated and plotted. The monitored glaucoma medications were: beta-adrenergic antagonists, dorzolamide, latanoprost, pilocarpine, brimonidine, Cosopt, and others. RESULTS: beta-adrenergic antagonists were the top prescribing drug (>35% of all glaucoma prescriptions). The prescription rates of pilocarpine and beta-adrenergic antagonists were in constant decline, while latanoprost and brimonidine increased steadily. The introduction of Cosopt changed the prescription trends of dorzolamide from increasing to rapidly decreasing, and accelerated the long-term decline of beta-adrenergic antagonists. Concomitant with the introduction of Cosopt the prescription rate of beta-adrenergic antagonists temporarily increased. This was due to a total increase in glaucoma prescriptions. When Cosopt was introduced, 37.5% of patients were prescribed Cosopt together with beta-adrenergic antagonists, and 16.5% also received dorzolamide. Thereafter the co-prescription decreased steadily. CONCLUSIONS: Introduction of a combination drug should be accompanied by physicians', pharmacists', and patients' education to prevent its inappropriate usage together with its components.