David C. Gritz

Epidemiology of ulcerative keratitis in Northern California

OBJECTIVE To determine the incidence and associated risk factors for ulcerative keratitis in northern California. METHODS In this large-population, retrospective, cohort study, all medical records with diagnosis coding for corneal ulcers during a consecutive 12-month period were reviewed. Incidence rates were calculated using a dynamic population model. Multivariate relative risk regression was conducted to evaluate potential risk factors for ulcerative keratitis. RESULTS Within the target population of 1 093 210 patients, 302 developed ulcerative keratitis. The incidence of ulcerative keratitis was 27.6 per 100 000 person-years (95% confidence interval, 24.6-30.9). The incidence of corneal ulceration in contact lens wearers was 130.4 per 100 000 person-years (95% confidence interval, 111.3-151.7), with an adjusted relative risk of 9.31 (7.42-11.7; P < .001) compared with non-contact lens wearers, who had an incidence of ulcerative keratitis of 14.0 per 100 000 person-years (11.7-16.6). Seven of 2944 people known to be infected with human immunodeficiency virus developed ulcerative keratitis, with 5 being contact lens wearers. The incidence of ulcerative keratitis in human immunodeficiency virus-positive patients was 238.1 per 100 000 person-years (95% confidence interval, 95.7-490.5), with an odds ratio of 9.31 (7.42-11.7; P < .001) compared with human immunodeficiency virus-negative patients, who had an incidence of ulcerative keratitis of 27.1 per 100 000 person-years (24.1-30.3). CONCLUSIONS The incidence of ulcerative keratitis in this population is higher than previously reported. This may be owing to the increasing prevalence of contact lens wear.

The Antioxidants in Prevention of Cataracts Study: effects of antioxidant supplements on cataract progression in South India.

Aim: To determine if antioxidant supplements (β carotene and vitamins C and E) can decrease the progression of cataract in rural South India. Methods: The Antioxidants in Prevention of Cataracts (APC) Study was a 5 year, randomised, triple masked, placebo controlled, field based clinical trial to assess the ability of interventional antioxidant supplements to slow cataract progression. The primary outcome variable was change in nuclear opalescence over time. Secondary outcome variables were cortical and posterior subcapsular opacities and nuclear colour changes; best corrected visual acuity change; myopic shift; and failure of treatment. Annual examinations were performed for each subject by three examiners, in a masked fashion. Multivariate modelling using a general estimating equation was used for analysis of results, correcting for multiple measurements over time. Results: Initial enrolment was 798 subjects. Treatment groups were comparable at baseline. There was high compliance with follow up and study medications. There was progression in cataracts. There was no significant difference between placebo and active treatment groups for either the primary or secondary outcome variables. Conclusion: Antioxidant supplementation with β carotene, vitamins C and E did not affect cataract progression in a population with a high prevalence of cataract whose diet is generally deficient in antioxidants.

Antibiotic Supplementation of Intraocular Irrigating Solutions: An In Vitro Model of Antibacterial Action

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

Predictive value of frequency doubling technology perimetry for detecting glaucoma in a developing country.

Purpose:To determine the feasibility and diagnostic precision of Frequency Doubling Technology (FDT) perimetry as a method to detect glaucoma in rural villages of a developing country. Design:Cross-sectional study. Methods:Testing included FDT perimetry (C-20-5 screening protocol), tonometry, anterior segment biomicroscopy, and dilated ophthalmoscopy in 296 rural, non-English speaking residents of Southern India over 35 years old. Participants repeated the FDT if they had a location with reduced sensitivity or an unreliable result. We defined an abnormal FDT as one location of reduced sensitivity present on both the initial and repeat examination. We determined the diagnostic precision of FDT separately for a glaucomatous optic disc, a cup to disc ratio (C/D) ≥ 0.7, and a C/D ≥ 0.8. Results:Ninety-three percent of subjects were able to complete the test satisfactorily. With repeat FDT testing, 37% of eyes with abnormal FDT results subsequently converted to normal and 67% of eyes with unreliable results subsequently became reliable. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for a glaucomatous optic disc were 7%, 87%, 13%, 76%, and 69%, respectively; for a C/D ≥ 0.7, they were 0%, 87%, 0%, 91%, and 81%, respectively; and for a C/D ≥ 0.8, they were 0%, 87%, 0%, 99%, and 87%, respectively. Conclusion:Clinicians can use FDT perimetry to rapidly screen for glaucoma in rural villages of a developing country. FDT testing had high specificity and negative predictive value, but low sensitivity and positive predictive value. The low sensitivity suggests that FDT has limited applicability as the sole test for glaucoma screening in this population. Repeat testing of FDT results that are unreliable or suspected of being abnormal is beneficial for this screening procedure.

OCULAR FLORA OF PATIENTS WITH AIDS COMPARED WITH THOSE OF HIV-NEGATIVE PATIENTS

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 (HIV)-negative patients. METHODS Forty patients with AIDS and 42 HIV-negative controls were sex and age matched. All subjects had a detailed anterior segment examination, including Schirmers test, rose bengal staining, and quantitative cultures of the conjunctiva and lids. Statistical evaluation of the relation between AIDS, keratoconjunctivitis sicca (KCS), and ocular flora was performed. RESULTS No differences were observed in the types or numbers of organisms isolated from the conjunctiva or lids of patients with AIDS and HIV-negative subjects. Ocular flora was not influenced by use of systemic antibiotics, level of immunosuppression as measured by CD4 lymphocyte counts, KCS, or other ocular-surface disease. One AIDS patient was colonized by large numbers of Haemophilus influenzae OU with minimal clinical signs of inflammation or infection. CONCLUSION There do not appear to be any differences in the ocular flora of HIV-negative patients and patients with AIDS. Presence of KCS and level of immunosuppression do not appear to affect the ocular flora in patients with AIDS.

Ocular and sinus microsporidial infection cured with systemic albendazole

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.

A novel arginine substitution mutation in 1A domain and a novel 27 bp insertion mutation in 2B domain of keratin 12 gene associated with Meesmann’s corneal dystrophy

Aim: To determine the disease causing gene defects in two patients with Meesmann’s corneal dystrophy. Methods: Mutational analysis of domains 1A and 2B of the keratin 3 (K3) and keratin 12 (K12) genes from two patients with Meesmann’s corneal dystrophy was performed by polymerase chain reaction amplification and direct sequencing. Results: Novel mutations of the K12 gene were identified in both patients. In one patient a heterozygous point mutation (429A→C = Arg135Ser) was found in the 1A domain of the K12 gene. This mutation was confirmed by restriction digestion. In the second patient a heterozygous 27 bp duplication was found inserted in the 2B domain at nucleotide position 1222 (1222ins27) of the K12 gene. This mutation was confirmed by gel electrophoresis. The mutations were not present in unaffected controls. Conclusion: Novel K12 mutations were linked to Meesmann’s corneal dystrophy in two different patients. A missense mutation replacing a highly conserved arginine residue in the beginning of the helix initiation motif was found in one patient, and an insertion mutation, consisting of a duplication of 27 nucleotides, was found before the helix termination motif in the other.

Incidence and prevalence of episcleritis and scleritis in Northern California.

Purpose: To evaluate the incidence and prevalence of episcleritis and scleritis in a large well-defined population in Northern California. Methods: Secondary analysis was performed on data from the Northern California Epidemiology of Uveitis Study. The patient database of a large regional health maintenance organization was searched for all patients who potentially experienced ocular inflammatory disease during the 12-month study period. Medical records were reviewed for all potential patients to confirm ocular inflammatory disease and specific diagnosis, establish the time of onset, and collect additional data. Age- and sex-stratified quarterly study population data were used to calculate incidence rates and prevalence ratios. Results: After reviewing 2011 possible cases, 297 new-onset cases of episcleritis, 39 prior-onset cases of episcleritis, 25 new-onset cases of scleritis, and 8 prior-onset cases of scleritis were confirmed. For episcleritis, the overall incidence was 41.0 per 100,000 person-years and an annual prevalence ratio of 52.6 per 100,000. The overall incidence of scleritis was 3.4 per 100,000 person-years and an annual prevalence ratio of 5.2 per 100,000 persons. For both episcleritis and scleritis, there was a statistically significant increase in eye disease in older patients (P = 0.05 and <0.001, respectively) and for women in comparison with men (P = 0.001 and <0.001, respectively). Patients with scleritis were older than those with episcleritis (P = 0.017). Conclusions: This study found that patients with scleritis were older than those with episcleritis and that women had higher rates of both episcleritis and scleritis compared with what men had.

Treatment and management of scleral disorders.

Scleral inflammatory disorders, with their extensive differential diagnoses and sometimes as controversial treatment options, pose both diagnostic and clinical challenges for physicians. Targeted laboratory investigations derived from careful history taking and physical examination are crucial in the early identification of patients with associated systemic conditions. Prompt discrimination between episcleritis and scleritis is of therapeutic importance, as management, prognosis, and complications differ for these diseases. Although immunomodulatory and new biologic agents have improved the management of scleritis, continued studies are warranted to establish effective treatment guidelines across patient populations, especially in refractory cases.

The Epidemiology of Herpes Simplex Virus Eye Disease in Northern California

Abstract Purpose: To calculate the incidence and prevalence of herpes simplex virus (HSV) eye disease in a large, well-defined population in Northern California, USA, and to determine the recurrence rate following an initial episode of disease in this cohort. Methods: A retrospective, observational, cohort study using population-based data and medical record review. The patient database of a large, regional health maintenance organization (Northern California Kaiser Permanente) was searched, and the study population consisted of 1,042,351 people over a 1-year study period from 1 July 1998 through 30 June 1999. Only ocular HSV cases with definitive clinical or laboratory confirmed diagnoses were included. Active and inactive cases were included, however only active cases were used in incidence and prevalence calculations. Bilateral disease was counted as one case. Newly diagnosed cases were followed for recurrence from initial presentation through 31 December 2002. Results: After chart review of 322 possible cases, 71 new cases and 59 previously diagnosed active cases of ocular HSV were confirmed. This resulted in an incidence rate of 6.8 new cases/100,000 person-years (95% confidence interval, CI, 5.3–8.6). Incidence increased with age, and rates were highest in people over 75 years of age (p < 0.001). The recurrence rate in new cases was 18% for the 3-year follow-up time, and was equal to 5% per year (95% CI 3–9%). Conclusion: The incidence and prevalence of ocular herpes simplex in this study was lower than previously reported. Incidence increased with age, and there were significantly higher rates in the older population.