Complications of Uveitis: The Northern California Epidemiology of Uveitis Study.

PURPOSE: To describe the uveitis complications in a large, community-based cohort. METHODS: Retrospective, community-based, cross-sectional cohort study analyzing complications and associations with complications. RESULTS: A total of 844 cases of uveitis were found; 342 were new-onset, and 462 were prior-onset. In total, 29.5% of patients were affected by one or more complications associated with age, gender, course, and anatomic location of uveitis. Visual loss was experienced by 19.1% of patients and was associated with age, course of disease, and anatomic location of uveitis. Of the patients who developed glaucoma or elevated intraocular pressure over 30 mmHg, 3.9% (n = 33) were related solely to uveitis; 5.2% (n = 44) had an unclear or combined mechanism; and 1.8% (n = 15) were related solely to steroid response. Cystoid macular edema was associated with course of disease and anatomic location of uveitis. CONCLUSIONS: Complications affect a significant portion of uveitis patients, and are often associated with demographic and clinical factors.

The epidemiology of herpes simplex virus eye disease in Northern California.

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.

Perivascular exudates in frosted branch angiitis.

Three cases of young, minimally symptomatic patients found to have vitritis and extensive perivenous vitreous exudates resembling frosted branch angiitis are presented. Optical coherence tomography showed that these exudates appear to be extravascated from the vasculature. The material persisted over 1 year on immunosuppressive therapy, suggesting that its resolution should not be a treatment end point. These cases add to our understanding of the spectrum of clinical findings in frosted branch angiitis.

Prefoveal vitreous condensation in chronic inflammation.

Uveitis can produce a host of signs throughout the eye. Cylinders, snowballs, condensations, and snowbanks in the vitreous have been described. The authors report two cases of chronic ocular inflammation with a novel sign of a prefoveal white vitreous condensation. One patient is a 6-year-old child with intermediate uveitis and positive results for PPD, and the second is a 65-year-old woman with bilateral recurrent intraocular lymphoma. Both cases responded well to vitrectomy and treatment of the inflammation.

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.

Morphologic assessment for glaucoma in the Multicenter Uveitis Steroid Treatment (MUST) trial.

PURPOSE: To compare Reading Center (RC) cup-to-disc ratio (CDR) assessment from stereoscopic photographs with clinician estimation in a uveitis clinical trial. METHODS: Clinical estimation of CDR was performed by ophthalmologists via dilated biomicroscopy. Photographic evaluation was performed at an independent RC by masked, certified evaluators. Quality control was performed by repeat grading of 77 randomly selected images. RESULTS: Among 479 eyes with uveitis, 353 eyes had clinical and photographic grades for CDR. Agreement between clinical and RC grading was fair, with exact agreement of 29%. Agreement within 0.1 and 0.2 CDR was 70 and 93%, respectively (weighted κ = .34). Intergrader reproducibility at the RC was better (weighted κ = .59, ICC 0.74). CONCLUSION: Morphologic assessment of cup to disc ratio is an important outcome and safety measure for determining glaucomatous damage in clinical trials. Masked RC measurements are more likely to be accurate than biomicroscopic grading in identifying meaningful anatomical change associated with glaucoma.

Topical metal chelation therapy ameliorates oxidation-induced toxicity in diabetic cataract.

Oxidative stress plays a critical role in cataractogenesis, the leading cause of blindness worldwide. Since transition metals generate reactive oxygen species (ROS) formation, metal chelation therapy has been proposed for treatment of cataracts. However, the effectiveness of most chelators is limited by low tissue penetrability. This study is the first to demonstrate that the topically applied divalent metal chelator ethylenediamine tetraacetic acid (EDTA) combined with the carrier and permeability enhancer methyl sulfonyl methane (MSM) ameliorates both oxidation-induced lens opacification and the associated toxic accumulation of protein-4-hydroxynonenal (HNE) adducts. Both in vitro (rat lens culture) and in vivo (diabetic rats), EDTA-MSM (1) significantly reduced lens opacification by about 40-50%, (2) significantly diminished lens epithelial cell proliferation and fiber cell swelling in early stages of cataract formation in vivo, and (3) notably decreased the levels of protein-HNE adducts. These findings have important implications specifically for the treatment of cataract and generally for other diseases in which oxidative stress plays a key pathogenic role.

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.

Severe Hypotony Associated With Parry-Romberg Syndrome.

Parry-Romberg syndrome is a rare inflammatory disorder characterized by progressive hemifacial atrophy and ocular involvement. Two patients with Parry-Romberg syndrome who had mild heterochromic uveitis but developed profound ocular hypotony were evaluated. A 17-year-old girl and a 32-year-old woman with Parry-Romberg syndrome developed chronic uveitis with gradual worsening of intraocular pressure to 0 mm Hg. For the first time, ultrasound biomicrosopy found evidence of inflammation of the ipsilateral ciliary muscle in patients with hemifacial atrophy. The profound hypotony concomitant with ciliary body edema in two patients with Parry-Romberg syndrome provides a clue linking the systemic disease to the ocular findings.

The effect of biomicroscope illumination system on grading anterior chamber inflammation.

PURPOSE: To determine how a biomicroscope illumination system affects the grading of anterior chamber (AC) inflammation. DESIGN: Laboratory investigation. METHODS: An artificial AC was designed to replicate optically a human AC and was filled with 5-mum polystyrene beads suspended in ethanol. A high-definition video eyepiece camera recorded the moving beads. Using image processing software, the main outcomes measures determined were the average number of beads in a 1 x 1-mm field at varying widths of the slit-beam. RESULTS: The volume of light and number of beads observed increased significantly as the slit-beam widened. Additionally, 3 separate biomicroscopes of identical make and model were found to produce different levels of luminance at the same aperture dial settings, influencing the number of beads observed, with the brighter biomicroscope yielding higher bead counts. CONCLUSIONS: Ability to count beads and perhaps the ability to count inflammatory cells in an inflamed eye depend on a number of factors, including the level of illumination and width of the slit-beam. This study demonstrated that the brighter the illumination and the wider the beam, the more beads were observed. This illustrates the importance of standardizing biomicroscopy, particularly where consecutive observations are used to make clinical decisions and in cases of multicenter clinical trials where clinical data are evaluated across different facilities.

Assessment of methylsulfonylmethane as a permeability enhancer for regional EDTA chelation therapy.

Pharmacologic chelators do not effectively penetrate cell membranes and blood-brain barrier. This study assesses methylsulfonylmethane (MSM) as a permeability enhancer and an excipient to facilitate EDTA transport across biologic membranes, and to make possible localized, regional chelation. Topical application of MSM with C(14)EDTA onto the rat cornea led to uptake of the C(14)EDTA in all tested ocular tissues. Without MSM, EDTA did not penetrate the eye. The ability of MSM to deliver EDTA into an eye provides an opportunity for regional chelation therapy. Additionally, these studies suggest that MSM could also be an adjuvant for delivering ciprofloxacin and other chemical compounds to specific, local tissue sites.

Atopic disease and herpes simplex eye disease: a population-based case-control study.

PURPOSE: To determine whether atopy is associated with herpes simplex virus (HSV) ocular disease. DESIGN: Retrospective, population-based, case-control study. SETTING: Large, regional health maintenance organization (Northern California Kaiser Permanente). STUDY POPULATION: 1,042,351 people over a one-year period. OBSERVATION PROCEDURES: Electronic database search for HSV ocular disease and subsequent chart review determined study eligibility. Two age-matched control groups (one population-based and one clinic-based) were randomly chosen. Medical record review determined the presence of atopy. Severe atopic disease was defined by diagnostic code or illness requiring an emergency room visit, hospitalization, or treatment with a systemic corticosteroid. MAIN OUTCOME MEASURES: Presence of HSV eye disease, presence of atopy, and characterization of atopy severity. RESULTS: HSV eye disease was found in 172 patients. HSV cases had a greater prevalence of atopy (34%, 58/172) than the clinic-based (25%, 43/172) or the population-based controls (21%, 36/172, odds ratio (OR) 1.5, 95% confidence interval (CI) 0.9 to 2.6 and OR 1.9, 95%, CI 1.1 to 3.3, respectively). The association of HSV ocular disease with severe atopy was even greater, with a history of severe atopic disease in 13% (22/172) of patients with HSV ocular disease as compared with 6% (11/172) of patients in the clinic control group and 3% (5/172) of patients in the population control group (OR 2.0, 95% CI 0.7 to 5.9 and OR 4.8, 95% CI 1.6 to 19.2, respectively). CONCLUSIONS: Patients with HSV ocular disease are more likely to have a history of atopic disease, especially severe atopic disease, than age-matched controls.

Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study.

PURPOSE: To determine the incidence and prevalence of uveitis in a large, well-defined population in Northern California. DESIGN: Cross-sectional study using retrospective database and medical record review. PARTICIPANTS: A group of 2070 people within 6 Northern California medical center communities (N = 731 898) who had a potential diagnosis of uveitis. METHODS: The patient database of a large health maintenance organization (2 805 443 members at time of the study) was searched for all patients who, during a 12-month period, had the potential diagnosis of uveitis. Detailed quarterly gender- and age-stratified population data were available. Medical records of patients who potentially had uveitis and who were members of the 6 target communities were reviewed by 2 uveitis subspecialists to confirm the diagnosis of uveitis and to establish time of onset. Demographic and clinical data were gathered for patients meeting the clinical definition of uveitis. Incidence rates were calculated by using a dynamic population model. Prevalence rates were based on the mid-study period population. MAIN OUTCOME MEASURES: Presence and date of onset of uveitis. RESULTS: At midstudy, the population for the 6 communities was 731 898. During the target period, 382 new cases of uveitis were diagnosed; 462 cases of uveitis were diagnosed before the target period. These data yielded an incidence of 52.4/100 000 person-years and a period prevalence of 115.3/100 000 persons. The incidence and prevalence of disease were lowest in pediatric age groups and were highest in patients 65 years or older (P<0.0001). The prevalence of uveitis was higher in women than in men (P<0.001), but the difference in incidence between men and women was not statistically significant. Comparison between the group of patients who had onset of uveitis before the target period (ongoing uveitis) and the entire cohort of uveitis patients showed that women had a higher prevalence of ongoing uveitis than men and that this difference was largest in the older age groups (P<0.001). CONCLUSION: In this largest population-based uveitis study in the United States to date, the incidence of uveitis was approximately 3 times that of previous U.S. estimates and increased with the increasing age of patients. Women had a higher prevalence of uveitis than men, and the largest differences were in older age groups.

A novel technique for harvesting keratolimbal allografts from corneoscleral buttons.

PURPOSE: To describe a method for obtaining partial-thickness keratolimbal allografts from corneoscleral buttons to be used in corneal limbal stem cell transplantation. DESIGN: Description of device design and technique for use. METHODS: Cyanoacrylate tissue adhesive, placed on the posterior side of a trephinated corneoscleral rim, is used to secure the allograft to a disposable acrylic sphere that is attached to a cylindrical base. RESULTS: After fixation of the corneoscleral rim to the acrylic sphere, keratolimbal allograft harvesting is performed as a continuous strip dissection with a 65 Beaver blade. This technique minimizes trauma to the epithelial stem cells, provides excellent stability of the corneoscleral rim during harvesting, and preserves the central corneal button. CONCLUSIONS: This method for obtaining keratolimbal allografts effectively provides tissue stabilization during harvesting, minimizing epithelial stem cell trauma and eliminating the need for whole donor globes.