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Purpose: To investigate possible alterations of erythrocyte aggregation and deformability, which are factors that can influence blood flow, in human immunodeficiency virus (HIV)-infected individuals and to determine whether these factors are related to the severity of immunodeficiency., Methods: Laboratory evaluations were performed on 46 HIV-infected individuals and 44 HIV-negative control subjects. Current and nadir (lowest previous) CD4+ T-lymphocyte counts were identified for each subject. Erythrocyte aggregation was measured using a fully automatic erythrocyte aggregometer. Factors related to erythrocyte aggregation were also determined: erythrocyte sedimentation rate (ESR), zeta sedimentation ratio (ZSR), and plasma fibrinogen levels. Erythrocyte deformability was observed at various fluid shear stress levels, with a laser diffraction ektacytometer. Correlations were sought between each of these measures and current or nadir CD4+ T-lymphocyte counts, and each measure was compared between three subgroups based on current and nadir CD4+ T-lymphocyte counts (severely immunosuppressed, immune reconstituted, never severely immunosuppressed)., Results: The following parameters were significantly different between HIV-infected subjects and controls: increased erythrocyte aggregation, at stasis (P < 0.001) and low shear stress (P < 0.001), increased ESR (P < 0.001), increased ZSR (P < 0.028), increased serum fibrinogen (P = 0.015), and decreased erythrocyte deformability (P < 0.001). Only erythrocyte aggregation at stasis correlated significantly with current CD4+ T-lymphocyte count (r = - 0.344, P = 0.022). None of the parameters was significantly different between HIV-infected subgroups., Conclusions: Increased aggregation and decreased deformability of erythrocytes are associated with HIV-infection regardless of the severity of immunodeficiency. HIV-infected individuals may be at risk for progressive retinal microvascular damage from persistent hemorheologic abnormalities, despite immune reconstitution associated with potent antiretroviral drug therapies.

Purpose: To evaluate retinal microvascular blood flow in human immunodeficiency virus (HIV)-infected individuals using scanning laser Doppler flowmetry (SLDF) and to seek correlations between flow and various laboratory measures that may predict alterations in flow., Methods: The Heidelberg Retina Flowmeter and SLDF software were used to acquire in vivo retinal blood flow data from 24 HIV-infected individuals and 16 HIV-negative control subjects. In each subject, separate scans were performed in each of six retinal regions: nasal parapapillary retina; macula; and the superior, nasal, inferior, and temporal periphery. Erythrocyte aggregation (assessed in vitro by a fully automatic erythrocyte aggregometer and by zeta sedimentation ratio [ZSR, a hematocrit-independent sedimentation rate]), serum fibrinogen level, plasma viscosity, and leukocyte rigidity (assessed in vitro with a cell transit analyzer) were compared with flow in selected regions., Results: Flow was significantly higher in the periphery (superior, nasal, inferior, temporal) than in the posterior retina (nasal parapapillary retina, macula). Flow was highest in the temporal periphery for both HIV-infected subjects and control subjects. Flow in the posterior retina was significantly lower in HIV-infected subjects than in control subjects (P < 0.0001). Among HIV-infected individuals, flow in the macula correlated negatively with ZSR (r = -0.397, P = 0.0547) and leukocyte rigidity (r = -0.505, P = 0.0119)., Conclusions: Microvascular blood flow in the posterior retina is reduced in HIV-infected individuals. Both increased erythrocyte aggregation and increased leukocyte rigidity contribute to this hemorheologic abnormality.

Purpose: To investigate the relationship between abnormal contrast sensitivity and abnormal color vision among human immunodeficiency virus (HIV)-infected individuals who have normal visual acuity and to seek host factors that predict these abnormalities., Design: Noninterventional, cross-sectional study., Methods: We evaluated 71 HIV-infected subjects with visual acuity of 20/25 or better, clear media, and no vision-threatening retinal lesions. Visual function was determined using the Pelli-Robson contrast sensitivity test and the Farnsworth-Munsell 100-Hue color test (FM-100). Results were compared with published values for normal populations and to measures of HIV disease severity. We evaluated two levels of impairment for each visual function. "Mild dysfunction" was defined as > or =1 standard deviation (SD), but <2 SD from normal means. "Abnormal" was defined as > or =2 SD from normal means., Results: The prevalences of abnormal contrast sensitivity and abnormal color vision were 7.0% and 9.9%, respectively. We did not identify relationships between impaired contrast sensitivity and impaired color vision. Impaired color vision was associated with increasing age (r = 0.36, P = .002). We could not identify significant correlations between either contrast sensitivity or color vision values and the following factors: current or nadir (lowest previous) CD4+ T-lymphocyte count, HIV blood level, and Karnofsky score., Conclusions: Abnormal contrast sensitivity and abnormal color vision can occur independently in HIV-infected individuals and can be present in the absence of severe immunosuppression.

Purpose: To compare the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease., Design: Retrospective comparative interventional case series., Settings: Nine international uveitis specialty clinics., Study Population: Forty-eight patients presenting over a three-year period to a study center with acute Vogt-Koyanagi-Harada disease., Intervention: Initial treatment with corticosteroid either orally (Oral only group) or intravenously followed by an oral taper (IV+Oral group)., Main Outcome Measures: Change in visual acuity with treatment; development of ocular complications, including visually significant cataract, choroidal neovascularization, subretinal fibrosis, fundus pigment migration, nummular hypopigmented lesions, and diffuse fundus depigmentation; use of immunosuppressive therapy., Results: The Oral only group comprised 15 patients (31%) and the IV+Oral group 33 patients (69%). Median follow-up was 15 months. There was no difference in duration of follow-up between groups (P = .234). There was no difference in the change in visual acuity between groups, adjusting for initial visual acuity (P = .402). There were no differences in the rates of development of visually significant cataract, fundus pigmentary changes, or in the rate of use of subsequent immunosuppressive therapy between treatment groups. No patients developed choroidal neovascularization or subretinal fibrosis over the study period., Conclusions: Route of administration of corticosteroid had no detectable effect on change in visual acuity nor on the development of visually significant complications over the study period. Prospective trials are necessary to address speed of resolution and definitively answer outcome questions.

Purpose: To describe the demographic and clinical characteristics of central serous chorioretinopathy (CSC) after solid organ transplantation., Design: Case series., Participants: Fifteen patients who presented to the authors with CSC after solid organ transplantation., Methods: We performed a retrospective chart review to identify patient demographics and clinical features of disease, including angiographic changes., Main Outcome Measures: Patterns of CSC. These patterns were compared with type of organ received, demographics, and visual outcome., Results: We identified 25 eyes of 7 women (46.7%) and 8 men (53.3%) that developed CSC after solid organ transplantation. Patient ages ranged from 27 to 55 years (median, 40). Seven of the 15 patients (46.7%) were Caucasian, including 3 Hispanic patients (20%). Of the 8 remaining patients (53.3%), 2 were African American (13.3%), 2 were Filipino (13.3%), and 4 were Asian (26.7%). The organs received included 13 kidneys (86.7%), 1 liver (6.7%), and 1 heart (6.7%). Systemic hypertension was reported in 14 of 15 patients (93.3%). All patients were receiving systemic immunosuppressive drugs at presentation; 14 of 15 (93.3%) were also receiving systemic corticosteroids. Visual acuity at presentation ranged from 20/20 to counting fingers. Patterns of CSC included (1) geographic or diffuse alterations in the retinal pigment epithelium (5 eyes; 2 bilateral, 1 unilateral), (2) focal CSC (6 eyes, all unilateral), (3) multifocal CSC (6 eyes; 2 bilateral, 2 unilateral), and (4) CSC with bullous retinal detachment (8 eyes, all bilateral). Follow-up, available for 21 affected eyes of 13 patients, ranged from 1 month to 6 years (median, 12 months). Compared with other solid organ transplant recipients at our institutions, renal transplant recipients (P = 0.003), as well as Hispanic and Asian patients (P = 0.05), were more prevalent in this cohort., Conclusion: Central serous chorioretinopathy after solid organ transplantation varies in presentation and severity. Our observations support a role for choroidal vascular compromise in the pathogenesis of this disorder.

Objective: To evaluate the prevalence of and risk factors for immune recovery uveitis (IRU) in eyes of patients with AIDS and cytomegalovirus (CMV) retinitis., Design: Enrollment data from a 19-clinical center cohort study., Participants: Three hundred seventy-four patients with AIDS and CMV retinitis affecting 539 eyes., Methods: Patients with AIDS were enrolled at 19 United States AIDS ophthalmology clinics. Data were collected by interview, review of medical records, ophthalmic examination, and phlebotomy., Main Outcome Measure: Immune recovery uveitis., Results: Thirty-six patients (9.6%) were diagnosed with IRU involving 50 eyes. The CD4+ T-cell count of 31 of these had risen by > or =50 cells per microliter above nadir to a level > or = 100 cells per microliter (immune recovery), making up 17.6% of the patients known to have immune recovery after diagnosis of CMV retinitis (95% confidence interval, 12.3%-24.1%). No patients with IRU were observed to have active retinitis or detectable CMV DNA in peripheral blood (P<0.001 and P<0.001 with respect to patients without IRU). Other factors associated with IRU were > or =25% retinal area (odds ratio [OR], 2.72; P = 0.014) or posterior pole involvement with CMV retinitis (odds ratio, 0.43; P = 0.039), treatment with intravitreous injection of cidofovir (OR, 10.6 with respect to eyes never exposed to intravitreous or IV cidofovir; P<0.001), and male gender (OR, 0.26; P = 0.012). More eyes with IRU had visual acuity (VA) of 20/50 or worse (38.0% vs. 26.3%, P = 0.077) relative to eyes without IRU, but the proportions with VA of 20/200 or worse were similar (14.0% vs. 13.8%, P = 0.96). Eyes with IRU more commonly had cystoid macular edema (CME) (45.5% vs. 3.7%, P<0.001) and epiretinal membrane (48.9% vs. 13.3%, P<0.001) than eyes without IRU., Conclusions: Among eyes of patients with immune recovery, the prevalence of IRU is substantial. Eyes with IRU have a high risk of additional morbidity over and above that seen with CMV retinitis, with several-fold higher risk of CME and epiretinal membrane. Large CMV lesions and use of intravitreous cidofovir are risk factors for IRU.

The city of Erechim, Brazil, has a 17% prevalence of ocular toxoplasmosis, and type 1 Toxoplasma gondii predominates. To examine risk factors for acute T. gondii infection in this area, we administered a questionnaire to recently infected persons (n = 131) and seronegative controls (n = 110). Eating undercooked meat; having a garden; working in the garden or yard more than once per week; eating rare meat; eating cured, dried, or smoked meat; eating frozen lamb; and being male increased risk for T. gondii infection in univariate analysis. Risk factors independently associated with acute T. gondii infection in multivariate analysis were working in the garden (odds ratio [OR] 2.35, 95% confidence interval [CI] 1.27-4.33) and eating frozen lamb (OR 2.06, 95% CI 1.15-3.67). Among women (n = 86), having had children markedly increased the risk for T. gondii infection (OR 14.94, 95% CI 3.68-60.73).

Purpose: To investigate complications associated with ganciclovir implants used to treat AIDS-related cytomegalovirus (CMV) retinitis, and to identify factors that predict poor outcomes., Design: Retrospective chart review., Participants: Consecutive patients with AIDS-related CMV retinitis from 3 clinical facilities who underwent implantation procedures during the period January 1, 1995 through December 31, 2001., Methods: Baseline for each patient was the date of the first implantation procedure performed during the study period by one of the facilities' surgeons (index implant). Medical and ophthalmological data were collected at baseline and at specific time points after baseline. The dates on which additional implantation procedures were performed and the dates on which complications or vision loss were identified were also recorded. Relationships between potential risk factors and outcomes were studied by Kaplan-Meier analyses and Cox proportional hazards regression models., Main Outcome Measures: Primary outcome measures included postoperative complications specifically related to or possibly related to ganciclovir implants. A secondary outcome measure was vision loss after implantation procedures., Results: The charts of 174 patients (one study eye per patient; 279 implants) were reviewed. Median follow-up was 14.4 months (range, 0-7 years). Complications specifically related to implants occurred throughout follow-up at a rate of 0.064 events per patient-year. Complications possibly related to implants occurred at an overall rate of 0.377 per patient-year, but seemed to be more common during the first 2 years after baseline. During the first 2 years of follow-up, retinal detachments occurred at a rate of 0.156 events per patient-year. The cumulative risk of vision loss (> or =3 lines of Snellen visual acuity) at 7 years was 70%. Poor outcomes were associated with disease factors (size and activity of lesions), lack of highly active antiretroviral therapy (HAART), and lack of HAART-associated immune reconstitution, but not with surgical factors or implant-specific complications., Conclusions: Complications specifically associated with ganciclovir implants can occur many years after implantation procedures, but the incidence of such complications is low. Continued vision loss is not attributable directly to complications of implants in most cases. This information will help in planning of treatment strategies for CMV retinitis in long-term survivors of human immunodeficiency virus disease.

Purpose: To investigate possible causes for, and implications of, variations in coding of glaucoma for patients with uveitis in the Medicare database., Patients and Methods: We identified 6,391 patients coded with one of several ICD-9 codes designating a form of uveitis from a 5% sample of the 1999 Medicare database. The proportion of patients with uveitis codes who also had codes for uveitic glaucoma, primary open-angle glaucoma (POAG), or unspecified open-angle glaucoma (OAG) were determined. The proportion with codes for argon laser trabeculoplasty (ALT), trabeculectomy, visual field examinations, fundus photographs, and gonioscopy were calculated in three groups: patients with both uveitis and uveitic glaucoma; those with both uveitis and POAG; and those with both uveitis and unspecified open-angle glaucoma. Summaries of the total allowed reimbursement related to eye visits and to eye codes were determined., Results: Of the 6,391 patients with uveitis who were studied, 1,260 (19.7%) also had the code for POAG; 412 (6.4%) had the code for OAG; and 117 (1.8%) had the code for uveitic glaucoma. Visual field testing was less common among patients with uveitic glaucoma (37%) than among those with POAG/uveitis (46%) or OAG/uveitis (44%) (P < 0.001). There were no statistically significant differences among the three groups in the amount of total reimbursement related to eye services or eye codes., Conclusions: The code for POAG appears to be used in lieu of uveitic glaucoma in many cases. Discrepancies are probably not influenced by expected reimbursements, as much as by a lack of understanding about the available ICD-9 codes.

Purpose: To present and evaluate research criteria for the diagnosis of birdshot chorioretinopathy., Design: Consensus statement., Methods: Investigators who attended an international conference on birdshot chorioretinopathy drafted diagnostic criteria, which were refined after comment by conference attendees. Sensitivity and specificity of the criteria were evaluated by review of 82 previously diagnosed cases and evaluation of 80 consecutive patients with other forms of uveitis., Results: Criteria, including presence of "birdshot lesions" and mild intraocular inflammation in both eyes, are based on clinical findings in the absence of systemic disease; HLA-A29 is supportive of diagnosis, but not required. Diagnostic criteria were found to be 100% specific and 97.5% sensitive. Positive predictive value was 100%; negative predictive value was 97.6%., Conclusions: Standardized criteria for the diagnosis of birdshot chorioretinopathy will facilitate clinical research and the comparison of results from studies performed at different institutions by ensuring a homogeneous population of study patients.

Purpose: To describe baseline clinical characteristics of a cohort of 80 patients with birdshot chorioretinopathy in anticipation of a longitudinal study, and to identify relationships between visual acuity, symptoms, and ophthalmic findings., Design: Single-center cross-sectional study., Methods: A standardized examination was performed in the same order on a single day for each patient. A grading system for birdshot lesions was established prospectively to evaluate the following lesion characteristics: quantity, distribution, morphology, and pigmentation. Relationships between clinical features of disease were sought in multivariate analyses that adjusted for age, duration of uveitis, and treatment., Results: Mean age at baseline examination was 55.6 years. Median best-corrected visual acuity (BCVA) was 0.8 (range, counting fingers to 1.2). There were no relationships between BCVA and any birdshot lesion characteristic. The most common cause of BCVA < or =0.4 was macular edema. Visual symptoms were present in 78 patients (97.5%), including 17 (94.4%) of 18 patients with BCVA > or =1.0 in both eyes. Blurred vision was associated with decreased BCVA (P = .02) and macular edema (P = .022). Increased lesion pigmentation was associated with complaints of blurred vision (P = .030), vibrating vision (P = .011), and nyctalopia (P = .056)., Conclusions: Symptoms are common in patients with birdshot chorioretinopathy, even among those with good BCVA. Lesion pigmentation may be a marker of decreased visual function that is not reflected in central visual acuity. These findings highlight the limitation of using visual acuity measurements for monitoring patients with birdshot chorioretinopathy and as an outcome measure for studies of this disease.

Herpes zoster ophthalmicus, although not uncommon in adults, is rarely found in children. Herein we present a case of pediatric herpes zoster ophthalmicus that is unique in 2 ways. First, the child had been vaccinated against varicella and otherwise had no known exposure to varicella-zoster virus. Second, the initial presentation of herpes zoster ophthalmicus was a painful and diffuse subconjunctival hemorrhage that appeared before any of its classic signs were observed. We report this case to document the possible occurrence of herpes zoster ophthalmicus in children who have been vaccinated against varicella and the possibility of a diffuse, painful subconjunctival hemorrhage as a presenting sign.

Birdshot chorioretinopathy is a well-known, yet poorly understood, form of posterior uveitis, characterized by multiple, distinctive, hypopigmented choroidal lesions, and strongly associated with human leukocyte antigen (HLA)-A29. We reviewed all English language publications regarding birdshot chorioretinopathy and performed analyses of combined patient data taken from these articles. The mean age at presentation was 53 years, with a slight female predominance (54.1%). At least 95.7% of reported patients have been HLA-A29-positive. Blurring of vision and floaters are the most prevalent presenting complaints, even in patients with visual acuity of 20/20 or better in both eyes. Birdshot chorioretinopathy is a slowly progressive disease with profound dysfunction of vision that may not be reflected in Snellen visual acuity. Two or more lines of Snellen visual acuity were lost in approximately 20% of eyes over a median follow-up of 3.5 years; macular edema was the most common cause of reduced visual acuity. Overall, patients had a slow decline in visual acuity, despite the fact that nearly all were treated with anti-inflammatory therapies. Final visual acuity in the better eye was 20/40 or better in 75.1% of patients and 20/200 or worse in 9.8% of patients. Oral corticosteroids and cyclosporine were the most commonly used medications. Using a regression model, patients in the literature that have been treated with cyclosporine alone had better final visual acuity than patients treated with oral corticosteroids alone. Further study is needed to determine the optimal methods for treating and monitoring patients with birdshot chorioretinopathy.

Purpose: To investigate the number of patient visits to ophthalmologists in the United States that are associated with ocular toxoplasmosis, and to assess ophthalmologists' knowledge and treatment practices with regard to the disease., Design: Written survey., Methods: A random sample of 1000 US ophthalmologists was surveyed by mail in early 2002 by a questionnaire that was developed to collect information about physician demographics, and with regard to toxoplasmosis, number of patients seen, management practices, and knowledge about pathogenesis and risk factors., Results: Among 478 respondents (48%), 261 (55%) indicated that they had seen one or more patients thought to have active toxoplasmic retinochoroiditis in the prior 2 years, and 445 (93%) indicated that they had seen one or more patients with inactive retinochoroidal scars thought to be inactive toxoplasmosis in the prior 2 years. There was a diversity of opinions regarding topics, including the timing of infection and risk factors for ocular involvement. Many ophthalmologists expressed uncertainty about questions regarding the disease., Conclusions: Ocular toxoplasmosis is associated with a substantial number of patient visits in the United States each year. A variable understanding of the disease indicates a need for continuing medical education regarding ocular toxoplasmosis.

Purpose: To compare clinician and fundus photograph reading center assessments of the cytomegalovirus (CMV) retinitis area and change in the CMV retinitis area over time, and to investigate how these assessments correlate with the visual field (VF) of eyes with CMV retinitis., Design: Analysis of pooled data from 2 multicenter randomized clinical trials and 1 prospective multicenter epidemiologic study., Participants: Ninety-five eyes of 79 patients. At baseline, each eye had CMV retinitis restricted to zone 1 and/or zone 2 (approximately the photographable postequatorial retina), as assessed by the evaluating clinician., Methods: Comparison of CMV retinitis area, change in area over time as assessed by clinicians and a fundus photograph reading center, and correlation of these assessments with VF measurement., Main Outcome Measures: Cytomegalovirus retinitis area, change in CMV retinitis area over time, and VF score., Results: Baseline assessments of the mean retinitis area were, by clinicians, 12.8% of the total retinal area and, by the reading center, 6.3% of the total retinal area (P<0.001). There was a positive correlation between clinician and reading center assessments of retinitis area at baseline (rho = 0.77 and P<0.0001 by Pearson correlation and rho = 0.54 and P<0.001 by concordance). Both clinician and reading center size measures correlated negatively with VF (Spearman correlation rhos = -0.38 and -0.52, respectively; P<0.001 each). Mean changes in area over a 3-month interval were, by clinicians, +1.2% and, by the reading center, +1.1% (P = 0.68). Regression analysis showed a positive concordance (rho = 0.42, P<0.001). Change in VF over a 3-month interval did not correlate with change in retinitis area as assessed by clinicians or the reading center., Conclusions: Awareness of the similarities and differences between clinician and reading center assessments of CMV retinitis area should permit clinicians to apply research data to clinical practice more effectively. Clinician assessment of retinitis area correlates negatively with VF, a clinically meaningful visual outcome in patients with CMV retinitis.

Purpose: To describe a keratopathy in patients with the human immunodeficiency virus (HIV) infection., Methods: Retrospective review of ophthalmic and medical records, including laboratory evaluations, of seven patients with HIV infection and posterior intracorneal opacities., Results: Each patient had a bilateral peripheral keratopathy located at the level of the Descemet membrane that was unassociated with intraocular inflammation. All patients were receiving highly active antiretroviral therapy (HAART). All patients had elevations in their CD4+ T-lymphocyte counts due to HAART prior to presenting with the corneal opacities. Five of the seven patients had elevated serum cholesterol, triglycerides, or both. Best-corrected visual acuity was 20/25 or better in six of the seven patients at the time of diagnosis, and vision remained stable through the follow-up period in all patients (median follow-up: 25 months; range: 14-82 months). The corneal opacities remained unchanged in all seven over the follow-up period., Conclusion: These patients have a bilateral keratopathy that appears to be non-progressive and has no effect on visual acuity.

Diagnosis and management of intraocular inflammation involves the assessment of cells and protein levels ("flare") in the aqueous humor. These factors are difficult to quantify precisely on clinical examination alone. Laser flare-cell photometry provides an automated technique to quantify these factors objectively, and it has been used in a variety of research and clinical situations to assess anterior segment inflammation. Any new technique requires evaluation to determine accuracy and reproducibility of measured values, and initial applications require critical appraisal to assess the value of the technique. Both in vitro and in vivo studies of laser flare-cell photometry have been performed to determine its validity and utility as a research and clinical tool. This article reviews published studies that describe the technique of laser flare-cell photometry; it provides new in vitro data that supplements information on the capabilities of this technique and factors that influence photometry results, and it reviews representative publications that have used laser flare-cell photometry for study of specific disease entities. This information can help clinicians and researchers to become familiar with the strengths and limitations of laser flare-cell photometry, to identify appropriate future uses for this technique, and to use it and interpret its results appropriately. Laser flare-cell photometry offers an opportunity to improve upon current techniques of inflammation assessment and should not be considered simply an objective surrogate for clinical grading of cells and flare at the slit-lamp biomicroscope. Its research applications and utility for monitoring patients with uveitis have not yet been fully explored.

We evaluated human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles as genetic markers for Vogt-Koyanagi-Harada (VKH) disease in Mestizo patients in Southern California. Mestizo individuals with VKH disease (n = 29) at two institutions were evaluated. Typing of HLA-DRB1 and DQB1 genes was performed using DNA-based techniques. Gene frequencies were compared to Mestizo individuals living in Southern California. All patients had HLA-DRB1*01, DRB1*04, DQB1*03 or DQB1*05, or a combination of these genes. The gene frequency of combined HLA-DR4 alleles was increased when compared to controls. The frequencies of HLA-DRB1*0404 and DRB1*0407 were increased compared to controls, but were not significant after Bonferroni correction. Three patients had the HLA-DRB1*0410 allele; this allele was not found in controls. All HLA-DRB1*01 positive patients had the DRB1*0102 subtype. No HLA-DQB1 allele was significantly increased compared to controls. This study is the first to identify a possible association between HLA-DRB1*0404 and VKH disease, as well as to find DRB1*0102 and DRB1*0410 in Mestizo patients.

Purpose: To determine whether birdshot retinochoroidopathy is associated with subtypes of the human leukocyte antigen (HLA)-A29 other than HLA-A*2902., Design: Experimental study., Methods: High-resolution DNA typing of HLA-A29 subtypes was performed on blood from 20 subjects with birdshot retinochoroidopathy using polymerase chain reaction-based typing methods. Results were compared with published controls., Results: Four of 20 subjects (20%) had the HLA-A*2901 allele; two were homozygous for HLA-A*29, and both had the HLA-A*2901 and HLA-A*2902 alleles. Among 18 subjects with only one HLA-A*29 allele, the HLA-A*2902 allele was found in 16 (89%) and the HLA-A*2901 allele was found in two (11%). No subject was found to have HLA-A*2903, HLA-A*2904, HLA-A*2905, or HLA-A*2906., Conclusions: Both HLA-A*2901 and HLA-A*2902 are associated with birdshot retinochoroidopathy. Our data do not support the previous suggestion that the HLA-A29.1 serotype may be protective against development of birdshot retinochoroidopathy. Additional studies will be required to determine whether the other, less common subtypes are associated with the disease. HLA-A29 subtype testing is not required for the clinical evaluation of HLA-A29-positive patients with birdshot retinochoroidopathy.

Purpose: To determine corneal levels of topically administered azithromycin and clarithromycin in a rabbit model., Design: Experimental animal study., Methods: Corneas of New Zealand albino rabbits were treated with topical azithromycin (2 mg/ml or 4 mg/ml) or clarithromycin (10 mg/ml). Topical azithromycin was prepared from an intravenous solution and topical clarithromycin from a suspension for oral use. All rabbits received one drop every 2 hours on the right eye. Groups of rabbits were treated for the following intervals: 6, 12, 24, and 48 hours (four rabbits for each combination of time point, drug, and dose). Corneal tissue was removed 1 hour after the last application. To investigate stability of tissue azithromycin levels, an additional group of four rabbits was treated for 24 hours, but corneal tissue was not removed until 24 hours later. Samples were homogenized, and drug concentrations were measured using high-pressure liquid chromatography (HPLC) analysis and bioactivity assay., Results: Corneal concentrations of azithromycin increased with drug dosage and duration of application. Rabbits treated with azithromycin tolerated the drug well without signs of irritation. Clarithromycin was undetectable in corneal tissue by HPLC and bioactivity assay for all rabbits. Some rabbits treated with clarithromycin had signs of ocular surface irritation., Conclusion: Measurable concentrations of azithromycin are achieved in corneal tissue after topical application in a rabbit model, and the drug is well tolerated. Azithromycin may be a useful antibiotic for the topical treatment of human corneal infections, but clarithromycin, in currently available formulations, may not be effective because of poor tissue penetration.

Purpose: To describe the presentation and management of the first identified case of ocular vaccinia infection associated with the current smallpox vaccination program., Design: Case report., Methods: Vaccinia virus was isolated by cell culture of a conjunctival swab. Direct staining with fluorescein isothiocyanate-labeled vaccinia antibody and polymerase chain reaction testing confirmed the diagnosis., Results: In February 2003, a 26-year-old woman developed right preseptal cellulitis and blepharoconjunctivitis following contact with a vaccinated member of the military. The preseptal cellulitis resolved with antibacterial therapy, and the conjunctival infection was treated successfully with a 14-day course of topical trifluridine and a single dose of intravenous vaccinia immune globulin., Conclusions: To facilitate rapid diagnosis and appropriate treatment, clinicians must maintain a high index of suspicion for ocular smallpox vaccine-associated adverse reactions in vaccine recipients and their close contacts.

Purpose: To review issues related to the diagnosis, examination, and treatment of children with uveitis that are important for ophthalmologists., Design: Literature review., Method: A review was made of pertinent reports from the medical literature, with commentary based on the authors' experiences and on discussions at an international workshop., Results: There are differences between children and adults in the differential diagnosis and manifestations of uveitis that should be considered during evaluation. There may be a higher risk of some ocular complications such as uveitic glaucoma, and the presence of other unique complications, such as amblyopia, in young patients during follow-up. With regard to treatment, children with uveitis may have unique dosing requirements and drug-associated risks such as growth retardation with systemic corticosteroids that must be considered. Examination and treatment may also be more difficult with children because of problems with patient cooperation., Conclusions: There are unique patient care issues associated with uveitis in children that must be considered by care providers. Attention to these issues will improve the well-being of this patient population.

Purpose: To investigate possible relationships between laser flare photometry values, complications of uveitis, and outcomes in children with chronic uveitis., Design: Retrospective chart review., Method: We evaluated patients with active, noninfectious anterior, intermediate, or panuveitis who were 16 years of age or younger and who had laser flare photometry at one of two academic institutions. Complications enumerated at baseline and during follow-up were compared with laser flare photometry values and to anterior chamber cell counts., Results: At least one laser flare photometry value ("flare"), defined as baseline measurement, was available for 59 patients (41 girls, 18 boys; mean age, 10.3 +/- 3.5 years); 38 of these patients had at least one additional measurement during follow-up (median 11 months). Complications of uveitis were present in 35 patients (59%) at baseline. There was a positive association between increased laser flare photometry values and complications at baseline (any complication [P =.007], posterior synechiae [P =.003]). The development of complications during follow-up was associated with the presence of complications at baseline (P =.018). A subgroup of patients with low flare at baseline had no complications during follow-up regardless of treatment given., Conclusions: There is a positive relationship between laser flare photometry values and the prevalence of complications of uveitis in children. Laser flare photometry provides a novel way to monitor children with uveitis. Future study will be needed to determine whether values have prognostic importance and whether a treatment strategy that minimizes flare results in fewer uveitic complications.

Purpose: To describe the effects of topical tacrolimus treatment of severe atopic eyelid disease., Design: Interventional consecutive case series., Methods: A description of clinical findings and therapeutic response for five consecutive adult patients (mean age, 56.2 years; range 44-62) treated with topical tacrolimus for severe atopic eyelid disease at one institution., Results: Five patients with bilateral atopic eyelid disease that was refractory to treatment with topical corticosteroids were treated with tacrolimus 0.03% ointment, applied to the affected eyelid skin of both eyes twice daily. Eyelid induration, erythema, and eczematous changes were substantially improved within 1 to 3 weeks after initiation of topical tacrolimus treatment in all patients. There was an associated decrease in ocular surface irritation and inflammatory signs in each of four patients who also had atopic keratoconjunctivitis. No adverse effect associated with tacrolimus treatment was noted during continued treatment for 5 to 14 months. All patients were able to discontinue longstanding use of topical corticosteroid drugs., Conclusions: Application of topical tacrolimus on eyelid skin may be effective for treatment of severe atopic dermatitis of the eyelids, and may have secondary benefits for atopic keratoconjunctivitis. Topical tacrolimus may be used for at least 1 year without apparent adverse reaction in some patients, although the rate of adverse reaction cannot be determined from this small series., (Copyright 2003 by Elsevier Science Inc.)

Purpose: To identify genetic markers for the tubulointerstitial nephritis and uveitis (TINU) syndrome by using human leukocyte antigen (HLA) genotyping., Methods: Eighteen patients who had TINU syndrome were evaluated at three institutions. Typing of class I and II genes was performed by using DNA-based techniques., Results: Significant associations were found with HLA-B14 (6/18 patients, 33.3%; control subjects, 5.5%; P = 0.0003; relative risk [RR] = 8.5), HLA-DQA1*01 (17/18 patients, 94.4%; control subjects, 46.6%, P = 0.0001; RR = 19.5), HLA-DQA1*0101 (14/18 patients, 77.8%; control subjects 22.2%; P < 0.0001; RR = 12.2), HLA-DQB1*05 (14/18 patients, 77.8%; control subjects 17.7%; P < 0.0001; RR = 16.3), HLA-DQB1*0501 (13/18 patients, 72.2%; control subjects 12.9%; P < 0.0001; RR = 17.6), HLA-DRB1*01 (14/18 patients, 77.8%; control subjects, 12.1%; P < 0.0001; RR = 25.5), and HLA-DRB1*0102 (13/18 patients, 72.2%; control subjects, 1.6%; P < 0.0001, RR = 167.1). The HLA haplotype most frequently identified in the study patients was HLA-DQA1*01/DQB1*05/DRB1*01 (13/18 patients, 72.2%)., Conclusions: TINU syndrome is strongly associated with HLA-DQA1*01, HLA-DQB1*05, and HLA-DRB1*01. The association with HLA-DRB1*0102 is one of the highest reported for any disease. Because these genes are in linkage disequilibrium, the role of the individual alleles is difficult to assess. Based on the results of the present study and on previously reported HLA associations in patients with TINU syndrome, the alphabeta dimer encoded by HLA-DQA1*01/DQB1*05 may be particularly important in conferring risk for development of this disease.

In 1952, Helenor Campbell Wilder (later Helenor Campbell Wilder Foerster) confirmed the growing suspicion that Toxoplasma gondii was a cause of uveitis in otherwise healthy adults by identifying the presence of parasites in eyes enucleated because of severe intraocular inflammation. Ocular toxoplasmosis was previously known to occur only in newborns with congenital T gondii infection. Her report ushered in a new era in the field of uveitis in which toxoplasmosis, rather than tuberculosis, was confirmed to be the most common cause of retinochoroiditis. Fifty years later, issues raised in her landmark publication are still being investigated.

Purpose: To determine the effect of long-term intermittent trimethoprim/sulfamethoxazole treatment on recurrences of toxoplasmic retinochoroiditis., Design: Prospective randomized open-labeled interventional clinical trial., Methods: A total of 124 patients with a history of recurrent toxoplasmic retinochoroiditis were randomized to treatment with one tablet of trimethoprim (160 mg)/sulfamethoxazole (800 mg) (Bactrim F; Roche Pharmaceuticals, Rio de Janeiro, Brazil) every 3 days (61 patients) or to observation without treatment (63 patients) and were followed monthly for up to 20 consecutive months for clinical signs of disease recurrence. A recurrence was defined as a new focus of necrotizing retinochoroiditis with active inflammation either adjacent to or remote from preexisting retinochoroidal scars., Results: Recurrences developed in four (6.6%) treated patients and in 15 (23.8%) controls (P =.01). Treatment was discontinued prematurely in four patients because of mild drug reactions., Conclusion: Long-term intermittent treatment with trimethoprim/sulfamethoxazole can reduce the rate of recurrent toxoplasmic retinochoroiditis.

Purpose: To update information that was published by the AMERICAN JOURNAL OF OPHTHALMOLOGY in 1991 about treatment practices for ocular toxoplasmosis by uveitis specialists., Design: Physician survey., Methods: A written questionnaire was distributed to all physician-members (n = 147) of the American Uveitis Society. The questionnaire was modeled after a similar device used to survey uveitis specialists in 1991. Information contained on 96 returned questionnaires was tabulated., Results: Among 79 respondents who evaluate and manage patients with ocular toxoplasmosis, 15% treat all cases regardless of clinical findings (in contrast to 6% in 1991). The major indications for treatment among other respondents were severe inflammatory responses and proximity of retinal lesions to the fovea and optic disk. The majority of clinical factors considered in five categories (vision, lesion location, lesion size, lesion characteristics, and vitreous inflammatory reaction) were identified to be relative or absolute indications for treatment by a greater proportion of respondents in the current survey than in the 1991 survey. A total of nine drugs (or commercially available combinations) were used in 24 different regimens as treatments of choice for typical cases of recurrent toxoplasmic retinochoroiditis, with the combination of pyrimethamine, sulfadiazine, and prednisone being the most commonly used regimen (29% of respondents)., Conclusions: Uveitis specialists appear to be more likely to treat patients with ocular toxoplasmosis in 2001 than in 1991. Although the majority of survey respondents adhere to a traditional approach to the management of toxoplasmic retinochoroiditis (a discrete course of systemic drug treatment during active disease using multiple antiparasitic drugs with or without corticosteroids), there is still no consensus regarding the choice of antiparasitic agents for treatment regimens. Survey results provide useful information for treating physicians and for clinical investigators interested in therapy.

Purpose: To determine whether polymorphonuclear leukocytes (PMNs) remain rigid after immune reconstitution in human immunodeficiency virus (HIV)-infected individuals with a history of severe immunosuppression., Methods: PMN rigidity was measured in vitro in three groups: (1) HIV-infected individuals with a history of CD4+ T-lymphocyte counts of less than 50/microL, but with current counts of more than 200/microL attributable to potent antiretroviral therapy (group 1); (2) HIV-infected individuals whose CD4+ T-lymphocyte counts had always been more than 200/microL (group 2); and (3) HIV-negative control subjects. Rigidity was determined with a cell transit analyzer (containing a micropore filter with 30 identical, 8-microm diameter pores), representing a simple in vitro model of a capillary bed. A longer PMN pore transit time reflects increased PMN rigidity., Results: PMN transit time (median) in group 1 (n = 11) was 3.34 ms, in group 2 (n = 9) was 3.19 ms, and in control subjects (n = 15) was 2.66 ms. PMN rigidity was significantly greater in groups 1 (P = 0.014) and 2 (P = 0.046) than in control subjects (Wilcoxon rank-sum test). A significant difference was not identified between groups 1 and 2 (P = 0.518)., Conclusions: The increased PMN rigidity known to occur in severely immunosuppressed HIV-infected individuals persists after immune reconstitution. Furthermore, PMN rigidity is increased in those HIV-infected individuals who do not have a history of severe immunosuppression. Because PMN rigidity can alter microvascular blood flow, HIV-infected individuals may remain at risk for retinal vascular damage in the era of potent antiretroviral therapy.

Objective: To assess the outcomes of clear lens extraction with intraocular lens (IOL) implantation during repair of retinal detachment by vitrectomy with silicone oil tamponade in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis., Design: Retrospective, noncomparative case series., Participants: Twelve eyes of 10 patients with AIDS, CMV retinitis, and retinal detachment., Intervention: All patients underwent phacoemulsification with posterior chamber IOL placement at the time of vitrectomy with silicone oil tamponade for repair of retinal detachment. A targeted postoperative refractive error of -5.00 diopters (D) to -3.00 D was chosen in an attempt to counteract the hyperopic effect of silicone oil., Main Outcome Measures: The following factors were evaluated: postoperative visual acuity, refractive error, and intraoperative and postoperative complications., Results: Median follow-up was 7 months (range, 1-46 months). For patients without macular necrosis, median best-corrected preoperative visual acuity was 20/75 (range, 20/20-20/800), and median best postoperative visual acuity was 20/50 (range, 20/20-20/400). Median final visual acuity was 20/140 (range, 20/25 to count fingers at 1 foot). The median postoperative refractive error (spherical equivalent) was -1.00 D (range, -4.00 D to +7.88 D). Reoperation was required in 3 of 12 eyes for recurrent macular detachment (1 with silicone oil underfill; 2 with proliferative vitreoretinopathy). The macula was attached in all eyes at last follow-up. Reattachment of the peripheral retina was achieved in 10 of 12 eyes. There were no anterior segment complications., Conclusions: Clear lens extraction with IOL placement during repair of retinal detachment with silicone oil tamponade does not seem to increase complications and may improve long-term visual rehabilitation, improve retinitis management by allowing better posterior segment visualization throughout the postoperative course, and decrease overall cost and morbidity associated with cataract extraction as a second procedure.

Purpose: To describe a cluster of Mycobacterium chelonae keratitis cases involving patients who underwent laser in-situ keratomileusis (LASIK) at a single refractive surgery center., Design: Descriptive case series of four patients and cohort study to identify disease associations., Methods: Examination schedules, diagnostic tests, and therapy were based on best medical judgment. Isolates from three patients were compared by pulsed-field gel electrophoresis. Epidemiologic studies were performed to identify the source of infection., Results: Seven of eight eyes developed M. chelonae keratitis following bilateral simultaneous LASIK. Each patient was thought to have diffuse lamellar keratitis initially, but all seven eyes were noted to have opacities suggestive of infectious keratitis by 13 to 21 days after surgery. All eyes had undergone hyperopic LASIK over four days in April 2001 by one surgeon in a community-based refractive surgery center. A cohort study of all patients undergoing LASIK at the same center in April 2001 revealed that M. chelonae keratitis occurred only in persons undergoing correction of hyperopia (seven of 14 eyes vs. none of 217 eyes undergoing myopic LASIK, P <.001). The only difference identified between procedures was use of masks created from a soft contact lens in hyperopic LASIK. Three isolates (three patients) were indistinguishable by pulsed-field gel electrophoresis. Eyes were treated with a combination of antimicrobial agents, including topical azithromycin in three patients, with resolution of infection in all eyes over 6 to 14 weeks. The source of infection was not identified on environmental cultures., Conclusion: Postoperative nontuberculous mycobacterial keratitis can occur in an epidemic fashion following LASIK. Topical amikacin, azithromycin, clarithromycin, ciprofloxacin, or a combination of these agents, appears to be effective treatment for these infections.

Objective: To determine whether relationships exist between elevated laser flare photometry values and common abnormalities and complications associated with uveitis., Methods: We retrospectively studied all patients with uveitis on whom laser flare photometry measurements ("flare") were obtained (N = 111) at 2 academic medical centers. The first laser flare photometry values obtained for each patient were compared with the presence or absence of the following abnormalities or complications associated with uveitis: keratic precipitates, posterior synechiae, cataract, macular edema, optic disc edema, and glaucoma. In bilateral cases, the eye with the higher flare was used in primary analyses., Results: Flare was significantly higher in patients with posterior synechiae (P<.001) and in those with macular edema (P =.02) than in patients with uveitis who did not have these complications. Flare was significantly higher in patients with prior cataract surgery or cataract at the study visit than in those without cataracts (P =.001). There was no significant difference in flare between patients with and without keratic precipitates, optic disc edema, or glaucoma. No relationships were found between abnormalities or complications and the level of inflammatory cells or flare as determined by clinical assessment. We also identified an inverse relationship between flare and visual acuity that was not completely explained by the presence of complications in a stepwise regression model., Conclusions: Although causal relationships were not established, associations between flare and some complications of uveitis suggest that aqueous humor protein may be an important factor in the development of these problems. Consequently, laser flare photometry could play a role in predicting outcomes or monitoring therapy for patients with uveitis.

Purpose: To determine whether human immunodeficiency virus (HIV)-infected individuals have decreased macular capillary blood flow in vivo., Design: Case control study., Methods: Macular leukocyte velocity and perceived leukocyte density were determined in 41 HIV-infected individuals without cytomegalovirus retinitis and 31 HIV-negative control subjects using the blue field simulation technique (BFS-2000, Oculix, Inc., Jenkintown, PA). Velocity and density measurements for HIV-infected individuals were compared to current and lowest previous CD4+ T-lymphocyte counts, HIV RNA blood levels, and blood leukocyte counts., Results: Mean macular leukocyte velocity was lower in HIV-infected individuals than in controls (P = 0.0006). No correlations were identified between velocity measurements and the following factors in HIV-infected individuals: current or lowest previous CD4+ T-lymphocyte count; or HIV RNA blood level. Mean perceived leukocyte density in HIV-infected individuals was lower than in controls (P = 0.003), but was not correlated with blood leukocyte count in HIV-infected individuals. No relationships were identified between macular leukocyte velocity and duration of medication use or duration of elevated CD4+ T-lymphocyte count in patients receiving potent antiretroviral therapy., Conclusions: Reduced macular leukocyte velocity may have important implications for understanding the retinal microvasculopathy of HIV disease, the pathogenesis of opportunistic retinal infections, and visual dysfunction in HIV-infected individuals who do not have opportunistic retinal infections. We found no evidence that macular leukocyte velocity increased with immune reconstitution.

Purpose: To describe the characteristics of ischemic maculopathy in patients with human immunodeficiency virus (HIV) infection, as a means of understanding this uncommon disorder more fully., Methods: This is a multicenter, retrospective review of clinical data available for five HIV-infected patients who were given the diagnosis of ischemic maculopathy., Results: All cases had been diagnosed on the basis of fluorescein angiograms obtained after patients complained of vision loss. Four of the five patients had bilateral macular disease. Visual acuity at presentation in the nine affected eyes ranged from 20/20 to count fingers. Vision loss was gradual in both eyes of one patient and was abrupt in onset in seven eyes. Each of the seven eyes with abrupt vision loss had opacification of the superficial retina and/or intraretinal hemorrhages near the fovea. Fluorescein angiography revealed enlargement of the foveal avascular zone and mild staining of the juxtafoveal vessels in affected eyes. Six eyes had active or clinically inactive cytomegalovirus retinitis at presentation, and a seventh eye developed cytomegalovirus retinitis 2 weeks later. All patients were receiving anticytomegalovirus drugs when they developed visual symptoms. Visual acuity remained stable in five eyes, became worse in two eyes, and improved in two eyes; final visual acuity ranged from 20/25 to count fingers., Conclusions: Ischemic maculopathy may cause profound and permanent vision loss in HIV-infected individuals. Fluorescein angiography should be considered in all HIV-infected patients with unexplained loss of vision. The pathogenesis of ischemic maculopathy remains unknown.

The world's medical literature on tubulointerstitial nephritis and uveitis (TINU) syndrome was reviewed, and data on 133 patients with TINU syndrome were identified. The median age of onset was 15 years (range 9-74 years) with a 3:1 female-to-male predominance. Common laboratory abnormalities included elevated Westergren erythrocyte sedimentation rates and elevated urinary beta-2-microglobulin levels. Ocular symptoms preceded systemic symptoms in 21% of cases, and followed systemic symptoms by up to 14 months in 65% of cases. Uveitis involved only the anterior segment in 80% of cases. Uveitis was bilateral at presentation in 77% of cases. Patients were treated with systemic corticosteroids in 80% of cases and with immunosuppressive drugs in 9% of cases. Uveitis recurred or followed a chronic course in 56% of patients and persisted for several years in some cases. Ocular complications (including posterior synechiae, cataracts, and elevated intraocular pressure) were reported in 21% of cases. The visual prognosis appears to be good. Persistent renal dysfunction was reported in 11% of cases, including five patients who required renal dialysis. TINU syndrome is a distinct clinical entity that may be under-recognized and may account for some cases of unexplained chronic or recurrent uveitis. It is important for ophthalmologists, nephrologists, and primary care providers to be familiar with this disorder to ensure early diagnosis and appropriate treatment.

Purpose: To determine whether there is a relationship between the aqueous humor protein level and outflow facility in patients with uveitis., Methods: Aqueous humor protein levels were determined by laser flare photometry, and outflow facility was determined by Schiotz tonography., Results: Thirty patients with uveitis and 10 control subjects were studied. Outflow facility was lower in patients with uveitis (0.21 +/- 0.12 microl/min x mm Hg) than in control subjects (0.33 +/- 0.05 microl/min x mm Hg, P < 0.001). Patients with uveitis and laser flare photometry results (flare) more than 20 photon units/msec (n = 21) had a lower outflow facility (0.17 +/- 0.07 microl/min x mm Hg) than patients with uveitis and flare less than 20 photon units/msec (n = 9, 0.32 +/- 0.14 microl/min x mm Hg, P = 0.004). Furthermore, no difference was identified between outflow facility in patients with active uveitis (those who had anterior chamber cells) and flare less than 20 photon units/msec and outflow in control subjects. In patients with uveitis, there was a linear correlation between flare and outflow facility (r = -0.50, P = 0.005). There was no relationship between flare measurements and either intraocular pressure or aqueous humor cell levels when scored with a clinical, semiquantitative system., Conclusions: Outflow facility is significantly reduced in patients with uveitis who have high aqueous humor protein levels. Outflow facility appears to be normal in patients with active uveitis whose flare levels are low, and therefore the association between flare and outflow facility does not appear to be an indirect reflection of elevated anterior chamber cells. It is possible that elevated aqueous humor protein levels contribute to the development of uveitic glaucoma in some individuals by decreasing aqueous humor outflow facility, although a causal relationship cannot be established on the basis of this study.

Purpose: To describe an association between Vogt-Koyanagi-Harada disease and Guillain-Barré syndrome., Methods: Case series, describing three patients., Results: In two patients, the disorders had their onsets within 2 weeks of each other; in the third patient, Vogt-Koyanagi-Harada disease occurred after 3 months, as Guillain-Barré syndrome resolved. All three patients had bilateral panuveitis typical of Vogt-Koyanagi-Harada disease. Each also developed well-accepted manifestations of Guillain-Barré syndrome, including paresis of the lower extremities (all patients), paresis of the upper extremities (two patients), paresis of cranial nerves (two patients), areflexia (all patients), and abnormal electromyography findings (two patients)., Conclusions: Vogt-Koyanagi-Harada disease may follow or occur simultaneously with Guillain-Barré syndrome. The fact that these two autoimmune disorders occur together in some patients suggest that they may share common disease mechanisms.

To better understand the relation of cytomegalovirus (CMV)-specific CD4+ T lymphocyte immunity and clinical outcome in AIDS-related CMV end-organ disease, 2 patient groups were prospectively studied: patients recently diagnosed with active CMV end-organ disease and survivors of CMV retinitis who had responded to highly active antiretroviral therapy and had quiescent retinitis when anti-CMV therapy was discontinued. Most patients with active CMV disease had negative CMV-specific CD4+ T lymphocyte responses at diagnosis, as measured by lymphoproliferation (7/7) or cytokine flow cytometry (3/5) assays. In contrast, all 10 subjects with quiescent retinitis and >150 absolute CD4+ T lymphocytes/microL whose anti-CMV therapy was discontinued during 6 months of follow-up had positive CMV-specific immune responses at least once by each assay. However, 6 of these 10 subjects also had negative CMV-specific immune responses > or =1 time. Such patients may be at risk for future CMV disease progression and should be closely monitored.

Purpose: To determine the causative virus in acute retinal necrosis (ARN) syndrome in a series of patients by calculation of modified Witmer coefficients., Design: Noncomparative case series., Participants: Ten patients with ARN syndrome from four medical centers., Methods: Aqueous samples, vitreous samples, or both were collected prospectively during surgery from patients with a clinical diagnosis of ARN syndrome. Serologic measures of intraocular and serum antibodies to potentially causative viruses were measured by enzyme-linked immunosorbent assay., Main Outcome Measures: Modified Witmer coefficients (immunoglobulin G and immunoglobulin A) for herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV), as well as adenovirus type 2, were calculated from aqueous or vitreous samples, or both., Results: Intraocular antibody measurements were strongly suggestive of a single diagnosis in 9 of 10 patients tested. Modified Witmer coefficients demonstrated intraocular antibody production to HSV in five patients and antibodies to VZV in four patients, and the measurement was inconclusive in one patient. No patients were positive for adenovirus or CMV. Strain-specific antibody titers demonstrated that all HSV-positive patients were reactive only to HSV-2. Herpes simplex virus type 2 was found predominantly in younger patients with ARN syndrome (mean age, 21.2 +/- 10 years; range, 17-39 years), whereas VZV was more commonly seen in older patients (mean age, 40.8 +/- 12.2 years; range, 29-58 years; P = 0.033). Immunoglobulin A testing confirmed immunoglobulin G testing in all patients examined., Conclusions: Although VZV is thought to be the most common cause of ARN syndrome, HSV-2 is an important cause of ARN syndrome, particularly in younger patients. Because infection with HSV-2 has important medical ramifications, these results suggest that determination of a causal agent should be considered in some cases of ARN syndrome.

Purpose: To understand better the natural history of ocular toxoplasmosis by reexamining a well-characterized population in Southern Brazil., Methods: Ophthalmological examination and serologic tests for Toxoplasma gondii infection were performed in 1997 on 383 individuals who had undergone the same evaluation in 1990., Results: Of 109 seronegative subjects in 1990, 21 (19.3%) became seropositive by 1997, and 2 (1.5% of previously seronegative patients; 9.5% of those known to have seroconverted) developed ocular toxoplasmosis. Seroconversion occurred more frequently in individuals under 17 years of age (16 of 46 patients, 34.8%) than in those greater than 17 years of age (5 of 63 patients, 7.9%; p = 0.002). Of 131 seropositive individuals who did not have ocular lesions in 1990, 11 (8.3%) had typical toxoplasmic lesions in 1997. Of the 13 individuals with non-specific hyperpigmented small retinal lesions in 1990, 3 (23%) presented with typical lesions in 1997., Conclusions: Acquired T. gondii infection can result in late development of ocular lesions. Small, non-specific hyperpigmented retinal lesions may represent sites of T. gondii infection in seropositive individuals.

Objectives: To describe ocular disease in 3 patients with posttransplant lymphoproliferative disorder (PTLD) and to identify the frequency of such ocular involvement., Methods: Medical record reviews. Using Kaplan-Meier analysis, we calculated the frequency of ocular involvement among pediatric patients with systemic PTLD after liver transplantation., Results: Each patient had bilateral anterior chamber cells. Biopsy of an iris nodule from a patient who had undergone cardiac transplantation confirmed the diagnosis of PTLD, but no signs of systemic PTLD were found. The other 2 patients had systemic PTLD after liver transplantation; 1 presented with iris nodules in both eyes and a subretinal mass in the left eye, while the other had bilateral anterior chamber cells only. Ocular signs improved slowly after reduction of immunosuppressive drug therapy. Ophthalmological examinations were performed on 22 of 25 pediatric patients with PTLD after liver transplantation; 2 had ocular disease. Kaplan-Meier analysis indicated a 20% risk of ocular involvement at 3 years after development of PTLD (95% confidence intervals, 0%-50%)., Conclusions: Posttransplant lymphoproliferative disorder should be considered in the differential diagnosis of uveitis after organ transplantation. Anterior chamber cells and iris nodules are the most common ocular signs, but the posterior segment can be involved. Ocular involvement can occur without evidence of systemic disease and can be asymptomatic. Reduction of immunosuppressive drug therapy is an appropriate treatment.

Purpose: To provide recommendations for the use of immunosuppressive drugs in the treatment of patients with ocular inflammatory disorders., Participants: A 12-person panel of physicians with expertise in ophthalmologic, pediatric, and rheumatologic disease, in research, and in the use of immunosuppressive drugs in patient care., Evidence: Published clinical study results. Recommendations were rated according to the quality and strength of available evidence., Process: The panel was convened in September of 1999 and met regularly through May 2000. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus., Conclusions: Although corticosteroids represent one of the mainstays in the management of patients with ocular inflammation, in many patients, the severity of the disease, the presence of corticosteroid side effects, or the requirement for doses of systemic corticosteroids highly likely to result in corticosteroid complications supports the rationale for immunosuppressive drugs (for example, antimetabolites, T-cell inhibitors, and alkylating agents) being used in the management of these patients. Because of the potential for side effects, treatment must be individualized and regular monitoring performed. With careful use of immunosuppressive drugs for treatment of ocular inflammatory disorders, many patients will benefit from them either with better control of the ocular inflammation or with a decrease in corticosteroid side effects.

Objective: To identify ocular and systemic factors that predict advancement of cytomegalovirus (CMV) retinitis during treatment., Methods: Patients with acquired immunodeficiency syndrome were enrolled in a multicenter clinical trial designed to evaluate foscarnet sodium and ganciclovir sodium as therapy for newly diagnosed CMV retinitis. Ocular characteristics at baseline and measurements of retinitis were assessed from fundus photographs by graders at a fundus photograph reading center. The following measures of advancement were assessed: (1) lesion border movement of at least 750 microm or development of a new lesion in involved eyes; (2) rate of increase in retinal area with CMV in involved eyes; and (3) development of retinitis in uninvolved eyes of patients with unilateral disease at baseline., Results: In eyes with retinitis, risk factors at baseline for advancement while receiving treatment included smaller area involved, active margins of retinitis, and posterior location. Risk factors for development of retinitis in uninvolved fellow eyes included blood and urine cultures positive for CMV and lower CD8(+) T-lymphocyte count., Conclusions: Lesion characteristics can be used to predict advancement of preexisting disease, whereas only systemic factors are associated with development of bilateral disease. These analyses describe retinitis activity before the introduction of potent antiretroviral therapies but provide an important reference point for patients in whom CMV retinitis develops after failure or intolerance of antiretroviral agents. Arch Ophthalmol. 2000;118:1196-1204