Outcomes associated with ganciclovir implants in patients with AIDS-related cytomegalovirus retinitis.

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.

Birdshot chorioretinopathy.

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.

Drusen-associated degeneration in the retina.

PURPOSE: Drusen are variably sized extracellular deposits that form between the retinal pigmented epithelium (RPE) and Bruch's membrane. They are commonly found in aged eyes, however, numerous and/or confluent drusen are a significant risk factor for age-related macular degeneration. The purpose of this study was to investigate the impact of drusen on overlying cells of the retina. METHODS: Tissue containing retina and RPE/choroid was dissected from human donor eyes, embedded in agarose, and sectioned at 100 micro m using a vibratome. Sections were immunostained with a panel of antibodies that labeled glial cells, first-, second-, and third-order retinal neurons and processed for confocal microscopy. RESULTS: Retinal cells that overlie both soft and hard drusen exhibited numerous structural and molecular abnormalities. Normally detectable only in the outer segments of rod photoreceptors, rod opsin immunolabeling was also observed in the inner segment, cell body, axon, and axon terminal of photoreceptors that overlie drusen. Labeling with this antibody also revealed the deflection and shortening of rod inner and outer segments. Cone photoreceptors displayed similar structural abnormalities, as well as a decrease in cone opsin immunoreactivity. Drusen-associated abnormalities in the synaptic terminals of photoreceptor cells were also observed. In addition, an increase in intermediate filament protein immunoreactivity (vimentin and glial fibrillary acidic protein) was observed within Müller glial cells in areas of retina overlying drusen. Both soft and hard drusen were associated with a similar spectrum of effects in both macular and extramacular regions. Second- and third-order neurons, including bipolar, horizontal, amacrine, and ganglion cells all appeared unaffected. The structural and molecular abnormalities observed in photoreceptors and Müller glial cells were confined to retinal regions directly overlying and immediately adjacent to drusen; more distant retinal regions appeared unperturbed. Remarkably, significant abnormalities were observed over small subclinical drusen. CONCLUSIONS: Retinal cells overlying both soft and hard drusen exhibit structural and molecular abnormalities indicative of photoreceptor degeneration and Müller glial activation. These abnormalities resemble the degenerative effects common to many forms of retinal degeneration, but are confined to areas directly overlying drusen. This suggests that photoreceptor cell function is compromised as a consequence of drusen formation.

Human leukocyte antigen A29 subtypes associated with birdshot retinochoroidopathy.

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.

Association between abnormal contrast sensitivity and mortality among people with acquired immunodeficiency syndrome.

PURPOSE: To investigate the relationship between contrast sensitivity (CS) and mortality among people with acquired immunodeficiency syndrome (AIDS); and to explore the hypothesis that abnormal CS is a marker of systemic, life-threatening microvascular disease. DESIGN: Longitudinal, observational cohort study. METHODS: We evaluated 3395 eyes of 1706 individuals enrolled in the Longitudinal Study of the Complications of AIDS (1998-2008). CS was evaluated as a risk factor for death, and was compared to the presence of systemic diseases characterized by microvasculopathy (diabetes, cardiovascular disease, stroke, renal disease) and to laboratory markers of those diseases. Abnormal CS was defined as logCS <1.5 (lower 2.5th percentile for a normal control population). RESULTS: CS was abnormal in 284 of 1691 (16.8%) study participants at enrollment. There was a positive relationship between the presence of abnormal CS at study entry and mortality (relative risk 2.0, 95% confidence interval 1.7-2.3, P < .0001). Abnormal CS was related to the presence of cardiovascular disease, stroke, and renal disease (all P values

Contrast sensitivity among patients with birdshot chorioretinopathy.

PURPOSE: To assess contrast sensitivity in patients with birdshot chorioretinopathy; to identify relationships between contrast sensitivity, other measures of visual function, clinical findings, and quality of life. DESIGN: Single-center, cross-sectional study. METHODS: We measured contrast sensitivity in 63 patients (126 eyes) at four spatial frequencies (3, 6, 12, 18 cycles/degree [cpd]) using the CSV-1000E instrument (VectorVision, Greenville, Ohio, USA). Abnormal contrast sensitivity was defined as two standard deviations below the mean for population norms. Results at spatial frequency 12 cpd were compared to the following parameters in per-eye analyses: best-corrected visual acuity (BCVA); presence of eight specified symptoms; color vision; visual field parameters (foveal threshold, mean deviation); and optical coherence tomography parameters (central macular thickness, loss of the third highly reflective band). Results were compared to the National Eye Institute Visual Function Questionnaire (VFQ)-25 in per-patient analyses. Results were adjusted for age, disease duration, treatment, BCVA, and lens status. RESULTS: Contrast sensitivity (spatial frequency 12 cpd) was abnormal in 99 eyes (92%), and was related to poor BCVA (P = .0004) and the symptom of poor contrast sensitivity (P = .025). Among 38 eyes with normal BCVA (> or =1.0), 31 eyes (82%) had abnormal contrast sensitivity. There was a positive correlation between contrast sensitivity in better eyes and the VFQ-25 composite scores (r = 0.51; P < .001). CONCLUSION: Decreased contrast sensitivity is common in patients with birdshot chorioretinopathy and may occur in the absence of other visual changes. Contrast sensitivity may be a useful measure for clinical studies of birdshot chorioretinopathy and for monitoring patients with the disease.