Peter R. Pavan

Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy

Summary Background In previous natural history studies and clinical trials, AIDS-related cytomegalovirus (CMV) retinitis has occurred primarily in patients with absolute CD4 counts of 50 cells/μL or less (0·05×10 9 /L) at the time of diagnosis. Methods We report five patients identified from our clinical practices who were diagnosed with CMV retinitis while their CD4 counts were above 195 cells/μL. We also analysed, based on CD4 counts, 76 AIDS patients with newly diagnosed CMV retinitis whose CD4 lymphocyte enumerations were done in laboratories that maintained certification in a common external quality control programme. Findings 5–24 weeks before retinitis was diagnosed, all five patients had had absolute CD4 lymphocyte counts of less than 85 cells/μL, and 4–7 weeks before diagnosis, all five patients had started taking highly active antiretroviral treatment (HAART) regimens. Only one (4%) of 27 patients enrolled in the trial between July, 1995, and February, 1996, had an absolute CD4 count of more than 50 cells/μL, and none of 27 had an absolute CD4 count of more than 100/μL on entry to the trial. However, from March, 1996 (when indinavir and ritonavir were approved by the FDA for marketing in the USA), to August, 1996, 14 (29%) of 49 patients had CD4 counts of more than 50/μL and seven (14%) of 49 had a CD4 count of more than 100 cells/μL on entry. Interpretation These findings suggest that the early immunological effects of HAART may not provide sufficient protection to prevent CMV retinitis in patients who have very low CD4 counts when therapy is started. Clinicians should note that CMV retinitis may now occur in patients who have CD4 counts of more than 100 cells/μL.

Rapidly Progressive Herpetic Retinal Necrosis: A Blinding Disease Characteristic of Advanced AIDS

Eleven patients with rapidly progressive herpetic retinal necrosis (RPHRN) complicating AIDS were investigated retrospectively to study the disease spectrum, systemic involvement, and therapy. The mean CD4 cell count was 24/microL. There was a characteristic disease pattern with rapid progression, 82% bilaterality, relative resistance to intravenous antiviral therapy, and 70% retinal detachment. Varicella-zoster virus was the probable cause in 10 patients (detected by polymerase chain reaction in two eyes investigated), and herpes simplex virus was the probable cause in one. Cutaneous zoster occurred previously in 73% but was not concurrent. Seventy-three percent had central nervous system disease, possibly virus-related. RPHRN may be a local herpetic recrudescence in an immune-privileged site with transneural spread. Only four of 20 affected eyes retained useful vision. Poor ocular bioavailability, retinal ischemia, acquired drug resistance, and strain pathogenicity may underlie treatment failure. Acyclovir therapy appears relatively ineffective. Combined intravenous and intravitreal therapy with foscarnet and ganciclovir may be the best current management. Research advances are needed urgently.

'Blow-outs' in the retinal pigment epithelium.

A hole was detected in the epithelium of a retinal pigment epithelium (RPE) detachment in two patients. Leakage through the hole led to an elevation of the overlying neurosensory retina in each case. The resulting vision was 20/70 in one eye and 20/30 in the other. The defects in the RPE occurred in a setting different from that usually seen with tears in the pigment epithelium and had a different clinical appearance.

Bilateral melanocytic uveal tumors associated with systemic non-ocular malignancy. Malignant melanomas or benign paraneoplastic syndrome?

A 90-year-old woman developed bilateral diffuse melanocytic tumors of the uveal tract nearly 1 year before she died from an occult ovarian carcinoma. Although the syndrome of bilateral diffuse melanocytic tumors of the uvea and systemic carcinoma has been described, the uveal tumors in this patient were different in that they were indistinguishable histologically from mixed cell-type malignant melanoma. Although the relationship between the systemic malignancy and the uveal tumors is unclear, the cytologic features of the uveal tumors in this syndrome are probably more variable than originally thought.

Exogenous endophthalmitis initially treated without systemic antibiotics.

PURPOSE In 1987, the authors reported the successful eradication of infection in 16 patients with culture-proven acute exogenous bacterial endophthalmitis using intravitreal but no systemic antibiotics. They retrospectively reviewed additional consecutive cases since then to determine if the initial omission of systemic antibiotics remained reasonable. METHODS Twenty patients had culture-proven endophthalmitis. Four patients initially received systemic antibiotics for orbital cellulitis (2 patients), prevention of a possible scleral buckle infection (1 patient), and ascending cholangitis (1 patient). The remaining 16 patients were treated initially with intravitreal antibiotics only. FINDINGS Three of these additional 16 patients ultimately required systemic antibiotics for orbital cellulitis (1 patient), infectious scleritis (1 patient), and prevention of central nervous system infection with Neisseria meningitidis (1 patient). Only in one patient who had a neglected endophthalmitis and in whom an orbital cellulitis ultimately developed were we unable to clear the intraocular infection. In the overall series of 32 patients, cultures yielded staphylococcal species in 16 eyes, gram-positive bacilli in 3, streptococcal infection in 5, gram-negative cocci in 1, and gram-negative bacilli in 7. Half of the 14 specimens (1 aqueous and 13 vitreal) collected at the time of 16 reinjections in 13 eyes yielded organisms. Half (16/32) of the eyes attained visual acuity of 20/40 or better; 87.5% (28/32) attained visual acuity of 20/400 or better. CONCLUSIONS Therapy with intravitreal antibiotics without systemic antibiotics is reasonable, unless the infection has extended (or is at risk to extend) beyond the globe. Such evidence includes an elevated temperature or leukocyte count, corneal ring abscess, proptosis, loss of extraocular movements, scleral abscesses or infectious scleritis, and, perhaps, the presence of a scleral buckle.

Exogenous Bacterial Endophthalmitis Treated Without Systemic Antibiotics

We treated 16 patients (16 eyes) with culture-proven exogenous bacterial endophthalmitis with intravitreal and subconjunctival antibiotics but without systemic antibiotics. After one to two sets of intravitreal injections, intraocular inflammation abated in all patients. After further surgery in four patients, all 16 eyes had clear media and attached retinas. Fifteen eyes attained a visual acuity of 20/400 or better; 12 eyes achieved 20/80 or better.

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 <or= .01), but abnormal CS remained associated with death even after adjustment for these diseases and for other known predictors of death among people with AIDS. Diseases characterized by microvasculopathy were more often identified as causes of death among individuals with abnormal CS than among those with normal CS, although the strength of the association was moderate (P = .06). CONCLUSIONS Abnormal CS among people with AIDS is associated with increased mortality, and is independent of other risk factors for death that are monitored routinely. The relationship may indicate life-threatening microvascular disease in other organs.

Submacular neovascular membrane and focal granulomatous inflammation

BACKGROUND Subretinal choroidal neovascular membranes in persons younger than 55 years old are commonly idiopathic or associated with the ocular histoplasmosis syndrome. There have been a few reports describing the histopathologic features of these membranes. Studies have shown that idiopathic membranes have the same morphologic features as membranes in age-related macular degeneration except for the absence of basal laminar deposits. METHOD The authors studied a clinicopathologic case of a macular lesion associated with two peripheral hypopigmented spots in a healthy 30-year-old woman. RESULTS The clinical and fluorescein angiographic findings in this patient were characteristic of submacular neovascular membranes, except that the edge of the lesion remained distinct in the late phase of the fluorescein angiogram. Results of histopathologic examination of the surgically excised membrane showed a well-circumscribed granuloma containing some eosinophils. Attenuated vascular spaces were present within the hard tubercle. Special stains for micro-organisms were negative. The patient had no evidence of a systemic inflammatory disease. CONCLUSIONS A visible edge despite intense staining in the late phases of a fluorescein angiogram may suggest the possibility of subretinal granulomatous inflammation in a lesion that otherwise appears like a neovascular membrane. The clinical distinction between this pattern of subretinal neovascularization and a typical idiopathic membrane may be important because subretinal granulomatous inflammation could respond to treatment with systemic corticosteroids.

Hypotony in Patients with Uveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial

Purpose: To assess the prevalence of hypotony in patients with severe forms of uveitis. Methods: The Multicenter Uveitis Steroid Treatment (MUST) Trial, a randomized study, enrolled 255 patients. Patients with hypotony at the baseline visit were identified. Results: Twenty (8.3%) of 240 patients with sufficient data had hypotony. Hypotony was more common in patients with uveitis ≥5 years duration (odds ratio [OR] = 5.0; p < .01), and in eyes with a history of ocular surgery (vitrectomy vs. none, OR = 3.1; p = .03). Hypotony was less in patients with older age of uveitis onset (>51 years vs. <51 years, OR = 0.1; p = .02), in Caucasian patients (OR = 0.1; p < .01) compared to African American patients. Hypotonous eyes were more likely to have visual impairment (OR = 22.9; p < .01). Conclusions: Hypotony is an important complication of uveitis and more commonly affects African-American patients, those with uveitis onset at a younger age, and those with longer disease duration. It is associated with visual impairment.

Cone electroretinograms and visual acuities of diabetic patients on Sorbinil treatment

Photopic, 30-Hz, and foveal electroretinograms were measured in 19 diabetic patients in an experimental study of the effects of short-term Sorbinil (an aldose-reductase inhibitor) on retinal function. Patients were assigned in double-blind fashion to Sorbinil (250 mg/day) or placebo groups and were tested at the outset and after four weeks of therapy. Comparisons (t-test) between the Sorbinil and placebo groups failed to show significant effects of treatment on electroretinograms, although there was a significant correlation within the Sorbinil group between foveal recordings and red cell sorbitol at the end of treatment. Analysis showed that increased foveal electroretinograms were found in patients with low initial retinopathy but not in those with greater retinopathy. Eight patients continued Sorbinil treatment for one year. Again patients improving their foveal measurements had less initial retinopathy than those not improving. This difference was significant after one year of treatment but not at four weeks.