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Biomedical subjects

D N Friedberg

Publications and source records attributed to D N Friedberg.

At least 19 recordsLinked to original sources

Use of the ganciclovir implant for the treatment of cytomegalovirus retinitis in the era of potent antiretroviral therapy: recommendations of the International AIDS Society-USA panel.

PURPOSE: To describe the risks, benefits, and recommended use of the ganciclovir implant for the treatment of human immunodeficiency virus-related cytomegalovirus (CMV) retinitis in the era of potent antiretroviral therapy. METHODS: A panel of physicians with expertise in the use of the ganciclovir implant and in the management of CMV retinitis was convened by the International AIDS Society-USA. The panel reviewed and discussed available data, and developed recommendations for the use of the ganciclovir implant, the surgical technique, and related management issues. Recommendations were rated according to the strength and quality of the supporting evidence. RESULTS: The effect of potent antiretroviral therapy on the immunologic status of patients with human immunodeficiency virus disease has changed the manifestation and course of CMV retinitis in many patients. The clinical management of CMV retinitis and the role of the ganciclovir implant are thus changing. Factors in the decision to choose the ganciclovir implant include the patient's potential for immunologic improvement, location and severity of CMV retinitis, and the risks and costs associated with implantation and concomitant oral ganciclovir therapy. CONCLUSIONS: The ganciclovir implant is safe and effective for the treatment of CMV retinitis. The indications for its use should be modified to account for increased patient survival and the potential for CMV retinitis to be controlled by effective antiretroviral therapy. Optimal use of the ganciclovir implant and discontinuation of therapy in selected patients with improvement in immunity may result in better long-term visual outcomes.

AIDS-Related Opportunistic Infections↗

Blurred vision during sexual arousal associated with narrow-angle glaucoma.

PURPOSE: To describe three women with narrow-angle glaucoma who had transient blurred vision during sexual arousal. METHOD: Case reports. RESULTS: Three women, aged 37, 45, and 55 years, were seen with bilateral narrow-angle glaucoma and were treated with bilateral laser iridotomy. In each patient, additional surgery was required to control the glaucoma. After establishing a rapport with her physician, each patient described transient blurred vision, from a few minutes to several hours in duration, which began during sexual arousal. This symptom resolved after peripheral iridotomy and, in one patient, after laser iridoplasty. CONCLUSION: The association of transient blurred vision with sexual activity may delay presentation of patients with symptomatic narrow-angle glaucoma.

Adult↗

Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA.

OBJECTIVE: To provide recommendations for the treatment of acquired immunodeficiency syndrome-related cytomegalovirus (CMV) end-organ diseases, including retinitis, colitis, pneumonitis, and neurologic diseases. PARTICIPANTS: A 17-member panel of physicians with expertise in clinical and virological research and inpatient care in the field of CMV diseases. EVIDENCE: Available clinical and virological study results. Recommendations are rated according to the quality and strength of available evidence. Recommendations were limited to the treatment of CMV diseases; prophylaxis recommendations are not included. PROCESS: The panel was convened in February 1997 and met regularly through November 1997. 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 the epidemiological features of CMV diseases are changing in the setting of potent, combination antiretroviral therapy, continued attention must be paid to CMV diseases in patients infected with the human immunodeficiency virus to prevent irreversible endorgan dysfunction. The initial and maintenance treatment of CMV retinitis must be individualized based on the characteristics of the lesions, including location and extent, specific patient factors, and characteristics of available therapies among others. Management of relapse or refractory retinitis must be likewise individualized. Ophthalmologic screening for patients at high risk for retinitis or who have a prior diagnosis of extraretinal disease is recommended. Recommendations for gastrointestinal, pulmonary, and neurologic manifestations are included.

AIDS-Related Opportunistic Infections↗

Uveitis associated with human immunodeficiency virus infection.

PURPOSE: To report uveitis associated with human immunodeficiency virus (HIV) infection and to suggest guidelines for treatment. METHODS: Six HIV-seropositive patients (10 eyes) with anterior or posterior uveitis or both were evaluated. After ineffective prolonged treatment with systemic and topical corticosteroids, specific systemic antiretroviral therapy with zidovudine was initiated in all patients. Aqueous humor was cultured in three eyes of three patients, and vitreous humor was cultured in one eye of one patient. RESULTS: In all 10 eyes of six patients, there was resolution of inflammation in 10 to 42 days after commencement of treatment with zidovudine (600 to 800 mg/day), despite no or minimal response to corticosteroids. Cultures of aqueous humor from three eyes of three patients and culture of vitreous humor from one eye of one patient were positive for HIV; no other organism was isolated. Systemic evaluation disclosed no other identifiable cause for the uveitis in any patient. CONCLUSIONS: Infection with HIV appears to be a cause of uveitis. A trial of zidovudine may be warranted in HIV-seropositive patients with uveitis that is poorly responsive to corticosteroid treatment when no other cause is identified. The efficacy of other retroviral agents was not determined.

Adult↗

Chronic multifocal retinal infiltrates in patients infected with human immunodeficiency virus.

PURPOSE: To describe the clinical features of a disorder characterized by chronic multifocal retinal infiltrates and uveitis in individuals with human immunodeficiency virus (HIV) disease. METHODS: We reviewed the medical records of HIV-infected patients with multifocal retinal infiltrates of unknown cause seen by investigators at four institutions. The following data were collected: demographic characteristics, presenting signs and symptoms, laboratory test results, and course of disease. RESULTS: We identified 26 HIV-infected patients (50 involved eyes) with this syndrome. Median CD4+ T-lymphocyte count at presentation was 272 per microl (range, 7 to 2,118 per microl). The most common presenting symptom was floaters. Median visual acuity of involved eyes at presentation was 20/20 (range, 20/15 to 20/100) and remained stable (median, 20/20; range, 20/15 to 20/70) after a median follow-up period of 9 months (range, 0 to 110 months). Typical retinal lesions were gray-white or yellow, irregular in shape, and less than 200 microm in greatest dimension. All were located in the midperiphery or anterior retina and enlarged slowly or remained static in size. Mild to moderate anterior chamber or vitreous humor inflammatory cells were present in 47 of 50 eyes (26 of 26 patients). Retinal lesions possibly responded to zidovudine but not to acyclovir or ganciclovir. Anterior chamber and vitreous humor inflammatory reactions responded to topical or periocular injections of corticosteroid. CONCLUSIONS: Uveitis with chronic multifocal retinal infiltrates is a distinct clinical entity of unknown cause that occurs in HIV-infected patients. Retinal lesions may respond to antiretroviral therapy. Visual prognosis is good.

Acyclovir↗

Cytomegalovirus retinitis: diagnosis and status of systemic therapy.

Cytomegalovirus (CMV) retinitis is a disease of advanced immunosuppression that occurs almost exclusively in patients with CD4+ counts of < or =50 cells/mm3. Therefore, this disease usually presents in patients who have already been diagnosed with acquired immunodeficiency syndrome (AIDS). The rate of progression of untreated CMV retinitis is variable. Typical initial complaints of patients with CMV retinitis may include blurred or decreased vision, loss of peripheral or central vision, and multiple "floaters." The diagnosis of CMV retinitis requires ruling out a number of other ocular disorders that may be confused with CMV retinitis. This review discusses the different appearances of CMV retinitis at presentation and the possible retinal responses to therapy for CMV retinitis. An overview of intravenous (i.v.) ganciclovir or i.v. foscarnet as systemic therapy for treatment of CMV retinitis and their use in combination is also presented. Results indicate that combination therapy with both ganciclovir and foscarnet is more effective in controlling progression of CMV retinitis in relapsed patients than is monotherapy with either drug. However, combination systemic therapy is time-consuming, and this regimen has the greatest negative impact on quality of life. Treatment should involve a cooperative effort between the patient's ophthalmologist and the primary AIDS-treating physician. Both must be aware of the location and activity of the retinitis and of other medical conditions and concomitant medications.

AIDS-Related Opportunistic Infections↗

Oral ganciclovir as maintenance treatment for cytomegalovirus retinitis in patients with AIDS. Syntex Cooperative Oral Ganciclovir Study Group.

BACKGROUND: Cytomegalovirus retinitis, a sight-threatening infection associated with the acquired immunodeficiency syndrome (AIDS), currently requires lifelong intravenous treatment. An effective oral treatment would be an important advance. METHODS: We compared oral with intravenous ganciclovir in an open-label, randomized study in patients with AIDS and newly diagnosed, stable cytomegalovirus retinitis (the disease was stabilized by three weeks of treatment with intravenous ganciclovir). Sixty subjects were randomly assigned to maintenance therapy with intravenous ganciclovir at a dose of 5 mg per kilogram of body weight daily, and 63 to maintenance therapy with oral ganciclovir at a dose of 3000 mg daily. The subjects were followed for up to 20 weeks, with photography of the fundi conducted every other week. The photographs were evaluated at the completion of the study by an experienced grader who was unaware of the subjects' treatment assignments. RESULTS: Efficacy could be evaluated in 117 subjects; photographs were ungradable for 2 of the 117. On the basis of the masked assessment of photographs from 115 subjects, the mean time to the progression of retinitis was 62 days in those given intravenous ganciclovir and 57 days in those given oral ganciclovir (P = 0.63; relative risk [oral vs. intravenous], 1.08; 95 percent confidence interval for the difference in means, -22 to +12 days). On the basis of funduscopy by ophthalmologists who were aware of the subjects' treatment assignments, the mean time to progression was 96 days in subjects given intravenous ganciclovir and 68 days in subjects given oral ganciclovir (P = 0.03; relative risk [oral vs. intravenous], 1.68; 95 percent confidence interval for the difference in means, -45 to -11 days). Survival, changes in visual acuity, the incidence of viral shedding, and the incidence of adverse gastrointestinal events were similar in the two groups. Neutropenia, anemia, intravenous-catheter-related adverse events, and sepsis were more common in the group given intravenous ganciclovir. CONCLUSIONS: Oral ganciclovir is safe and effective as maintenance therapy for cytomegalovirus retinitis and is more convenient for patients to take than intravenous ganciclovir.

AIDS-Related Opportunistic Infections↗

Risk factors for development of rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis.

We studied 259 patients to determine the time-dependent risk and risk factors for the development of retinal detachment in patients with cytomegalovirus retinitis. The six-month and one-year retinal detachment rates (by eye) were 11% and 24%, respectively. Increasing retinal surface involvement outside of the posterior pole and the presence of retinitis activity were found to be the two covariates that best predicted retinal detachment. Eyes with peripheral involvement greater than 25% had a fivefold risk for detachment, compared to eyes with 10% involvement. If there was retinitis activity and more than 25% peripheral (external to major vascular arcades) involvement, the risk increased to 24-fold. The presence of a fellow eye with retinal detachment was not an independent risk factor. These observations should help in the design of a prophylactic trial intended to prevent retinal detachment and should also help ophthalmologists counsel patients with cytomegalovirus retinitis.

AIDS-Related Opportunistic Infections↗

Concurrent use of ganciclovir and foscarnet to treat cytomegalovirus infection in AIDS patients.

Ten patients with AIDS and progressive cytomegalovirus disease were treated with ganciclovir and foscarnet concurrently. The patients had received ganciclovir and foscarnet monotherapy a median of 330 days before receiving combination therapy for a median of 80 days. Nine of the 10 patients responded to the combination. No electrolyte abnormalities were noted during combination therapy, but rates of neutropenia (relative rate, combination vs. ganciclovir, 1.99; P = .229) and thrombocytopenia (relative rate, combination vs. ganciclovir, 1.53; P = .616) were higher with combination therapy than with either drug alone. The relative rate of anemia was significantly increased with combination therapy compared with monotherapy (relative rate, combination vs. ganciclovir, 2.69; P = .025). These data suggest that combination ganciclovir and foscarnet therapy after failure of either alone appears to be as effective as standard therapy with single agents. The rate of anemia with combination therapy was significantly greater than either agent alone, but no significant difference was noted among the other parameters of toxicity studied.

AIDS-Related Opportunistic Infections↗

Epibulbar molluscum contagiosum in acquired immune deficiency syndrome. Case report and review of the literature.

BACKGROUND: While molluscum contagiosum of the eyelid skin is commonly complicated by conjunctivitis, primary involvement of the conjunctiva or cornea by molluscum lesions is exceedingly rare. The authors studied a 34-year-old man with acquired immune deficiency syndrome (AIDS) in whom multiple molluscum lesions of the lids and a single nodule of the limbus developed. METHODS: The nodular lesion was excised from the limbus and processed for histologic examination by light microscopy. Pertinent literature concerning epibulbar molluscum contagiosum was reviewed. RESULTS: Histopathology of the excised lesion showed molluscum bodies within the acanthotic, hyperkeratotic conjunctival epithelium with surrounding chronic, nongranulomatous inflammation. Only 10 previous cases of conjunctival or corneal primary lesions have been reported, half of which showed associated cutaneous involvement. Lesions tended to be single, noninflamed, dome-shaped, and umbilicated, often with a yellowish central core. Patients were otherwise well and ranged in age from 3 to 55 years. Simple excision was effective in eradicating the lesions. CONCLUSION: Primary epibulbar molluscum contagiosum is rare. Although cutaneous molluscum is common in AIDS, this report is the first to document conjunctival molluscum in a patient with AIDS.

Acquired Immunodeficiency Syndrome↗

Isolation and characterization of a new human microsporidian, Encephalitozoon hellem (n. sp.), from three AIDS patients with keratoconjunctivitis.

A new human microsporidian was isolated from cultures of Madin-Darby canine kidney cells incubated with conjunctival scrapings or corneal tissues from three AIDS patients with keratoconjunctivitis. The three isolates were morphologically similar to Encephalitozoon cuniculi. The spores averaged 1 x 1.5-2.0 microns, had six to eight polar filament coils, displayed monokaryotic nuclei, and possessed relatively thick endospores with irregularly shaped exospores. Organisms developed within a parasitophorous vacuole. By SDS-PAGE analysis, the three isolates appeared to be identical but were different from E. cuniculi. Identical banding patterns on Western blots of the three isolates were expressed by each patient's serum. By Western immunoblotting, murine antisera to E. cuniculi reacted to several antigens of the new AIDS-related microsporidian, whereas murine antisera bound weakly to Nosema corneum. The name Encephalitozoon hellem (n. sp.) is proposed to identify this new human microsporidian.

Acquired Immunodeficiency Syndrome↗

Microsporidial keratoconjunctivitis in acquired immunodeficiency syndrome.

We describe three patients with acquired immunodeficiency syndrome who presented with a bilateral coarse superficial epithelial keratitis due to infection with the protozoal parasite Microspora, Encephalitozoon cuniculi. Despite the extent of the corneal surface disease, conjunctival inflammation was minimal. Visual acuity ranged from 20/20 to 20/200. In one patient, the keratitis was complicated by the development of a surface defect with secondary Pseudomonas species infection. All patients had a history of exposure to household pets. Standard cultures were negative. Diagnosis was established in two of the three cases based on characteristic appearance of the protozoan in conjunctival scrapings. Electron microscopy of a conjunctival biopsy specimen in one patient confirmed the species. No recognized effective treatment is available for this infection.

Acquired Immunodeficiency Syndrome↗