Cytomegalovirus Retinopathy Research Articles

Transscleral Iontophoresis of Foscarnet

Current local treatments of cytomegalovirus retinopathy may result in serious intraocular complications. Using an animal model, we investigated transscleral iontophoresis as a technique for delivery of foscarnet to the vitreous. Using a probe tip surface area of 0.19 mm2, a current of 1 mA, and a duration of ten minutes, transscleral iontophoresis of 0.5 ml of a 24-mg/ml foscarnet solution was administered to 72 normal rabbits. Vitreous aspiration was performed at 12 intervals (15 minutes, 30 minutes, and one, two, four, eight, 16, 24, 32, 40, 48, and 60 hours) after iontophoresis, and samples were analyzed by high-performance liquid chromatography to determine the vitreous pharmacokinetics of foscarnet. A peak foscarnet concentration of 200 +/- 31 microM (mean +/- standard deviation) was attained four hours after iontophoresis and was well below the concentration reported to cause retinal toxicity. Therapeutic levels were maintained until 60 hours after iontophoresis. The elimination half-life was approximately 24 hours. No toxic effects to anterior chamber structures were observed by biomicroscopy. Transscleral iontophoresis of foscarnet may provide an effective and safe technique for local treatment of cytomegalovirus retinopathy in patients with acquired immunodeficiency syndrome.

Cytomegalovirus Retinopathy as the Initial Manifestation of the Acquired Immunodeficiency Syndrome

Of 100 consecutive patients with human immunodeficiency virus infection and cytomegalovirus retinopathy, 15 did not have a previous diagnosis of the acquired immunodeficiency syndrome before the ocular infection. All had other HIV-related disorders that would place them in Group IV of the Centers for Disease Control hierarchical classification system for HIV infections. In nine patients, cytomegalovirus retinopathy was the only disorder that fulfilled the Centers for Disease Control criteria for diagnosis of AIDS. In the other six, examination disclosed additional preexistent or concurrent nonocular disorders that were also diagnostic of AIDS. No demographic, medical, or ophthalmic characteristics distinguished the nine patients for whom cytomegalovirus retinopathy was initially the only manifestation of AIDS. On the basis of published figures for the prevalence of cytomegalovirus retinopathy in patients with AIDS, and the incidence with which HIV-infected persons develop AIDS, it is estimated that approximately 1.8% of patients with AIDS have cytomegalovirus retinopathy as the first manifestation and that less than 1% of HIV-infected persons will develop cytomegalovirus retinopathy as the initial manifestation of AIDS during the first seven years after infection with HIV.

The Management of Retinal Detachments in Patients With Acquired Immunodeficiency Syndrome

Rhegmatogenous retinal detachments are common complications of necrotizing infections of the retina, including cytomegalovirus (CMV) retinopathy in patients with acquired immunodeficiency syndrome (AIDS). As the length of survival of patients with AIDS increases, and as we improve our ability to control CMV retinopathy with new antiviral drugs, attention has been focused on the appropriate management of these retinal detachments. The article by Jabs and associates 1 in this issue of theArchivesis a major contribution to the literature addressing this important problem. Issues of concern extend far beyond the techniques of repair of CMV retinopathy. They include risk factors, indications for surgical referral, and expected outcomes. The severity of AIDS and the high mortality of patients with AIDS and CMV retinopathy must be considered in planning the management of these retinal detachments. It is on these issues, which should concern all ophthalmologists, that I will concentrate. Cytomegalovirus retinopathy is

Rhegmatogenous Retinal Detachments in Patients with AIDS and Necrotizing Retinal Infections

Rhegmatogenous retinal detachments can occur in patients with acquired immune deficiency syndrome (AIDS) and necrotizing retinal infections. Of 68 patients with AIDS and necrotizing retinal infections seen between 1983 and 1987, rhegmatogenous retinal detachments developed in 16 patients (27 eyes). In this group, cytomegalovirus retinopathy was present in 75% (12 of 16) of patients, 18.8% (3 of 16) had probable herpes simplex virus retinopathy, and 6.2% (1 of 16) had toxoplasmic retinochoroiditis. Retinal detachment was bilateral in 68.8% (11 of 16) of patients. The retina was reattached successfully in 91% (10 of 11) of operated eyes. Proliferative vitreoretinopathy was present preoperatively in 95% of these eyes. Seven of 11 operated eyes had initial improvement in visual acuity. However, 5 of 11 continued to lose vision despite successful reattachment. Techniques included pneumatic reattachment, scleral buckle, vitrectomy, and silicone oil injection. Complicated retinal detachments in AIDS patients with rhegmatogenous retinal detachments and necrotizing retinal infections are common and can be repaired, but the prognosis is guarded in many patients.

Rhegmatogenous Retinal Detachments In Patients With AIDS and Necrotizing Retinal Infections

Rhegmatogenous retinal detachments can occur in patients with acquired immune deficiency syndrome (AIDS) and necrotizing retinal infections. Of 68 patients with AIDS and necrotizing retinal infections seen between 1983 and 1987, rhegmatogenous retinal detachments developed in 16 patients (27 eyes). In this group, cytomegalovirus retinopathy was present in 75% (12 of 16) of patients, 18.8% (3 of 16) had probable herpes simplex virus retinopathy, and 6.2% (1 of 16) had toxoplasmic retinochoroiditis. Retinal detachment was bilateral in 68.8% (11 of 16) of patients. The retina was reattached successfully in 91% (10 of 11) of operated eyes. Proliferative vitreoretinopathy was present preoperatively in 95% of these eyes. Seven of 11 operated eyes had initial improvement in visual acuity. However, 5 of 11 continued to lose vision despite successful reattachment. Techniques included pneumatic reattachment, scleral buckle, vitrectomy, and silicone oil injection. Complicated retinal detachments in AIDS patients with rhegmatogenous retinal detachments and necrotizing retinal infections are common and can be repaired, but the prognosis is guarded in many patients.

Survival of Patients With the Acquired Immune Deficiency Syndrome After Development of Cytomegalovirus Retinopathy. UCLA CMV Retinopathy Study Group

Survival of Patients With the Acquired Immune Deficiency Syndrome After Development of Cytomegalovirus Retinopathy. UCLA CMV Retinopathy Study Group

Cytomegalovirus retinopathy and the immune deficiency syndrome: Results of treatment with ganciclovir

Cytomegalovirus (CMV) infection of the retina is the commonest potentially blinding ocular manifestation of AIDS. Recently the acyclic nucleoside dihydroxypropoxymethyl guanine (DHPG, ganciclovir) has become available to treat sight-threatening CMV retinopathy. This paper reports the clinical features and results of ganciclovir therapy in 48 patients seen over a four-year period. Seven patients were excluded from the study due to inadequate follow-up, leaving 41 patients as the study group. All patients responded clinically to this therapy. Patients were treated initially with high-dose ganciclovir (10 mg/kg/day) and then continued on lower dose treatment (5 mg/kg/day) indefinitely. Significant bone marrow toxicity developed in 12 patients (29.3%) requiring temporary cessation of therapy. Patients treated with ganciclovir retained vision and had increased survival times when compared to untreated patients. A poor visual outcome occurred when there was involvement of the macula or optic nerve head at presentation or when there was an interruption of ganciclovir therapy.

Survival of Patients with the Acquired Immune Deficiency Syndrome after Development of Cytomegalovirus Retinopathy

To study the survival of patients with acquired immune deficiency syndrome (AIDS) who develop cytomegalovirus (CMV) retinopathy, the medical records of 100 consecutive patients with AIDS and CMV retinopathy were reviewed. Dates of AIDS diagnosis, CMV retinopathy diagnosis, and death were determined for each patient. The median interval from CMV retinopathy diagnosis to death for patients whose infection was diagnosed between May 1984 and September 1987 was 5 months. The interval had increased significantly since 1981. The interval from AIDS diagnosis to CMV retinopathy diagnosis (median, 9 months) did not increase. Based on extent and location of retinal lesions at the time patients were first examined, increased survival could not be attributed to earlier diagnosis of CMV retinopathy. Patients treated with ganciclovir lived longer after diagnosis of CMV retinopathy (median, 7 months) than untreated patients (median, 2 months; P < 0.001). Although this finding suggests that ganciclovir may prolong survival, the effect of treatment cannot be established conclusively because patients were not randomly assigned to treatment or no treatment groups. The location of retinal lesions had no apparent prognostic significance for survival. Survival after diagnosis of AIDS was significantly shorter if CMV retinopathy was the initial manifestation of the syndrome.

A Controlled Retrospective Study of Ganciclovir Treatment for Cytomegalovirus Retinopathy

To evaluate more accurately the clinical response of cytomegalovirus retinopathy to ganciclovir, a system for the assessment of disease outcome was developed that uses retinal photographs and three factors: development of new lesions, enlargement of preexisting lesions, and change in retinal opacification of lesion borders. With this system a retrospective comparison was performed of 24 ganciclovir-treated patients and 17 untreated patients with cytomegalovirus retinopathy. A masked assessment showed disease progression in 10 treated patients (43%) during a median period of 22 days. In contrast, 16 untreated patients (94%) had progression of disease during a median period of 25 days. Comparison of treated and untreated eyes also suggests that treatment may prevent deterioration of visual acuity during the same period. This study supports the conclusions of previous uncontrolled studies that ganciclovir is beneficial in the treatment of patients with acquired immunodeficiency syndrome and cytomegalovirus retinopathy. It also demonstrates the utility of the proposed system for assessment of disease outcome that can be used in future studies of therapy for necrotizing viral retinopathies.

Treatment of Cytomegalovirus Retinopathy with Ganciclovir

Ganciclovir is an experimental antiviral drug with activity against human cytomegalovirus (CMV). Forty patients with acquired immune deficiency syndrome (AIDS) and CMV retinopathy were treated with ganciclovir on a compassionate protocol basis. Initial treatment doses ranged from 5.0 to 14.0 mg/kg/day for 9 to 26 days. Signs of drug response were a halt to enlargement of lesions, decreased opacification of retinal tissue, and resolution of hemorrhage and vasculitis. Complete response was seen in 88% of patients and incomplete response was seen in 9%. Vision improved or remained stable in 88% of patients. Initial treatment did not eradicate live virus from the eye. To prevent reactivation of disease, 26 patients received low-dose maintenance therapy ranging from 1.5 to 7.5 mg/kg/day, once or twice daily, 3 to 7 days per week. Reactivation of disease developed for unknown reasons in 50% of patients on continuous, uninterrupted maintenance therapy for longer than 3 weeks. Reversible neutropenia, requiring cessation of treatment, developed in 30% of patients on initial treatment and in 38% of patients on maintenance therapy. Rhegmatogenous retinal detachment was a late complication in seven patients. By reducing or delaying visual loss, ganciclovir appears to be useful in the management of CMV retinopathy in patients with AIDS.

Pathologic Features of Cytomegalovirus Retinopathy after Treatment with the Antiviral Agent Ganciclovir

Ganciclovir is a new antiviral compound (also called BW B759U, DHPG, BIOLF-62, and 2'NDG) that has been used for the treatment of cytomegalovirus (CMV) retinopathy in immunocompromised patients (bone marrow recipients or acquired immune deficiency syndrome [AIDS] victims). The authors studied the eyes of three AIDS patients with CMV retinopathy who died while receiving ganciclovir chemotherapy. Gross, microscopic, and ultrastructural studies of these cases showed varying degrees of retinal scarring and active CMV lesions at the margins of the scars. CMV antigens were localized in cells at all layers of retina at the border of the lesions and in isolated cells in a perivascular location within histologically normal appearing retina. These areas probably represent sites of recrudescence when the drug is discontinued. In situ hybridization using a cloned complementary DNA (cDNA) probe of human CMV corroborated the immunocytologic localization of the virus. Ultrastructural studies showed megalic syncytial cells containing mostly capsids exclusively in the cell nucleus. The cytoplasmic electron-dense membrane-bound bodies that have characterized untreated cases of CMV retinopathy were absent in the treated cases. An attempt to isolate CMV in tissue culture from the vitreous and retina of one of the cases yielded a negative result. Our results indicate that ganciclovir does not effectively eliminate CMV from the retina nor does it suppress expression of all viral genes. Ganciclovir appears to function by limiting viral DNA synthesis and subsequent packaging of viral DNA into infectious units, thereby acting as a virostatic chemotherapeutic agent.

Treatment of Cytomegalovirus Retinopathy in Patients With Acquired Immunodeficiency Syndrome

Treatment of Cytomegalovirus Retinopathy in Patients With Acquired Immunodeficiency Syndrome

Treatment of cytomegalovirus retinopathy in patients with acquired immunodeficiency syndrome. Use of the experimental drug 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine.

Cytomegalovirus (CMV) retinopathy, a relentlessly progressive disease that results in permanent blindness, is the most common opportunistic infection of the eye in patients with the acquired immunodeficiency syndrome. Twenty patients with the acquired immunodeficiency syndrome with CMV retinopathy were treated with a new, experimental, antiviral drug, 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine (BW B759U), in dosages ranging from 5.0 to 14.0 mg/kg/d for a ten- to 20-day course. In 19 patients (95%), treatment halted the progression of infection and decreased retinal opacification, hemorrhage, and vasculitis. Vision remained stable in most cases. Six patients received no additional treatment. Fourteen patients received continued treatment with a lower maintenance dosage. Retinal disease reactivated in all patients who did not receive maintenance therapy immediately after initial treatment, indicating persistence of live virus despite drug therapy. Reactivation of disease also developed in four (40%) of ten patients receiving continuous, uninterrupted maintenance therapy for longer than three weeks. Reversible neutropenia, requiring cessation of treatment, developed in five (25%) of 20 patients on initial treatment and five (36%) of 14 patients receiving maintenance therapy. Rhegmatogenous retinal detachment was a late complication in four patients. BW B759U appears to be useful in the management of CMV retinopathy by reducing or delaying visual loss.

Immunocytologic Localization of Herpes Simplex Type 1 Viral Antigens in Herpetic Retinitis and Encephalitis in an Adult

An immunoperoxidase technique was utilized to identify herpes simplex type I viral antigens in the retina, optic nerve and brain of an adult with herpetic retinitis and encephalitis. Viral antigens were demonstrated in all layers of retina, retinal pigment epithelium and, to a lesser extent, in choroid. Oligodendroglia in the right optic nerve and neuronal and glial cells in the grey and white matter of the left frontal, inferior parietal and temporal lobes of the brain also expressed herpes simplex antigens. The sensitive immunoperoxidase method allowed detection of viral antigens in many cells without intranuclear inclusions or surrounding inflammation, and thereby added valuable information regarding the anatomic and cellular localization of herpetic infection. The clinicopathologic features that characterize herpes simplex retinitis in the adult are compared to cytomegalovirus retinopathy.