acyclovir and Cytomegalovirus-Retinitis

Acute retinal necrosis (ARN), also known as Kirisawa-type uveitis, is an uncommon condition caused by infection of the retina by one of the herpes family of viruses, most typically varicella zoster virus or herpes simplex virus and less commonly cytomegalovirus. Clinical diagnosis can be challenging and is often aided by PCR-based analysis of ocular fluids. Treatment typically involves extended use of one or more antiviral agents. Long term retinal detachment risk is high. We review the literature on ARN and present an approach to the diagnosis and management of this serious condition.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Cytomegalovirus Retinitis; Eye Infections, Viral; Famciclovir; Fluorescein Angiography; Ganciclovir; Herpes Simplex; Humans; Laser Coagulation; Retinal Necrosis Syndrome, Acute; Valacyclovir; Valganciclovir; Valine

Progressive outer retinal necrosis is a necrotizing herpetic retinopathy usually seen in immunocompromised patients. The authors describe two patients with this disease who initially had findings suggestive of an optic neuropathy. Vision declined after treatment with methylprednisolone, after which fundus examination became consistent with progressive outer retinal necrosis. These cases underscore the importance of careful examination of the retinal periphery before management of any presumed optic neuropathy with steroids.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Diagnostic Errors; Diplopia; Disease Progression; Encephalitis, Viral; Female; Foscarnet; Herpes Zoster; Humans; Magnetic Resonance Imaging; Methylprednisolone; Middle Aged; Necrosis; Optic Neuritis; Paresis; Prednisone; Retina

More than 90% of patients with HIV have been infected at some time with cytomegalovirus (CMV) and up to 40% of those with advanced HIV will develop CMV disease. The incidence of CMV disease is increasing but the prognosis for the patient remains poor.. It is therefore important to monitor patients with low CD4+ counts in order to identify those most at risk of developing CMV disease and to treat them before the disease becomes established. Polymerase chain reaction (PCR) is probably the most effective and sensitive method of detecting CMV and a positive result is predictive for development of CMV disease; more than 80% of patients with CMV retinitis are CMV PCR-positive at the time of diagnosis. PCR can also detect the presence of CMV up to 14 months before the development of retinitis.. In patients with detectable CMV, but no evidence of active infection, pre-emptive treatment with ganciclovir or valaciclovir has been shown to reduce the risk of developing retinitis in these high-risk patients. Such oral therapy, which is generally better tolerated than intravenous therapy and results in a better quality of life for the patient, is likely to be more effective at this stage whilst viral loads are low.. CMV PCR can be used to prospectively monitor patients in order to identify those most at risk of developing CMV retinitis. If CMV infection is diagnosed early, while viral loads are still low, pre-emptive oral therapy can be instituted which will reduce the chances of developing retinitis in those patients most at risk.

Topics: Acyclovir; Administration, Oral; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Ganciclovir; Humans; Polymerase Chain Reaction; Risk Factors; Valacyclovir; Valine

Questions are being raised about the efficacy of oral ganciclovir (Cytovene) in preventing cytomegalovirus (CMV), and the toxicity of valaciclovir, a derivative of acyclovir, when administered in high doses. Two government studies (Syntex 1654 and CPCRA 023) of oral ganciclovir have resulted in conflicting results. The studies are under investigation in an attempt to resolve the differences. CPCRA has led to concerns about Cytovene, including its potential for resistance and its relatively high cost. Another study shows two grams of valaciclovir, four times per day, produces the same blood levels as intravenous acyclovir. However, both are toxic levels and neither drug is viewed as particularly effective.

Topics: Acyclovir; Administration, Oral; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Ganciclovir; Humans; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome; Valacyclovir; Valine

Topics: Acyclovir; Adult; Antiviral Agents; Aqueous Humor; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cytomegalovirus; Cytomegalovirus Retinitis; Diagnosis, Differential; DNA, Viral; Genome, Viral; Humans; Immunocompromised Host; Male; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute

To identify factors related to variations in the appearance of untreated AIDS-related cytomegalovirus (CMV) retinitis in severely immunodeficient individuals before the availability of highly active antiretroviral therapy (HAART) and to draw inferences regarding early events in the natural history of CMV retinitis based on clinical findings.. Retrospective, observational case series.. We evaluated a series of 100 adult patients with AIDS and newly diagnosed CMV retinitis before the HAART era who were not being treated with specific anti-CMV therapy. Demographic factors, ophthalmic findings, and the influence of drug therapy (zidovudine, acyclovir) on lesion characteristics were evaluated. Lesion border opacity was scored using a four-point scale of severity.. Lesions could be categorized by type (fulminant/edematous or indolent/granular) in only 66% of eyes. Severe lesion border opacity (4+) was related to presence of zone 1 lesions (P = .032) and greater extent of disease (P = .004). Acyclovir use was associated with less severe opacity (P = .029) and less zone 1 involvement (P = .016). Early lesions were adjacent to vessels in 73% of eyes; the fovea was involved in 13% of eyes.. Lesion location and drug use that affects virus activity may influence the severity of lesion border opacity, a measure that may be more useful than lesion type in future clinical studies of CMV retinitis. In contrast to earlier concepts, CMV retinitis does not seem to be a fovea-sparing disease. Findings in this study can serve as a reference for investigations into possible changes in CMV retinitis since the introduction of HAART.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; Cytomegalovirus Retinitis; Drug Therapy, Combination; Female; Humans; Male; Retrospective Studies; Zidovudine

To describe host characteristics (use of highly active antiretroviral therapy [HAART]; CD4+ T-lymphocyte count; HIV ribonucleic acid [RNA] blood level) of people who were diagnosed with AIDS-related cytomegalovirus (CMV) retinitis after HAART became available and to investigate effects of HAART on ophthalmic findings.. Retrospective, observational case series.. We collected demographic, medical, laboratory, and ophthalmic data for all patients with AIDS and newly diagnosed, untreated CMV retinitis from January 1997 through December 2000 at 10 sites in Los Angeles and Orange Counties, California.. The proportions of Hispanic and African-American patients were equivalent to or greater than their prevalences in the AIDS and general populations of Los Angeles County. Most patients (n = 80; 63.5%) were known to be receiving HAART at the time of CMV retinitis diagnosis; only 22 patients (17.5%) were HAART-naïve. Median CD4+ T-lymphocyte count was 15 cells/microl and median HIV RNA blood level was 103,000 copies/ml for all patients, but in 10 patients, CMV retinitis developed despite good immunologic and virologic responses to HAART. When compared with HAART-naïve patients, HAART-failure patients with CMV retinitis had more asymptomatic disease (P = .073), better visual acuity in the better eye (P = .003), more bilateral disease (P = .007), less zone 1 involvement (P = .042), and lower lesion border opacity scores (P = .054).. Most patients with AIDS and newly diagnosed CMV retinitis in an urban setting are HAART-experienced. HAART may influence characteristics of new CMV retinitis lesions at presentation, despite laboratory evidence of treatment failure, possibly because of residual CMV-specific immunity.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cytomegalovirus Retinitis; Drug Therapy, Combination; Female; HIV; Humans; Los Angeles; Male; Retrospective Studies; RNA, Viral; Urban Population; Zidovudine

To explore the possibility of oral antiviral therapy in lieu of intravenous acyclovir for treating acute retinal necrosis (ARN), a necrotizing retinopathy caused by herpes simplex virus type 1 or 2 or by varicella zoster virus.. Retrospective, interventional, small case series.. Four patients (6 eyes).. Patients were treated with oral antiviral therapy. Medications included valacyclovir (1 g 3 times daily), oral famciclovir (500 mg 3 times daily), and topical and oral corticosteroids.. Improvement of symptoms, including photophobia, blurred vision, ocular discomfort, and floaters; increase in visual acuity; and resolution of vitreitis, retinitis, and retinal vasculitis, where present.. Symptoms and visual acuity improved within 2 weeks to 1 month in 3 of 4 patients (75%) treated with oral antiviral medication. One patient required surgical treatment for asymptomatic retinal detachment after 3 weeks of treatment; retinal detachment in the fellow eye was repaired 2 months later. Duration of antiviral therapy ranged from 5 weeks to 3 months.. For 4 patients with relatively indolent cases of ARN, oral antiviral therapy alone was effective in eliminating signs and symptoms of the disease. In particular, oral valacyclovir and famciclovir appeared to be effective, although further study is necessary to determine whether these drugs are as effective as intravenous acyclovir for initial treatment of ARN.

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Adult; Aged; Antiviral Agents; Cytomegalovirus Retinitis; Drug Therapy, Combination; Famciclovir; Female; Glucocorticoids; Herpes Simplex; Herpes Zoster Ophthalmicus; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 3, Human; Humans; Male; Middle Aged; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Valacyclovir; Valine; Visual Acuity; Vitreous Body

To evaluate the clinical outcome and medical management in a series of patients diagnosed with acute retinal necrosis.. Between 1993 and 2000, 22 patients suffering from acute retinal necrosis were referred to our department. We retrospectively reviewed the clinical course, delay between diagnosis and first clinical manifestation, biological profiles, treatment and complications.. All patients had vitreous inflammation; retinitis was seen upon examination in 82% of the cases. Nevertheless, for six patients (27% of the cases), failure to recognize the diagnosis led to delay (mean, 5.5 days) between the first ophthalmological examination and antiviral therapy. Nineteen patients underwent laboratory evaluation, and virological diagnosis was made in 16 of them: varicella zoster virus was found in 11 cases, herpes simplex type 1 in three cases, and herpes simplex type 2 and cytomegalovirus in one case each. Nine patients were treated with a combination of aciclovir and foscarnet and 13 with aciclovir alone. Among the 16 patients who received aciclovir, one did not respond to therapy after 2 days and was cured only after foscarnet was added. Recurrence occurred at the end of treatment in only one patient. Retinal detachment complicated the course for 11 patients and was always associated with proliferative vitreoretinopathy. Among those, seven of the ten patients who accepted surgery were successfully treated. Eleven out of 22 patients had a final visual acuity up to 20/200 and two up to 20/40.. In our series, acyclovir alone was sufficient to cure the majority of cases. Even with antiviral therapy, the prognosis of acute retinal necrosis remains poor. Retinal detachment is the main complication.

Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Cytomegalovirus Retinitis; Drug Therapy, Combination; Eye Infections, Viral; Female; Foscarnet; Herpes Simplex; Herpes Zoster Ophthalmicus; Humans; Infant; Male; Middle Aged; Prognosis; Retinal Detachment; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Visual Acuity; Vitreoretinopathy, Proliferative

Four cases of cytomegalovirus (CMV) retinitis (CMVR) after allogeneic blood stem cell transplant (SCT) were documented in Huddinge University Hospital between 1994 and 1999. Prior to 1994, only one case was documented. All five patients were transplanted due to malignant disease, two with sibling donors and three with matched unrelated donors. Despite adequate antiviral treatment against CMV retinitis, the result has been almost total unilateral blindness in three patients. However rare, the complication seems to have become more common since we began doing more matched unrelated donor transplants, which leads to a more pronounced T-cell defect and to a delayed immune reconstitution compared to sibling transplants. We conclude that CMV retinitis is a rare but important complication to allogeneic blood stem cell transplantation.

Topics: Acyclovir; Adult; Antiviral Agents; Bone Marrow Transplantation; Cytomegalovirus Retinitis; Female; Foscarnet; Humans; Immunosuppressive Agents; Male; Middle Aged; Time Factors

To assess a two-drug combination of antiviral therapy for the progressive outer retinal necrosis syndrome (PORN), given the current poor outcome with acyclovir alone.. A retrospective review was performed on six consecutive patients who were diagnosed with PORN and were treated with various combinations of intravenous or oral plus intravenous antiviral therapy. The relative efficacies of these modalities were compared.. Six eyes of six patients showed active retinitis at the time of presentation. Three patients had unilateral retinitis, and the remaining patients had necrotic, end-stage disease in their fellow eye. All the patients were treated with combination therapy, consisting of either ganciclovir and acyclovir (three patients), foscarnet and ganciclovir (two patients), or foscarnet and acyclovir (one patient). Standard induction doses were employed. During the combination therapy, all six eyes showed resolution of the retinitis, manifested by complete fading of the original retinal lesions and an absence of new lesion formation. At the final follow-up, the areas of prior active retinitis had resolved and remained quiescent. A mild recurrence developed in one eye when ganciclovir and foscarnet were both tapered to a single daily dose. This recurrence promptly resolved with reinduction (twice daily) dosing. Two patients maintained a visual acuity of 20/50 or better in their involved eye for the duration of follow-up (38 and 27 weeks, respectively). One patient maintained a visual acuity of 20/40 for 14 weeks. The remaining three patients had macula-off retinal detachments despite resolution of active retinitis. In addition, for the duration of follow-up, one of the three patients with unilateral disease had retinitis in the uninvolved eye; all three uninvolved fellow eyes maintained a visual acuity of 20/20. One patient had progressive optic atrophy.. Prolonged combination antiviral therapy for PORN may successfully arrest the progression of retinitis, maintain remission, and prevent involvement of the fellow eye. Furthermore, if aggressive therapy is begun early, good vision may be preserved.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Retinitis; Disease Progression; Drug Therapy, Combination; Female; Follow-Up Studies; Foscarnet; Ganciclovir; Herpes Zoster Ophthalmicus; Humans; Male; Middle Aged; Recurrence; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Treatment Outcome; Visual Acuity

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Retinitis; Drug Resistance, Microbial; Drug Therapy, Combination; Exudates and Transudates; Foscarnet; Fundus Oculi; Ganciclovir; Humans; Infusions, Intravenous; Male; Recurrence; Retinal Detachment; Visual Acuity

A novel ocular microdialysis-perfusion technique was developed that allowed for the continuous sampling of the vitreous humor for drug. The technique produced accurate and rapid vitreous drug concentration time profiles with a resolution of 20 minutes on the time axis. The vitreous elimination of ganciclovir (GCV) and acyclovir (ACV) was extremely rapid, having vitreous half lives of 2.62 and 2.98 hours, respectively, and a transretinal mechanism of clearance was established for these compounds. Further, it was shown that the compounds do not exhibit saturation kinetics over the dosage ranges used in the clinical setting. Ocular pigmentation had a dramatic effect on the vitreous pharmacokinetics of GCV and ACV. The rate of elimination of GCV and ACV from the vitreous of the pigmented rabbit was much slower than the elimination from the albino rabbit (t 1/2 = 5.59 vs. 2.62 for GCV and 8.63 vs. 2.98 for ACV). The mean residence time of GCV was 2 times greater in the pigmented rabbit than in the albino rabbit and 3 times greater for ACV. Further, the volumes of distribution increased by 3.5 fold for GCV and 6.2 fold for ACV, respectively.

Topics: Acyclovir; Animals; Antiviral Agents; Cytomegalovirus Retinitis; Disease Models, Animal; Drug Delivery Systems; Ganciclovir; In Vitro Techniques; Male; Melanins; Microdialysis; Rabbits; Vitreous Body

In persons with AIDS (PWAs), cytomegalovirus (CMV) infection can cause a broad spectrum of clinical manifestations. The most common clinical manifestations associated with CMV infection in PWAs and the most current approaches to treatment and prevention of CMV disease are reviewed. Manifestations discussed include those involving ocular disease, and diseases of the gastrointestinal and central nervous systems. Prophylactic treatment for CMV disease includes the use of oral ganciclovir and valaciclovir. Concluding comments address the development of antiviral resistance by CMV. Tables include listings of potential strategies for use of oral ganciclovir prophylaxis in PWAs, and mechanisms by which CMV strains become resistant to ganciclovir, foscarnet, and cidofovir.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Central Nervous System Diseases; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Digestive System Diseases; Foscarnet; Ganciclovir; Humans; Valacyclovir; Valine

The Second Human Retroviruses Conference covered many topics, including statistics on the viruses' prevalence in American society and some survey results on sexual behavior. Conference meetings were dominated by discussions on protease inhibitors and current clinical trial data on two inhibitors in particular, 3TC and ZDV. Evidence of a new herpes virus causing Kaposi's sarcoma (KS), and research on anti-KS agents, were discussed, including assessments concerning the struggle between the virus and the immune system, and arguments about using immune-based therapies versus attacking the virus directly. Of particular interest concerning immune-based therapy was the National Institute of Allergy and Infectious Diseases' (NIAID) interleukin-2 trial which is showing impressive results in affecting CD4+ counts, if CD4+ counts are not too low initially. Antiretroviral information centered on two investigations surrounding Parke-Davis' PD121871 and PD144975, which seem to prevent activation of latently-infected cells, and return activated cells to a quiescent state. Other conference topics covered acyclovir survival levels, the new therapies and renewed concerns about cytomegalovirus, planning an overall prophylactic strategy, the slow progress in developing a vaccine, and whether low-dose chemotherapy for lymphoma was as good as the standard dose.

Topics: Acyclovir; AIDS Vaccines; AIDS-Related Opportunistic Infections; Antineoplastic Agents; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Herpesviridae; HIV Infections; Humans; Interleukin-2; Lamivudine; Lymphoma, Non-Hodgkin; Retroviridae; Sarcoma, Kaposi; Zalcitabine; Zidovudine

The Durable Medical Equipment Regional Carriers has recommended excluding ganciclovir, acyclovir, and vancomycin from the list of Medicare-covered drugs. Only drugs infused by a pump, as indicated in the drug's product labeling, will be covered. IV ganciclovir is not covered, even though it is the drug of choice for treating cytomegalovirus retinitis. IV acyclovir, a standard therapy for disseminated herpes simplex infection among people with AIDS, is also not covered.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Retinitis; Foscarnet; Ganciclovir; Humans; Infusions, Intravenous; Insurance, Pharmaceutical Services; Medicare; Neoplasms; Vancomycin

Cytomegalovirus retinopathy is the most frequent opportunistic infection of the eye in patients with acquired immunodeficiency syndrome (AIDS). We studied 71 patients with cytomegalovirus retinopathy (n = 69) or acute retinal necrosis (n = 2) with respect to the frequency and management of retinal detachment. Retinal detachment was seen in 14 patients (relative frequency, 19.7%). In 2 patients, the retinal detachment was bilateral. In 5 patients, pars plana vitrectomy and silicone-oil tamponade was performed, and in 1 of these patients scleral buckling was applied before vitrectomy. In 3 other patients scleral buckling was performed, and 1 of these individuals had sulfur-hexafluoride injection. In 8 eyes (6 patients), retinal detachment occurred in eyes with completely burned-out retinopathy without relevant function, and no surgical treatment was performed. Long-term retinal reattachment was seen in all 5 patients undergoing pars plana vitrectomy with silicone-oil tamponade. Visual acuity was preserved until the last follow-up in 4 of these 5 patients. In the patients undergoing a buckling procedure alone, no anatomic or functional success was observed. During vitrectomy, reduced retinal vascular perfusion and blood-flow sludging was observed in 2 patients. As the duration of survival of patients with AIDS and cytomegalovirus retinopathy or acute retinal necrosis is increasing, more cases of retinal detachment will be observed. Overall, 5% of patients with AIDS are expected to develop retinal detachment. In conclusion, treatment of cytomegalovirus-associated retinal detachment by pars plana vitrectomy with silicone-oil tamponade seems to be successful and safe and may maintain the patient's quality of life.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Cytomegalovirus Retinitis; Follow-Up Studies; Foscarnet; Ganciclovir; Humans; Incidence; Male; Retinal Detachment; Retinal Necrosis Syndrome, Acute; Visual Acuity