Cytomegalovirus infection in patients with HIV infection.

Cytomegalovirus (CMV) is responsible for the most common viral opportunistic infection in persons with acquired immunodeficiency virus syndrome (AIDS). Clinical disease due to CMV has been recognized in up to 40% of patients with advanced HIV disease. The most common presentation is retinitis, although colitis, esophagitis, pneumonitis and neurological disorders are also reported frequently. CMV retinitis is usually diagnosed clinically, and serological testing for CMV immunoglobulin is useful to support the diagnosis. Parts of the gastrointestinal tract (esophagus and colon) are the most common extraocular sites of CMV infection in AIDS patients. Therapy with systemic agents, including intravenous ganciclovir, intravenous foscarnet, and intravenous cidofovir, is effective. Ganciclovir is associated mainly with hematological toxicity, while foscarnet and cidofovir are nephrotoxic. Intravitreal injections with these antiviral agents are also effective, but inconvenient, and there is a need for repeated injections. Intraocular implants that slowly release ganciclovir have been effective for both acute therapy and long-term maintenance, but the occurrence of contralateral ocular and extraocular disease is a serious concern. New agents, as for example an anti-sense agent against CMV, appear promising.

Periumbilical pseudoxanthoma elasticum associated with chronic renal failure and angioid streaks--apparent regression with hemodialysis.

Pseudoxanthoma elasticum (PXE) is a heritable connective tissue disease involving progressive fragmentation and dystrophic calcification of elastic fibers. Periumbilical disease as the exclusive site of cutaneous involvement is most commonly seen in the rare entity termed periumbilical perforating pseudoxanthoma elasticum (PPPXE). Patients with this disorder are generally obese, middle aged, multiparous black women with hypertension. The cutaneous lesions are well-demarcated, hyperpigmented, periumbilical plaques with keratotic papules on the periphery. Extracutaneous manifestations have rarely been described. We describe a patient with periumbilical PXE associated with chronic renal failure and bilateral angioid streaks. Histopathologic examination demonstrated typical calcification of elastic fibers with additional amorphous calcium deposits in the superficial dermis. Transepidermal elimination was not present. Normalization of the serum calcium-phosphate product resulted in regression of the lesions--both clinically and histopathologically. The relation between PPPXE and hereditary PXE is discussed. The role of chronic renal failure in precipitating PPPXE is considered.

Management of varicella zoster virus retinitis in AIDS.

AIMS/BACKGROUND: Varicella zoster virus retinitis (VZVR) in patients with AIDS, also called progressive outer retinal necrosis (PORN), is a necrotising viral retinitis which has resulted in blindness in most patients. The purposes of this study were to investigate the clinical course and visual outcome, and to determine if the choice of a systemic antiviral therapy affected the final visual outcome in patients with VZVR and AIDS. METHODS: A review of the clinical records of 20 patients with VZVR from six centres was performed. Analysis of the clinical characteristics at presentation was performed. Kruskall-Wallis non-parametric one way analysis of variance (KWAOV) of the final visual acuities of patients treated with acyclovir, ganciclovir, foscarnet, or a combination of foscarnet and ganciclovir was carried out. RESULTS: Median follow up was 6 months (range 1.3-26 months). On presentation, 14 of 20 patients (70%) had bilateral disease, and 75% (15 of 20 patients) had previous or concurrent extraocular manifestations of VZV infection. Median initial and final visual acuities were 20/40 and hand movements, respectively. Of 39 eyes involved, 19 eyes (49%) were no light perception at last follow up; 27 eyes (69%) developed rhegmatogenous retinal detachments. Patients treated with combination ganciclovir and foscarnet therapy or ganciclovir alone had significantly better final visual acuity than those treated with either acyclovir or foscarnet (KWAOV: p = 0.0051). CONCLUSIONS: This study represents the second largest series, the longest follow up, and the first analysis of visual outcomes based on medical therapy for AIDS patients with VZVR. Aggressive medical treatment with appropriate systemic antivirals may improve long term visual outcome in patients with VZVR. Acyclovir appears to be relatively ineffective in treating this disease.

Evaluation of a new self-screening chart for cytomegalovirus retinitis in patients with AIDS.

AIDS patients often present without visual symptoms despite severe vision-threatening cytomegalovirus (CMV) retinitis. A new self-examination chart, the Teich Target (copyright 1993, Steven A. Teich, pat. no. 370259), which tests the central 45 degrees of vision, was evaluated for its ability to screen AIDS patients for CMV retinitis. It was compared with the Amsler grid (which tests the central 20 degrees of vision) in 50 consecutive AIDS patients referred for ophthalmologic evaluation by a single practitioner. Of 19 patients found to have CMV retinitis, 12 (63%) noted scotomas with the Teich Target compared with 7 (37%) with the Amsler grid (p < 0.05). Overall, 13 of 20 (65%) infectious retinitis cases were detected by the Teich Target. and 7 of 20 (35%) with the Amsler grid (p < 0.05). All scotomas noted on the Amsler grid were detected by the Teich Target. Four visually asymptomatic patients with newly diagnosed CMV retinitis noted scotomas only with the Teich Target. Both methods detected a branch retinal artery occlusion, but only the Teich Target detected a quadrantanopsia due to cerebral toxoplasmosis. There were no false positives with either method. In this small series, the Teich Target was more effective than the Amsler grid in screening AIDS patients for CMV retinitis primarily because it detected lesions beyond the central 20 degrees of vision. Peripheral CMV retinitis beyond the central 40 degrees occurred in 37% of patients and was net detected by either method. The Teich Target therefore augments but does not replace periodic ophthalmologic evaluations. The Teich Target may have potential utility for home use as a patient self-screening test for CMV retinitis or for mass screening in an AIDS clinic.

Successful treatment of progressive outer retinal necrosis syndrome.

PURPOSE: Progressive outer retinal necrosis is a destructive retinopathy found in patients with acquired immune deficiency syndrome. Treatment of this disorder has been unsuccessful in reported patient series, with the patients experiencing profound bilateral loss of vision. METHODS: We treated six patients with combination antiviral therapy, usually with intravenous foscarnet and either ganciclovir or acyclovir. RESULTS: These six patients retained a visual acuity of 20/100 or better in at least one eye for the remainder of their lives (a period > 4 months for each patient). Retinal detachments developed in four patients, for which vitrectomy and silicone oil tamponade were required. CONCLUSIONS: A combination of intravenous antiviral therapy and aggressive vitrectomy techniques to repair any associated detachments may allow the preservation of useful visual acuity in patients with progressive outer retinal necrosis. This is the first reported series of successful long-term treatment of patients with this disorder.

Systemic antiviral drugs used in ophthalmology.

Over the past two decades, the recognition of viral enzymes and proteins that can serve as molecular targets of drugs has revolutionized the treatment of viral infections. Beginning with acyclovir, a number of systemically administered agents which are both relatively safe and effective for the treatment of herpetic infections and human immunodeficiency virus (HIV) infections have become widely available. Because of increased numbers of herpes virus infections, as well as the rising epidemic of HIV infections, the ophthalmologist is, more likely than ever before to be involved in the treatment of severe and frequent ocular infections caused by herpes viruses. In addition, the acute retinal necrosis (ARN) syndrome has been demonstrated to be caused by herpes viruses and a once rare retinal infection caused by cytomegalovirus is common in patients with the acquired immunodeficiency syndrome (AIDS). In this article, four systemic antiviral drugs (Vidarabine, Acyclovir, Ganciclovir, and Foscarnet) that have demonstrated usefulness in the treatment of ophthalmic disease are reviewed in detail with regard to their mechanisms, applications, effectiveness, and side effects.

Treatment of retinal detachments in patients with the acquired immune deficiency syndrome.

Thirty-nine eyes from 31 patients with retinal detachment due to cytomegalovirus (CMV) retinitis were treated by either laser photocoagulation (22 eyes), scleral buckle (9 eyes), pars plana vitrectomy (5 eyes), or no therapy (3 eyes). The success rates for photocoagulation (77.2%), scleral buckle (77.7%), and vitrectomy (with gas or oil, 80%) were similar. The median survival time was 95 days (range, of 7 to 280 days). The extent of detachment, the presence of active disease in either the periphery or the posterior pole, and overall health served to determine what type of therapy was best suited for each patient. Although silicone oil appears to be best for patients with a total retinal detachment and active disease, this small series suggests that conservative modes of therapy such as laser photocoagulation and scleral buckles can be used successfully to treat these patients if there is an absence of active retinitis.

Ocular toxoplasmosis in AIDS patients.

We describe 16 cases of ocular and, in some patients, associated CNS toxoplasmosis in AIDS patients. T gondii is commonly associated with infection in the immunocompromised host. The lesions are most often seen in the CNS and eyes; involvement in the brain, heart, lung, liver, spleen, and lymph nodes may be observed. CNS involvement by toxoplasmosis may be an initial manifestation of AIDS and may be associated with discrete or diffuse lesions. CT scan and MR imaging may demonstrate a multitude of lesions often displaying the characteristic ring-shaped enhancement after contrast injection. Ocular involvement by toxoplasmosis, though less common than CNS involvement, is characterized by several features. These may be manifested as single or multifocal retinal lesions in one or both eyes or massive areas of retinal necrosis. Invariably these lesions are unassociated with a pre-existing retinochoroidal scar suggesting that the lesions are a manifestation of acquired rather than congenital disease. Presence of IgM antibodies may support this observation although antibody levels in AIDS patients may not reflect the magnitude of disease. Vitreous reaction is often minimal. Anterior uveitis has been reported in one case. Treatment of the ocular infection with pyrimethamine, clindamycin and sulfadiazine is effective in over 75% of patients. Once resolution of the ocular infection is observed, maintenance therapy is continued as relapses occur in the absence of treatment. Corticosteroid treatment is unnecessary and its use has been associated with the development of CMV retinitis. Other retinal infections in AIDS patients which should be considered in the differential diagnosis include CMV, herpetic-associated ARN and syphilis. Concomitant CMV and toxoplasmosis in the same eye have been seen.

Treatment of cytomegalovirus retinitis with ganciclovir (9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (BW B759U).

Six patients (11 eyes) with virologically confirmed cytomegalovirus (CMV) retinitis involving the posterior pole of the eye were treated with a new drug, ganciclovir. Treatment with intravenous ganciclovir consistently halted progression of retinitis and produced improvement in measures of visual function. However, within three weeks after cessation of therapy renewed CMV activity and worsening of visual function were observed in most cases. Maintenance therapy with ganciclovir extended the period of remission from CMV retinitis.

Active cytomegalovirus particles in the eyes of an AIDS patient being treated with 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (Ganciclovir).

The eyes of an AIDS patient with cytomegalovirus (CMV) retinitis and pneumonitis who died while receiving maintenance therapy with the antiviral agent 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (Ganciclovir) were obtained for pathological examination. While under treatment the patient had significant improvement but not complete regression of retinitis. Electron microscopic and immunofluorescent techniques revealed cytomegalovirus particles in the retina, sclera, iris, and ciliary body. These findings are consistent with a virostatic type of inhibition of CMV by this agent. They also suggest that CMV involvement in the eye and other organs may be more widespread than is clinically apparent in AIDS patients.

Combined short- and long-term therapy for the treatment of cytomegalovirus retinitis using ganciclovir (BW B759U).

A total of 66 eyes in 41 patients were treated for cytomegalovirus (CMV) retinitis with a new acyclic nucleoside, ganciclovir (BW B759U). At the completion of the short-term therapy period of 21 days, 87.7% of eyes had stabilized or improved. Seventy-two percent of eyes stabilized or improved during long-term home maintenance therapy. Leukopenia and increased liver function abnormalities were the most common adverse drug reactions seen in this series. Ganciclovir dramatically improved the quality of life in these patients, but clinical evidence suggests that it is a virostatic medication requiring indefinite long-term maintenance therapy.

Acquired immunodeficiency syndrome (AIDS).

The Acquired Immunodeficiency Syndrome (AIDS), caused by the human immunodeficiency virus (HIV), also called the human T-lymphotropic virus type III/lymphadenopathy-associated virus [HTLV-III/LAV], has affected over 23,000 people; more than half of those with the disease have died. The actual case fatality rate approaches 100%. AIDS affects all groups and classes of people, although some are at special risk. Distribution of the disease is worldwide. The illness' effects on the body are widespread; of special interest are the ophthalmologic manifestations. The eye may be infected by various viruses (cytomegalovirus, varicella-zoster virus, herpes simplex virus or HIV itself), toxoplasma gondii, candida sp, cryptococcus neoformans, M. tuberculosis, or M. avium-intracellulare. Kaposi's sarcoma may affect the eye as well. Retinal vascular abnormalities (e.g., cotton-wool spots, vasculitis) are not uncommon in AIDS. The syndrome may present with neuro-ophthalmologic manifestations. No effective treatment for the illness is currently available, although several hold promise and there is hope for an AIDS vaccine. Prevention of infection through reduction of risks appears to be the only defense against AIDS at this time.

Viral particles in the conjunctiva of a patient with the acquired immune deficiency syndrome.

Conjunctival biopsy from a 39-year-old man with the acquired immune deficiency syndrome revealed the presence of herpes virus particles by electron microscopy. The finding of herpes virus particles in the conjunctiva may be of prognostic significance in documenting the presence of systemic viral infection.