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The purpose of this study is to report retinal manifestations of lues in human immunodeficiency virus (HIV)-positive patients and to suggest a method for treatment of rhegmatogenous retinal detachments in these patients. Two HIV-positive patients with bilateral retinitis were examined and treated at the authors' institution for a period of 14 months. Ocular syphilis was diagnosed clinically, confirmed by cerebrospinal fluid serologic testing, and treated with intravenous penicillin. Both patients experienced bilateral rhegmatogenous retinal detachments complicated by proliferative vitreoretinopathy after resolution of the active retinitis. All four eyes underwent surgical repair with trans pars plana vitrectomy, epiretinal membrane delamination, gas-fluid exchange, endolaser, scleral buckle, and silicone oil instillation. The recognition of ocular syphilis as a cause of retinal detachment in HIV-positive patients is important. Prompt intervention with the appropriate medical and surgical treatments may result in the preservation of vision in these patients.

Purpose: The authors compare the intravitreal efficacy of ciprofloxacin, vancomycin and imipenem, in treating experimental Bacillus cereus endophthalmitis., Methods: Thirty-three Yorkshire pigs received a surgically induced injury to the right eye, which was then repaired and injected with 8400 colony forming units of live B. cereus. Nine pigs received no therapy and served as a natural history group. Twenty-four other pigs then were randomized into a treatment group with ciprofloxacin (n = 6), vancomycin (n = 6), imipenem (n = 6), or normal saline (n = 6). Eyes were examined clinically 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours after inoculation. After 24 hours, the eyes were enucleated for histologic study., Results: Experimental disease was characterized by an aggressively developing endophthalmitis, with retinitis and vitritis developing at 4 hours. Histologic examination showed vitreous abscess and retinal necrosis. Both vancomycin- and imipenem-treated group had less inflammation and tissue destruction than control animals, based on the Wilcoxon rank sum test (P < 0.05). Ciprofloxacin-treated animals showed significantly more intraocular destruction and were indistinguishable from controls., Conclusion: Vancomycin and imipenem appear to limit inflammation and tissue destruction when given early in the course of experimental posttraumatic endophthalmitis caused by B. cereus. Results with ciprofloxacin are less conclusive and warrant further investigation.

Purpose: The authors report sequential fluorescein angiographic and color photographic findings of the fundi and response to treatment in a patient with chronic Lyme neuroretinitis., Methods: A Lyme enzyme-linked immunosorbent assay with purified 41-kd flagellin as antigen was used to detect immunoglobulin G and immunoglobulin M antibodies to Borrelia burgdorferi in serum, cerebrospinal fluid, and vitreous. The changes were documented by fluorescein angiography and color photography tests performed during a 5 1/2 year follow-up., Results: The diagnosis of Lyme neuroretinitis was based on the history of erythema migrans and positive Lyme enzyme-linked immunosorbent assay tests from cerebrospinal fluid and vitreous and by the exclusion of other infectious and systemic diseases and uveitis entities. Fluorescein angiography results disclosed bilateral chronic neuroretinal edema with areas of cystoid, patchy, and diffuse hyperfluorescence peripapillary and in the macular areas. The hyperfluorescent lesions enlarged despite a 9-month period of antibiotic therapy., Conclusion: Lyme borreliosis may cause neuroretinitis with unusual angiographic findings. Chronic Lyme neuroretinitis may be unresponsive to antibiotic therapy.

Bartonella (Rochalimaea) henselae causes a variety of diseases, including bacillary angiomatosis, peliosis hepatis, lymphadenitis, aseptic meningitis with bacteremia, and cat-scratch disease (CSD). Cases of B. henselae-related disease were collected from September 1991 through November 1993. Patients with suspected CSD, unexplained fever and lymphadenitis, or suspected B. henselae infection who were seen in the Infectious Diseases Clinic at Wilford Hall Medical Center (Lackland Air Force Base, TX) underwent physical and laboratory examinations. In addition to three previously described cases, 23 patients with R. henselae-related infection were identified. The patients included 19 immunocompetent individuals presenting with lymphadenitis (11), stellate neuroretinitis (5), Parinaud's oculoglandular syndrome with retinitis (1), chronic fatigue syndrome-like disease (1), and microbiologically proven adenitis without the presence of immunofluorescent antibodies to B. henselae (1) and four patients infected with human immunodeficiency virus type 1 presenting with isolated lymphadenitis (1), diffuse upper-extremity adenitis (1), neuroretinitis (1), and aseptic meningitis (1). A couple with neuroretinitis and their pet cat, a persistently fatigued patient, and a patient with Parinaud's oculoglandular syndrome were shown to have bacteremia. Tissue cultures were positive for B. henselae in three recent cases of adenitis. Twenty-two patients were exposed to cats. This series further demonstrates the similarities between B. henselae-related diseases and CSD and identifies several new syndromes due to B. henselae.

Reports of oral lesions associated with cytomegalovirus (CMV) infection in human immunodeficiency virus (HIV) infected patients are uncommon. In this article a case of CMV infection associated with oral mucosal ulceration and a brief review of the subject is presented. Establishing the cause of ulceration is important in determining a definitive diagnosis and prescribing appropriate therapy. It is important to recognize that CMV associated oral mucosal ulceration may be the initial manifestation of human immunodeficiency virus (HIV) infection.

The purpose of this study was to examine B cell participation in experimental herpes simplex virus (HSV) retinitis. Passive immunization with anti-herpes antibody protects BALB/c mice from herpes simplex retinitis (HSR). Using anti-Mu antibody treatment, we modified the B cell population of C.B-17 mice, normally resistant to HSR, in order to test the hypothesis that such treatment would render them susceptible to HSR by impairing their early antibody response to anterior chamber (AC) inoculation with HSV. We analysed the effect of anti-Mu treatment on their susceptibility to HSR and then employed Polymerase Chain Reaction (PCR) and ELISA techniques to study the patterns of immunoglobulin gene and protein expression, and the T-cell receptor alpha/beta (TCR alpha/beta) gene expression after AC inoculation of HSV. Immunohistopathologic analysis revealed that 100% of the B cell deficient mice (B-) developed contralateral retinitis following AC inoculation, confirming the hypothesis that anti-Mu antibody treatment would convert HSR-resistant mice into HSR-susceptible ones. Transfer of B cells from naive congenic donor mice resulted in 67% of recipient B- mice developing contralateral retinitis. Transfer of anti-HSV antibody conferred nearly complete protection, with only 11% of mice developing retinitis (P < 0.005). PCR and ELISA analysis showed that both untreated and B- C.B-17 mice showed similar dynamic patterns of mRNA IgG isotype expression and of anti-HSV IgG isotypic antibody response following AC inoculation. Thus, we were forced to reject the hypothesis that an impaired early antibody response is primarily responsible for the increased HSR susceptibility seen in B- mice. In contrast, PCR analysis of TCR alpha/beta mRNA expression revealed dramatic differences between susceptible and resistant mice, suggesting that TCR V beta selection and usage may be a critical factor influencing HSR-sensitivity in this murine model, and that B cells (and immunoglobulin isotype) may play a role in TCR V beta selection and usage after ocular encounter with HSV.

Purpose: To determine whether CD4+ T cells, CD8+ T cells, or both CD4+ and CD8+ T cells are required for preservation of the ipsilateral retina after uniocular anterior chamber inoculation of herpes simplex virus type 1 (HSV-1)., Methods: Adult-thymectomized BALB/c mice were T cell depleted by administration of anti-CD4 monoclonal antibody (mAb), anti-CD8 mAb, or anti-CD4 mAb and anti-CD8 mAb together. Control mice were thymectomized but were not T cell depleted. HSV-1 (KOS) was inoculated in one anterior chamber. At intervals after inoculation, the injected eyes were examined histopathologically or homogenized to determine the kinetics of infectious virus recovery. Additional groups of in vivo depleted mice were injected with wild type KOS and RH116 (a mutant of KOS containing the Escherichia coli beta-galactosidase gene) to determine whether viral genes were expressed in the retina in any of the mice., Results: In the inoculated eyes of mice depleted of both CD4+ and CD8+ T cells, there was a significantly higher incidence of acute destructive retinitis at days 9 and 14 postinoculation (PI), and the titer of virus recovered at day 14 PI was significantly higher. Viral gene expression in the retina and the optic nerve was observed after day 7 PI only in the group of mice depleted of both CD4+ and CD8+ cells. In contrast, acute destructive retinitis was not observed in nondepleted mice or in mice depleted of either CD4+ or CD8+ T cells alone, and virus recovery was not significantly different among these three groups of mice. No virus-infected cells were observed in the optic nerve or the sensory retina of nondepleted mice, of mice depleted of only CD4+ cells, or of mice depleted of only CD8+ cells., Conclusion: The results of these studies suggest that either CD4+ or CD8+ T cells can spare the retina of the injected eye after uniocular anterior chamber inoculation of HSV-1. Because virus appeared after day 7 PI in the ipsilateral optic nerve and retina only in mice depleted of both CD4+ and CD8+ T cells, these results suggest that spread of virus to the ipsilateral retina occurs via the optic nerve and that either CD4+ or CD8+ T cells can prevent spread of virus to the inoculated eye resulting in sparing of the ipsilateral retina.

We injected herpes simplex virus type 2 of MS- or G-strain into the anterior chamber of BALB/c mice. In the contralateral eye inflammatory cell infiltration began in the ciliary body; focal retinitis, detected by day 8, led to total destruction of the retina by day 10. Contralateral disease was observed in 75% of mice inoculated with 8 x 10(3) pfu herpes simplex virus type 2, but in only 20% of mice receiving 80 pfu herpes simplex virus type 2. Still this low concentration, however, produced a suppressed delayed-type hypersensitivity response. Anti-herpes simplex virus type 2 antibody, first detected on day 8, reached high titers on day 10; by then, most of the mice had died of encephalitis. The G-strain of herpes simplex virus type 2 was more neurotoxic than the MS-strain, but produced the same incidence of contralateral retinitis. Herpes simplex virus type 2 products contralateral necrotizing retinitis comparable to that produced by herpes simplex virus type 1. These findings, like those of other authors, suggest a role for herpes simplex virus type 2 in some cases of acute retinal necrosis in humans.

Unilateral intravitreal inoculation of herpes simplex virus type 1 (HSV) induced bilateral retinitis and encephalitis in rats. In a previous paper, we demonstrated immunohistochemical localization of HSV in the ipsilateral retina. In this paper, we report immunohistochemical localization of antigen to HSV in the brain and opposite eye. HSV was found in the optic chiasm, and bilaterally in the suprachiasmatic nuclei, lateral geniculate nuclei, superior colliculus, pretectum, and visual cortex. HSV was also found in the retinal ganglion cells, neural cells in the inner nuclear layer, and Müller cells in the opposite eye. We demonstrated HSV infection in the retina of the opposite eye via the optic nerve, visual pathway, and nuclei, but not through the blood stream.

(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), a high-potency antiherpes and anticytomegalovirus (CMV) drug was evaluated in the treatment of experimental retinitis caused by preretinal herpes simplex virus (HSV-1) injection in rabbits. HPMPC (100 micrograms/0.1 mL) was intravitreally injected 10, 15, 21, 30, or 46 days before, concurrently, or 3, 5, or 7 days after viral inoculation. Ganciclovir (200 micrograms/0.1 mL) was intravitreally injected 3, 7, or 10 days before HSV-1 inoculation, concurrent with viral inoculation, or 3, 5, or 7 days after viral inoculation. Eyes pretreated with HPMPC were protected from retinitis for 15-21 days. Ganciclovir did not protect completely even if administered 3 days before inoculation. Early treatment of established retinitis with HPMPC markedly delayed the progression of the infection. However, with ganciclovir there was delayed progression only in rabbits treated 3 days after viral inoculation. HPMPC had a remarkably potent and prolonged (< or = 1 month) antiviral effect in this retinitis model and may prove more useful than ganciclovir in local treatment of CMV retinitis.

Purpose: To investigate the contribution of CD4+ and CD8+ T lymphocytes to retinitis in the contralateral eye after anterior chamber inoculation of herpes simplex virus type 1 (KOS strain)., Methods: T-cell-depleted BALB/c mice were prepared by adult thymectomy and treatment with anti-L3T4 (anti-CD4) monoclonal antibody and/or anti-Lyt2.2 (anti-CD8) monoclonal antibody. On days 9 and 14 after inoculation of herpes simplex virus type 1 (KOS strain) via the anterior chamber, the titer of virus in the uninoculated eye was determined by plaque assay. The eyes were examined microscopically, and the severity of retinitis was evaluated using a histopathologic scoring system., Results: At day 14 postinoculation, significantly less severe destruction of the parenchyma and less inflammatory cell infiltration were observed in the retina of the uninoculated eye of CD4+ T-cell-depleted mice and of mice depleted of both T-cell subsets. The titer of virus in the uninjected eye of CD4+ T-cell-depleted mice and of mice depleted of both CD4+ and CD8+ T cells was also significantly higher at day 14 postinoculation., Conclusions: The results of the studies suggest three ways CD4+ T cells might contribute to the pathogenesis of herpes simplex virus type 1 retinitis in the uninoculated contralateral eye: (1) accumulation of massive inflammatory cell infiltrates in the retina, (2) induction of retinal destruction, and (3) clearance of herpes simplex virus type 1 from the contralateral eye. In infection of the contralateral retina of nondepleted mice after uniocular anterior chamber inoculation of KOS, CD4+ T cells are required to induce fulminant retinitis and to mediate clearance of virus from the uninoculated eye by day 14 postinoculation. The exact mechanism by which CD4+ T cells contribute to contralateral retinitis remains to be identified.

Background: An experimental sustained release intraocular device has been designed to deliver ganciclovir over a long period of time. As part of an efficacy trial, the ganciclovir intraocular device was used to treat cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS)., Methods: All patients had active CMV retinitis that had progressed despite intravenous ganciclovir therapy. The ganciclovir intraocular device was inserted into the vitreous cavity by making an inferotemporal full-thickness circumferential sclerotomy and anchored to the incision. Intravenous therapy was then discontinued and patients were followed up at 2-week intervals until death. Seven eyes from five patients were obtained 2 to 10 hours postmortem and submitted for histopathologic examination. Light and electron microscopic studies were performed and correlated to the clinical outcome. Follow-up period after device placement ranged from 16 to 82 days (median, 70 days)., Results: All seven eyes showed clinical stabilization of the CMV retinitis. Light microscopy showed varying degrees of retinal atrophy with areas of gliosis. In addition, we observed syncytial megalic cells containing Cowdrey type A inclusions affecting all layers of the retina. Concurrent choroidal infections with Pneumocystis carinii (1) and Mycobacterium avium (2) also were seen. Electron microscopy showed virus particles located mostly at the junction of uninvolved and "healed" retinitis. No evidence of retinal toxic effects or inflammation at the site of ganciclovir intraocular device implant was noted., Conclusion: The ganciclovir intraocular device appeared to be effective in controlling the progression of CMV retinitis. The clinical and pathologic results are similar to those observed in the eyes of patients with intravenously administered ganciclovir. The lack of toxic effects and sustained levels of intravitreal ganciclovir may provide an improved therapeutic method of local treatment of CMV retinitis.

Purpose: To determine the incidence, pathophysiology, clinical outcome, and survival in patients with clinically resistant retinitis., Methods: Cytomegalovirus (CMV) retinitis was prospectively studied in 100 patients with acquired immune deficiency syndrome (AIDS). In 11 of these patients, clinically resistant retinitis developed, defined as new activity or progression, despite at least 8 consecutive weeks of induction doses of either foscarnet or ganciclovir. Fundus photography, pharmacokinetics, CMV cultures and sensitivities, and survival analyses were studied. The therapeutic interventions attempted after clinically resistant retinitis was identified included continuing a high dose (induction level) of the same antiviral drug, changing the antiviral drug, and combining antiviral therapy with foscarnet and ganciclovir., Results: Clinically resistant retinitis occurred in 11 (11%) of 100 patients with CMV retinitis and appeared to be a manifestation of acquired CMV antiviral drug resistance. Drug metabolism and pharmacokinetics in these patients were normal. The use of combination therapy with foscarnet and ganciclovir was effective in halting the progression of retinitis in three (75%) of four patients (6 of 7 eyes able to be evaluated) receiving combination therapy., Conclusion: Clinically resistant retinitis is a manifestation of infection by CMV that has acquired drug resistance. In these patients, combination antiviral drug treatment should be considered. It is likely that clinically resistant retinitis will become more frequent as patients with CMV retinitis and AIDS survive longer.

We prospectively studied 132 patients with acquired immunodeficiency syndrome (AIDS) to determine the cross-sectional prevalence of cytomegalovirus retinitis. All patients had serum CD4+ lymphocyte counts to determine the degree of immune dysfunction. Correlations between CD4+ counts, the presence of cytomegalovirus retinitis or human immunodeficiency virus (HIV)-related noninfectious retinal vasculopathy, and ocular symptoms were made. The study disclosed that 26 of 132 patients with AIDS (20%) had cytomegalovirus retinitis. However, subset analysis according to CD4+ count disclosed that in patients with CD4+ counts of 50 cells/mm3 or less, 26 of 87 (30%) had cytomegalovirus retinitis, whereas in patients with CD4+ counts of 50 cells/mm3 or more, none of 45 was noted to have cytomegalovirus retinitis. Similarly, 46 of 132 patients (35%) were noted to have HIV-related noninfectious retinal vasculopathy, with a trend toward increasing prevalence associated with declining CD4+ count. In patients with CD4+ counts of 50 cells/mm3 or less, 39 of 87 (45%) had HIV-related noninfectious retinal vasculopathy, whereas seven of 45 patients (16%) with CD4+ counts of 50 cells/mm3 or more were noted to have these changes. We confirmed the clinical impression that cytomegalovirus retinitis and HIV-related noninfectious retinal vasculopathy are late manifestations of AIDS, demonstrated an increased risk for patients with low CD4+ counts, and suggested a basis for coherent chemoprophylaxis and screening strategies for cytomegalovirus retinitis.

In recent years an enormous amount of new information in the area of retinitis and retinal disease in immunosuppressed patients has been acquired. There have been exciting new developments in our understanding of the pathogenesis of retinal disease in AIDS patients as well as important advances in the diagnosis and therapy of infectious retinitis. This article will summarise the recent advances in this area and outline the direction of future research as it applies to the clinical management of patients with retinal manifestations of AIDS. Diagnostic and therapeutic difficulties will be addressed including the appropriate selection of antiviral drugs and other therapeutic modalities in patients with sight-threatening retinitis.

Two cases of cytomegalovirus retinitis in pediatric acquired immunodeficiency syndrome (AIDS) are described. The first case was a 7-month-old infant who received an HIV-infected blood transfusion in 1983. The infant was treated with specific anti-cytomegalovirus immunoglobulin. The second case was an 8-year-old hemophiliac child who received HIV-infected factor VIII concentrates. Intravenous ganciclovir therapy resulted in marked improvement of ocular lesions. This is, to our best knowledge, the first report of pediatric AIDS-induced retinopathy resulting from postnatal intravenous causes.

Intracerebral inoculation of mice with the MS strain of type 2 herpes simplex virus (HSV-2) causes a brief encephalitis associated with multifocal central nervous system demyelination. Many of the mice develop unilateral or bilateral impairment of the pupillary light reflex. We have examined the development of ocular disease in inbred NIH mice inoculated intracerebrally with a low dose (10 pfu) of HSV-2 (MS). The resulting acute encephalitis was fatal in 30-50% of the mice. By 1 month after inoculation, the pupillary response to light was absent or impaired in approximately 80% of the surviving mice. Infectious virus could be isolated from the trigeminal ganglia and optic nerves from day 2 and from the eyes by day 4. Viral antigen was first immunohistochemically detectable in the optic nerves on day 5 and in the retinae on day 6. During the second week after inoculation up to half of the mice developed unilateral or bilateral necrotising retinitis associated with high titres of virus in the eyes and abundant viral antigen in the retinae. Electron microscopy confirmed the presence of viral particles in the retinae, in glia and degenerating neurons. No viral antigen was detected in the corneas and only rarely was antigen found in the ciliary body or iris. Infectious virus persisted longer in the eyes than in the trigeminal ganglia or optic nerves and could still be isolated from a few of the animals 2 weeks after inoculation. By 1 month the titres of virus within the eyes had fallen to undetectable levels.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to examine transfer of herpes simplex virus type 1 (HSV-1) in the retina and optic nerve in rats with experimental retinitis, an HSV-1 suspension (Miyama strain, 1 x 10(7) plaque-forming units per ml, 10 microliters) was inoculated into the vitreous body. One to seven days after HSV-1 inoculation, the animals were perfused through the heart with Zamboni's fixative. Fifty-microns-thick cryostat-cut sections through the retina and optic nerve were immunostained for HSV-1 antigen with rabbit anti-HSV-1 antiserum and avidin-biotin-peroxidase complex. Some sections were counterstained with hematoxylin. At an early stage of the postinoculation period, HSV-1 immunoreactivity was first seen in the cytoplasm of Müller cells and then in various cells of the inner nuclear layer. HSV-1 immunoreactivity was extremely dense in the nuclei of these cells, suggesting that HSV-1 replicates in the nuclei and propagates through the cytoplasm to the membrane of cell processes. At a later stage of the postinoculation period, HSV-1 immunoreactivity was seen in some retinal ganglion cells and optic nerve fibers. The labeling of the optic nerve fibers was found even in the optic tract and often accompanied by labeled glial cells adjacent to the nerve fibers.

We describe a patient with systemic lupus erythematosus who developed myelopathy, optic neuropathy, retinopathy, and aseptic meningitis unresponsive to immunosuppressive and antimicrobial therapy. Although cultures and brain biopsy were unrevealing, a Herpes virus was suggested by retinal biopsy. The patient recovered dramatically after institution of acyclovir therapy and optic-nerve-sheath decompression. This case demonstrates that herpetic retinitis can occur in an iatrogenically suppressed host and underscores the value of tissue diagnosis.

Objective: To assess the frequency with which HIV-seropositive patients treated with corticosteroids develop cytomegalovirus (CMV) disease., Design: Retrospective case-controlled study., Methods: All 130 patients receiving systemic corticosteroids over a 20-month period at the HIV Unit, Westminster Hospital, London, UK were reviewed for the development of clinical CMV disease within 28 days. The incidence of CMV disease in this group was compared with that in a cohort admitted during the same period, which was matched for admission diagnosis, HIV risk group, antiretroviral therapy and CD4 lymphocyte subset count (+/- 20%) at admission., Results: Eleven of the 130 patients given corticosteroids developed CMV disease within 28 days, compared with two patients in the case-controlled cohort. All patients who developed CMV disease had a CD4 count < 50 x 10(6)/l on admission., Conclusion: The use of corticosteroids in patients with advanced immunosuppression due to HIV infection should be reviewed carefully in view of the possible increased incidence of CMV disease.

Viruses are one of the most common causes of infections involving the posterior segment of the eye. Such infections can occur either on a congenital or an acquired basis, and may affect primarily the retina or the choroid. Congenital cytomegalovirus (CMV) and rubella infections may result in retinitis. CMV retinitis is also the most common cause of acquired viral retinitis, primarily because of the acquired immunodeficiency syndrome (AIDS). Other types of viral retinitis, such as those caused by herpes simplex or herpes zoster, can occur in immunocompromised or immunocompetent individuals. Retinitis or choroiditis caused by viruses such as measles, influenza, Epstein-Barr virus, and Rift Valley fever virus, typically occurs subsequent to an acute viral systemic illness. The systemic and ocular manifestations, as well as the histopathology, laboratory tests, differential diagnoses, and treatment regimens for each of the individual viruses are discussed in detail.

Purpose: To evaluate the impact of foscarnet on the longevity of persons with human immunodeficiency virus, type 1 (HIV-1) infection and cytomegalovirus (CMV) retinitis., Patients and Methods: A cohort of 24 patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis received sodium phosphonoformate (foscarnet) as part of a controlled efficacy trial at the National Institutes of Health. Foscarnet was continued for as long as it was tolerated. Antiretroviral therapy was given to the patients as tolerated. Long-term follow-up was available on all patients., Results: Seventeen patients received zidovudine during or after receiving foscarnet, 2 patients received dideoxyinosine, 2 patients zidovudine and dideoxyinosine, and 3 patients received no specific antiretroviral agent. Patients received foscarnet for a mean of 6.2 months (median, 4 months; range, 10 days to 22 months). Ten patients required a change to ganciclovir therapy at some time after receiving foscarnet. The median time from the diagnosis of CMV retinitis until death was 13.5 months (range, 3 to 34 months). Patients lived longer than untreated or ganciclovir-treated historical controls with AIDS and CMV retinitis. There was no difference in the survival of patients treated with foscarnet at the time of diagnosis and those patients treated with foscarnet only after progression of their CMV retinitis., Conclusions: These data suggest that foscarnet may prolong the survival of persons with AIDS and CMV retinitis and should be the initial treatment of choice in these patients.

Retinitis reminiscent of the acute retinal necrosis syndrome was recognized in a patient with AIDS-related complex after he had experienced several episodes of a sacral, dermatomic zosteriform eruption. Varicella-zoster virus (VZV) was subsequently recovered from cell culture of retinal tissue. The literature on VZV retinitis, including that on acute retinal necrosis, is reviewed. Dissemination of VZV infection in AIDS is also reviewed. Features that differentiate the findings and course of VZV retinitis in patients with AIDS from those in otherwise healthy adults are noted and related to potentially different pathogenic mechanisms. This unusual and recently recognized complication of herpesvirus infection may be promoted by AIDS-related immunosuppression. Acute retinal necrosis and other more-recently described forms of VZV retinitis, which have primarily been subjects of the ophthalmologic literature, merit the attention of clinicians and investigators of infectious diseases.

Rapid and sensitive techniques with a high degree of accuracy are necessary for the diagnosis and management of cytomegalovirus (CMV) retinitis presenting with atypical clinical manifestations. Light microscopy and immunohistochemical studies have limitations in the identification of this virus, but in situ DNA hybridization offers a rapid, highly specific, and easily interpretable means of identifying CMV. A new procedure of enzymatic amplification of DNA in vitro, called the polymerase chain reaction (PCR), has yielded excellent results in the identification of various viruses. In the study described herein, we evaluated the diagnostic usefulness of PCR and compared its reliability with that of in situ DNA hybridization for the detection of CMV in ocular tissues. We found that the reliability of the PCR method is similar to in situ DNA hybridization for the detection of CMV, although morphologic correlation is provided only by the latter technique. False-negative results can occur in PCR if the correct primer is not used.

Neonatal Herpes simplex infections are usually contracted from the birth canal, and the systemic lesions develop several days to weeks after delivery. We present the clinicopathologic findings in a newborn with a prenatal diagnosis of hydrocephalus who died at 1 day of age. Severe liquefaction necrosis and foci of calcification were present in the brain, adrenal glands, and retina. Cowdry type A intranuclear inclusions were present in the adrenal glands and retina. There was no clinical evidence of genital herpes in either parent. This is the first documented case of in utero transmission of Herpes simplex infection, confirmed by the polymerase chain reaction, and causing fulminant necrotizing retinitis and encephalitis.

Following anterior chamber injection of the KOS strain of herpes simplex virus type 1 into Balb/c mice a characteristic pathologic response occurs. When examined 10-14 days later there is intense anterior segment inflammation of the injected eye, but the retina is spared. In contrast, the contralateral eye undergoes intense and destructive retinitis with little or no involvement of the anterior segment. Coincident with these observations is the induction of ACAID (for anterior chamber associated immune deviation) which is characterized by a suppressed DTH response, normal antibody titers, and normal cytolytic T-cell responses to HSV antigens. Since we have recently demonstrated that ACAID does not take place in the absence of light (i.e., is light dependent), we have examined the effect of light on the HSV-retinitis model. When Balb/c mice are either dark-reared or dark-adapted prior to AC injection of HSV-1, contralateral retinitis is abolished. Concurrent with the abrogation of retinitis, is the elimination of ACAID to HSV-1 antigens. In addition, although contralateral retinitis and ACAID do not develop in dark-reared mice if they are placed in the light immediately following injection, both can be re-established in dark-reared animals following a 2 week period of re-adaptation to light. Our results demonstrate that the entrance of light into the eye is not only important for ACAID, but also for the development of contralateral HSV-induced retinitis.

Vitreous specimens can be useful for diagnosis of intraocular infection, inflammation, and neoplasms. Concern has been raised that obtaining vitreous specimens through a guillotine cutter might result in suboptimal cytologic changes. To determine if aspiration yields better cytologic information than vitrectomy, the authors performed experimental vitreous biopsies on rabbit eyes with vitritis to compare specimens taken by aspiration or vitrectomy with cutting rates of 100, 300, 600 per minute. The specimens were processed by cytospin preparations and stained with Papanicolaou and May-Grünwald-Giemsa stain. There was no difference in the adequacy of the specimens. Cell loss or damage to cell morphologic features when obtaining specimens through aspiration or vitrectomy at different cutting rates could not be differentiated by a blinded cytologic evaluation. A theoretical model of shear stress on cells passing through a guillotine cutter was also developed. The experimental and theoretical data show that vitrectomy with a cutting rate as fast as 600 per minute yields an adequate specimens with a sufficient number of well preserved cells to make definite cytologic interpretations, and that vitreous aspiration is not necessary.

Cytomegalovirus (CMV) retinitis has been well documented in the literature, both in patients with acquired immune deficiency syndrome (AIDS) and in other immunocompromised hosts. The clinical and histopathologic findings in three patients with AIDS and CMV retinitis are presented. In areas of healed retinitis, focal, yellow-white, plaque-like lesions and small refractile retinal lesions were noted clinically. Histopathologic studies confirmed the plaque-like lesions to be intraretinal calcifications. Detailed clinical pathologic correlation between fundus photographs and histologic material is made and its clinical importance discussed.

To study local intravitreal therapies for retinitis due to herpes viruses, an animal model of focal, subacute, relatively nonlethal herpes family retinitis is needed. Herpes simplex virus type 1 (HSV-1) was injected into the subretinal space of 33 Dutch pigmented rabbit eyes. The animals were observed for up to 42 days after the inoculation. All inoculated eyes developed a focal, enlarging area of retinitis in a predictable manner, showing focal enlarging areas of retinal opacification and necrosis with variable retinal hemorrhage. In the inoculated eyes, retinal detachment developed in all animals within 21 days; 33% of the animals developed focal retinitis in the uninoculated eye. Histologic examination showed encephalitis to be present in 11 (73%) of the 15 animals studied after 1 week. This model may be used to evaluate the therapeutic efficacy of new antiviral agents and modalities in the treatment of herpes family viral retinitis. The model is most similar to herpes simplex or zoster retinitis in humans, but also shares some similarities (and differences) with cytomegalovirus (CMV) retinitis in humans.

We treated a patient who had acquired immunodeficiency syndrome and cytomegalovirus retinitis of the left eye. After anesthetic had been topically administered, the patient received intravitreal injections of 1,200 micrograms of foscarnet. Plasma and vitreous foscarnet levels were measured by high-performance liquid chromatography. Systemic absorption of the drug was not evident. Elimination half-life from the vitreous after one injection was 54.0 hours. Vitreous levels remained above the mean 50% inhibition value for cytomegalovirus for approximately 56 hours and above the mean inhibition value for human immunodeficiency virus for approximately 241 hours. The patient's visual acuity improved from 20/30 to 20/25 in the left eye. Ophthalmoscopy showed the retinal lesion to have become inactive, and no reactivation occurred during the follow-up period of more than four months. The drug was well tolerated and no retinal toxicity was evident. We suggest an induction treatment regimen of two injections weekly for three weeks, followed by a maintenance treatment regimen of one injection weekly.

Cytomegalovirus (CMV) retinitis occurs in immunocompromised patients and can be treated by repeated intravenous or intravitreal injections of ganciclovir (GCV) or foscarnet. Due to toxicity and complications these modalities are not ideal. The development of alternative administration routes is hindered by a lack of pharmacokinetic data. Devices giving pseudo zero order release of GCV were implanted intravitreally first in rabbits and then in patients with AIDS associated CMV retinitis as part of a Phase I clinical trial. Steady state intravitreal GCV levels were obtained immediately after death and the elimination rate constants were calculated assuming first order pharmacokinetics. Normalizing for retinal surface area, distribution volume and anatomic volume, the retinal elimination rate constants were calculated. These were found to be 0.017 cm-2hr-1 in rabbits and 0.015 cm-2hr-1 in man. This indicates that the rabbit eye is a good model for studying intravitreal pharmacokinetics of ganciclovir and suggests a common elimination mechanism which may be trans-retinal.

Between January 1988 and May 1991 intravenous ganciclovir (GCV) treatment was administered to eight male AIDS-patients with unilateral cytomegalovirus (CMV)-retinitis. Despite of continuous therapy with at least the recommended dose of GCV, three patients developed slowly progressive CMV-retinitis in the fellow eye after 4 to 13 months. The progression could not be stopped by GCV and thus bilateral blindness resulted after 12 to 22 months. The number of CD4-lymphocytes in the blood was reduced in all patients, but particularly in patients with progressive disease. Treatment failure was partly related to the duration of CMV-retinitis and partly to the degree of immunodeficiency. Intravenous treatment with GCV alone can not stop the progression of CMV-retinitis in long-term survivors and in those with advanced immunodeficiency.

A 37-year-old man with acquired immunodeficiency syndrome and cytomegalovirus retinitis developed primary intraocular and central nervous system lymphoma. Intraocular involvement was documented before death with vitrectomy. Autopsy demonstrated the presence of cytomegalovirus retinitis in the right eye and lymphoma in both eyes and the brain. We believe this is the first report of autopsy-confirmed primary intraocular lymphoma in a patient with the acquired immunodeficiency syndrome.

To study the effect of immunosuppression on the development of murine cytomegalovirus (MCMV) retinitis, BALB/c mice were immunosuppressed with methylprednisolone (a corticosteroid) and/or with antibodies against CD4+ and CD8+ T cells and inoculated with low-dose MCMV (5 x 10(2) plaque-forming units) by the supraciliary route. Nonimmunosuppressed mice inoculated with low-dose MCMV by the supraciliary route did not develop necrotizing retinitis. By contrast, 78-100% of immunosuppressed mice developed retinitis after inoculation of low-dose MCMV. To study the effect of depletion of individual T cell subsets, mice were depleted of either CD4+ or CD8+ T cells and inoculated with low-dose MCMV by the supraciliary route. The frequency of retinitis in CD4-depleted mice (30%) was not significantly different from that of nonimmunosuppressed control mice (0%). The frequency of retinitis in the CD8-depleted group (80%) was similar to that observed in mice immunosuppressed with corticosteroid alone (90.9%), with antibodies to both T cell subsets (100%), or with steroid and both T cell subset antibodies (100%). These results support the conclusion that the CD8+ T cell subset is responsible for control of ocular MCMV infection. Furthermore, these results suggest that the CD8+ T cell subset may be important in preventing ocular CMV infection in immunosuppressed patients.

Patients with AIDS or ARC may develop ocular manifestations falling in four broad categories: (1) conjunctival and periorbital disease, (2) neuro-ophthalmologic abnormalities, (3) retinal microangiopathy, and (4) opportunistic retinal and choroidal infections. Careful ophthalmologic examination generally permits identification and differentiation of these entities. Although ocular involvement is frequently a harbinger of an unfavorable systemic prognosis, specific drug therapy may be of some benefit in arresting disease in selected individuals. Further advances in the diagnosis and treatment of AIDS-related ocular tumors and infections may improve the quality of life for these patients.