Cytomegalovirus retinitis and low CD4+ T-lymphocyte counts.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
D A Jabs
Publications and source records attributed to D A Jabs.
Cytomegalovirus retinitis in HIV-infected patients with elevated CD4+ counts.
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AIDS-Related Opportunistic Infections↗
Viral sensitivity testing in patients with cytomegalovirus retinitis clinically resistant to foscarnet or ganciclovir.
PURPOSE: Resistance to antiviral therapy is a potential cause of progression of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. We investigated the results of viral sensitivity testing in a series of patients with clinically resistant retinitis who had positive results of blood or urine cytomegalovirus cultures. METHODS: All patients with newly diagnosed cytomegalovirus retinitis between January 1990 and December 1991 were prospectively studied. Blood and urine cultures for cytomegalovirus were obtained in a nonrandomized subgroup of this group. The results of in vitro sensitivity to foscarnet and ganciclovir, determined by a DNA hybridization assay, were then analyzed in seven patients with clinically resistant cytomegalovirus retinitis and whose blood or urine culture results, or both, were positive for cytomegalovirus while on a treatment regimen. RESULTS: Foscarnet-resistant cytomegalovirus (ID50 > 300 microM) was isolated from two patients, one of whom was being treated with foscarnet. Ganciclovir-resistant cytomegalovirus (ID 50 > 6.0 microM) was isolated from four patients, three of whom were being treated with ganciclovir. Foscarnet- and ganciclovir-resistant cytomegalovirus occurred with previous ganciclovir therapy in one patient. Clinical improvement occurred in three patients whose change in therapy was based on viral sensitivity testing. In general, prolonged therapy with one drug was associated with a progressive increase in the ID 50 for that drug. CONCLUSIONS: Viral resistance to foscarnet or ganciclovir may explain refractory cytomegalovirus retinitis in some patients.
AIDS-Related Opportunistic Infections↗
Controversies in the treatment of cytomegalovirus retinitis: foscarnet versus ganciclovir.
Cytomegalovirus (CMV) retinitis is the most common intraocular infection in patients with AIDS. Untreated, CMV retinitis is a binding disease. Ganciclovir, a nucleoside analog, and foscarnet, a pyrophosphate analog, are both effective in controlling CMV retinitis. A randomized, controlled, comparative trial of foscarnet and ganciclovir demonstrated that they were equivalent in terms of controlling CMV retinits, but that foscarnet was associated with a longer survival, possibly due to an antiretroviral effect of foscarnet. However, foscarnet was less well tolerated than ganciclovir, primarily due to the nature of its side effects. Because foscarnet and ganciclovir have different side effects, initial treatment of CMV retinitis should be individualized. Newer technological developments, including oral ganciclovir and the ganciclovir intraocular device, may influence the choice of initial treatment, particularly because of their effect on the quality of life when compared to chronic intravenous therapy. The occurrence of relapse and the development of resistance remain long-term concerns, which may alter the use of anti-CMV drugs over time.
AIDS-Related Opportunistic Infections↗
Ocular manifestations of HIV infection.
OBJECTIVE: To evaluate the frequency of ocular complications and the clinical outcomes of these complications in patients with various stages of HIV infection. METHODS: Retrospective review of all HIV-infected patients seen in an AIDS ophthalmology clinic from November 1983 through December 31, 1992. RESULTS: Eleven-hundred sixty-three patients were seen for ophthalmologic evaluation. Of these, 781 had the acquired immune deficiency syndrome (AIDS), 226 had symptomatic HIV infection (AIDs-related complex [ARC]), and 156 had asymptomatic HIV infection. Non-infectious HIV retinopathy was the most common ocular complication, affecting 50% of the patients with AIDS, 34% of the patients with ARC, and 3% of the patients with asymptomatic HIV infection. Cytomegalovirus (CMV) retinitis was the most common opportunistic ocular infection, affecting 37% of the patients with AIDS. Other opportunistic ocular infections, including ocular toxoplasmosis, varicella zoster virus retinitis, and Pneumocystis choroidopathy were all much less common, each occurring in < or = 1% of the patients with AIDS. Treatment of CMV retinitis with either foscarnet or ganciclovir was successful in initially controlling the retinitis. However, relapse represented a significant problem and required frequent re-inductions. As a consequence of the retinal damage associated with relapse, loss of visual acuity occurred. The median time to a visual acuity of 20/200 or worse for all eyes with CMV retinitis was 13.4 months, and the median time to a visual acuity of 20/200 or worse in the better eye was 21.1 months. At last follow-up, 75% of the patients had a final visual acuity of 20/40 or better in at least one eye. Retinal detachments were a frequent ophthalmologic complication of CMV retinitis with a cumulative probability of a retinal detachment in at least one eye of 57% at 12 months after the diagnosis of CMV retinitis. Herpes zoster ophthalmicus developed in 3% of the overall series and was seen in all stages of HIV infection. Fifty-six percent of the cases of ocular toxoplasmosis had simultaneous toxoplasmic cerebritis. Ocular toxoplasmosis responded to standard anti-microbial therapy. Varicella zoster virus retinitis, when manifested by the acute retinal necrosis (ARN) syndrome, responded to intravenous acyclovir therapy. Conversely, in a limited number of patients with the progressive outer retinal necrosis syndrome, the disease responded poorly to intravenous acyclovir therapy, but appeared to respond to combination foscarnet and acyclovir therapy. Neuro-ophthalmic lesions were present in 6% of the patients with AIDS. The most common cause of a neuro-ophthalmic lesion was cryptococcal meningitis, and 25% of the patients with cryptococcal meningitis developed a neuro-ophthalmic complication. CONCLUSIONS: Ocular manifestations are common in patients with AIDS. CMV retinitis represented a major vision-threatening problem in these patients. While available therapy was successful in initially controlling the retinitis, the phenomenon of relapse resulted in some degree of long-term visual loss. Preservation of the patient's visual acuity in at least one eye was generally successful. Other opportunistic ocular infections were substantially less common than CMV retinitis but require aggressive therapy.
AIDS-Related Opportunistic Infections↗
The eye in bone marrow transplantation. VI. Retinal complications.
OBJECTIVE: To evaluate the posterior segment ocular complications of patients undergoing bone marrow transplantation (BMT). DESIGN: Retrospective analysis. SETTING: Academic ophthalmology department at a tertiary care hospital with a BMT unit. PATIENTS: Patients undergoing BMT were seen by an ophthalmologist for clinical care and enrolled in a long-term follow-up study, during which they were seen 6 and 12 months after the transplantation and annually thereafter. RESULTS: Of 397 patients undergoing BMT, 51 (12.8%) developed posterior segment complications. Fourteen patients (3.5%) developed hemorrhagic complications with either intraretinal and/or vitreous hemorrhages and 17 patients (4.3%) developed cotton-wool spots in the fundus of both eyes. Eleven patients (2.8%) had bilateral optic disc edema, with eight cases attributed to the toxic effects of cyclosporine and three to other causes. Two patients (0.5%) developed serious retinal detachments. Eight patients (2.0%) developed infectious retinitis and/or endophthalmitis. Fungal infections with Candida or Aspergillus usually occurred within 120 days after BMT, while viral infections with herpes zoster or cytomegalovirus and parasitic infections with Toxoplasma occurred later. Intraocular lymphoma occurred in one patient (0.2%). CONCLUSION: Severe, potentially vision-threatening, posterior segment complications following BMT occur due to a variety of causes.
Adult↗
Effects of early and late treatment with anti-CD4 monoclonal antibody on autoimmune disease in MRL/MP-lpr/lpr mice.
MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop a systemic autoimmune disease, characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation, with target organ inflammatory lesions composed largely of CD4+ (helper) T cells. Previous reports have demonstrated that anti-CD4 monoclonal antibody (mAb) treatment of MRL/lpr mice from 1 to 5 months of age resulted in a dramatic reduction in both the frequency and the severity of autoimmune disease. In order to investigate the effects of early, short-course and late, short-course anti-CD4 mAb therapy on the autoimmune disease in MRL/lpr mice, groups of 12 to 15 animals were treated with weekly intraperitoneal injections according to one of four regimens: (i) anti-CD4 mAb from age 1 to 5 months (continuous treatment); (ii) anti-CD4 mAb from age 1 to 3 months (early treatment); (iii) anti-CD4 mAb from age 3 to 5 months (late treatment); and (iv) either normal saline or rat immunoglobulin (control treatment). Continuous treatment resulted in a dramatic reduction of both frequency and severity of the autoimmune disease, as demonstrated histologically and serologically. Early treatment also resulted in a significant reduction in autoimmune disease, while late treatment had little effect. Glomerulonephritis was detected in none of the animals in the continuously treated group (P < 0.05), 38% of those in the early-treated group (P = < 0.05), 92% of the late-treated group, and 100% of controls. The titer of antinuclear antibodies, of anti-dsDNA antibodies, and total immunoglobulin levels were all significantly reduced in the continuous-treatment and early-treatment groups, but not in the late-treatment group. Murine antibodies to rat anti-CD4 mAb were present in the late-treatment group. These results indicate that early short-course anti-CD4 mAb treatment of MRL/lpr mice is effective in ameliorating the autoimmune disease in this model, while late-treatment is ineffective, probably due to the induction of antibody directed against anti-CD4 mAb itself.
Animals↗
Murine models of Sjögren's syndrome.
Autoimmune MRL/lpr, MRL/+, and NZB/W mice all develop lacrimal gland inflammatory lesions, which consist of focal mononuclear inflammatory cell infiltrates. Each strain has a different immunocytochemical profile, which appears to be related to the underlying immunologic defects present in that mouse. The appearance of these lesions parallels the evolution of the systemic autoimmune disease. The lesions are dynamic over time with the early appearance of CD4+ T cells (helper T cells) for each strain. Subsequently, there is an accumulation of B cells over time in MRL/+ and NZB/W mice. In the two more rapidly evolving mouse models, MRL/lpr and NZB/W, there is a progressive decline in the percentage of CD8+ cells. Conversely, in the slowly evolving MRL/+ lacrimal gland lesions, there is a persistent and unchanging percentage of CD8+ T cells (suppressor/cytotoxic T cells). Autoimmune mice provide models for the human disorder Sjögren's syndrome and a mechanism for better understanding the immunopathogenesis of autoimmune lacrimal gland disease.
Animals↗
Ocular toxoplasmosis misdiagnosed as cytomegalovirus retinopathy in immunocompromised patients.
BACKGROUND: Cytomegalovirus (CMV) and Toxoplasma gondii both cause necrotizing retinopathy in immunosuppressed hosts. Because of the high prevalence of serum antibodies to these agents in the general population and the risks associated with retinal biopsies, diagnosis of these infections is usually based on clinical findings alone, but the two infections can be confused with one another because of similar clinical features. Accurate diagnosis is critical, however, because both diseases are treatable but require different medical therapies. METHODS: Case histories were reviewed for five immunosuppressed patients with necrotizing retinopathy, which was initially diagnosed incorrectly as CMV retinopathy but was subsequently found to be toxoplasmic retinochoroiditis. Correct diagnosis was based on retinal biopsy (2 cases) or rapid response to antiparasitic drug therapy (3 cases). Factors were sought that might help differentiate toxoplasmic retinochoroiditis from CMV retinopathy at presentation. RESULTS: In all cases, the character of retinal opacification (densely opaque, thick) and the appearance of lesion borders (smooth, nongranular) was different from that typically seen with CMV retinopathy. These cases also were characterized by prominent anterior chamber and vitreous inflammatory reactions (four of five cases) and relative lack of retinal hemorrhage. One patient subsequently developed CMV retinopathy; characteristics of the two lesions in the same eye highlighted the differences between these two infections. CONCLUSION: Clinicians should consider ocular toxoplasmosis as a cause of necrotizing retinopathy in immunosuppressed patients and consider an empiric course of antiparasitic therapy for lesions with features described in this report.
Adult↗
Improved visual results after surgical repair of cytomegalovirus-related retinal detachments.
PURPOSE: This study was conducted to determine whether visual outcomes have improved after repair of retinal detachments (RDs) associated with cytomegalovirus (CMV) retinitis, and, if so, whether factors such as earlier intervention and changes in surgical technique have led to these results. METHODS: The authors performed a retrospective review of 35 eyes in 30 immunocompromised patients with CMV retinitis and RD who underwent pars plana vitrectomy with the use of silicone oil injection. Visual and anatomic results in eyes treated between January 1991 and April 1992 (group 1) were compared with eyes treated before January 1991 (group 2). Follow-up was limited due to patient mortality; median follow-up was 4.1 months in group 1 and 2.5 months in group 2. RESULTS: Best-attained postoperative visual acuities were better for group 1 than group 2 eyes, with 71% of group 1 eyes attaining visual acuity of 20/200 or better compared with 17% of group 2 eyes (chi-square1 trend = 12.3; P < 0.001). A similar result was found among eyes with macula-off detachments. Ambulatory visual acuity of 5/200 or better was achieved in 86% of group 1 versus 33% of group 2 eyes. There was a longer interval between diagnosis and surgery in group 2 compared with group 1 (7 versus 3 days); scleral buckling in conjunction with pars plana vitrectomy and silicone oil injection was used in more group 1 eyes. CONCLUSION: Earlier intervention, absence of preoperative optic atrophy, and macular CMV correlate with better postoperative visual acuity results. Pars plana vitrectomy combined with silicone oil for eyes with macula-off RDs can result in improved visual acuity.
Adult↗
Antiepiligrin cicatricial pemphigoid. A subepithelial bullous disorder.
BACKGROUND: Epiligrin is a glycoprotein complex deposited in extracellular matrix by cultured human keratinocytes that serves as the major integrin ligand of these cells. In human skin, epiligrin is found at the interface of the lamina lucida and lamina densa in epidermal basement membrane where it is believed to be associated with anchoring filaments and plays an important role in keratinocyte adhesion. METHODS AND RESULTS: We have identified six patients with a subepithelial bullous disorder of mucous membranes and skin who have IgG anti-basement membrane autoantibodies that immunoprecipitate epiligrin from human keratinocyte extracts and culture media. These patients' IgG autoantibodies also bind epiligrin in human keratinocyte extracellular matrix and epidermal basement membrane as determined by immunofluorescence and immunoelectron microscopy. Studies of 10 patients who are clinically indistinguishable from subjects with anti-epiligrin autoantibodies (ie, cicatricial pemphigoid patients) found that while seven had anti-basement membrane autoantibodies, the latter are directed exclusively against a region of epidermal basement membrane that does not contain epiligrin, are present in low titer (ie, < or = 1:10), do not react with keratinocyte extracellular matrix, and do not bind epiligrin (or any other specific antigen) in immunoprecipitation studies of human keratinocyte extracts or media. Antiepiligrin autoantibodies were also not detected in studies of 36 additional patients with bullous diseases or six normal volunteers. CONCLUSIONS: Cicatricial pemphigoid is a disease phenotype in which patients' autoantibodies may target different constituents of epidermal basement membrane. Antiepiligrin autoantibodies are a specific immunologic marker for a group of patients with a disease entity that we propose to designate antiepiligrin cicatricial pemphigoid.
Adult↗
Bone marrow transplantation and cataract development.
OBJECTIVES: To evaluate risk factors for the development of posterior subcapsular cataract following bone marrow transplantation (BMT) and the results of patients undergoing cataract extraction. DESIGN: Retrospective case-control study. SETTING: Tertiary referral center. PATIENTS: Three hundred sixty-six patients (59% male, 41% female) undergoing BMT at one institution who survived for at least 1 month and underwent full ophthalmologic examination. Risk factors were then compared between patients who developed posterior subcapsular cataract and those who did not. INTERVENTION: Cataract surgery in six eyes of four patients. MAIN OUTCOME MEASURE: Formation of posterior subcapsular cataract. Data were obtained on all patients for type of BMT, pretransplantation regimen, underlying malignancy, demographic background, complications of BMT, and medications. RESULTS: Forty (10.9%) of 366 patients developed posterior subcapsular cataract. By univariate analysis, cataract formation was associated with total body irradiation, chronic graft-vs-host disease, the use of allogeneic bone marrow, and the total dose and duration of corticosteroid therapy. Multivariate analysis revealed that the total dose and duration of corticosteroid therapy were the most important risk factors, while total body irradiation was not a statistically significant risk factor. Cataract surgery was performed in six eyes of four patients, all of whom developed visual acuities of 20/40 or better. CONCLUSION: Posterior subcapsular cataract following BMT is uncommon and rarely requires surgery. Total dose and duration of corticosteroid therapy are the most important risk factors for development of cataract, but total body irradiation is not a statistically significant risk factor.
Adolescent↗
Ocular microvasculopathy after bone marrow transplantation.
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Bone Marrow Transplantation↗
Thalidomide for the treatment of chronic graft-versus-host disease.
BACKGROUND: Allogeneic bone marrow transplantation is an accepted therapy for hematologic cancer, aplastic anemia, and inherited immunodeficiencies. Chronic graft-versus-host disease (GVHD) is the principal complication in patients surviving more than 100 days. Thalidomide has been shown experimentally to be effective in treating GVHD. METHODS: We treated 23 patients with chronic GVHD refractory to conventional treatment and 21 patients with "high-risk" chronic GVHD (identified as having at least two of the following three risk factors: chronic GVHD that has evolved from acute GVHD, lichenoid skin or mucous-membrane changes, and hepatic dysfunction. Such patients have a high mortality rate.) with thalidomide in a dose that produced a plasma level of 5 micrograms per milliliter two hours after administration. Therapy was continued for three months after a complete response or for six months after a partial response. RESULTS: The overall actuarial survival of all enrolled patients was 64 percent. Survival was 76 percent among the patients receiving salvage therapy for refractory GVHD and 48 percent among those with high-risk GVHD. A complete response was observed in 14 patients, a partial response in 12 patients, and no response in 18. Side effects were minor, most notably sedation in almost all patients. CONCLUSIONS: In this preliminary trial, thalidomide appeared to be safe and effective for the treatment of chronic GVHD. A trial comparing thalidomide with prednisone in patients with newly diagnosed chronic GVHD will be required to demonstrate its relative efficacy.
Adolescent↗
Treatment of cytomegalovirus retinitis--1992.
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Acquired Immunodeficiency Syndrome↗
Anti-CD4 monoclonal antibody therapy suppresses autoimmune disease in MRL/Mp-lpr/lpr mice.
MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop systemic autoimmune disease, characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation. The target organ inflammatory lesions are composed largely of CD4+ "helper" T cells, while the massively enlarged lymph nodes are composed primarily of CD3+ CD4- CD8- TCR alpha/beta + "double-negative" T cells. In this study we investigated the effect of treatment of MRL/lpr mice with anti-CD4 monoclonal antibody (mAb); control groups consisted of animals treated with normal saline or rat immunoglobulin (Ig). Anti-CD4 mAb treatment, which was started at 4 weeks and continued through 20 weeks of age, resulted in a dramatic reduction of both the frequency and severity of the autoimmune disease, as demonstrated histologically and serologically. Anti-CD4 mAb therapy markedly reduced the frequency of glomerulonephritis and eliminated vasculitis of the major renal arterial branches. Glomerulonephritis was detected in 9 of 9 saline-treated, 9 of 9 rat Ig-treated, but in only 1 of 9 anti-CD4 mAb-treated mice; vasculitis was detected in 6 of 9 saline-treated, 7 of 9 rat Ig-treated, but in none of 9 anti-CD4 mAb-treated mice. The frequency of antinuclear antibodies, titer of anti-dsDNA antibodies, and total Ig levels were all significantly reduced by anti-CD4 mAb therapy. These data support the hypothesis that CD4+ T cells play a central role in the disease process in this autoimmune strain.
Animals↗
Decrease in the risk of bilateral acute retinal necrosis by acyclovir therapy.
We reviewed the course of 54 patients who had unilateral acute retinal necrosis at initial examination. Thirty-one patients were treated with acyclovir, whereas 23 were not. Of the 31 patients treated with acyclovir, 27 (87.1%) had fellow eyes that remained disease-free throughout a median follow-up of 12 months. Of the 23 patients not treated with acyclovir, seven (30.4%) had fellow eyes that remained disease-free throughout a median follow-up of 11 months. Survival analysis indicated that the fellow eyes of the group of patients treated with acyclovir were more likely to remain disease-free than the fellow eyes of the group not treated with acyclovir (P = .0013). Two years after initial onset, the proportion of fellow eyes that remained disease-free was 75.3% for the group treated with acyclovir and 35.1% for the group not treated with acyclovir. These results suggest that acyclovir treatment reduces the risk of involvement of the fellow eye in patients with acute retinal necrosis.
Acyclovir↗
Current practices in the management of ocular toxoplasmosis.
To determine current practices in the management of ocular toxoplasmosis, 72 of 85 uveitis specialists (85%) in the American Uveitis Society completed a detailed questionnaire. Questions involved the indications for beginning treatment, choice of antiparasitic/antimicrobial agents, and experience with treatment of ocular toxoplasmosis in special situations including pregnancy, neonatal infections, and immunocompromised patients. Most of the respondents treat patients whose visual acuity had decreased to worse than 20/200, lesions located in the peripapillary, perifoveal, or maculopapillary bundle regions, and lesions associated with severe vitreous inflammation. Most would not treat patients who retained visual acuity of 20/20, lesions located in the far peripheral retina, or lesions associated with only trace to mild vitreous inflammation. Treatment of other combinations of factors remains controversial. Eight different antimicrobial drugs are used in various combinations for lesions threatening the macula or optic nerve head. Systemic corticosteroids are used by 59 of 62 respondents (95%) as part of their initial treatment regimen. The most commonly used regimens are pyrimethamine/sulfadiazine/corticosteroids (20 of 62 [32%]) and pyrimethamine/sulfadiazine/clindamycin/corticosteroids (17 of 62 [27%]). Adjunctive therapies (photocoagulation, cryotherapy, or vitrectomy) have been used by 20 of 60 respondents (33%). Most alter treatment during pregnancy, in newborn patients, and in patients with the acquired immunodeficiency syndrome.
Adult↗