Ocular microvasculopathy after bone marrow transplantation.
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Bone Marrow Transplantation↗
Biomedical subjects
D A Jabs
Publications and source records attributed to D A Jabs.
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↗
Retinal detachments in patients with cytomegalovirus retinitis.
Retinal detachments are a recognized complication of cytomegalovirus retinitis. In a series of 145 patients with cytomegalovirus retinitis, 38 (26%) developed retinal detachments. The cumulative probability of a retinal detachment 1 year after the diagnosis of cytomegalovirus retinitis was 50%. Detachments were associated with increased size of the cytomegalovirus lesion and with lesions extending anteriorly up to the ora serrata. Treatment with an anticytomegalovirus drug appeared to delay the time to detachment. Median survival time after the diagnosis of retinal detachment was 9 months. In our study, vitrectomy with silicone oil as the initial surgical procedure was the most effective approach. Successful anatomic reattachment of the retina was achieved in 70% of patients undergoing this procedure. Despite the success of surgery, the visual outcome was disappointing, with only 20% of eyes achieving a final visual acuity of 5/200 or better.
Acquired Immunodeficiency Syndrome↗
Optic disc edema after bone marrow transplantation. Possible role of cyclosporine toxicity.
Bone marrow transplantation has become widely used in the treatment of aplastic anemia and leukemia. Cyclosporine is used as prophylaxis against graft-versus-host disease. The authors report on eight cases of optic disc edema in patients taking cyclosporine after allogenic bone marrow transplant. Thorough evaluation revealed a possible alternate cause in two cases. In all cases, the optic disc edema resolved after discontinuing or decreasing the cyclosporine. Although cyclosporine has not previously been associated with optic disc edema, it has been implicated as the cause of a variety of neurologic side effects. Bone marrow transplant patients taking cyclosporine should be followed for the development of optic disc edema.
Adolescent↗
Autoimmune ocular disease in MRL/Mp-lpr/lpr mice is suppressed by anti-CD4 antibody.
MRL/Mp-lpr/lpr(MRL/lpr) mice spontaneously have a systemic autoimmune disease, characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation. Among the many autoimmune lesions present are focal ocular inflammatory infiltrates, involving the choroid and sclera. These lesions appear to be related to the vasculitis seen in MRL/lpr mice and are mediated by L3T4-positive helper T-cells (CD4-positive T-cells). Systemic treatment of MRL/lpr mice with a monoclonal anti-L3T4 antibody (anti-CD4) resulted in a dramatic reduction of both the frequency and severity of the ocular disease, supporting the hypothesis that the CD4-positive T-cells play an essential role in the pathogenesis of the choroiditis and scleritis in this strain.
Animals↗
Murine models of Sjögren's syndrome. Evolution of the lacrimal gland inflammatory lesions.
Lacrimal gland inflammation develops in a number of autoimmune mice, including the MRL/Mp-lpr/lpr (MRL/lpr), MRL/Mp(-)+/+ (MRL/+), and NZB x NZW F1 hybrid (NZB/W) strains. The authors studied the evolution of this process, MRL/lpr mice had inflammatory lesions at 4 weeks old. The lesions had enlarged by 2 months and were fully developed by 4 to 5 months of age. In MRL/+ mice, 4-week-old mice had no lesions, although some focal inflammation was detectable at 3 months old. Significant abnormalities were present at 6 months, and persisted and increased throughout life, with all mice having extensive lesions at 18 months or older. In NZB/W mice, the authors detected no lesions until 6 months of age, and these lesions were fully developed in 9 months. Immunocytochemical profiles, of the cell types infiltrating the lacrimal gland, showed differences not only between the strains, but also in each strain as inflammation progressed. All three types of mice had L3T4+ T cells as the major lymphocyte component, although MRL/+ had significantly more Lyt 2+ T cells than the other strains. NZB/W mice had significantly more B cells than the two MRL substrains. In both NZB/W and MRL/+ mice, there was a significant increase in the B cell population, and a decrease in the percentage of L3T4+ T cells. There was a significant decline in Lyt 2+ T suppressor/cytotoxic cells in both NZB/W and MRL/lpr mice. This last finding was consistent with the more rapid development of inflammation in these strains than in the MRL/+ mice, where Lyt 2+ T suppressor/cytotoxic cells persist. Together, these results indicate that the autoimmune response in murine models of Sjögren's syndrome is a dynamic, evolving process with strain-related changes in lymphocyte subsets.
Animals↗
Ocular inflammation in MRL/Mp-lpr/lpr mice.
A systemic autoimmune disease spontaneously developed in MRL/Mp-lpr/lpr (MRL/lpr) mice. The disease was characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation. Among the many autoimmune lesions are focal ocular inflammatory infiltrates involving the choroid and sclera. Of 104 mice examined histologically, the sclera was most often involved, with 30% of mice 5 months of age or older having scleral lesions that were often centered around small arteries. The choroid was the second most frequently involved tissue, with focal inflammation developing in 16% of these mice. Immunohistologic analysis of the ocular infiltrates showed that most of the mononuclear cells seen were L3T4 + T cells (CD4+ helper T cells), suggesting that the process was largely T cell-mediated. Smaller numbers of B cells and Lyt 2+ T suppressor/cytotoxic cells were seen. No such lesions were seen in congenic MRL/Mp- +/+, (NZBxNZW) F1 hybrid mice, and control BALB/c mice; vasculitis did not develop in all of the mice. These results suggest that the ocular lesions in MRL/lpr mice may be a model for ocular involvement in patients who have systemic necrotizing vasculitis.
Animals↗
Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia.
BACKGROUND AND METHODS: We describe five patients with underlying neoplasms in whom painful mucosal ulcerations and polymorphous skin lesions developed, usually with progression to blistering eruptions on the trunk and extremities. Histologic examination showed vacuolization of epidermal basal cells, keratinocyte necrosis, and acantholysis. Immunofluorescence testing revealed atypical pemphigus-like autoantibodies in perilesional epithelium and serum from all five patients. We studied the antigenic specificities of the autoantibodies by indirect immunofluorescence and immunoprecipitation, using extracts of 14C-labeled human keratinocytes. IgG purified from the serum of one patient was passively transferred to four neonatal mice to test for pathogenicity. RESULTS: Immunofluorescence testing showed that the autoantibodies bound to the surface of tissues containing desmosomes, including complex and simple epithelia, and myocardium. An identical and unique complex of four polypeptides with molecular weights of 250, 230, 210, and 190 was immunoprecipitated by all serum samples. The 250-kd polypeptide comigrated with desmoplakin I (a protein found in the desmosomes of all epithelia), and the 230-kd antigen comigrated with the antigen of bullous pemphigoid. Cutaneous blisters, a positive Nikolsky's sign, and epidermal and esophageal acantholysis developed in all mice into which the autoantibody was injected. Electron microscopy showed epidermal acantholysis similar to lesions of experimentally induced pemphigus vulgaris. CONCLUSION: These five patients with cancer had a novel acantholytic mucocutaneous disease characterized by autoantibodies that were pathogenic after passive transfer. The autoantibodies from these patients reacted with an antigen complex composed of desmoplakin I and the 230-kd antigen of bullous pemphigoid and two as yet unidentified epithelial antigens. We suggest the term "paraneoplastic pemphigus" for this disease.
Acantholysis↗
Trabeculectomy with 5-fluorouracil for adult inflammatory glaucoma.
We reviewed the records of 12 eyes of ten adult patients with inflammatory glaucoma who underwent trabeculectomy with the adjuvant use of 5-fluorouracil between January 1986 and January 1989. Intraocular pressure decreased from 36 +/- 10 mm Hg (range, 17 to 50 mm Hg) preoperatively to 11 +/- 4 mm Hg (range, 3 to 17 mm Hg) postoperatively after a median follow-up of 7.75 months (range, six to 38 months). All eyes achieved an intraocular pressure of less than 20 mm Hg, and ten of 12 required no intraocular pressure lowering medications. The mean (+/- S.D.) amount of 5-fluorouracil used was 33 +/- 10 mg (range, 20 to 55 mg). During the period of observation, five of 12 eyes had an episode of uveitis, but in no patient did this result in loss of intraocular pressure control. Preoperative and postoperative systemic and topical corticosteroid use was the same. Trabeculectomy with 5-fluorouracil is an effective treatment for selected cases of adult inflammatory glaucoma refractory to medical management.
Adult↗
Cytomegalovirus retinitis and acquired immunodeficiency syndrome.
In a series of 157 patients with acquired immunodeficiency syndrome (AIDS), 46 (29%) developed cytomegalovirus (CMV) retinitis. In five patients, CMV retinitis was the initial AIDS-defining opportunistic infection (11% of patients with CMV retinitis and 3% of patients with AIDS). Retinal detachments developed in seven patients (15%) and in four were present before the institution of ganciclovir therapy. Bilateral CMV retinitis was present in 35% of patients at presentation and subsequently developed in nine (60%) of 15 patients while not being treated with ganciclovir. Conversely, none of 18 patients with unilateral disease developed bilateral disease while receiving ganciclovir. Of patients treated with ganciclovir for their CMV retinitis, 81% had a response to the drug, and 61% achieved a complete response, resulting in a nonprogressive and inactive scar. Patients who achieved a complete response with ganciclovir had a significantly longer survival than those who did not, suggesting greater immune compromise in those patients who failed to respond to ganciclovir.
Acquired Immunodeficiency Syndrome↗
Regression of cytomegalovirus retinitis with zidovudine. A clinicopathologic correlation.
A 55-year-old man with the acquired immunodeficiency syndrome had cytomegalovirus (CMV) retinitis develop in his left eye. The patient declined treatment with ganciclovir but elected to be treated with zidovudine. Two months later his CMV retinitis regressed, and it remained inactive for a total of 9 months. The most likely explanation was zidovudine-mediated improvement in the patient's immune function with subsequent suppression of the CMV retinitis in the left eye. The patient ultimately and preterminally had CMV retinitis develop in his right eye. He subsequently died and his eyes were examined at autopsy. Active CMV retinitis lesions were noted in the right eye while inactive scars were noted in the left eye. Immunoperoxidase staining and in situ hybridization studies demonstrated the presence of CMV in the right eye but not in the left eye. While ganciclovir remains the treatment of choice for CMV retinitis, zidovudine treatment may have a beneficial effect on CMV retinitis in some patients.
Acquired Immunodeficiency Syndrome↗
The eye in bone marrow transplantation. III. Conjunctival graft-vs-host disease.
Of a series of 263 patients undergoing allogeneic bone marrow transplantation (BMT), 24 patients developed conjunctival involvement by graft-vs-host disease (GVHD). In each case, a distinct-appearing conjunctivitis developed that representing GVHD of the conjunctiva. In 19 cases (79%), conjunctival GVHD presented with pseudomembrane formation due to loss of the conjunctival epithelium; in 4 of these cases, the corneal epithelium was lost as well. Nineteen patients developed this feature in association with acute GVHD, and mortality among these patients was 89.5%. Kaplan-Meier analysis of survival demonstrated a decreased survival of patients with conjunctival involvement compared with all marrow transplant recipients and compared with all patients with GVHD. However, survival was similar to that seen in patients with severe systemic GVHD (overall stages II through IV). Five patients developed conjunctival GVHD in association with chronic GVHD, and all had severe chronic GVHD. four of these five with chronic GVHD subsequently died. Conjunctival involvement by GVHD represents a distinct clinical finding and is a marker for severe systemic involvement by GVHD. A clinical staging system for ocular involvement was formulated.
Biopsy↗
Ocular manifestations of acquired immune deficiency syndrome.
The ocular complications of acquired immune deficiency syndrome (AIDS) include: (1) a noninfectious microangiopathy, most often seen in the retina, consisting of cotton-wool spots with or without intraretinal hemorrhages and other microvascular abnormalities; (2) opportunistic ocular infections, primarily cytomegalovirus (CMV) retinitis; (3) conjunctival, eyelid, or orbital involvement by those neoplasms seen in patients with AIDS (i.e., Kaposi's sarcoma and lymphoma); and (4) neuro-ophthalmic lesions. In a series of 200 AIDS patients evaluated clinically, AIDS retinopathy was present in 66.5%. Sixty-four percent had cotton-wool spots, and 12% had intraretinal hemorrhages. Cytomegalovirus retinitis was diagnosed in 28% of AIDS patients. Neuro-ophthalmic lesions were found in 8% of all AIDS patients and were present in 33% of those patients with cryptococcal meningitis. Acquired immune deficiency syndrome retinopathy was present in 40% of 35 patients with the AIDS-related complex (ARC) and in 1.3% of 232 patients with asymptomatic human immunodeficiency virus (HIV) infection, evaluated photographically. These results suggest that the prevalence of AIDS retinopathy increases with increasing severity of HIV infection, and that CMV retinitis presents a significant vision-threatening problem in AIDS patients.
Acquired Immunodeficiency Syndrome↗