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1.
Active cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) was treated with an intraocular sustained-release ganciclovir implant. A total number of 19 implants were performed in 15 eyes of 9 AIDS patients. The intraocular sustained-release ganciclovir was effective in preventing reactivation of CMV retinitis in 15 of the 19 implants, ineffective in 3, and undetermined in 1. All ineffective cases had been resistant to ganciclovir therapy before the implants. Vision after the therapy was maintained at better than 0.5 except for one eye. There were no serious ocular complications caused by the therapy. Among 5 patients with unilateral CMV retinitis, 2 unaffected eyes developed CMV retinitis during this therapy. In addition, another patient developed presumed CMV infection in other systemic organs. Based on these data, the intraocular sustained-release ganciclovir implant was considered to be useful for the treatment of CMV retinitis in AIDS.  相似文献   

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BACKGROUND: CMV retinitis is the most common opportunistic ocular infection and the main cause of blindness in AIDS patients with a T-helper cell count < or = 50/microliter. Cidofovir is a nucleotide analogue with a long half-life time after phosphorylation intracellularly. It is effective against CMV and can be given intravenously and intravitreally. The aim was to offer an alternative therapy for CMV retinitis to patients who could not receive standard treatment because of contraindications or refused it. The efficacy and tolerance of intravitreal injections of cidofovir should be evaluated. PATIENTS AND METHODS: We treated 16 eyes of 12 patients. The total number of injections with 15 micrograms of cidofovir each was 49, with an average of 3 injections per eye. The duration of follow-up was 75-295 days (median 170 days). Probenecid was given concomitantly. Injections were repeated after 6-10 weeks. Secondary prophylaxis of CMV organ infection was done with oral ganciclovir. RESULTS: Within a few days all areas with active retinitis turned into scars following the first injection. Under consequent treatment no reactivation was observed. Four eyes developed a mild iritis with hypotony within a mean time of 12 days after injection. All responded rapidly to topical steroids. None had a persisting loss of vision. Two eyes developed cystoid macular edema (CME). Two patients stopped anti-CMV treatment (ganciclovir orally and injections), followed by a recurrence after an average of 64-days. CONCLUSIONS: Intravitreal injection therapy with 15 micrograms cidofovir and concomitant oral probenecid is a valuable and safe alternative treatment for CMV retinitis in AIDS patients. Its main complication is iritis with hypotony, which is effectively treatable with topical steroids. No complications caused by the injection technique itself were noted. The occasional observation of CME in otherwise quiet eyes, however, is probably drug-related.  相似文献   

4.
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.  相似文献   

5.
Patients with acquired immunodeficiency syndrome (AIDS) who present with cytomegalovirus (CMV) retinitis show pathognomonic endothelial precipitates suggestive of primary anterior uveitis or secondary changes due to a spill-over from the posterior chamber. Laser flare photometry allows quantification of the intensity of anterior affection. We wanted to establish anterior-chamber flare values in AIDS patients with and without CMV retinitis and to find out whether CMV retinitis is preceded by an elevation of the flare value. In all, 25 men with AIDS who presented with CMV retinitis and 27 who did not have CMV retinitis but showed a CD4 count of < or = 200 cells/microliter blood were enrolled in a prospective study. Slit-lamp examination was performed, followed by indirect ophthalmoscopy and laser flare photometry after dilation of the pupil with tropicamide eye drops. Patients with CMV retinitis were followed every 10 days and the others, every 4 weeks. A group of 51 human immunodeficiency virus (HIV)-negative men served as a control group. AIDS patients with CMV retinitis showed a significantly higher flare count in the affected eye (12.4 photons/ms; n = 26) as compared with the unaffected partner eye (4.2 photons/ms; P < or = 0.0001; n = 18) and with eyes of AIDS patients without CMV retinitis (4.1 photons/ms; P < or = 0.0001; n = 50). The count in the latter eyes was also significantly higher than the control value (3.1 photons/ms; P < or = 0.0001; n = 102). Typical reticulate endothelial precipitates were found in 92% of AIDS patients with CMV retinitis. During the study, five eyes of three patients developed a fresh CMV retinitis, but a preceding rise in the flare count was not observed. Laser flare photometry follows the occurrence of pathognomonic reticulate endothelial precipitates. It lags behind the development and the extension of CMV retinitis. Therefore, it cannot be used as a screening test for early detection of CMV retinitis.  相似文献   

6.
Vitreous from patients with cytomegalovirus (CMV) retinitis was studied in order to identify mutations in the CMV UL97 gene associated with clinical resistance to ganciclovir. Point mutations known to confer resistance (V460, I460, V594, and S595) were found in 6 of 11 study eyes. Rapid genetic screening by restriction enzyme analysis of viral DNA amplified directly from the vitreous was as effective as conventional sequencing in detecting these mutations. Repeat biopsy of 3 eyes revealed no change in the UL97 genotype. The UL97 genotype differed between eyes in 2 of 3 patients with bilateral, clinically resistant CMV retinitis. In summary, resistance mutations of the CMV UL97 gene are found in the vitreous of some, but not all, eyes with CMV retinitis that have not responded to ganciclovir therapy. These mutations can differ between eyes in patients with bilateral disease and can be rapidly detected using restriction digest analysis of polymerase chain reaction-amplified viral DNA.  相似文献   

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OBJECTIVE: To evaluate the safety and efficacy of 1000- and 5000-centistoke silicone oil as retinal tamponades for the treatment of retinal detachments secondary to necrotizing retinitis in patients with human immunodeficiency virus (HIV) infection. DESIGN: A prospective observational study. SETTING: Community and university-based ophthalmology clinics. PATIENTS: Three hundred fifty patients with HIV infection, who had 407 eyes with retinal detachments secondary to necrotizing retinitis. INTERVENTION: Vitrectomy surgery for retinal detachment with 1000- or 5000-centistoke silicone oil as the retinal tamponade. OUTCOME MEASURES: Efficacy was measured both by anatomic success (defined as complete retinal attachment or macular attachment) and by visual acuity success (defined as preservation of visual acuity or ambulatory vision). Safety was determined by the rate of complications, including abnormal intraocular pressure and corneal and lens opacification. RESULTS: At the last follow-up examination, the retina was completely attached in 287 (73%) of 393 eyes, the macula was attached in 370 eyes (94%), 268 eyes (68%) had ambulatory vision, and visual acuity was preserved in 219 (56%) of 388 eyes. Corneal opacification, hypotony, and silicone oil emulsification were present in 4%, 2%, and 1% of eyes, respectively. One eye had elevated intraocular pressure. Of the 57 patients who had both eyes treated, 35 died, of whom four (11%) had nonambulatory vision in both eyes. Of the 293 patients who had one eye treated, 122 died, of whom 44 (36%) died with nonambulatory vision in the treated eye. The median time to cataract was 192 days; to nonambulatory vision, 474 days; and to death, 204 days. CONCLUSIONS: Silicone oil repair of retinal detachments in necrotizing retinitis is an efficacious and safe procedure that delays or prevents loss of vision in advanced HIV disease.  相似文献   

8.
An 11-year-old boy with severe aplastic anemia underwent unrelated BMT following TBI, antithymocyte globulin and CY. On day +23, CMV antigenemia was detected which resolved with ganciclovir. Eight days after discontinuing ganciclovir, he complained of impaired visual acuity. Ophthalmologic findings and a positive PCR study using anterior chamber fluid from the right eye confirmed the presumptive diagnosis of CMV retinitis, although CMV antigenemia and PCR studies using PBMC were then negative. He was successfully re-treated with ganciclovir. CMV retinitis should be considered even when CMV antigenemia is not present or PCR using PBMC is negative.  相似文献   

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OBJECTIVE: To determine whether maintenance therapy can be discontinued safety in patients with quiescent cytomegalovirus retinitis (CMVR) and increased CD4+ counts after treatment with highly active antiretroviral therapy (HAART). DESIGN: A prospective observational case series. PARTICIPANTS: Eight human immunodeficiency virus (HIV)-positive patients with quiescent CMVR who were taking HAART and had CD4+ counts above 100 cells/microliter elected to discontinue anti-CMV maintenance treatment. INTERVENTION: Biweekly-to-monthly indirect ophthalmoscopy and fundus photographs, monthly-to-quarterly CD4+ counts, and quarterly HIV viral loads were ordered. MAIN OUTCOME MEASURES: Twelve previously affected eyes were examined for evidence of recurrent retinitis, which was defined as any retinal whitening, border opacification, or expansion of areas of retinal pigment epithelial (RPE) atrophy greater than 750 microns. Four previously unaffected fellow eyes were observed for new CMVR. RESULTS: There was no reactivation or progression of retinitis in any patient during the mean follow-up interval of 11.4 months (range, 3-16 months). No previously unaffected eye developed CMVR. CD4+ remained elevated in all patients (range, 70-725; mean, 255). The HIV viral load ranged from undetectable to 139,000 copies. CONCLUSION: Discontinuation of maintenance therapy may be considered in patients with HAART-induced elevated CD4+ counts above 100 cells/microliter, prolonged relapse-free intervals during the reconstitution period before CD4+ counts rise above 100 cells/microliter, and completely quiescent retinitis characterized by RPE scarring only. Reduced risks of drug toxicity and drug-resistant organisms are potential benefits. Close observation for evidence of recurrent retinitis is indicated.  相似文献   

10.
BACKGROUND: Of those patients with acquired immune deficiency syndrome in whom cytomegaloviral retinitis develops, cytomegaloviral papillitis reportedly develops in up to 4% as well. Although occasionally patients have a good visual outcome, the majority have a poor visual prognosis, with a visual acuity of 20/200 or worse, even with treatment. METHODS: To evaluate the effects of prolonged induction with foscarnet or ganciclovir on the visual prognosis of cytomegalovirus (CMV) papillitis, the records of 22 patients seen between 1990 and 1995 at the Los Angeles County-University of Southern California Eye Clinic were reviewed. Papillitis was defined as greater than 270 degrees of disc edema/blurring of the disc margins as seen on direct examination and on color fundus photographs. RESULTS: Eighteen patients with a mean initial visual acuity of 20/69 (range, 20/ 15-20/400) were treated with induction doses of intravenous ganciclovir (range, 5-7.5 mg/kg twice daily) or foscarnet (range, 60-90 mg/kg twice or 3 times daily) for a mean of 3.3 weeks. The mean follow-up period was 4.8 months (range, 1-13 months). These patients maintained a mean final visual acuity of 20/68 (range, 20/ 25-20/400) with greater than 90% resolution of the papillitis. The remaining four patients had poor outcomes (visual acuity < 20/400) because of progressive CMV papillitis or retinitis. The median survival time was 4.5 months from the diagnosis of papillitis, but 7 months from the onset of CMV ocular infection. CONCLUSION: Patients with CMV papillitis have good visual prognosis when managed with high and prolonged doses of intravenous foscarnet and/or ganciclovir.  相似文献   

11.
OBJECTIVE: To describe the clinical characteristics and risk of progression of asymptomatic rhegmatogenous retinal detachments. METHODS: We retrospectively reviewed the clinical records of 28 patients (31 eyes) with asymptomatic rhegmatogenous retinal detachments followed up without surgery for 0.5 to 12.1 years (mean, 3.4 years). Tractional tears were present in six eyes and atrophic holes in 25 eyes. In five patients, the asymptomatic retinal detachment was noted when the patient presented with a symptomatic retinal detachment in the fellow eye. RESULTS: Twenty-nine of the 31 eyes remained asymptomatic without progression of the retinal detachment. Two eyes progressed to a symptomatic retinal detachment 2.25 and 3.3 years after the initial examination, underwent a successful scleral buckling procedure, and maintained 20/20 visual acuity. CONCLUSIONS: Observation can be considered a reasonable option in the treatment of patients with asymptomatic retinal detachments. Chart documentation of the risks and benefits of observation and instruction of the patient on self-monitoring of the peripheral visual field are necessary in such patients.  相似文献   

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The suppression of human immunodeficiency virus (HIV) replication and elevation in CD4 cells observed with protease inhibitor combination regimens known as HAART (highly active antiretroviral therapy) may allow AIDS patients to undergo an immune recovery that allows them to suppress the progression of cytomegalovirus (CMV) retinitis. Eleven AIDS patients receiving HAART with healed CMV retinitis in whom CMV-specific maintenance therapy was discontinued were studied. Median CD4 cell counts were 42 before the initiation of HAART and 183 at discontinuation of anti-CMV therapy. While a median 1.1 log10 drop in plasma HIV-1 RNA was obtained between starting HAART and withdrawal of maintenance therapy for CMV, only 3 of 11 patients maintained plasma HIV RNA below the limits of detection. Reactivation of CMV retinitis after withdrawal of anti-CMV therapy did not occur in any of the patients observed for a median of 156 days (range, 92-558).  相似文献   

13.
BACKGROUND: Rapid quantifiable diagnostic techniques for the diagnosis of cytomegalovirus (CMV) infection may predict patients at risk of CMV pneumonitis and allow preemptive antiviral treatment. METHODS: Using CMV antigenemia as a prospective surveillance technique for CMV infection, we compared the outcome of preemptive treatment (PT) with ganciclovir, 10 mg/kg/day for 21 days directed by "high levels" of CMV antigenemia (PT group, n= 19), with the outcome in a group of historical controls (n=18) treated with ganciclovir when CMV illness occurred. Greater than 50 antigen-positive cells per 2 x 10(5) polymorphonuclear leukocytes was considered to be high-level antigenemia. RESULTS: Nine of the 18 controls developed high-level CMV antigenemia at a median of 33 days (range: 13-65 days) and 5 of the 9 developed CMV disease. Ten of the 19 PT group had high levels of CMV antigenemia detected at a median of 47 days (range: 20-63 days) and were given ganciclovir; none developed CMV disease. There was a significantly lower incidence of CMV disease in the PT group in comparison to controls (0 of 19 vs. 5 of 18: P=0.019). CONCLUSION: We have reduced the incidence of CMV disease using preemptive treatment, and because of a 100% negative predictive value, we omitted unnecessary antiviral prophylaxis for many at-risk patients.  相似文献   

14.
PURPOSE: A scleral plug made of biodegradable polymer implanted at the pars plana was evaluated to determine its ability to control the intravitreal release of ganciclovir. METHODS: Scleral plugs containing 25% ganciclovir were prepared with poly(lactic-glycolic acid) (molecular weight, 121 kDa). The release of ganciclovir was evaluated in vitro by spectrophotometry. In vivo intravitreal ganciclovir concentrations were measured by high performance liquid chromatography following plug implantation in pigmented rabbits. The biocompatibility of the device was determined by indirect ophthalmoscopy, electroretinography, and light and electron microscopy. RESULTS: The in vitro study showed that the plug released ganciclovir throughout a 10-week period. The in vivo study demonstrated that the plugs maintained the drug concentration in the vitreous in a therapeutic range adequate to treat cytomegalovirus (CMV) retinitis for 12 weeks. No significant retinal toxicity was observed. CONCLUSIONS: This study demonstrated that this drug delivery system can potentially be useful to treat CMV retinitis.  相似文献   

15.
This study was conducted to determine the likelihood of the development of a new ocular inflammatory syndrome (immune recovery vitritis, IRV), which causes vision loss in AIDS patients with cytomegalovirus (CMV) retinitis, who respond to highly active antiretroviral therapy (HAART). We followed 30 HAART-responders with CD4 cell counts of >/=60 cells/mm3. Patients were diagnosed with IRV if they developed symptomatic vitritis of >/=1+ severity associated with inactive CMV retinitis. Symptomatic IRV developed in 19 (63%) of 30 patients and in 26 (59%) of 44 eyes over a median follow-up from HAART response of 13.5 months. The annual incidence of IRV was 83/100 person-years. Excluding patients with previous cidofovir therapy did not significantly alter the time course of IRV (P=.79). These data suggest that IRV develops in a significant number of HAART-responders with CMV retinitis and is unrelated to previous cidofovir therapy.  相似文献   

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BACKGROUND: Treatment with prophylactic oral acyclovir, intravenous ganciclovir, or immunoglobulins to prevent cytomegalovirus (CMV) infection and disease in renal transplantation is associated with variable efficacy and significant expense. We studied control of CMV in renal transplant recipients using either prophylactic oral ganciclovir or deferred therapy with intensive monitoring with polymerase chain reaction (PCR) analysis. METHODS: Forty-two recipients were followed for 6 months after transplantation. Ganciclovir (1000 mg p.o. t.i.d.; n=19) or acyclovir (200 mg p.o. b.i.d.; n=23) was begun at transplantation and continued for 12 weeks. PCR for CMV was performed on buffy-coat specimens every week for 15 weeks and at months 5 and 6. RESULTS: No patients in the ganciclovir group, compared with 14 of 23 patients (61%) in the deferred-therapy group (P<0.0001), developed CMV disease during the first 12 weeks. In the ganciclovir group, 4 of 19 patients (21%) subsequently experienced 5 episodes, whereas 14 patients in the deferred-therapy group experienced 18 episodes (P=0.013 for subjects and P=0.026 for episodes). The time to disease was also delayed in the ganciclovir group compared with the deferred-therapy group (133+/-17 days vs. 51+/-7 days; P<0.0001). Oral ganciclovir also prevented CMV viremia during prophylaxis (2/19 patients [11%] vs. 23/23 patients [100%]). Time to CMV viremia was delayed in the ganciclovir group; however, 13/19 patients (68%) ultimately showed PCR evidence for CMV viremia (P=0.005). CONCLUSIONS: An initial 12-week course of oral ganciclovir prevents CMV disease and infection in renal transplant recipients during prophylaxis, and the benefits persist after discontinuation.  相似文献   

17.
OBJECTIVES: To determine the incidence of clinical resistance to intraocular cidofovir injection for treatment of acquired immunodeficiency syndrome (AIDS)-related cytomegalovirus (CMV) retinitis, and to identify virologic features associated with cidofovir treatment failure. PATIENTS and METHODS: Clinical resistance to intravitreal cidofovir was examined in 64 patients with CMV retinitis who received at least 1 injection of 20 pg of cidofovir. Histopathologic examination, culture, and polymerase chain reaction were used to detect CMV in ocular specimens. Antiviral resistance was assessed by plaque reduction assay and DNA sequencing. RESULTS: Clinical resistance to intravitreal cidofovir injections was identified in 3 patients (5%) and was associated with prior oral ganciclovir or intravenous cidofovir use. Ganciclovir- and cidofovir-resistant CMV isolates were cultured from 2 patients and harbored resistance-associated mutations in the UL97 and polymerase genes. Resistance mutations were also detected by direct analysis of vitreous. In 1 patient, different resistance mutations were identified in ocular vs extraocular CMV strains. CONCLUSIONS: Clinical failure of intravitreal cidofovir occurs infrequently, but may be associated with cidofovir-resistant CMV selected by prior ganciclovir or cidofovir treatment. Ocular CMV disease can result from a localized infection with a resistant CMV strain, and antiviral resistance may develop at a local site of infection independently from resistance that develops systemically.  相似文献   

18.
INTRODUCTION: Cytomegalovirus retinitis (CMV) is the most frequently found opportunistic eye infection in adults with AIDS, with mean incidence of 20%-50%. However, only 5% of children with AIDS have this infection. CLINICAL CASE: We present the case of a six year old girl with stage C3 AIDS diagnosed at the age of 20 months, who developed unilateral diffuse retinitis due to CMV. The infection involved the posterior pole of the right eye, with retinal atrophy along the temporal vascular arcodes, and an active advance front in the temporal macula. The optic nerve was not found to be involved although the peripheral areas of the retina were involved leading to rhegmatogenous detachment of the superotemporal retina. In view of the systemic deterioration of the patient, no specific anti-CMV treatment was given. The patient died of respiratory insufficiency a few weeks later. CONCLUSIONS: CMV retinitis in paediatric AIDS patients is usually associated with more severe illness and a poorer general health than the adult population. In view of the absence of symptoms in these patients, periodic ophthalmoscopic examinations should be done in those who have severe immunological deterioration.  相似文献   

19.
Seven AIDS patients who were receiving suppressive therapy for previously diagnosed cytomegalovirus (CMV) retinitis were offered treatment with protease inhibitors (PIs). Secondary prophylaxis for CMV was discontinued after 3 months of therapy with PIs if patients had >150 CD4 cells/mm3 and a human immunodeficiency virus (HIV) load of <200 copies/mL and if they were negative for CMV as determined by qualitative CMV polymerase chain reaction (PCR). Ophthalmologic exams were done periodically. After a median follow-up of 9 months (range, 9-12), no new episodes of CMV retinitis were observed. CD4 cell counts were >150 cells/mm3 in all cases, HIV loads were <200 copies/mL, and results for qualitative CMV PCRs remained negative. These observations suggest that for selected patients with healed CMV retinitis who have immunologic and virologic evidence of a clinical response to potent combination antiretroviral therapy, temporary discontinuation of a chronic anti-CMV suppressive therapy may not result in further retinal necrosis. However, the long-term immunologic benefit of PIs and hence the safety of prolonged withdrawal of anti-CMV therapy is unknown.  相似文献   

20.
OBJECTIVE: To study the temporal relationships between cytomegalovirus (CMV) viral load and specific UL97 mutations in polymorphonuclear leukocytes (PMNL) and plasma samples from a patient with AIDS who developed ganciclovir-resistant CMV retinitis. METHODS: Sequential PMNL and plasma samples were analysed for determination of the CMV viral load using non-molecular methods and a quantitative polymerase chain reaction (PCR) assay. Screening of the same samples for the most common mutations conferring ganciclovir resistance was performed using nested PCR and restriction enzyme analysis. RESULTS: At the time of progression of CMV retinitis (after 6 months of ganciclovir), a rapid increase in the CMV DNA load was found in both PMNL and plasma samples. This increase paralleled the emergence of a specific mutation (V594) in the same samples and recovery of ganciclovir-resistant blood isolates. In this patient, however, the only tests that substantially predicted the progression of CMV disease were the quantitative PCR assay using PMNL and to a lesser extent the pp65 antigenemia assay. CONCLUSIONS: Quantitative evaluation of the CMV viral load in PMNL using sensitive assays such as PCR appears to be a promising approach for monitoring antiviral therapy in subjects with AIDS. In addition, common mutations conferring ganciclovir resistance can be detected directly in PMNL and plasma samples.  相似文献   

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