Indication, medical course and postoperative complications after implantation of an intraocular sustained release ganciclovir implant in patients with AIDS and cytomegalovirus retinitis

Summary We performed an open clinical trial to assess the safety and efficacy of a 1 μg/h ganciclovir implant for the treatment of newly and pretreated cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Patients and methods: Thirty-two eyes (20 patients) received the ganciclovir intraocular device and were prospectively followed up from 30 to 365 days. We used a modified technique for fixation of the device in half of the patients. The modification improved the fixation of the implant with a two-hole technique in the strut. Results: Thirty eyes showed stabilization of the retinitis over the time, but in two patients resistance against ganciclovir and other nucleosid analogue compounds developed. Postoperative complications included vitreous hemorrhage (n = 1), cataract (n = 1), and uveitis anterior (n = 1). Late retinal detachment was seen in five eyes (25 %) at 30 to 60 days after implantation. Followup until 1 year after implantation did not show progression of CMV retinitis in 18 of 20 patients. All received antiviral CMV therapy to protect noninfected eyes and intestinum against CMV infection. Conclusions: The ganciclovir intraocular device seemed to be effective in most cases of CMV retinitis and offers a promising alternative for cytomegalovirus retinitis. Patients pretreated longer than 6 months with i. v. ganciclovir have to be carefully selected for implantation, because resistance against ganciclovir could be three times more likely than in i. v.-therapy naive patients.      

Reproduction of antiviral effect in an in vivo model of human cytomegalovirus retinal infection

· Background: Cytomegalovirus retinitis remains a serious problem in AIDS patients, and the species specificity of human cytomegalovirus (HCMV) has hindered the development of animal models suitable for testing new therapeutic agents. Having previously described an in vivo model of HCMV retinal infection, we investigated its ability to reproduce the antiviral effects of the established anti-HCMV agent ganciclovir in order to determine the model’s potential for evaluating novel agents. · Methods: Athymic rats had human fetal retinal tissue implanted in both anterior chambers. At 14 or 28 days post implantation, a suspension of a β-galactosidase (lacZ⁺) mutant of HCMV was injected into each anterior chamber. Commencing 3 days prior to the injection of virus, rats in the treatment group received twice-daily intraperitoneal injections of ganciclovir (≡ a total of 100 mg/kg per day) for the duration of the study. The control rats received no drug. Twenty days after virus injection, the eyes of all rats were removed, sectioned and developed with X-gal substrate to detect any β-galactosidase expression in the human tissue implants. · Results: Blue-staining foci of infection were detected in the implanted retinal tissue in 8 of 10 eyes from untreated control rats, but no β-galactosidase expression was found in any of 12 eyes from animals which had received ganciclovir treatment. · Conclusion: Intraperitoneal administration of ganciclovir successfully prevented HCMV replication in the intraocular retinal implants. This model of HCMV retinal infection is therefore suitable for preliminary evaluation of systemically administered antiviral agents. Received: 21 July 1997 Revised version received: 3 November 1997 Accepted: 11 November 1997     

Prophylactic argon laser coagulation for rhegmatogenous retinal detachment in AIDS patients with cytomegalovirus retinitis

· Background: The incidence of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) reaches 20–45%. Despite aggressive medical treatment, rhegmatogenous retinal detachments develop in up to 30% of the affected eyes. Surgical repair is often difficult due to multiple, large and hardly visible retinal holes with vitreal traction. Pars plana vitrectomy with instillation of silicone oil is the procedure of choice, giving limited functional results with anatomical reattachment. · Methods: We performed prophylactic laser coagulation in AIDS patients with medically treated CMV retinitis to prevent a progressive retinal detachment. Twenty-two quiescent CMV lesions in 22 eyes of 20 patients were treated with argon green laser coagulation. Each CMV lesion was completely surrounded with a double or triple row of laser spots (500–600 μm; 0.2 s; gray-white lesions). · Results: The duration of follow-up was 2–24 months. Histopathologic evaluation was possible in two eyes of one patient. Reactivated or smoldering CMV retinitis crossed the laser scars in 11 eyes, making additional laser coagulation necessary. In four eyes retinal holes in the CMV scar tissue led to retinal detachment, which stopped at the laser scar. In three eyes the detachment is still controlled by the laser scar. In one eye, the detachment stopped at the laser scar for 6.5 months and then slowly progressed across it. There were no complications associated with our laser treatment. · Conclusion: Prophylactic argon laser coagulation in quiescent CMV retinitis seems to reduce the rate of progressive retinal detachment with no need for vitrectomy and silicone oil tamponade. Received: 25 January 1997 Revised version received: 20 August 1997 Accepted: 1 October 1997     

Intravitreal injection of cidofovir in CMV retinitis

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 ≤ 50/μl. 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 μg 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 μg 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.      

Outcomes of cytomegalovirus retinitis following the use of ganciclovir implants

Purpose: To determine the results and complications from the use of ganciclovir implants to treat patients with HIV infection and cytomegalovirus (CMV) retinitis. Methods: The present study was a retrospective review of 87 consecutive ganciclovir implant surgeries performed in 60 patients over a 3 year period. Results: Based on the results of the present study, ganciclovir implants are an efficacious therapy for CMV retinitis but are associated with significant postoperative complications, including retinal detachment (12.0%), vitreous haemorrhage (7.2%) and cataract formation (6.0%). In this series, all implanted eyes responded to treatment and the mean time to progression was 252 days. Only a small number of patients developed second eye involvement (n= 9) or clinically significant CMV infection of other organ systems (n= 5). Conclusions: This small retrospective study provides additional data confirming the effectiveness of ganciclovir implants and the complications from their use.     

Cystoid macular edema following immune recovery and treatment with cidofovir for cytomegalovirus retinitis

· Background: Cytomegalovirus (CMV) retinitis is the most common opportunistic ocular infection in AIDS patients. Cidofovir has proved to be highly effective in treatment of CMV retinitis. Iritis and bulbar hypotony are known as the major complications after intravenous and intravitreal use of this antiviral drug. Cystoid macular edema (CME) after intravenous application of cidofovir has not been reported. · Methods: We analyzed retrospectively the incidence of CME after intravitreal or intravenous application of cidofovir and its correlation with CD4 cell counts of the patients. · Results: Two (22.2%) of 9 eyes in the intravenous and 3 (18.8%) of 16 eyes in the intravitreal injection group developed CME. It occurred between 3 and 48 weeks after cidofovir administration. In all eyes CMV retinitis was inactive. All patients received highly active antiretroviral treatment (HAART). CME was correlated with a rapid and sustained improvement in CD4 cell counts. · Conclusion: We interpret the occurrence of CME as an immune recovery phenomenon for the following reasons. All CMEs were seen in eyes with inactive CMV retinitis and the unaffected contralateral side never developed CME. The time range of appearance between 3 and 48 weeks after cidofovir administration makes direct toxicity of cidofovir unlikely. All patients had a sustained improvement of CD4 cell counts due to HAART. No CME was reported during the use of cidofovir before the HAART era. Received: 22 December 1998 Revised version received: 3 March 1999 Accepted: 30 March 1999     

Bilateral cystoid macular edema following successful treatment of AIDS-associated CMV retinitis

Background: Cystoid macular edema (CME) in AIDS patients with inactive cytomegalovirus (CMV) retinitis is an uncommon but potentially sight-threatening complication. The pathogenesis of CME in these patients is unclear. This study tries to identify possible risk factors by analyzing the charts of five patients. Methods: Ten eyes of 5 patients that finally developed CME were followed for an average of 18 months. The initial retinal lesions, their response to antiviral treatment, the development of CME, and the patients' immune status were prospectively monitored. Results: CMV retinitis was diagnosed at a median CD4+ count of 3 cells/mm³ (range 0–11). All eyes responded to the initial systemic anti-viral treatment. At the onset of CME, CMV retinitis was controlled by antiviral maintenance therapy in all patients [ganciclovir (n = 2), cidofovir (n = 2), foscarnet (n = 1)]. The median time between diagnosis of CMV retinitis and onset of CME was 11.5 months (range 5–24). Development of CME was associated with significant visual loss: acuity ranged from 0.05 to 0.7 when CME was first noticed, compared to 0.8–1.25 at diagnosis of CMV retinitis. Duration of inflammation, size or zone of retinal necrosis did not favor the development of CME, neither did the antiviral therapy. A weak correlation of CME development and immune status (expressed as increase of CD4+ cells) was found. Due to systemic corticosteroids CME resolved. Conclusions: CME is a new visual threat to AIDS-patients with CMV retinitis whose immune status improved under the latest combined antiretroviral therapy. Therapy with oral corticosteroids may positively influence this condition.      

Intravitreal endoscopic visualization of intraocular ganciclovir devices: improved long-term treatment of CMV retinitis

BACKGROUND: The recent development of 20- and 19-gauge diameter endoscopes allows an excellent direct intravitreal visualization of intraocular morphology. A gradient index (GRIN) endoscope (Insight Instruments, Lake Mary, FL, USA), which combines a small diameter (0.89 mm, 20 gauge) and an exceptional optical resolution, can be used as a diagnostic tool for the assessment of the safety and vitreous interaction of sustained release intraocular devices which have been designed to deliver ganciclovir (Vitrasert) over a period of 8-12 months and were successively implanted in several eyes. PATIENTS AND METHODS: 78 eyes of 49 patients received 100 ganciclovir implants between November 1995 and July 1998. In six patients who received additional implants, the GRIN endoscope was used as an optical control of wound healing processes and Vitrasert positioning after implantation of prior devices (two-point suturing technique). RESULTS: In all of these six eyes, a clinical stabilization of the cytomegalovirus retinitis was noted. Endoscopic observation of the scleral 5-mm incision revealed no gaps after two-point suturing of the device. Only one of six eyes showed significant vitreous tractions around the Vitrasert. However, the struts of all pellets were completely covered by a fibrous membrane. Occasional fibrous plaques were noted on the surface of devices which presumably had been damaged by surgical manipulations. In one case, the endoscopic examination disclosed the suprachoroidal implantation of a device. In this eye, no signs of retinal toxicity or recurrence of CMV retinitis were observed. CONCLUSIONS: High resolution endoscopy of the vitreous cavity appears to be an effective method for the control of intraocular drug delivery devices. Basically, the repeated implantation of intraocular ganciclovir implants can be considered a safe method in the management of relapsing CMV retinitis. However, the endoscopic observation of fibrous membranes covering the struts suggest that the explanation of an intraocular device has the potential for various intraoperative complications (e.g. hemorrhages, traction, tears, retinal detachment). Therefore, we would recommend the additional implantation of further implants rather than a replacement.     

Intravitreal ganciclovir in the treatment of AIDS-associated cytomegalovirus retinitis

Ganciclovir (BW B759U, DHPG, dihydroxy propoxymethyl guanine) was injected directly into the vitreous in 14 eyes of 11 patients with severe acquired immune deficiency syndrome (AIDS)-associated cytomegalovirus (CMV) retinitis. All 11 patients either demonstrated serious myelosuppression which precluded the continuation of intravenous ganciclovir therapy (5 patients) or were experiencing progressive CMV retinitis despite therapy with maximum-tolerable dosages of intravenous ganciclovir (6 patients). Suppression of the retinitis was observed in 11 (78%) of the 14 treated eyes. Three eyes (22%) showed no improvement after the initial intravitreal injection. One rhegmatogenous retinal detachment (RD) occurred during an injection. There were no other complications, and no intraocular drug toxicity was observed. Reactivation of CMV retinitis necessitated repeated injections in 9 (64%) of the 14 eyes. The authors' experience with these 30 intravitreal injections indicates that the procedure is safe and effective both as an alternative to intravenous ganciclovir therapy in myelosuppressed patients and as a supplement to intravenous therapy in uncontrolled CMV retinitis.     

Biodegradable scleral implant for intravitreal controlled release of ganciclovir

· Background: The aims of this study were to develop biodegradable scleral implants that could overcome previously reported disadvantages such as an adverse burst in the late phase of release and to investigate the release profile of modified scleral implants in vitro and in vivo. · Methods:The modified scleral implants (weight 8.5 mg, length 5 mm) were made of mixtures of poly(dl-lactide) (PLA) with different molecular weights and contained 25 weight % of ganciclovir (GCV). The release of GCV was evaluated in vitro by spectrophotometry. Intravitreal GCV concentrations in vivo were measured by high- performance liquid chromatography following plug implantation in pigmented rabbits. The biocompatibility of the device was determined by indirect ophthalmoscopy and light microscopy. · Results:The in vitro release studies showed stable, long-term sustained and slow release. The in vivo release studies showed that the implants had long-term release in the diffusional phase of the triphasic release pattern and only a minor adverse burst of GCV in the late phase. No significant retinal toxicity was observed by histologic examination.  · Conclusion: Our findings showed that this newly modified scleral implant may provide suitable intravitreal drug delivery for treatment of cytomegalovirus retinitis. Received: 5 May 1999 Revised: 30 June 1999 Accepted: 22 July 1999     

High-dose (5000-microg) intravitreal ganciclovir combined with highly active antiretroviral therapy for cytomegalovirus retinitis in HIV-infected patients in Venezuela

PURPOSE: To describe the use of high doses of intravitreal ganciclovir combined with highly active antiretroviral therapy (HAART) for the treatment of cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected patients. METHODS: Thirteen HIV-infected patients (18 eyes) with active CMV retinitis (83.3% in zone 1 and 38.4% resistant) participated in this prospective interventional case series. Patients were treated with high dose intravitreal ganciclovir (5.0 mg/0.1 mL once a week) in combination with HAART therapy. Intravitreal injections were discontinued once CMV retinitis healed if there was a significant increase in CD4+ count (any increase of > or 50 cells/microL to levels over 100 cells/microL sustained for at least 3 months). Mean follow-up was 15.6 months. Main outcome measures included assessment of visual acuity and retinal inflammation (CMV retinitis activity). A matched historical control group of 20 eyes (15 patients) with CMV retinitis treated with systemic ganciclovir (intravenous [induction] and oral [maintenance]) was included. RESULTS: Complete regression of the retinitis was obtained with high doses of intravitreal ganciclovir in 88.8% of eyes (two patients died during follow-up) at a mean of 4.5 weeks (2 to 8 weeks). Visual acuity improved two or more lines in 61.1% of eyes. No ganciclovir retinal toxicity was identified. Three eyes presented CMV retinitis reactivation at a mean of 25.6 days after their last injection. Complications (33.3%) included retinal detachment (RD; 3 eyes), immune recovery uveitis (IRU; 2 eyes), and endophthalmitis (1 eye). In our control group complete regression of the retinitis was obtained in 100% of eyes at a mean of 4 weeks (3 to 7 weeks). However, 12 eyes (60%) presented with CMV retinitis relapse at a mean of 29 days (21 to 32 days) after initiating oral ganciclovir (maintenance). Complications included RD (7 eyes, 35%) and IRU (3 eyes, 15%). Severe neutropenia occurred in 2 patients (13%). CONCLUSIONS: High doses of intravitreal ganciclovir (5.0 mg) once a week in combination with HAART therapy is effective to control CMV retinitis, and may be discontinued after CMV retinitis has healed if immune reconstitution with a significant increase in CD4+ count has occurred.     

Outcome of cytomegalovirus retinitis in immunocompromised patients without Human Immunodeficiency Virus treated with intravitreal ganciclovir injection

Purpose

To study the outcomes of treatment with intravitreal ganciclovir injection for cytomegalovirus (CMV) retinitis in patients without Human Immunodeficiency Virus (HIV) infection.

Methods

In this retrospective cohort study, demographic and clinical characteristics of patients with CMV retinitis without HIV were noted. Patients received intravitreal ganciclovir injection (2 mg/0.1 ml) alone until quiescence. The outcome measures were time taken for the lesions to heal, number of injections, change in best-corrected visual acuity (BCVA), recurrence of retinitis, occurrence of immune recovery uveitis (IRU) or injection-related complications and retinal detachment (RD).

Results

18 eyes of ten patients (six males) with mean age of 33.7 years from June 2004 to March 2013 were included. Thirteen eyes with active lesions (mean BCVA of 0.51?±?0.41) received 5.54?±?3.36 intravitreal ganciclovir injections with complete healing within 1.81?±?1.25 months. The final BCVA was 0.43?±?0.52. IRU was observed in six eyes (33.33 %) and RD developed in one eye. One eye had recurrence 1 month after stopping ganciclovir injections. The rest of the patients had recurrence-free follow-up at 9.46?±?12.42 months.

Conclusions

Non-HIV patients with CMV retinitis can be successfully treated with intravitreal ganciclovir injection alone, avoiding the systemic side effects of systemic anti-CMV therapy.     

Treatment of recurrent cytomegalovirus retinitis with the ganciclovir implant

PURPOSE: To evaluate preoperative characteristics and outcome of the treatment of recurrent cytomegalovirus (CMV) retinitis with the ganciclovir implant. METHODS: Records of 54 patients with acquired immunodeficiency syndrome and active, previously treated CMV retinitis who received a ganciclovir implant in one (n = 31) or both (n = 23) eyes were reviewed. Entry criteria included prior insertion and removal of an indwelling catheter or failure to respond to tolerated doses of ganciclovir and foscarnet. Preoperative factors that might correlate with outcome were analyzed, including demographic factors, duration of human immunodeficiency virus disease and CMV retinitis, indications for surgery, prior anti-CMV treatment, and extent of retinitis. RESULTS: Forty-six patients completed 1 month of follow-up and were analyzed for outcome. Thirty-one (67.4%) had inactive retinitis at 1 month vs 15 (32.6%) with active retinitis, and they received a mean of 23.5 +/- 22.9 weeks of preoperative ganciclovir vs 58.0 +/- 52.0 weeks in patients with active retinitis (P = .003). Involvement of more than 25% of retinal area by CMV retinitis was also correlated with activity at 1 month (P < .001). Patients who received implants because of lack of venous access had a median time to progression of 8.0 +/- 3.0 months vs 2.0 +/- 1.2 months for patients who had inadequate response or intolerance to intravenous medication (P = .073). Patients with 6 months or less vs more than 6 months of preoperative ganciclovir treatment had progression at a median time of 8.0 +/- 1.7 months vs 2.0 +/- 0.3 months, respectively (P = .016). CONCLUSION: Longer duration of preoperative ganciclovir or larger area of CMV retinitis correlates with lower success of ganciclovir implant therapy for recurrent retinitis.     

Fluocinolone Acetonide Implant (Retisert) for Chronic Cystoid Macular Edema in Two Patients with AIDS and a History of Cytomegalovirus Retinitis

Purpose: To report the authors’ experience using fluocinolone acetonide (Retisert) to treat cystoid macular edema (CME) resulting from immune recovery uveitis (IRU) in 2 acquired immunodeficiency syndrome (AIDS) patients with a history of cytomegalovirus (CMV) retinitis.

Design: Interventional case series.

Methods: Medical records were reviewed of 2 patients who received Retisert implantation in 3 eyes for IRU-associated inflammation and CME. Suppression of CMV disease was achieved with oral medication in one patient and with simultaneous implantation of a ganciclovir implant in the other patient.

Results: After Retisert implantation in 3 eyes in AIDS patients on HAART, improvement in CME was seen in 2 eyes. No CMV reactivation was detected during the several-month follow-up period.

Conclusions: Retisert may be an effective treatment for CME in AIDS patients with IRU reactivation and a history of CMV retinitis.     

获得性免疫缺陷综合征并发巨细胞病毒性视网膜炎的临床分析

目的探讨获得性免疫缺陷综合征(acquiredimmunodeficiencysyndrome,AIDS)并发巨细胞病毒(cytomegalovirus,CMV)性视网膜炎的眼底表现特点、全身症状及治疗预后。方法观察8例(15只眼)AIDS并发CMV性视网膜炎的临床表现,分析其眼底、视力、荧光素眼底血管造影及CD4+T淋巴细胞检测结果,并对其中2例(4只眼)行更昔洛韦玻璃体腔注药治疗。随访时间2～34个月,平均16个月。结果初诊视力≤0.2者10只眼(66.7%),其中无光感者2只眼,眼前光感者2只眼,0.04～0.20者6只眼;0.8和0.9者各1只眼(13.3%);≥1.0者3只眼(20.0%)。12只眼的眼底表现为视网膜血管炎特点,呈沿血管分布的浓厚黄白色病损,其上有片状出血,边缘为不规则的黄白色颗粒,可形象描述为“奶酪加番茄酱样视网膜炎”;玻璃体透明或反应轻微。2只眼的眼底呈晚期表现,视网膜萎缩呈灰色,视网膜血管硬化、狭窄,视网膜色素上皮萎缩,可透见脉络膜血管及视神经萎缩。1只眼视网膜脱离。8例患者的CD4+T淋巴细胞计数在0～36个/mm3之间,平均(15.0±12.9)个/mm3。4只眼玻璃体注药后视力均显著提高。眼底病变明显消退,出血吸收。结论CMV性视网膜炎是AIDS最常见、最严重的眼部并发症。眼底表现特点为进行性、坏死性视网膜炎伴出血,同时合并有视网膜血管炎。但玻璃体反应无或轻微。对原因不明的黄白色病损、视网膜出血及视网膜血管炎应行血清人类免疫缺陷病毒(humanimmunodeficiencyvirus,HIV)抗体检测。反之,HIV阳性者应常规进行眼底检查。(中华眼科杂志,2005,41:803806)     

Effect of potent antiretroviral therapy on recurrent cytomegalovirus retinitis treated with the ganciclovir implant

PURPOSE: To determine the effect of highly active antiretroviral therapy on cytomegalovirus (CMV) retinitis treated with ganciclovir implants. METHODS: A retrospective cohort study was performed of 15 patients with recurrent CMV retinitis treated with the ganciclovir implant and highly active antiretroviral therapy (cases) and 38 patients with recurrent retinitis treated with ganciclovir implants before availability of improved antiretroviral therapy (controls). Progression was defined as occurrence of new lesions in the treated eye or advancement of the retinitis border by more than 750 microm. RESULTS: Cases and controls were statistically similar in age, ethnicity, and duration of acquired immunodeficiency syndrome (AIDS). Controls had received intravenous ganciclovir for 9.5 +/- 9.5 months vs 3.5 +/- 4.6 months in cases (P = .003). The mean (+/- SE) time to progression of retinitis after implantation of the device was 26.7 +/- 2.4 months (95% confidence interval, 22.1 to 31.3) in the cases receiving highly active antiretroviral therapy vs 6.2 +/- 0.9 months (95% confidence interval, 4.5 to 7.9) in the controls (P = .001). Multivariate analysis, adjusted for preoperative variables, confirmed a significantly prolonged time to progression in patients receiving highly active antiretroviral therapy (P = .0003). The odds ratio for progression in the cases vs controls was 0.034 (95% confidence interval, 0.003 to 0.350). Cases had higher CD4+ T-lymphocyte counts (P = .004) and longer survival (P < .001) than controls. CONCLUSION: Highly active antiretroviral therapy is associated with improved outcomes in patients with AIDS and recurrent CMV retinitis treated with the ganciclovir implant.     

Management of acute submacular hemorrhage using recombinant tissue plasminogen activator and gas

· Purpose: To assess the effects of intravitreal injection of recombinant tissue plasminogen activator (rTPA) and gas on submacular hemorrhage in age-related macular degeneration (ARMD). · Methods: Eleven consecutive patients (11 eyes) with subretinal hemorrhage due to ARMD involving the fovea with elevation of the neurosensory retina were included in this study. Subretinal hemorrhage occured 12 h to 14 days before onset of therapy. Injection of rTPA through the pars plana in a dose of 50 or 100 μg was performed. Gas instillation (0.2–0.4 ml) followed rTPA injection, either immediately after injection (7 patients) or during the following day (4 patients). · Results: After intravitreal injection of rTPA, subretinal clots were totally or partially liquefied when treatment started up to 3 days after onset of bleeding. In all patients treated with 100 μg rTPA a large exudative retinal detachment of the inferior retina resulted, which reabsorbed spontaneously within 2 weeks. After reattachment of the exudative retinal detachment hyperpigmentation of the retinal pigment epithelium was noted. Temporary opacification of the vitreous was observed between the 2nd and 7th postoperative day in 5 eyes (45.5%). Postoperative visual acuity increased in 5 patients (45.5%). · Conclusion: Intravitreal application of rTPA followed by gas injection is a sufficient and convenient technique for effective removal of freshly formed submacular hemorrhage. Removal is mediated through combined enzymatic (rTPA) and mechanical (gas) effects. This technique offers a quick recovery of vision in eyes with less severe ARMD. Received: 5 January 1998 Revised version received: 25 March 1998 Accepted: 23 June 1998     

人类免疫缺陷病毒感染及获得性免疫缺陷综合征患者眼部病变的诊断与治疗

目的 探讨人类免疫缺陷病毒(HIV)感染及获得性免疫缺陷综合征(AIDS)患者的眼部病变特点、临床症状及治疗原则.方法 回顾性系列病例研究.回顾性分析110例(220只眼)HIV感染和AIDS患者的临床资料,包括患者视力、眼前节、眼底检查和荧光素眼底血管造影及外周血CD_4~+T淋巴细胞检测结果,其中2例(4只眼)AIDS合并巨细胞病毒(CMV)性视网膜炎患者施行了更昔洛韦玻璃体腔注药治疗.患者年龄、HIV感染时间与HIV视网膜病变及CMV性视网膜炎的相关性采用Pearson相关分析法,性别与HIV视网膜病变及CMV性视网膜炎的相关性采用Pearson ChiSquare分析法,正常眼底组、HIV视网膜病变组、CMV性视网膜炎组间CD_4~+T淋巴细胞计数比较采用多个独立样本的秩和检验.结果 患者初诊视力为无光感者5只眼,光感至0.04者10只眼,0.05～0.2者14只眼,0.3～0.7者62只眼,0.8及以上者129只眼.110例(220只眼)HIV感染和AIDS患者中,有25只眼角膜后有灰白色细小或色素性沉着物.22只眼房水闪光(+)或(++).4只眼虹膜后粘连.28只眼晶状体混浊.34只眼确诊为HIV视网膜病变,眼底表现为棉絮斑、视网膜出血及微血管瘤.32只眼确诊为AIDS合并CMV性视网膜炎,26只眼的眼底表现为沿血管分布的浓厚黄白色病损区,其上片状出血,边缘有不规则黄白色颗粒.3只眼为眼底病变晚期,表现为视网膜萎缩、视网膜血管硬化和狭窄、视神经萎缩.3只眼合并视网膜脱离.正常眼底的HIV感染者及AIDS患者CD_4~+T淋巴细胞计数中位数为100.0个/mm~3,HIV视网膜病变患者CD_4~+T淋巴细胞计数中位数为41.0个/mm~3,CMV性视网膜炎患者CD_4~+T淋巴细胞计数中位数为18.0个/mm~3.CD_4~+T淋巴细胞计数比较,正常眼底组与HIV视网膜病变组相比,差异有统计学意义(x~2=4.848,P=0.028);正常眼底组与CMV性视网膜炎组相比,差异有统计学意义(x~2=15.696,P=0.000);HIV视网膜病变组与CMV性视网膜炎组相比,差异有统计学意义(x~2=4.860,P=0.027).2例(4只眼)CMV性视网膜炎患者行更昔洛韦(400 μg)玻璃体腔注药后,视力提高,眼底病变明显消退.结论 视网膜微血管病变是HIV感染及AIDS常见的眼部并发症,CMV性视网膜炎是AIDS晚期最严重的眼部并发症.高效抗逆转录病毒治疗可重建患者的免疫功能,更昔洛韦玻璃体腔注药可有效治疗CMV性视网膜炎并挽救患者视力.     

Intravitreal sustained-release ganciclovir implants for severe bilateral cytomegalovirus retinitis after stem cell transplantation

PURPOSE: To describe the treatment of cytomegalovirus (CMV) retinitis with intravitreal sustain-release ganciclovir devices in a 16-year-old patient in third remission of acute lymphoblastic leukemia after stem cell transplantation. METHODS: The patient received a stem cell transplant from an unrelated bone marrow donor after which he contracted a serious CMV infection manifested in the lungs and retinae. His immune system at this time was almost completely depleted. Implantation of a sustained-release ganciclovir device was performed in both eyes when retinitis progressed in spite of aggressive antiviral intravenous treatment. RESULTS: No per- or postoperative complications were noted. Infiltrates, hemorrhages and macular edema present preoperatively dissolved over a period of six months. The final visual acuity was 1.0 in both eyes. The patients immune system and lung function slowly recovered during the same time period. CONCLUSIONS: The intravitreal ganciclovir implant provides safe and effective therapy against CMV retinitis, and should be considered in patients acquiring the infection after stem cell transplantation.     

Cytomegalovirus Retinitis in a Human Immunodeficiency Virus-negative Cohort: Long-term Management and Complications

Abstract

Purpose: To examine the clinical outcomes achieved by using intravitreal ganciclovir injections combined with systemic anti-viral therapy in treating cytomegalovirus (CMV) retinitis in patients without human immunodeficiency virus (HIV) infection.

Methods: Twenty-three eyes of 15 HIV-negative patients diagnosed with CMV retinitis were included in this retrospective study.

Results: The median follow-up was 68 weeks (range, 12–156), and median number of injections was 10 (range, 2–22). The retinal lesions stopped progressing within 1–2 weeks following treatment. All of the eyes showed either unchanged or ≥2?line improvements of BCVA at last visit. There was no development of CMV retinitis in a fellow eye, or recurrence in a studied eye. Systemic complications such as neutropenia were not detected.

Conclusions: Intravitreal ganciclovir injections combined with systemic anti-viral treatment is a good therapeutic option for treating CMV retinitis without HIV infection. Such treatment provided favorable visual outcomes, with minimal ocular and systemic complications.