Robert E. Engstrom

The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: IV. Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS report no. 19.

OBJECTIVE To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I(125)) brachytherapy in patients with choroidal melanoma treated and followed up in a large randomized clinical trial. DESIGN Prospective, noncomparative, interventional case series within a randomized, multicenter clinical trial. PARTICIPANTS Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) trial of enucleation versus brachytherapy between February 1987 and July 1998; tumors measured 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal dimension. METHODS I(125) brachytherapy was administered via episcleral plaque according to a standard protocol. Follow-up ophthalmic evaluations, including ophthalmic ultrasound and fundus photography, were performed according to a standard protocol at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Survival analysis methods were used to estimate the cumulative risk of postirradiation treatment failure and enucleation. Factors associated with treatment failure and enucleation of plaqued eyes were evaluated using Cox proportional hazards analysis. MAIN OUTCOME MEASURES Reports of enucleation and of local treatment failure, defined as tumor growth, recurrence, or extrascleral extension, derived from clinical reports based on echographic and photographic documentation. RESULTS As of September 30, 2000, 638 of the 650 patients randomized to brachytherapy and so treated had been followed up for 1 year or longer, and 411 had been followed up for at least 5 years. Sixty-nine eyes were enucleated during the first 5 years after brachytherapy, and treatment failure was reported for 57 eyes. The Kaplan-Meier estimate of proportion of patients undergoing enucleation by 5 years was 12.5% (95% confidence interval [CI], 10.0%-15.6%); the risk of treatment failure was 10.3% (95% CI, 8.0%-13.2%). Treatment failure was the most common reason for enucleation within 3 years of treatment; beyond 3 years, ocular pain was most common. Risk factors for enucleation were greater tumor thickness, closer proximity of the posterior tumor border to the foveal avascular zone, and poorer baseline visual acuity in the affected eye. Risk factors for treatment failure were older age, greater tumor thickness, and proximity of the tumor to the foveal avascular zone. Local treatment failure was associated weakly with reduced survival after controlling for baseline tumor and personal characteristics (adjusted risk ratio, 1.5; P = 0.08). CONCLUSIONS Local treatment failure and enucleation were relatively infrequent events after I(125) brachytherapy within the COMS. Treatment failure typically occurred early and was associated weakly with poorer survival. The COMS randomized trial documented the absence of a clinically or statistically significant difference in survival for patients randomly assigned to enucleation versus brachytherapy. This analysis documents the efficacy of brachytherapy to achieve sustained local tumor control and to conserve the globe.

Ocular toxoplasmosis in patients with the acquired immunodeficiency syndrome

In seven of eight cases of presumed ocular toxoplasmosis in patients with AIDS, the diagnosis was supported by a reduction or resolution of intraocular inflammation and healing of necrotic retinal lesions after initiation of antiparasitic drug therapy including one or more of the following medications: pyrimethamine, sulfadiazine, clindamycin, tetracycline, or spiramycin. In two cases the diagnosis was confirmed histologically. The cases differed clinically and histopathologically from those in immunocompetent patients. There was no evidence that disease originated in preexisting retinochoroidal scars. Lesions frequently were bilateral and multifocal. Vitreous inflammatory reaction was a common clinical finding, but histopathologic examination demonstrated scant retinal inflammation in areas of necrosis. Ocular toxoplasmosis in these patients with AIDS probably resulted from newly acquired infection or dissemination of organisms from nonocular sites of disease. Infections became clinically inactive with drug therapy in all treated patients, but reactivation and progression of disease occurred when therapy was stopped in two of three patients. Severe retinal necrosis led to retinal tears or detachment in three cases. Ocular lesions were the first manifestation of Toxoplasma gondii infection in four of five patients with evidence of multisystem infection.

Use of the ganciclovir implant for the treatment of cytomegalovirus retinitis in the era of potent antiretroviral therapy: Recommendations of the international AIDS society-USA panel

PURPOSE To describe the risks, benefits, and recommended use of the ganciclovir implant for the treatment of human immunodeficiency virus-related cytomegalovirus (CMV) retinitis in the era of potent antiretroviral therapy. METHODS A panel of physicians with expertise in the use of the ganciclovir implant and in the management of CMV retinitis was convened by the International AIDS Society-USA. The panel reviewed and discussed available data, and developed recommendations for the use of the ganciclovir implant, the surgical technique, and related management issues. Recommendations were rated according to the strength and quality of the supporting evidence. RESULTS The effect of potent antiretroviral therapy on the immunologic status of patients with human immunodeficiency virus disease has changed the manifestation and course of CMV retinitis in many patients. The clinical management of CMV retinitis and the role of the ganciclovir implant are thus changing. Factors in the decision to choose the ganciclovir implant include the patients potential for immunologic improvement, location and severity of CMV retinitis, and the risks and costs associated with implantation and concomitant oral ganciclovir therapy. CONCLUSIONS The ganciclovir implant is safe and effective for the treatment of CMV retinitis. The indications for its use should be modified to account for increased patient survival and the potential for CMV retinitis to be controlled by effective antiretroviral therapy. Optimal use of the ganciclovir implant and discontinuation of therapy in selected patients with improvement in immunity may result in better long-term visual outcomes.

Postoperative Hemorrhagic Occlusive Retinal Vasculitis: Expanding the Clinical Spectrum and Possible Association with Vancomycin.

PURPOSE To describe a syndrome of hemorrhagic occlusive retinal vasculitis (HORV) that developed after seemingly uncomplicated cataract surgery. DESIGN Retrospective case series. SUBJECTS Eleven eyes of 6 patients from 6 different institutions. METHODS Cases were identified after discussion among retina specialists. The findings on presentation, clinical course, and outcome of a series of 7 eyes of 4 patients were compared with a previous report of 4 eyes of 2 patients, and data from both series were combined for a comprehensive analysis. MAIN OUTCOME MEASURES Historical data, examination findings, imaging results, systemic evaluation findings, treatment regimens, and visual outcomes. RESULTS Eleven eyes of 6 patients underwent otherwise uncomplicated cataract surgery, receiving viscoelastic and prophylactic intracameral vancomycin during the procedure. Despite good initial vision on postoperative day 1, between 1 to 14 days after surgery, all eyes demonstrated painless vision loss resulting from HORV. Extensive ocular and systemic evaluations were unrevealing in all patients. All patients were treated with aggressive systemic and topical corticosteroids. Additional treatments included systemic antiviral medication in 4 patients, intravitreal antibiotics in 4 eyes, and pars plana vitrectomy in 4 eyes. Skin testing for vancomycin sensitivity showed negative results in 3 patients and was not performed in the others. Neovascular glaucoma developed in 7 eyes, and all eyes received intravitreal anti-vascular endothelial growth factor (VEGF) injection, panretinal photocoagulation, or both for retinal ischemia. Final visual acuity was less than 20/100 in 8 of 11 eyes. CONCLUSIONS Postoperative HORV is an exceedingly rare and potentially devastating condition that can occur after otherwise uncomplicated cataract surgery. Although the precise cause remains unknown, this disease may represent a delayed immune reaction similar to vancomycin-induced leukocytoclastic vasculitis. Despite treatment with high-dose corticosteroids, antiviral medication, and early vitrectomy in many patients, visual outcomes typically were poor in this series. Early intervention with intravitreal anti-VEGF medication and panretinal photocoagulation may help to prevent additional vision loss resulting from neovascular glaucoma.

Mortality after deferral of treatment or no treatment for choroidal melanoma

PURPOSE To report mortality of patients who were eligible for enrollment in the Collaborative Ocular Melanoma Study (COMS) clinical trials of medium-sized choroidal melanoma or large-sized choroidal melanoma but chose to defer treatment or receive no melanoma treatment. DESIGN Prospective nonrandomized multicenter cohort study as an adjunct to the COMS randomized clinical trials. METHODS Patient follow-up procedures included examinations, correspondence, telephone contacts, and National Death Index searches. Primary outcome was patient death measured by all-cause mortality. Secondary outcomes were melanoma treatment and melanoma metastasis. RESULTS Of 77 patients eligible for the COMS clinical trials who chose to defer or receive no melanoma treatment, 61 were appropriate candidates and 45 (74%) enrolled in the natural history study. Forty-two patients (42 eyes) had medium melanoma, and median follow-up was 5.3 years (range, 4-10.7 years). Twenty-two patients (52%) had subsequent melanoma treatment, and 20 (48%) had no melanoma treatment. For the 42 patients, the Kaplan-Meier estimate of 5-year mortality was approximately 30% (95% confidence interval [CI], 18%-47%). For the COMS medium melanoma trial, 5-year mortality was 18% (95% CI, 16% -20%), not statistically significantly different from the natural history study patients. After adjusting for differences in age and longest basal diameter, the 5-year risk of death for natural history study patients vs COMS trial patients was 1.54 (95% CI, 0.93-2.56). Three patients had large melanoma. Melanoma metastasis was confirmed or suspected in eight (42%) of 19 deaths. CONCLUSION Greater mortality and higher risk of death for natural history study patients are probative but not conclusive evidence of a beneficial, life-extending effect of medium melanoma treatment.

External Ocular Disease And Anterior Segment Disorders Associated With Aids

A. wide variety of ophthalmic disorders have been associated with the acquired immunodeficiency syndrome (AIDS). They generally fall into four groups: vascular disorders, infections, neoplasms, and neuroophthalmic abnormalities that result from intracranial disease [1-5]. To date, attention has focused primarily on posterior segment disorders, the most devastating of which are opportunistic infections of the choroid and retina. Less attention has been directed toward external disease and anterior segment disorders, yet they too may cause severe morbidity and may provide diagnostic clues in persons at risk for AIDS.

The coms randomized trial of iodine 125 brachytherapy for choroidal melanoma

arms, 5- and 10-year all-cause mortality rates were 19% and 35%, respectively; by 12 years, cumulative all-cause mortality was 43% among patients in the 125 I brachytherapyarmand41%amongthoseintheenucleationarm. Five-, 10-, and 12-year rates of death with histopathologicallyconfirmedmelanomametastasiswere10%,18%, and 21%, respectively, in the 125 I brachytherapy arm and 11%,17%,and17%,respectively,intheenucleationarm. Olderageandlargermaximumbasaltumordiameterwere the primary predictors of time to death from all causes and death with melanoma metastasis. Conclusion:Longer follow-up of patients confirmed the earlier report of no survival differences between patients whose tumors were treated with 125 I brachytherapy and those treated with enucleation.

Ischemic maculopathy in patients with acquired immunodeficiency syndrome

PURPOSE To describe the characteristics of ischemic maculopathy in patients with human immunodeficiency virus (HIV) infection, as a means of understanding this uncommon disorder more fully. METHODS This is a multicenter, retrospective review of clinical data available for five HIV-infected patients who were given the diagnosis of ischemic maculopathy. RESULTS All cases had been diagnosed on the basis of fluorescein angiograms obtained after patients complained of vision loss. Four of the five patients had bilateral macular disease. Visual acuity at presentation in the nine affected eyes ranged from 20/20 to count fingers. Vision loss was gradual in both eyes of one patient and was abrupt in onset in seven eyes. Each of the seven eyes with abrupt vision loss had opacification of the superficial retina and/or intraretinal hemorrhages near the fovea. Fluorescein angiography revealed enlargement of the foveal avascular zone and mild staining of the juxtafoveal vessels in affected eyes. Six eyes had active or clinically inactive cytomegalovirus retinitis at presentation, and a seventh eye developed cytomegalovirus retinitis 2 weeks later. All patients were receiving anticytomegalovirus drugs when they developed visual symptoms. Visual acuity remained stable in five eyes, became worse in two eyes, and improved in two eyes; final visual acuity ranged from 20/25 to count fingers. CONCLUSIONS Ischemic maculopathy may cause profound and permanent vision loss in HIV-infected individuals. Fluorescein angiography should be considered in all HIV-infected patients with unexplained loss of vision. The pathogenesis of ischemic maculopathy remains unknown.

Clear lens extraction with intraocular lens implantation during retinal detachment repair in patients with autoimmune deficiency syndrome and cytomegalovirus retinitis

Abstract Objective To assess the outcomes of clear lens extraction with intraocular lens (IOL) implantation during repair of retinal detachment by vitrectomy with silicone oil tamponade in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis. Design Retrospective, noncomparative case series. Participants Twelve eyes of 10 patients with AIDS, CMV retinitis, and retinal detachment. Intervention All patients underwent phacoemulsification with posterior chamber IOL placement at the time of vitrectomy with silicone oil tamponade for repair of retinal detachment. A targeted postoperative refractive error of −5.00 diopters (D) to −3.00 D was chosen in an attempt to counteract the hyperopic effect of silicone oil. Main outcome measures The following factors were evaluated: postoperative visual acuity, refractive error, and intraoperative and postoperative complications. Results Median follow-up was 7 months (range, 1–46 months). For patients without macular necrosis, median best-corrected preoperative visual acuity was 20/75 (range, 20/20–20/800), and median best postoperative visual acuity was 20/50 (range, 20/20–20/400). Median final visual acuity was 20/140 (range, 20/25 to count fingers at 1 foot). The median postoperative refractive error (spherical equivalent) was −1.00 D (range, −4.00 D to +7.88 D). Reoperation was required in 3 of 12 eyes for recurrent macular detachment (1 with silicone oil underfill; 2 with proliferative vitreoretinopathy). The macula was attached in all eyes at last follow-up. Reattachment of the peripheral retina was achieved in 10 of 12 eyes. There were no anterior segment complications. Conclusions Clear lens extraction with IOL placement during repair of retinal detachment with silicone oil tamponade does not seem to increase complications and may improve long-term visual rehabilitation, improve retinitis management by allowing better posterior segment visualization throughout the postoperative course, and decrease overall cost and morbidity associated with cataract extraction as a second procedure.

An association between Vogt-Koyanagi-Harada disease and Guillain-Barré syndrome.

PURPOSE To describe an association between Vogt-Koyanagi-Harada disease and Guillain-Barré syndrome. METHODS Case series, describing three patients. RESULTS In two patients, the disorders had their onsets within 2 weeks of each other; in the third patient, Vogt-Koyanagi-Harada disease occurred after 3 months, as Guillain-Barré syndrome resolved. All three patients had bilateral panuveitis typical of Vogt-Koyanagi-Harada disease. Each also developed well-accepted manifestations of Guillain-Barré syndrome, including paresis of the lower extremities (all patients), paresis of the upper extremities (two patients), paresis of cranial nerves (two patients), areflexia (all patients), and abnormal electromyography findings (two patients). CONCLUSIONS Vogt-Koyanagi-Harada disease may follow or occur simultaneously with Guillain-Barré syndrome. The fact that these two autoimmune disorders occur together in some patients suggest that they may share common disease mechanisms.