CLINICAL OUTCOMES AND TREATMENT COURSE OF EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION FOLLOWING THE DEVELOPMENT OF ENDOPHTHALMITIS.

PURPOSE: To evaluate the clinical course of patients with neovascular age-related macular degeneration (nAMD) after developing endophthalmitis during their treatment with intravitreal injections. METHODS: Multicenter, retrospective series. RESULTS: From April 2013 to October 2018, 196,598 intravitreal anti-vascular endothelial growth factor (VEGF) injections were performed, with 75 cases of endophthalmitis (incidence 0.0381%). There was no association between intravitreal anti-VEGF drug (P = 0.29), anesthetic method (P = 0.26), povidone concentration (P = 0.22), or any intraprocedure variable and endophthalmitis incidence. Seventy-two patients (96%) were treated with intravitreal tap and inject , while 3 underwent immediate pars plana vitrectomy. After endophthalmitis resolution, 17 patients (22.7%) were not re-treated for nAMD (in 10 cases due to inactive disease; follow-up, 115 ± 8.4 weeks). Patients required less frequent anti-VEGF injections after infection (7.4 ± 0.61 weeks vs. 11.5 ± 1.8 weeks; P = 0.004). Preinfection logarithm of the minimum angle of resolution visual acuity was 0.585 ± 0.053 (∼20/77). It worsened with endophthalmitis (1.67 ± 0.08, ∼20/935; P < 0.001) and again on postendophthalmitis treatment day 1 (1.94 ± 0.064; count fingers; P < 0.001), but improved after reinitiating nAMD therapy (1.02 ± 0.11; ∼20/209; P < 0.001). Better visual acuity on postendophthalmitis week 1 (P = 0.002) and reinitiation of nAMD treatment (P = 0.008) were associated with better final visual acuity, and streptococcal culture with worse visual acuity (P = 0.028). The postendophthalmitis treatment interval was associated with the anti-VEGF drug used (aflibercept = ranibizumab > bevacizumab; P < 0.001). CONCLUSION: Patients with nAMD required fewer injections after endophthalmitis, suggesting a biological change in disease activity. Neovascular age-related macular degeneration became quiescent in 13.3% of eyes. Most achieved better outcomes with anti-VEGF reinitiation.

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 (I125) 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: I125 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 I125 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.

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 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 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 (NHS). In all, 42 patients (42 eyes) had medium melanoma, and the median follow-up was 5.3 years (range, 4-10.7 years). In all, 22 patients (52%) had subsequent melanoma treatment, and 20 (48%) had no melanoma treatment. For the 42 patients, Kaplan-Meier estimate of 5-year mortality was approximately 30% [95% confidence interval (CI), 18%-47%]. For COMS medium melanoma trial, 5-year mortality was 18% (95% CI, 16%-20%), not statistically significantly different from the NHS patients. After adjusting for differences in age and longest basal diameter, the 5-year risk of death for NHS patients versus COMS trial patients was 1.54 (95% CI, 0.93-2.56). Three patients had large melanoma. Melanoma metastasis was confirmed or suspected in 8 (42%) of 19 deaths. CONCLUSION: Greater mortality and higher risk of death for NHS patients are probative but not conclusive evidence of a beneficial, life-extending effect of medium melanoma treatment.

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.

Outcomes associated with ganciclovir implants in patients with AIDS-related cytomegalovirus retinitis.

PURPOSE: To investigate complications associated with ganciclovir implants used to treat AIDS-related cytomegalovirus (CMV) retinitis, and to identify factors that predict poor outcomes. DESIGN: Retrospective chart review. PARTICIPANTS: Consecutive patients with AIDS-related CMV retinitis from 3 clinical facilities who underwent implantation procedures during the period January 1, 1995 through December 31, 2001. METHODS: Baseline for each patient was the date of the first implantation procedure performed during the study period by one of the facilities' surgeons (index implant). Medical and ophthalmological data were collected at baseline and at specific time points after baseline. The dates on which additional implantation procedures were performed and the dates on which complications or vision loss were identified were also recorded. Relationships between potential risk factors and outcomes were studied by Kaplan-Meier analyses and Cox proportional hazards regression models. MAIN OUTCOME MEASURES: Primary outcome measures included postoperative complications specifically related to or possibly related to ganciclovir implants. A secondary outcome measure was vision loss after implantation procedures. RESULTS: The charts of 174 patients (one study eye per patient; 279 implants) were reviewed. Median follow-up was 14.4 months (range, 0-7 years). Complications specifically related to implants occurred throughout follow-up at a rate of 0.064 events per patient-year. Complications possibly related to implants occurred at an overall rate of 0.377 per patient-year, but seemed to be more common during the first 2 years after baseline. During the first 2 years of follow-up, retinal detachments occurred at a rate of 0.156 events per patient-year. The cumulative risk of vision loss (> or =3 lines of Snellen visual acuity) at 7 years was 70%. Poor outcomes were associated with disease factors (size and activity of lesions), lack of highly active antiretroviral therapy (HAART), and lack of HAART-associated immune reconstitution, but not with surgical factors or implant-specific complications. CONCLUSIONS: Complications specifically associated with ganciclovir implants can occur many years after implantation procedures, but the incidence of such complications is low. Continued vision loss is not attributable directly to complications of implants in most cases. This information will help in planning of treatment strategies for CMV retinitis in long-term survivors of human immunodeficiency virus disease.

Iris and anterior chamber angle neovascularization after iodine 125 brachytherapy for uveal melanoma.

PURPOSE: Iris neovascularization (INV) and anterior chamber angle neovascularization after radiotherapy for uveal melanoma may lead to neovascular glaucoma and enucleation. However, neovascularization of the anterior ocular segment may respond favorably to treatment with panretinal photocoagulation. The purpose of this study was to evaluate the frequency, interval to development, and predisposing factors of anterior ocular segment neovascularization following iodine 125 (I125) brachytherapy for uveal melanoma. DESIGN: Retrospective, interventional, consecutive case series. PARTICIPANTS: Sixty-five patients (65 eyes), consecutively treated with I125 brachytherapy for uveal melanoma from 1995 through 2000 and followed up after radiation therapy for 24 months or more. METHODS: Clinical findings and ultrasonography characteristics as well as treatment parameters were analyzed. MAIN OUTCOME MEASURES: The frequency of INV was determined and the interval to development of INV as well as the predisposing factors were analyzed statistically. RESULTS: In 15 of 65 eyes (23%), INV was detected after I125 brachytherapy at a mean +/- standard deviation of 26.66+/-11.63 months (median, 24 months; range, 9-48 months). Risk factors displaying the stronger correlation with INV were greater maximal tumor height (P<0.01), greater tumor vascularity (P<0.01), and disinsertion of horizontal rectus muscles (P = 0.01). CONCLUSIONS: After I125 brachytherapy for choroidal melanoma, INV developed in 23% of eyes and was correlated with larger tumor size, greater tumor vascularity, and disinsertion of a horizontal rectus muscle.

Functional anatomy of the anophthalmic socket: insights from magnetic resonance imaging.

PURPOSE: Changes in anophthalmic socket anatomy can significantly compromise esthetics and motility after enucleation. This study evaluated such changes by using magnetic resonance imaging (MRI) of enucleated and fellow orbits. METHODS: High-resolution, surface coil MRI was performed in five patients after enucleation for uveal melanoma. Images were analyzed quantitatively to determine extraocular muscle (EOM) volume, maximum diameter, and length; orbital, optic nerve (ON), and orbital fat tissue (OFT) volume; and implant position. The fellow orbit was used as the control. Patients evaluated their satisfaction with the surgical results and were clinically examined. RESULTS: Rectus EOM volume was slightly but not significantly reduced on the surgical compared with the control side. Oblique EOM and OFT volumes were unchanged. Rectus EOM length was significantly reduced in the surgical side, but maximum EOM diameter in central gaze position was slightly but not significantly greater on the enucleated side. Rectus EOM paths were not qualitatively changed by enucleation and continued to exhibit the influence of the connective tissue pulleys, which retained motility, as appropriate to EOM contraction. Implants were located significantly posterior to the normal globe location. CONCLUSIONS: Enucleation does not significantly change EOM volume, but shortens EOM paths, a change that would be expected to alter their mechanical properties. EOM pulleys appear to retain their functional role in enucleated orbits.

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.

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.

Bovine hydroxyapatite orbital implant: a preliminary report.

PURPOSE: To determine the safety and efficacy of bovine hydroxyapatite as an orbital implant material. METHODS: Prospective, consecutive case series of patients undergoing enucleation, evisceration, or secondary orbital implantation. A motility peg was placed in all consenting candidates. Patients were followed 1 week, 1 month, and several months after surgery for signs of inflammation, infection, extrusion, or other complication. RESULTS: Twenty-seven patients received a bovine hydroxyapatite orbital implant. Magnetic resonance imaging was obtained in 3 patients (3 orbits) approximately 4 weeks after surgery and showed signs of peripheral fibrovascular ingrowth in all three cases. Magnetic resonance imaging was obtained in 9 patients (9 orbits) 4 to 12 months after surgery and showed signs of incomplete fibrovascular ingrowth in 1 of 9 (11%) cases, subtotal fibrovascular ingrowth in 2 of 9 (22%) cases, and complete fibrovascular ingrowth in 6 of 9 (67%) of cases. Complications included postoperative chemosis in 3 cases (11%) and exposure requiring reoperation in 2 cases (7%). Motility peg placement was performed successfully in 5 patients (5 orbits). CONCLUSIONS: Bovine hydroxyapatite appears to be a safe and effective orbital implant material. The material appears to be biocompatible and nonallergenic. Bovine hydroxyapatite allows for fibrovascular integration and motility peg placement.

Clear lens extraction with intraocular lens implantation during retinal detachment repair in patients with Acquired Immune Deficiency Syndrome (AIDS) [correction of autoimmune deficiency syndrome] and cytomegalovirus retinitis.

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.