Timothy G. Murray

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.

FACTORS ASSOCIATED WITH REDUCED VISUAL ACUITY DURING LONG-TERM FOLLOW-UP OF PATIENTS WITH IDIOPATHIC CENTRAL SEROUS CHORIORETINOPATHY

Purpose To investigate factors associated with reduced visual acuity during long-term follow-up of patients with idiopathic central serous chorioretinopathy (ICSC). Methods Retrospective consecutive case series that included patients with ICSC who were younger than 50 years of age at the time of initial examination and were followed up for ≥3 years. Results The mean follow-up for 101 involved eyes of 61 patients was 9.8 years (median, 8.0 years). Eyes were stratified into two groups based on visual acuity at the final examination: Group 1, visual acuity of 20/40 or better; and Group 2, visual acuity of worse than 20/40. Findings identified as potential risk factors for reduced vision at the final follow-up examinations for Group 1 versus Group 2 included the following: macular retinal pigment epithelium atrophy (90.8% versus 96.0%, respectively;P = 0.68); persistent pigment epithelial detachment or persistent subretinal fluid (5.3% versus 28.0%, respectively;P = 0.004); recurrences (39.5% versus 68.0%, respectively;P = 0.020); laser treatment (28.9% versus 32.0%, respectively;P = 0.80); and submacular choroidal neovascularization (0.0 versus 8.0%, respectively;P = 0.059). Conclusions Factors associated with reduced visual acuity during long-term follow-up of patients with ICSC included persistent pigment epithelial detachment and/or subretinal fluid, recurrences, and submacular choroidal neovascularization.

Endophthalmitis after Pars Plana Vitrectomy

Purpose: To describe the clinical course and incidence of culture-proven Postvitrectomy endophthalmitis in 18 patients from five academic centers and three private practices. Methods: Patients undergoing pars plana vitrectomy for recent trauma or endophthalmitis were excluded. The average age was 58 years (range, 21–85 year). Sixty-one percent of the patients (11/18) had diabetes mellitus. The indication for initial vitrectomy was vitreous hemorrhage (n = 10), macular epiretinal membrane (n = 3), recurrent retinal detachment with proliferative vitreoretinopathy (n = 2), retinal detachment with retinoschisis (n =1), proliferative diabetic retinopathy with tractional retinal detachment (n =1), and dislocated intraocular lens (n =1). None of these eyes received prophylactic intraocular antibiotics during the vitrectomy. Results: All eyes were treated with intraocular antibiotics after the diagnosis of Postvitrectomy endophthalmitis was made. Final visual acuity ranged from 20/20 to no light perception and included five eyes with 20/50 or better visual acuity and 11 eyes with less than 5/200 visual acuity. Nine eyes had a final visual acuity of no light perception. Of the 16 eyes infected with a single organism, 71 % (5J7) of eyes infected with coagulasenegative staphylococci retained 20/50 or better final visual acuity compared with no eyes (0/9) infected with other organisms ( P = 0.005). Two eyes infected with both coagulase-negative Staphylococcus and Streptococcus had a final visual acuity of 20/ 400. Three eyes with a total hypopyon later had enucleation or evisceration. Based on the data from four medical centers, the incidence of endophthalmitis after pars plana vitrectomy performed over the last 10 years was 9/12,216 (0.07%). Conclusion: Endophthalmitis after vitrectomy is rare. Postvitrectomy bacterial endophthalmitis caused by organisms other than coagulase-negative staphylococci has a poor visual prognosis.

Off-label use of intravitreal bevacizumab (Avastin) for salvage treatment in progressive threshold retinopathy of prematurity.

Purpose: To report the short term anatomic response of intravitreal bevacizumab (Avastin, Genentech) as salvage treatment in progressive retinopathy of prematurity (ROP) in a small series of patients. Methods: The study included five eyes of three patients with progressive ROP despite peripheral laser ablation. Patients received intravitreal injections of bevacizumab (Avastin, Genentech). RetCam (Clarity Medical Systems, Inc., Pleasanton, CA) photography and ultrasonography were used to document effect. Results: Three patients were transferred to the Bascom Palmer Eye Institute/Jackson Memorial Hospital for management of progressive ROP despite laser therapy at an outside facility. RetCam fundus photography and ultrasonography were used to document all cases. After informed consent was obtained from the parents, the patients received off-label intravitreal bevacizumab as salvage treatment. Repeat intravitreal injections of bevacizumab were utilized in several cases. The ROP stabilized allowing laser supplementation. There was varying development of tractional retinal detachments in several of the eyes but the ROP component quieted in all cases. Conclusions: Off-label use of bevacizumab appears to be useful as a salvage treatment for ROP when laser treatment is precluded. It improves dilation, quiets the disease when visibility is difficult, and temporizes the disease until laser can be supplemented.

Emerging ciprofloxacin-resistant Pseudomonas aeruginosa

PURPOSE To report a clinical series of ciprofloxacin-resistant ocular isolates of Pseudomonas aeruginosa from a tertiary care ophthalmic center. METHODS Review of in vitro sensitivities of all ocular isolates of P. aeruginosa be tween July 1991 and September 1998. In vitro resistance was defined as a minimum inhibitory concentration of 4 or more microg per ml. RESULTS Nine of 423 ocular isolates of P. aeruginosa showed in vitro resistance to ciprofloxacin. From 1991 to 1994, 0.44% (1/227) of ocular isolates were resistant to ciprofloxacin, whereas from 1995 to 1998, 4.1% (8/ 196) of ocular isolates showed in vitro resistance (P = .014). CONCLUSIONS Ciprofloxacin-resistant P. aeruginosa has been identified in recent clinical ocular specimens. Ciprofloxacin resistance among ocular isolates of P. aeruginosa is a local and worldwide concern.

Intraoperative Echographic Localization Of Iodine 125 Episcleral Radioactive Plaques For Posterior Uveal Melanoma

Purpose Plaque radiotherapy has been reported to have a higher relapse rate than charged-particle radiotherapy for posteriorly located uveal melanomas, which also are more technically difficult to localize accurately. The authors used intraoperative echography in patients with posterior uveal melanoma to determine the rate of inaccurate localization of iodine 125 (125I) episcleral plaques using standard localization techniques. Methods The authors reviewed the records of 29 consecutive patients with medium-sized posterior uveal melanomas who underwent 125I episcleral plaque radiotherapy with intraoperative echographic verification of plaque placement. Results After careful plaque placement using standard localization techniques, 4 of 29 plaques (14%) did not cover at least one tumor margin. All four of these plaques were associated with posterior tumors with at least one margin posterior to the temporal arcades. Two (7%) additional juxtapapillary plaques were displaced away from the sclera by the optic nerve. In all six cases, it was possible to immediately reposition the plaque to achieve coverage of all tumor margins. Conclusions Placement of 125I episcleral radioactive plaques for posteriorly located uveal melanomas using standard localization techniques occasionally results in suboptimal plaque positioning. Intraoperative echography can identify plaques that are localized poorly and allows immediate adjustment to achieve optimal plaque positioning.

Pars plana vitrectomy with internal limiting membrane peeling for diabetic macular edema

Purpose: To evaluate anatomic and visual acuity (VA) results of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling for diffuse diabetic macular edema (DME), and to review the literature on the topic. Methods: Retrospective noncomparative case series of patients who underwent PPV with ILM peeling for diffuse DME between January 1, 2000, and December 1, 2005, performed by three surgeons at Bascom Palmer Eye Institute. Main outcome measures included pre- and postoperative optical coherence tomography (OCT) and visual acuity. Mean follow-up period was 8 months (range, 43 days–2 years). Results: Twenty-four eyes of 23 patients meeting the criteria were evaluated. Duration of DME ranged from 1 to 93 months. Mean preoperative logMAR vision was 0.782 (range, 0.30–1.82). Mean logMAR visual acuity at final follow-up was 0.771 (range, 0.10–2.00). At last follow-up, 25% of eyes had ≥2 line increase in VA from baseline, 54% of eyes had no improvement in VA, and 21% of eyes had ≥2 line decrease in VA. Of 9 eyes with pre- and postoperative OCT, there was an overall reduction in central macular thickness of 141 &mgr;m at postoperative month 3 and 120 &mgr;m at last follow-up. Postoperative complications included progression of cataract in 6 (60%) of 10 phakic eyes, postoperative intraocular pressure ≥30 mmHg in 6 (24%) eyes, and postoperative vitreous hemorrhage in 2 (8%) eyes. Conclusions: Pars plana vitrectomy with ILM peeling was associated with a reduction in DME when measured by OCT in the majority of eyes, but visual acuity outcomes showed minimal improvement compared to baseline. These results suggest the efficacy of PPV with ILM peeling for eyes with DME has not been well established and should be reserved for therapy with selected cases.

One-year Safety And Efficacy Of Intravitreal Triamcinolone Acetonide For The Management Of Macular Edema Secondary To Central Retinal Vein Occlusion

Purpose: To evaluate the safety and efficacy of intravitreal triamcinolone acetonide (IVTA) as treatment for macular edema associated with central retinal vein occlusion (CRVO). Methods: A retrospective review was performed of data for 40 consecutive patients (40 eyes) with CRVO and macular edema treated with IVTA at the Bascom Palmer Eye Institute (Miami, FL). Results: Median duration of symptoms before the first injection was 3 months (range, 1 day to 8 years). Median Snellen visual acuity was 20/400 at baseline (range, 20/60 to light perception; n = 40), 20/300 at 1 month (P = 0.010; n = 37), 20/300 at 3 months (P = 0.007; n = 33), 20/400 at 6 months (P = 0.726; n = 28), and 8/200 at 1 year (P = 0.569; n = 17). Vision improved by ≥3 lines in 21% of eyes at 1 month, 27% at 3 months, 14% at 6 months, and 12% at 1 year. Visual acuity was unchanged from baseline in 71% of eyes at 6 months and 1 year. By 1 year, 50% of eyes received more than one injection (mean = 1.6 injections; range 1–4 injections). Overall, intraocular pressure increased by ≥10 mmHg in 24% of eyes at 1 year. Trabeculectomy was performed on 2 of 12 eyes with preexisting open-angle glaucoma. Conclusion: IVTA can substantially improve vision in some patients, but most patients have stable visual acuity compared with baseline at 1 year despite repeated injections.

MELANOMAS THAT DEVELOP WITHIN THE EYE INHIBIT LYMPHOCYTE PROLIFERATION

Experiments were performed to compare the ability of ocular and skin melanoma cells to stimulate T cells. Primary melanoma cell lines were obtained from a series of patients with either eye or skin melanoma. The ability of tumor cells to stimulate T cells in the absence of exogenous growth factors was assessed in mixed‐lymphocyte tumor cell cultures in which allogeneic lymphocytes were stimulated with irradiated ocular or skin melanoma cells. Expression of HLA class I and class II on tumor cells, in the presence or absence of IFN‐γ, was determined by flow cytometry. The ability of tumor cells to inhibit T‐cell proliferation was determined by adding various concentrations of irradiated tumor cells to standard mixed‐lymphocyte cultures. Our results indicate that primary skin melanoma cells induce vigorous proliferation of allo‐antigen‐specific T cells. By contrast, ocular melanoma cells failed to induce significant T‐cell proliferation. The failure of ocular melanoma cells to stimulate lymphocyte proliferation was not due to low levels of either class I or class II on tumor cells since tumor cells treated with IFN‐γ expressed high levels of class I and class II but still failed to induce lymphocyte proliferation. Ocular melanoma cells inhibited lymphocyte proliferation, as shown by experiments in which a small number of tumor cells prevented proliferation of T cells in mixed‐lymphocyte cultures. Inhibition of lymphocyte proliferation required cell‐to‐cell contact, and supernatants from tumor cell cultures did not prevent lymphocyte proliferation. Moreover, the ability of ocular melanoma cells to inhibit T‐cell proliferation was lost when tumor cells migrated from the eye and formed hepatic metastases. We conclude that there is a fundamental difference in the immunogenicity of ocular and skin melanoma cells. Ocular melanomas, but not primary skin melanomas, are poorly immunogenic tumors that inhibit T‐cell proliferation. Our results imply that the immunogenicity of melanoma cells is altered when they develop within the unique ocular micro‐environment. Int. J. Cancer 73:470–478, 1997.

Corneal graft survival and intraocular pressure control after penetrating keratoplasty and glaucoma drainage device implantation

OBJECTIVE To investigate corneal graft survival rates and intraocular pressure (IOP) control in eyes after penetrating keratoplasty (PK) and glaucoma drainage device (GDD) implantation. DESIGN Retrospective, comparative, consecutive case series. PARTICIPANTS All patients who underwent PK and GDD implantation at the Bascom Palmer Eye Institute between January 1, 1993 and October 31, 1998. MAIN OUTCOME MEASURES Graft clarity and IOP control. RESULTS Of the 72 eyes in 72 patients identified, 47 (65%) underwent combined PK and GDD implantation, and 25 (35%) underwent GDD placement after PK (2-30 months after PK; median, 13 months). The GDD type was Baerveldt 350 mm(2) in 57 eyes, Ahmed in 9, Krupin in 2, and other in 4 eyes. The GDD was placed in the anterior chamber in 54 eyes (75%) and in the vitreous cavity in 18 eyes (25%). Preoperative IOP was 11 to 53 mmHg with or without antiglaucoma medications in 16 eyes (30%) with the GDD implanted in the anterior chamber and in 4 eyes (22%) with the GDD placed in the vitreous cavity (P = 0.76). At 1 year after GDD implantation, the graft was clear in 26 eyes (48%) with the GDD in the anterior chamber compared with 15 eyes (83%) with the GDD in the vitreous cavity (P = 0.013). Forty-eight eyes (89%) with the GDD in the anterior chamber and 18 eyes (100%) with the GDD in the vitreous cavity had IOP between 5 and 21 mmHg with or without antiglaucoma medications (P = 0.33). The mean reduction in IOP, 1 year after surgery, was 12 mmHg among eyes with the GDD in the anterior chamber, compared with 17 mmHg among eyes with the GDD in the vitreous cavity (P = 0.13) CONCLUSIONS Corneal graft survival at 1 year is significantly higher among eyes with the GDD implanted in the vitreous cavity compared with those in which the GDD is implanted in the anterior chamber. The IOP was significantly lower at 1 year after surgery compared with before surgery in both groups, and there was no significant difference between the groups in IOP control and amount of IOP reduction. There was no significant difference in corneal graft survival or IOP control between eyes with the GDD implanted concurrently with the PK versus after the PK.