Daniel B. Roth

The 1-year Results of CLEAR-IT 2, a Phase 2 Study of Vascular Endothelial Growth Factor Trap-Eye Dosed As-needed After 12-week Fixed Dosing

OBJECTIVE To evaluate anatomic outcomes and vision, injection frequency, and safety during the as-needed (PRN) treatment phase of a study evaluating a 12-week fixed dosing period followed by PRN dosing to week 52 with vascular endothelial growth factor (VEGF) Trap-Eye for neovascular (wet) age-related macular degeneration (AMD). DESIGN Multicenter, randomized, double-masked trial. PARTICIPANTS We included 159 patients with subfoveal choroidal neovascularization (CNV) secondary to wet AMD. METHODS Patients were randomly assigned to 1 of 5 intravitreal VEGF Trap-Eye treatment groups: 0.5 mg or 2 mg every 4 weeks or 0.5, 2, or 4 mg every 12 weeks during the fixed-dosing period (weeks 1-12). From weeks 16 to 52, patients were evaluated monthly and were retreated PRN with their assigned dose (0.5, 2, or 4 mg). MAIN OUTCOME MEASURES Change in central retinal/lesion thickness (CR/LT), change in total lesion and CNV size, mean change in best-corrected visual acuity (BCVA), proportion of patients with 15-letter loss or gain, time to first PRN injection, reinjection frequency, and safety at week 52. RESULTS The decrease in CR/LT at week 12 versus baseline remained significant at weeks 12 to 52 (-130 μm from baseline at week 52) and CNV size regressed from baseline by 2.21 mm(2) at 48 weeks. After achieving a significant improvement in BCVA during the 12-week, fixed-dosing phase for all groups combined, PRN dosing for 40 weeks maintained improvements in BCVA to 52 weeks (5.3-letter gain; P<0.0001). The most robust improvements and consistent maintenance of visual acuity generally occurred in patients initially dosed with 2 mg every 4 weeks for 12 weeks, demonstrating a gain of 9 letters at 52 weeks. Overall, a mean of 2 injections was administered after the 12-week fixed-dosing phase, and the mean time to first reinjection was 129 days; 19% of patients received no injections and 45% received 1 or 2 injections. Treatment with VEGF Trap-Eye was generally safe and well tolerated, with few ocular or systemic adverse events. CONCLUSIONS PRN dosing with VEGF Trap-Eye at weeks 16-52 maintained the significant anatomic and vision improvements established during the 12-week fixed-dosing phase with a low frequency of reinjections. Repeated dosing with VEGF Trap-Eye was well tolerated over 52 weeks of treatment. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Vitreous Surgery for Chronic Macular Holes

OBJECTIVE The purpose of the study is to compare the results of vitreous surgery for a group of patients with chronic macular holes with a group of patients with acute-onset macular holes undergoing identical surgery. DESIGN A case-control study design was used. PARTICIPANTS The duration of symptoms of visual loss due to macular holes was greater than 1 years duration in 11 eyes in each group consecutively operated on within a few days. INTERVENTION All patients underwent macular hole surgery. MAIN OUTCOME MEASURES Ophthalmoscopic resolution of the macular hole, improvement of 2 lines of visual acuity or greater, improvement in mean and median visual acuity, and rate of 20/40 or greater final visual acuity. RESULTS The hole resolved in 9 of 11 eyes in the chronic group and 10 of 11 eyes in the acute group. The mean (median) preoperative visual acuity was 20/151 (20/200) in the chronic group and 20/139 (20/200) in the acute group. The 3-month mean (median) postoperative visual acuity was 20/85 (20/80) in the chronic group and 20/62 (20/63) in the acute group. The final mean (median) postoperative visual acuity was 20/96 (20/ 100) in the chronic group and 20/48 (20/50) in the acute group (P = 0.022). The mean interval to final follow-up examination was 70 weeks for the chronic group and 44 weeks for the acute group. Five (45%) of 11 eyes with chronic holes and 8 (73%) of 11 eyes in the acute group had a final visual acuity of 2 lines or better than the preoperative visual acuity. Cataract extraction had been performed by the final follow-up examination in 7 chronic eyes (64%) and 2 acute eyes (18%). CONCLUSIONS Chronic macular holes have a similar anatomic success rate, but a poorer visual prognosis than acute holes after macular hole surgery. Vitreous surgery benefits some patients with idiopathic macular holes of greater than 1 years duration.

Incidence of Choroidal Neovascularization in the Fellow Eye in the Comparison of Age-related Macular Degeneration Treatments Trials

OBJECTIVE To assess the influence of drug; dosing regimen; and traditional, nontraditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab. DESIGN Cohort study of patients enrolled in a multicenter, randomized clinical trial. PARTICIPANTS Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). METHODS Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different regimens for dosing over a 2-year period. The genotypes for 4 single nucleotide polymorphisms (SNPs) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. The CATT ophthalmologists examined patients every 4 weeks through 2 years and recorded treatment for CNV in the fellow eye. MAIN OUTCOME MEASURES Development of CNV in the fellow eye. RESULTS Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At 2 years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and in 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference, 4.0%; 95% confidence interval [CI], -1.7% to 9.6%; P = 0.17). The risk ratio for pro re nata dosing relative to monthly dosing was 1.1 (95% CI, 0.8-1.6). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3; P>0.35). CONCLUSIONS Through 2 years, there was no statistically significant difference between ranibizumab and bevacizumab in incidence of CNV in the fellow eye. Genotype on 4 SNPs previously found to be associated with AMD did not affect the risk of CNV in the fellow eye among CATT patients. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

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.

Bilateral blindness as the initial presentation of lymphoma of the sphenoid sinus.

PURPOSE To report a patient with large-cell lymphoma of the sphenoid sinus presenting with bilateral blindness and no other signs or symptoms. METHOD Case report. A previously healthy 5-year-old boy complained of sudden vision loss without other systemic complaints. RESULTS Ophthalmologic examination revealed no light perception bilaterally. The pupils of the patient were fixed at 8 mm without reaction to the brightest light stimulus. Systemic examination was unremarkable, and neuroimaging revealed a large sphenoid tumor extending intracranially. Biopsy of the tumor proved to be large-cell lymphoma. CONCLUSION Large-cell lymphoma affecting children may present initially with blindness, without other systemic symptoms.