Long-Term Efficacy of a Treat-and-Extend Regimen with Ranibizumab in Patients with Neovascular Age-Related Macular Disease: An Open-Label 12-Month Extension to the CANTREAT Study.

INTRODUCTION: The objective of this study is to assess the long-term effectiveness of a treat-and-extend (T&E) anti-vascular endothelial growth factor regimen in patients with neovascular age-related macular degeneration who remain on T&E and those switched from once-monthly (OM) dosing to T&E (OM-T&E). METHODS: In this 12-month extension of the 2-year CANTREAT study, patients received intravitreal ranibizumab 0.5 mg in a T&E regimen. Main outcome measures included mean change in best-corrected visual acuity (BCVA) from baseline and from month 24 to month 36; percentages of patients who gained ≥5, ≥10, or ≥15 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters or lost ≥5, ≥10, or ≥15 letters from baseline and from month 24 to month 36; and number of injections administered from baseline and from month 24 to month 36 for both groups. RESULTS: Of the 139 patients (73 T&E, 66 OM-T&E) in the extension, 121 (68 T&E, 53 OM-T&E) completed 36 months. Mean (standard deviation [SD]) BCVA changes from baseline to the extension last visit (month 33-36) were +6.6 (11.4) letters in the T&E group and +4.8 (14.3) letters in the OM-T&E group, representing maintenance of 24-month gains. The mean (SD) numbers of injections during the extension were 7.3 (2.7) for T&E and 7.1 (2.8) for OM-T&E. DISCUSSION/CONCLUSION: These findings suggest that after 36 months of treatment, the mean BCVA improvement achieved at 24 months is maintained for both the patients exclusively treated with the T&E regimen and those that switched to T&E after 24 months in the OM regimen.

Canadian Treat-and-Extend Analysis Trial with Ranibizumab in Patients with Neovascular Age-Related Macular Disease: One-Year Results of the Randomized Canadian Treat-and-Extend Analysis Trial with Ranibizumab Study.

PURPOSE: To compare the efficacy of ranibizumab using a treat-and-extend (T&E) regimen with monthly dosing in treatment-naive patients with neovascular age-related macular degeneration (nAMD). DESIGN: Prospective, randomized, open-label, multicenter, noninferiority, postauthorization study. PARTICIPANTS: Treatment-naive patients with choroidal neovascularization secondary to AMD. METHODS: Patients with nAMD were randomized 1:1 to receive intravitreal ranibizumab at a dose of 0.5 mg in either a T&E or monthly dosing regimen. The noninferiority of T&E compared with the monthly dosing regimen was to be shown using a margin of 5 letters in best-corrected visual acuity (BCVA) improvement. MAIN OUTCOME MEASURES: Mean change in BCVA in Early Treatment Diabetic Retinopathy Study letters from baseline to month 12. RESULTS: Baseline and 12-month visual acuity data are available for 526 patients (T&E, n = 268; monthly, n = 258). At baseline, mean age was 78.8 years (standard deviation [SD], 7.8 years), 60.3% were women, and 94.3% were white. No significant between-group baseline differences were observed. The primary outcome of noninferiority regarding visual acuity was met with mean BCVA improvement of 8.4 letters (SD, 11.9 letters) and 6.0 letters (SD, 11.9 letters; P = 0.017) in the T&E and monthly regimens, respectively, with a between-group mean difference of 2.38 letters (95% confidence interval, 0.32-4.45 letters). Per protocol, a secondary analysis was performed to test for superiority of number of injections received up to month 12. This analysis demonstrated significantly fewer injections with T&E versus monthly dosing (9.4 and 11.8 injections, respectively), with a mean difference of -2.46 injections (95% confidence interval, -2.68 to -2.23 injections). CONCLUSIONS: The 12-month results of this 2-year study demonstrated that regarding visual outcomes, the T&E regimen was noninferior to a monthly dosing regimen. Similar visual outcomes in the T&E group as in the monthly dosing group were achieved with significantly fewer injections.

CORRELATION OF VISUAL ACUITY WITH FIBROTIC SCAR LOCATION IN TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION EYES.

PURPOSE: To determine whether the optical coherence tomography location of a subfoveal fibrovascular scar is correlated with visual outcome in eyes successfully treated with antivascular endothelial growth factor agents for neovascular age-related macular degeneration. METHODS: Fifty-six eyes from 56 patients with a subfoveal disciform scar after antivascular endothelial growth factor treatment were included. The initial and final visual acuity, fluorescein angiography, and spectral domain optical coherence tomography scar characteristics were retrospectively reviewed. RESULTS: Thirty-five of 56 eyes (62.5%) were classified as having entirely subretinal pigment epithelial (sub-RPE) scars, and 21 eyes (37.5%) had subretinal component scars. Mean initial visual acuity was similar between sub-RPE and subretinal scars (20/100 vs. 20/125, P = 0.517); mean final visual acuity was better in the sub-RPE scar group (20/60 vs. 20/200, P = 0.001). Eyes with sub-RPE scar had better preservation of the external limiting membrane, ellipsoid layer, and retinal thickness (P < 0.001, P = 0.017, P = 0.004, respectively) than subretinal component scar eyes. There was no difference between the groups in scar thickness or scar area (P = 0.707, P = 0.186, respectively). CONCLUSION: Sub-RPE location of subfoveal scarring in eyes treated for neovascular age-related macular degeneration is associated with better preservation of outer retinal structures and better vision, when compared with a subretinal scar.

DELAYED-ONSET STREPTOCOCCUS INTERMEDIUS ENDOPHTHALMITIS FOLLOWING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INTRAVITREAL INJECTION.

PURPOSE: Endophthalmitis following intravitreal anti-vascular endothelial growth factor injections is frequently caused by Streptococcus viridans organisms and tends to be aggressive. Herein, we present a case of postinjection Streptococcus viridans endophthalmitis presenting in an atypically delayed fashion with good visual outcome. METHODS: Single clinical case report. RESULTS: A 91-year-old woman treated with aflibercept for exudative age-related macular degeneration of the left eye presented to the emergency department with mild pain and visual acuity decline to counting fingers, pigmented anterior chamber cells and vitreous haze 7 weeks after her most recent intravitreal injection. She had no symptoms of systemic infection. The presumptive diagnosis initially was vitreous hemorrhage. Over 10 days of observation, she developed worsening pain and vitritis suggestive of endophthalmitis, leading us to perform vitrectomy with intravitreal vancomycin and ceftazidime. Vitreous biopsy was culture positive for Streptococcus intermedius , a type of viridans streptococcus typically associated with head and neck abscesses. The infection resolved and the patient's visual acuity returned to her baseline of 20/100, with no recurrence of infection after 4 months of follow-up. CONCLUSSION: The virulence of viridans streptococci capable of producing postinjection endophthalmitis may vary widely. Infection ought to be suspected even in cases of delayed-onset intraocular inflammation.

Human Amniotic Membrane Plug for Chronic or Persistent Macular Holes.

PURPOSE: To report on the use of human amniotic membrane for macular holes at 2 Canadian tertiary care centers. DESIGN: Retrospective cohort study. SUBJECTS: Twenty-two patients with persistent or chronic macular holes. METHODS: Macular hole surgery was performed by 3 vitreoretinal surgeons. MAIN OUTCOME MEASURES: Macular hole closure with complete plugging by human amniotic membrane on spectral-domain OCT. RESULTS: The closure rate was 91% (20 of 22; median follow-up, 7 months), with no statistically significant visual acuity change overall. Complications included subretinal silicone oil (5%), choroidal neovascularization (5%), atrophy (5%), and cystoid macular edema (9%). CONCLUSIONS: Anatomical success with limited visual recovery was observed.

Efficacy of a Treat-and-Extend Regimen With Ranibizumab in Patients With Neovascular Age-Related Macular Disease: A Randomized Clinical Trial.

Importance: Although the Canadian Treat-and-Extend Analysis Trial With Ranibizumab in Patients With Neovascular Age-Related Macular Disease (CANTREAT) reported herein and the Treat and Extend study provided data to show noninferiority of treat-and-extend (T&E) at 12 months, to date there are few data on 24-month T&E trials compared with monthly dosing. Objective: To compare the efficacy of ranibizumab using a T&E regimen to monthly dosing in treatment-naive patients with neovascular age-related macular degeneration (nAMD) after 24 months. Design, Setting, and Participants: A randomized, open-label, multicenter, noninferiority intention-to-treat trial with a margin of -5 letters in best-corrected visual acuity (BCVA) from baseline to 12 months between groups was conducted at 27 treatment centers in Canada. Participants included 580 patients with treatment-naive choroidal neovascularization secondary to AMD. The study was conducted from May 8, 2013, to August 28, 2018, and data analysis was performed between August 29 and September 12, 2018. Interventions: Patients with nAMD were randomized 1:1 to receive intravitreal ranibizumab, 0.5 mg, in either a T&E or monthly dosing regimen. Main Outcomes and Measures: Mean change in BCVA in Early Treatment of Diabetic Retinopathy Study letters from baseline to month 24. Results: Of the 580 randomized patients, 350 were women (60.3%) and 547 were white (94.3%). Mean (SD) age was 78.8 (7.8) years. By the end of month 24, 466 of the 580 randomized patients (80.3%) had completed the study and participants in the T&E arm received a mean of 17.6 injections compared with 23.5 injections for the monthly arm, for a difference of 5.9 injections and visits over 2 years (95% CI, 5.4-6.5; P < .001). The mean (SD) BCVA improvement was not worse with the T&E arm, 6.8 (14.1) letters vs 6.0 (12.6) letters, compared with the monthly arm (difference, 0.9; 95% CI, -1.6 to 3.3; P = .21). There was a gain of 15 or more letters in 25.5% of the T&E group and 23.1% of the monthly treatment group (difference, 2.4%; 95% CI, -6.8% to 11.6%; P = .59) and a loss of 15 or more letters in 6.5% of the T&E group and 5.8% of the monthly treatment group (difference, -0.7%; 95% CI, -9.9% to 8.5%; P = .85). Conclusions and Relevance: These findings suggest that change in vision from baseline is not worse with a T&E compared with a monthly regimen of ranibizumab for nAMD through 24 months, achieving clinically meaningful improvements in BCVA despite fewer injections and visits. Trial Registration: ClinicalTrials.gov identifier: NCT02103738.

Disorganization of Retinal Inner Layers and Ellipsoid Zone Disruption Predict Visual Outcomes in Central Retinal Vein Occlusion.

PURPOSE: To assess the associations and predictive value of spectral-domain (SD) OCT inner and outer retinal structural parameters and visual acuity (VA) outcomes in macular edema (ME) secondary to central retinal vein occlusion (CRVO). DESIGN: Retrospective, longitudinal cohort study. PARTICIPANTS: Eighty-four patients with ME secondary to CRVO receiving pro re nata anti-vascular endothelial growth factor (VEGF) therapy at 3 tertiary-level retina referral centers. METHODS: In all participants, VA, demographic and clinical parameters, and SD OCT images from baseline, 3 months, and 12 months were reviewed. Spectral-domain OCT-based morphologic features in the 1500-µm foveal zone were analyzed by masked graders for disorganization of the retinal inner layers (DRIL), ellipsoid zone (EZ) and external limiting membrane disruption, cone outer segment tip (COST) visibility, cysts, subretinal and intraretinal fluid, and epiretinal membranes. MAIN OUTCOME MEASURES: Spectral-domain OCT-based retinal structural parameters and VA outcomes. RESULTS: In multivariate analyses adjusting for baseline VA, worsening VA over 1 year was associated with 1-year increases in DRIL (point estimate, 0.06 per 100 µm; P < 0.001) and EZ disruption (0.07 per 100 µm; P = 0.023), but decreased COST visibility (-0.09 per 100 µm; P = 0.018). A 3-month increase in DRIL (0.05 per 100 µm; P = 0.003) and EZ disruption (0.10 per 100 µm; P < 0.001) were the only factors predicting VA worsening over 1 year, after controlling for baseline VA. A multivariate model including 3-month evolution in DRIL, EZ disruption, and VA accounted for 86.3% of variability in 1-year VA change. Absolute differences between predicted and actual 1-year VA were within 2 lines in 80.9%. When DRIL increased by 250 µm or more over 3 months, no eyes showed VA improvement of 1 line or more in 1 year. When EZ disruption decreased by 250 µm or more over 3 months, no eyes worsened by 1 line or more over 1 year. CONCLUSIONS: Early recovery over 3 months in both DRIL and EZ parameters are key drivers of 1-year VA outcomes. Predictive models incorporating 3-month changes in DRIL and EZ disruption support their usefulness as potential robust determinants of future VA.