The RESTORE Study: Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy for Diabetic Macular Edema

The REVEAL Study: Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy in Asian Patients with Diabetic Macular Edema

AimsTo demonstrate non-inferiority of ranibizumab treat-and-extend (T&E) with/without laser to ranibizumab pro re nata (PRN) for best-corrected visual acuity (BCVA) in patients with diabetic macular oedema (DMO).MethodsA 24-month single-masked study...

Two-Year Safety and Efficacy of Ranibizumab 0.5 mg in Diabetic Macular Edema: Interim Analysis of the RESTORE Extension Study

To assess the efficacy, duration of effect and safety of one intravitreal injection of bevacizumab in diabetic macular oedema (DMO). Bevacizumab (1 mg/0.04 ml) was injected intravitreally into eyes with DMO (29 with and nine without previous treatments). Best corrected visual acuity (BCVA), intraocular pressure and central retinal thickness (CRT) were measured; slit-lamp examination, macular biomicroscopy, optical coherence tomography and fluorescein angiography were performed before and at 2-4, 8 and 12 weeks post-injection. Best corrected VA and CRT were analysed in both groups. In the non-pretreated group, mean BCVA improved from 0.76 +/- 0.33 (baseline) to 0.57 +/- 0.30 and 0.54 +/- 0.27 at 2-4 weeks and 8 weeks post-injection, respectively (p = 0.02, p = 0.014, paired t-test). Mean CRT decreased from 632.4 +/- 196.0 microm (baseline) to 392.3 +/- 113.6 microm and 370.4 +/- 141.7 microm at the same time-points, respectively (p = 0.01, p = 0.01). There was no difference in BCVA or CRT at 12 weeks. In the pretreated group, mean BCVA improved from 0.62 +/- 0.30 (baseline) to 0.53 +/- 0.33 at 2-4 weeks post-injection (p = 0.01), and mean CRT decreased from 583.9 +/- 180.7 microm (baseline) to 404.1 +/- 197.9 microm at 2-4 weeks post-injection (p < 0.001). Mean BCVA was unchanged at 8 weeks and 12 weeks post-injection, although mean CRT remained lower at 8 weeks (p = 0.004). No ocular or systemic side-effects developed during follow-up. One intravitreal injection of bevacizumab for DMO seems to be effective and safe in both eyes that have been treated previously and eyes that have not. The therapeutic effect is temporary and repeat treatment may be needed.

Objectives: To evaluate the efficacy and safety of bevacizumab monotherapy and bevacizumab therapy combined with laser therapy versus laser monotherapy in Mongolian patients with visual impairment due to diabetic macular edema (DME). Methods: One hundred twelve eligible patients, aged ^18 years, with type 1 or 2 diabetes mellitus and best corrected visual acuity (BCVA) in the study eye of 35 to 69 Early Treatment Diabetic Retinopathy Study letters at 4 m (Snellen equivalent: &gt;6/60 or &lt;6/12), and with visual impairment due to center-involved DME were included in the study. Patients were randomized into three treatment groups: (1) intravitreal bevacizumab monotherapy (n = 42), (2) intravitreal bevacizumab combined with laser therapy (n = 35), and (3) laser monotherapy (n = 35). Bevacizumab injections were given for three initial monthly doses and then pro re nata thereafter based on BCVA stability and DME progression. The primary efficacy endpoints were the mean change in BCVA and central retinal subfield thickness from baseline to month 12. Results: Bevacizumab monotherapy and bevacizumab + laser were superior to laser monotherapy in improving the mean change in BCVA letter score from baseline to month 12 (+8.3 and +11.3 vs +1.1 letters; both p &gt;&lt;0.0001). At month 12, a greater proportion of patients gained &gt;10 and &gt;15 letters and had a BCVA letter score &gt;73 (Snellen equivalent: &gt;6/12) with bevacizumab monotherapy (23.8% and 7.1% and 4.8%, respectively) and bevacizumab + laser (57.1% and 28.6% and 14.3%, respectively) versus laser monotherapy (0% and 0% and 0%, respectively). The mean central retinal subfield thickness was significantly reduced from baseline to month 12 with bevacizumab (-124.4 pm) and bevacizumab + laser (-129.0 pm) versus laser (-62.0 pm; both p = 0.002). Conjunctival hemorrhage was the most common ocular event. No endophthalmitis cases occurred. Conclusion: Bevacizumab monotherapy or bevacizumab + laser showed superior BCVA improvements over macular laser treatment alone in Mongolian patients with visual impairment due to DME.

To evaluate the responsiveness of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) in patients with diabetic macular edema using data from the RIDE and RISE trials. Patients were randomized to monthly intravitreal ranibizumab 0.3 mg, 0.5 mg, or sham injections for 2 years. The NEI VFQ-25 was administered at baseline and at Months 6, 12, 18, and 24. The least-squares mean change in NEI VFQ-25 for ≥15 letters gained or lost was derived from analysis of covariance models. The mean improvement in NEI VFQ-25 composite score associated with a ≥15-letter gain in best-corrected visual acuity over 24 months was 9.0 (95% confidence interval, 6.3-11.7) points in RIDE and 7.1 (95% confidence interval, 4.7-9.6) points in RISE. In patients who lost ≥15 letters, the mean worsening in overall NEI VFQ-25 composite score was -6.6 (95% confidence interval, -13.6 to 0.5) in RIDE and -2.7 (95% confidence interval, -8.9 to 3.5) in RISE. This exploratory analysis of data from the RIDE and RISE studies supports the responsiveness of the NEI VFQ-25 to changes in best-corrected visual acuity over time in patients with diabetic macular edema.

To evaluate the efficacy and safety of ranibizumab 0.5mg in Japanese patients with visual impairment due to macular oedema secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) and to support the applicability of the phase III results from Caucasian to Japanese populations. This is a 3-month, open-label, single-arm, multicentre, phase III study. Thirty-one patients (15 BRVO and 16 CRVO) aged ≥18years with a best-corrected visual acuity (BCVA) letter score of 19-73 (BRVO) or 24-73 (CRVO) were included. The primary end-point was the mean average change in BCVA from baseline to month 1 through month 3 after three consecutive monthly intravitreal injections of ranibizumab 0.5mg. Secondary end-points were mean change in BCVA and central subfield thickness (CSFT), categorized BCVA, and safety over 3months. At month 3, the mean average change in BCVA improved substantially from baseline for BRVO (11.3 letters, p=0.001) and CRVO (6.7 letters, p=0.019). The mean BCVA improved (12.8 and 9.1 letters) and the mean CSFT decreased (212.5 and 442.1μm) from baseline to month 3. At month 3, 26.7% (BRVO) and 31.3% (CRVO) of the patients had a gain of ≥15 letters from baseline. Safety findings in this study were similar to those reported in the previous clinical trials. Ranibizumab was effective in improving BCVA and was well tolerated in Japanese patients with BRVO and CRVO. The findings from this study were consistent with those reported in the Caucasian population.

Intravitreal anti-VEGF injections are the current gold standard for treating diabetic macular edema (DME). However, injection practice patterns of retina specialists have varied markedly based on physician discretion. This retrospective study analyzes the impact of injection protocol selection on change in best-corrected visual acuity (BCVA) and central macular thickness (CMT) in 170 eyes treated by 4 retina specialists practicing a pro re nata (PRN) strategy between 2010 and 2020. DME patients received an average of 7.25 injections every 6.24 weeks over 56.6 weeks. There were significant differences between retina specialists in mean number of injections (p = 0.0001) and mean length of treatment (p = 0.0007) but not in mean interval between injections. Over the treatment period, average change in BCVA was −0.053 logMAR, and average change in CMT was −51.1 µm, neither of which had significant differences between retina specialists. BCVA and CMT at initial visit were found to be significantly associated with improved BCVA and CMT over the treatment period (p < 0.001). Number of injections administered and interval between injections were not found to be significant factors affecting change in BCVA or CMT. Despite significant differences in injection dosing regimen, retina specialists achieved similar outcomes in change in BCVA and CMT over the treatment period.

Efficacy and Safety of Ranibizumab in Asian Patients with Branch Retinal Vein Occlusion: Results from the Randomized BLOSSOM Study

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Background: Diabetic macular oedema can occur at any stage of retinopathy and is typically characterized by retinal thickening and leakage of extracellular fluid, which are linked with hypoxia and up regulation of vascular endothelial growth factor (VEGF). Objective: The aim of this study was to compare central macular thickness using optical coherence tomography (OCT) between Ranibizumab 0.5 mg monotherapy vs Ranibizumab 0.5 mg combined with laser based on mean average change in best-corrected visual acuity (BCVA) over 6 months in diabetic macular edema (DME). Patients and methods: The study was carried out on forty eyes of patients aged 30-75 years old, with type 1 or 2 diabetes mellitus and have visual impairment due to DME. The patients were selected from the Outpatient Ophthalmology Clinic of Aswan University Hospital. Results: Visual acuity measured as log MAR values in Group A, when comparing the baseline visual acuity with that at the end of follow-up period, there was a significant improvement in vision. Some patients achieved improvement of two lines at the end of six months. In Group B, there was a significant improvement in vision when comparing the baseline reading with the six months reading with an average gain in visual acuity of two or more lines. The central macular thickness improved in both groups without statistically significant difference between them in the first three months post-injection. However, the combined group achieved the highest reduction in the macular thickness at the end of follow-up period. Conclusion: Ranibizumab monotherapy provided significantly superior benefit over standard-of-care laser in patients with visual impairment due to DME being rapidly improved and sustained BCVA over the 6-month treatment period.

To our knowledge, this is the first randomized clinical trial to compare visual outcomes and injection loads between ranibizumab and aflibercept using an identical treat-and-extend (TE) regimen for neovascular age-related macular degeneration (nAMD). To report the results of the preplanned 12-month interim analysis of 2 predefined secondary efficacy end points of a randomized clinical trial. The Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients (RIVAL) trial was conducted in 24 sites in Australia and included 281 treatment-naive eyes from 281 participants with active choroidal neovascularization secondary to nAMD and a visual acuity letter score of 23 or greater who were recruited between April 11, 2014, and October 31, 2015. A preplanned interim analysis was performed at month 12. Best-corrected visual acuity (BCVA) assessors and the central reading center, which determined treatment intervals, were masked to treatment assignments. Participants were randomized (1:1) to receive intravitreal injections of 0.5 mg of ranibizumab or 2.0 mg of aflibercept. After receiving 3 initial monthly injections, participants entered the TE phase. Mean change in BCVA and the number of injections from baseline to month 12. Of 281 participants, 148 (52.7%) were women and the mean (SD) age was 77.7 (8.1) years. The baseline mean BCVA letter score (approximate Snellen equivalent) was 65.3 (20/50) in the ranibizumab arm and 65.1 (20/50) in the aflibercept arm. One hundred twenty-seven ranibizumab participants (90.1%) and 121 aflibercept participants (88.3%) completed month 12 with a mean (SD [Snellen equivalent]) BCVA letter score of 72.9 (15.5 [20/32]) and 70.5 (14.6 [20/40]), respectively. The mean change in BCVA letter scores from baseline to month 12 was 7.2 (95% CI, 5.5-8.9) for ranibizumab and 4.9 (95% CI, 3.1-6.6) for aflibercept (letter score difference, 2.3; 95% CI, -0.1 to 4.7; P = .06). The mean number of injections from baseline to month 12 was 9.7 in both the ranibizumab (SD, 2.8) and aflibercept (SD, 2.6) arms with a rate ratio of 1.00 (95% CI, 1.0-1.1; P = .86). Our findings suggest that neither aflibercept nor ranibizumab for nAMD are superior to the other regarding the average visual acuity gains and number of injections during 1 year in a TE regimen. Further follow-up to 2 years may determine if advantages of one over the other can be identified. Clinicaltrials.Gov identifier: NCT02130024.

Purpose:To report the 12-month results of laser (treatment G1) versus intravitreal bevacizumab combined with laser (treatment G2) in patients with diffuse diabetic macular edema (DME).Methods:In this single-center randomized independent controlled trial, 32 patients were randomized to G1 (n = 15) or G2 (n = 17). In G1, laser was given at baseline and then pro re nata (PRN). In G2, three intravitreal bevacizumab (1.25 mg) injections were given once every 6 weeks, then laser and then PRN. Analysis was performed by treatment as administered. This study was registered in clinicaltrials.gov as NCT01572350 and EU Clinical Trial Registry as 2009-014654-15.Results:G2 was superior to G1 improving best corrected visual acuity (BCVA) with respect baseline (+8.0 vs + 3.0; p < 0.01). At month 12, a significantly greater proportion of patients had a BCVA letter score >15 and >73 in G2 (3 of 15 (20%) and 8 of 15 (53%), respectively) versus G1 (1 of 17 (6%) and 4 of 18 (23%), respectively). Health-related quality of life, assessed through National Eye Institute Visual Function Questionnaire, at 12 months was statistically indistinguishable between both groups.Conclusion:G2 provided superior visual acuity gains over G1 in patients with visual impairment due to center-involving diffuse DME, associated with significant gains in VFQ-25 scores.

PurposeTo demonstrate the efficacy and safety of ranibizumab 0.5 mg pro re nata (PRN) versus laser photocoagulation for the treatment of Chinese patients with visual impairment due to diabetic macular edema (DME).MethodsREFINE was a phase III, 12-month, double-masked, multicenter, laser-controlled study in patients (aged ≥ 18 years) with DME. Patients were randomized 4:1 to receive either ranibizumab 0.5 mg or laser dosing regimen. Efficacy was evaluated as mean average change in best-corrected visual acuity (BCVA) from Months 1 to 12 versus baseline (primary endpoint), anatomical outcomes, treatment exposure, and safety were also assessed.ResultsRanibizumab was statistically superior (p < 0.001) to laser treatment, with a mean average BCVA gain of 6.8 letters (ranibizumab) over 12 months versus 1.1 letters (laser). At Month 12, mean BCVA gain was 7.8 letters (ranibizumab) and 2.5 letters (laser) from baseline. Patients in the ranibizumab arm received a mean number of 7.9 intravitreal injections, whereas those in the laser arm received a mean of 2.1 treatments. There were no new safety signals.ConclusionRanibizumab 0.5 mg PRN demonstrated a statistically significant and clinically meaningful treatment effect versus laser and was well tolerated in Chinese patients with visual impairment due to DME over 12 months.