Mean Number Of Ranibizumab Injections Research Articles

LUCENTIS IN THE TREATMENT OF DIABETIC MACULAR EDEMA, TWO-YEAR RESULTS.

To evaluate, on the basis of two-year observations, the effectiveness of intravitreal treatment with Ranibizumab in patients with diabetic macular edema (DME) unresponsive to the previous laser treatment. Cohort and Methods: A retrospective study evaluates 29 eyes of 29 patients with diffuse DME unresponsive to their previous laser treatment. The group of the patients consisted of 16 males (55.1%) and 13 females (44.8%); their mean age was 71.3. The mean duration of diabetes mellitus was 13 years (3-20). 19 patients (65.5%) were treated with insulin, 10 patients (34.4%) were treated with peroral antidiabetics (PAD); the mean HbA1c value was 52 mmol/l. The treatment was started with 3 initial doses of intravitreal injections of Ranibizumab 0.5 mg. There was a one- -month interval between the applications. Subsequent evaluations and administrations of the following injections were made in the pro re nata (PRN) mode; the check-ups were carried out every month during the first year and on average every 3 months in the second year. The monitored parameters: the best corrected visual acuity (BCVA) measured on ETRDS (Early Treatment Diabetic Retinopathy Study) optotypes, the central retinal thickness (CRT). These parameters were monitored prior to the treatment and then in the 3rd, 6th, 9th, 12th, 18th and 24th months. A statistically significant improvement in the mean value of BCVA was detected. From the initial 65.4 ±10.61 letters it improved by 11.2 letters (p.

The randomized ZIPANGU trial of ranibizumab and adjunct laser for macular edema following branch retinal vein occlusion in treatment-na\xefve patients

The ZIPANGU study assessed the efficacy and safety of ranibizumab as a one loading dose + pro re nata (one + PRN) regimen with/without focal/grid laser among treatment-naïve patients suffering from macular edema (ME) following branch retinal vein occlusion (BRVO). ZIPANGU was a phase IV, prospective, randomized, open-label, active-controlled, 12-month, two-arm, multicenter study. Treatment-naïve patients with visual impairment (19–73 letters) caused by ME, defined as central subfield thickness (CSFT) > 300 µm, due to BRVO were randomly assigned to ranibizumab monotherapy (n = 29) or combination therapy (ranibizumab + focal/grid short-pulse laser, n = 30). The primary endpoint was the number of ranibizumab injections. Secondary endpoints were mean changes in best-corrected visual acuity (BCVA) and CSFT, and safety. There were no statistically significant differences in the mean number of ranibizumab injections between monotherapy (4.3 injections) vs. combination (4.1 injections) therapy, or in CSFT. BCVA improvement in the monotherapy arm (22.0 letters) was better than the combination therapy arm (15.0 letters) (p = 0.035). Overall, both regimens appeared to be safe and well tolerated. One + PRN ranibizumab is safe and efficacious in treatment-naïve patients with ME secondary to BRVO. A conjunctive laser treatment did not lead to better functional outcomes or fewer ranibizumab injections.

Functional versus functional and anatomical criteria-guided ranibizumab treatment in patients with neovascular age-related macular degeneration \u2013 results from the randomized, phase IIIb OCTAVE study

BackgroundTo evaluate the efficacy and safety of two individualized ranibizumab retreatment schemes in neovascular age-related macular degeneration.MethodsPatients (N = 671) were randomized (1:1) to receive three initial monthly ranibizumab 0.5 mg injections, then retreatment guided by either best-corrected visual acuity (BCVA) loss (Group I) or BCVA loss and/or signs of disease activity on optical coherence tomography (OCT; Group II). The study was terminated prematurely and the decision to discontinue the study was made by the sponsor. Efficacy analyses were performed on patients who completed 12 months of the originally planned 24-month study. Safety analyses are presented for all safety analyzable patients.ResultsOf 671 randomized patients, 305 completed 12 months of the study. For the 12-month completers, baseline mean (standard deviation) BCVA and reading-center evaluated central subfield thickness (CSFT) were comparable [Group I: 60.9 (13.10) letters and 517.7(201.79) μm; Group II: 60.2 (12.21) letters and 515.3 (198.37) μm]. The change from baseline at Month 12 in BCVA was 6.7 (13.48) letters in Group I and 8.3 (13.53) letters in Group II and the change in CSFT was − 161.3 (163.48) μm and − 175.3 (170.45) μm, respectively. The mean number of ranibizumab injections was 8.2 in Group I and 8.4 in Group II.ConclusionRanibizumab treatment resulted in visual and anatomic gains at 12 months for both retreatment strategies, with a trend in favor of OCT-guided vs BCVA loss guided retreatment. No new safety signals were seen.Trial registrationwww.ClinicalTrials.gov (NCT01780935). Registered 31 January 2013.

Our experience in visual functions' improvement in patiens with “wet” age-related macular degeneration at switching from one anti-VEGF agent to another

Purpose. To assess mean changes in visual acuity, central retinal thickness and macular volume as well as to determine the duration of clinical choroidal neovascularization inactivity after single aflibercept injection in neovascular age-related macular degeneration (nAMD) patients switched from ranibizumab (preliminary date). Methods. Open-label prospective study. The study enrolled 23 patients with nAMD previously treated with ranibizumab.
 Results. Mean age of patients was 70.5 years, 16 were women. Mean number of ranibizumab injections given prior to switching to aflibercept was 8.7. After single aflibercept inravitreal injection mean visual acuity has significantly improved from 0.40 to 0.47 Snellen chart. Mean central retinal thickness has significantly reduced from 323.1 to 246.9 m and mean macular volume has significantly reduced from 7.71 to 6.74 mm3. Duration of choroidal neovascularization (CNV) inactivity was 2.91 months.
 Conclusion. Single aflibercept intravitreal injection has resulted in significant visual gain as well as in significant central retinal thickness (CRT) and macular volume reduction. This provides evidence of aflibecept efficacy in nAMD patients previously treated with anti-VEGF. Duration of CNV inactivity provides clinical data supporting aflibercept injection every 8 weeks in nAMD patients.

ARMS2 A69S polymorphism is associated with the number of ranibizumab injections needed for exudative age-related macular degeneration in a pro re nata regimen during 4 years of follow-up.

To investigate whether single-nucleotide polymorphisms (SNPs) known to be strongly associated with the development of age-related macular degeneration (AMD) have an influence on recurrence rate of choroidal neovascularization (CNV) activity during 4-year ranibizumab treatment for exudative AMD. This prospective study included 103 treatment-naïve patients (103 eyes) that received initially a loading dose of 3 monthly ranibizumab injections and thereafter, were treated according to an as-needed regimen for a 4-year follow-up period. Baseline values, visual outcome, and recurrence rate were examined. CFH Y402H and ARMS2 A69S polymorphisms were determined and their association with lesion recurrence and visual outcome was analyzed using a one-way analysis of variance (ANOVA) with post hoc comparison tested by Fisher's LSD method. Multivariate linear regression analysis was then used to identify factors associated with recurrence rate. The cumulative total mean number of ranibizumab injections at the end of each year of the follow-up was 5.3±1.8, 9.2±2.9, 12.6±4.6, and 15.7±6.1. There was great inter-patient variability. Nineteen eyes (18.5%) did not experience recurrence during the first year, and five (4.8%) still displayed inactive CNV after 4years of follow-up. No significant association was found between the number of injections and mean best corrected visual acuity (BCVA) change or final BCVA at the end of the study period. Genotypes had no influence on baseline characteristics or visual outcome but a significant association was found between the A69S polymorphism and the number of injections needed by the patients. Homozygous for the T risk allele required more retreatments over the 48-month follow-up. The ARMS2 A69S polymorphism was associated with CNV recurrence rate in our patient cohort. Prediction of a greater risk of recurrence could help to design more appropriate follow-up treatment strategies for patients with neovascular AMD.

A Retrospective Analysis of the Real-Life Utilization of Ranibizumab in Patients with Wet Age-Related Macular Degeneration from Portugal.

Anti-vascular endothelial growth factor therapy has revolutionized the treatment of wet age-related macular degeneration;however, it is important to monitor actual use of ranibizumab and related treatment outcomes in routine practice. This was a retrospective, observational study to monitor the 2-year outcomes following ranibizumab treatmentfor wet age-related macular degeneration in Portugal. Patients treated between January 2009 and December 2009 were retrospectivelyevaluated. All decisions were made by the treating physician in accordance with their usual routine clinical practice. The primaryassessment was mean change in visual acuity score using Early Treatment Diabetic Retinopathy Study or Snellen equivalent. A total of 128 patients with wet age-related macular degeneration were analyzed (mean age 79.4 years; mean visual acuityscore 54.2 letters). Mean change in visual acuity score from baseline was -1.6 letters (n = 82) at year one and -5.1 letters (n = 72) atyear two. The mean number of ranibizumab injections was 3.8 (year one) and 1.6 (year two). On average, patients attended 8.6 and 5.0visits and optical coherence tomography was used in 75.0% of patients in year one and in 56.3% of patients in year two, respectively. Despite a relatively high number of visits, including monitoring visits and use of optical coherence tomography - guidedtherapy, few injections were administered and visual acuity was not improved. These findings indicate that as-needed treatment resulted in under-dosing in a real-life setting in Portugal. Such limitationsmay also be related to increasing numbers of patients, resulting in clinic saturation.

Success of Intravitreal Ranibizumab for Myopic Choroidal Neovascularization After 2 Years of Treatment

Purpose: To analyze the anatomical and functional outcomes in patients with choroidal neovascularization (CNV) secondary to pathological myopia (PM). Methods: Retrospective review of the medical records of 40 patients with CNV secondary to PM treated exclusively with intravitreal ranibizumab 0.5 mg and at least 24 months of follow-up. The initial dose comprised 1 or 3 monthly injections followed by a pro re nata regimen. Best-corrected visual acuity (BCVA), central retinal thickness (CRT) measured with spectral domain optical coherence tomography (OCT), and ocular and systemic adverse event were recorded. Results: Mean patient age was 62.5 ± 12.5 years. The mean spherical equivalent refractive error was −12.3 ± 6.9 diopters, and a single intravitreal injection was initially performed in 72.5% of cases. Mean baseline BCVA was 0.33 ± 0.20 logMAR (Snellen equivalent, 20/60), and mean CRT by OCT was 340.65 ± 80 µm. Both BCVA and OCT revealed significant improvement compared to baseline at all established cutoff points ( P < .001). Final BCVA was 0.50 ± 0.3 logMAR (Snellen, 20/40), and final CRT was 255.69 ± 47.7 µm ( P < .001). The mean number of ranibizumab injections was 2.75 ± 1.97. No cases of endophthalmitis or retinal detachments were reported, and no serious adverse systemic events were identified. Conclusion: Excellent anatomical and functional outcomes were obtained after treatment with intravitreal ranibizumab for CNV secondary to PM.

Assessment of Corneal Sensation, Innervation and Retinal Nerve Fiber Layer in Patients Treated with Multiple Intravitreal Ranibizumab Injections.

PurposeTo evaluate the effects of repeated intravitreal ranibizumab injections on corneal sensitivity, corneal sub-basal nerve plexus (SBNP) and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with neovascular age-related macular degeneration (AMD).MethodsSixty-six eyes of 33 patients who had received unilateral repeated intravitreal ranibizumab injections (0.5 mg/0.05 ml) for the treatment of AMD and 25 eyes of 25 healthy subjects were included in the study. Central corneal sensation was measured using the contact Cochet-Bonnet esthesiometer. The laser scanning in vivo corneal confocal microscope was used to determine corneal SBNP parameters. The peripapillary RNFL thickness was assessed with spectral-domain optical coherence tomography. Data obtained from the ranibizumab-injected eyes were compared with those of the fellow non-treated eyes and the eyes of the healthy control subjects.ResultsThe mean number of ranibizumab injections per eye was 8.9±5.0 (range 3–20). There were no statistically significant differences in the central corneal sensitivity threshold and corneal SBNP parameters between the ranibizumab-injected eyes and the fellow untreated eyes or between those with neovascular AMD and the healthy control group (P>0.05 for all). The average peripapillary RNFL thickness of the treated eyes did not differ significantly to the fellow eyes (P = 0.237), and the eyes of healthy control subjects (P = 0.918). There were no significant correlations between the number of ranibizumab injections and any of the study parameters.ConclusionsMultiple intravitreal injections of ranibizumab seem to have no harmful effects on corneal sensitivity, innervation and peripapillary RNFL thickness in patients with AMD.

Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion: Twelve-Month Results of the CRYSTAL Study

To assess the 12-month efficacy and safety profile of an individualized regimen of ranibizumab 0.5mg driven by stabilization criteria in patients with macular edema secondary to central retinal vein occlusion (CRVO). A 24-month, prospective, open-label, single-arm, multicenter study. Three hundred fifty-seven patients. Patients were treated with monthly ranibizumab 0.5-mg injections (minimum of 3 injections) until stable visual acuity (VA) was maintained for 3 consecutive months. Thereafter, ranibizumab 0.5 mg was dosed as needed if monthly monitoring indicated a loss of VA resulting from disease activity. Mean change from baseline at month 12 in best-corrected VA (BCVA; primary end point) and safety over 12 months. The efficacy of this regimen in subgroups categorized by baseline BCVA score, CRVO duration, or presence of macular ischemia (exploratory analysis). At baseline, the mean BCVA was 53.0 letters and mean CRVO duration was 8.9 months (median, 2.4 months). Ranibizumab 0.5-mg treatment resulted in a statistically significant mean gain in BCVA from baseline at month 12 of 12.3 letters (standard deviation [SD], 16.72 letters; P < 0.0001). The mean number of ranibizumab injections up to month 12 was 8.1 (SD, 2.77). At month 12, mean BCVA gains were similar with or without macular ischemia at baseline (11.6 vs. 12.1 letters); the mean BCVA gain was higher with baseline CRVO duration of less than 3 months (13.4 letters) than with a longer duration (≥3-<9 months, 11.1 letters; ≥9 months, 10.9 letters). Patients with lower baseline BCVA had larger mean BCVA gains at month 12 than those with higher baseline BCVA (≤39/40-59/≥60 and 18.0/12.7/8.9 letters, respectively), although the absolute BCVA at month 12 was higher with higher baseline BCVA. No new ocular or nonocular safety events were observed. An individualized dosing regimen of ranibizumab 0.5 mg driven by stabilization criteria for up to 12 months resulted in significant BCVA gain in a broad population of patients with macular edema secondary to CRVO, including those with macular ischemia at baseline. The safety findings were consistent with those reported in previous ranibizumab studies in patients with CRVO.

Ranibizumab and retinal photocoagulation in the treatment of ischemic retinal vein occlusion

Introduction. This investigation was focused on the post-RVO (retinal vein occlusion) macular edema treatment in cases with peripheral retinal ischemia, and on methods to estimate the ischemic area. Aim. To develop an examination and treatment algorithm for patients with chronic macular edema due to ischemic RVO. Material and methods. A prospective non-randomized study included 250 patients with RVO, the mean follow-up was 24.5 ± 6.5 months. Results. The drop-out of retinal capillary perfusion was detected in 175 patients (70 %). Peripheral ischemia was found in 125 cases, that is in 50% of all RVO patients and 71.4 % of all patients with ischemia. The mean number of ranibizumab injections performed after retinal photocoagulation was 2.9 ± 1.4. Patients treated with ranibizumab monotherapy for 24 months received 10.6 ± 2.5 intravitreal injections. Conclusions. The combination of ranibizumab intravitreal injections with retinal photocoagulation in the capillary non-perfusion areas can significantly reduce the number of injections and reduce the amount of neovascular complications.

Neovaskulinės amžinės geltonosios dėmės degeneracijos gydymo ranibizumabu 24 mėnesių morfologiniai ir funkciniai pokyčiai

Key words: ranibizumab, age-related macular degeneration, central macular thickness. Research objective. To evaluate influence of treatment with vascular endothelial growth factor inhibitor, ranibizumab, for best corrected visual acuity and central macular thickness in patients with neovascular age-related macular degeneration. Materials and methods. In this retrospective study were included treatment – naive patients. Intravitreal injections were performed at Lithuanian University of Health Sciences Kaunas Clinics Eye clinic. In this study were analysed the 24-month morphological and functional outcomes of intravitreal ranibizumab injections. Best corrected visual acuity was meassured using the Snellen chart (Landolt’s rings C optotypes). Optical coherence tomography images were obtained using the spectral – domain OCT (NIDEK RS – 3000 Advance (NIDEK CO LTD, Japan). The central thickness measurements were obtained from macular thickness maps using the digital caliper tool. Results. In this study were included 88 patients. Best corrected visual acuity before treatment was 0.36 ± 0.22. The difference between visual acuity before and after first injection was 0.04 ± 0.22 (p = 0.03). Before fifth injection visual acuity was 0.41 ± 0.21, after – 0.46 ± 0.22 (p = 0.05). Central macular thickness before treatment was 297.81 ± 106.04 μm. The difference between central macular thickness before and after first injection was 85.21 ± 113.37 μm (p &amp;lt; 0.001). Before second injection central macular thickness was 273.57 ± 87.49 μm, after – 234.51 ± 58.96 μm (p = 0.002). Before fourth injection central macular thickness was 237.20 ± 40.87 μm, after – 219.10 ± 42.26 μm (p = 0.04). The mean central macular thickness significantly decreased from 298.15 ± 104.78 to 229.08 ± 56.57 (p &amp;lt; 0.001). In 24 month of treatment the average number of ranibizumab injections was 3.61 ± 1.55. Conclusions. Our study’s results showed that over 24 month best corrected visual acuity improvement was statistically significant after first and fifth injection. Baseline compared with last injection, there was not statistically significant difference. Central macular thickness improvement statistically significant was after first, second and fourth injection. There was statistically significant decreased baseline compared with the last injection. The mean number of ranibizumab injections was 3.61 ± 1.55 in 24 month.

Risk Factors for Geographic Atrophy After Intravitreal Ranibizumab Injections for Retinal Angiomatous Proliferation

To describe the risk factors for the development of geographic atrophy (GA) following intravitreal ranibizumab injection treatment for retinal angiomatous proliferation (RAP). Retrospective interventional series. Forty-three eyes (38 South Korean patients) from patients being treated for naïve RAP with intravitreal ranibizumab injection were included in this study. All patients were treated with an initial series of 3 monthly loading injections, followed by further injections as required. Baseline ocular characteristics and lesion features assessed using fluorescein angiography (FA), indocyanine angiography (ICGA), and spectral-domain optical coherence tomography (SD OCT) were evaluated as potential risk factors for GA through 2 years of follow-up. At 2 years follow-up, GA had developed in 16 of 43 eyes (37.2%). The mean number of ranibizumab injections was 7.52 ± 2.11. Using multiple logistic regression, thinning of the subfoveal choroid at baseline (odds ratio [OR], 0.955; 95% confidence interval [CI], 0.929-0.982; P = .002), presence of reticular pseudodrusen (OR, 1.092; 95% CI, 1.017-1.485; P = .039), and presence of GA in the fellow eye at baseline (OR, 1.433; 95% CI, 1.061-1.935; P = .025) were identified as significant risk factors for GA development. GA developed in 37.2% of eyes with RAP during the 24 months following intravitreal ranibizumab injections. Subfoveal choroidal thinning at baseline, the presence of reticular pseudodrusen, and the presence of GA in the fellow eye at baseline were associated with increased risk of GA development after treatment.

Twenty-four-Month Efficacy and Safety of 0.5 mg or 2.0 mg Ranibizumab in Patients with Subfoveal Neovascular Age-Related Macular Degeneration

To evaluate the 24-month efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered monthly or as needed (pro re nata [PRN]) in patients with neovascular age-related macular degeneration (wet AMD). Twenty-four-month, multicenter, randomized, double-masked, active treatment-controlled phase 3 trial. Patients (n = 1098) ≥ 50 years of age with treatment-naïve subfoveal wet AMD. Patients were randomized to receive intravitreal injections of ranibizumab 0.5 mg or 2.0 mg monthly or PRN after 3 monthly loading doses. The primary efficacy end point was the mean change in best-corrected visual acuity (BCVA) from baseline at month 12. Key secondary end points included mean change in BCVA from baseline at month 24, proportion of patients who gained ≥ 15 letters in BCVA, mean number of ranibizumab injections, and mean change in central foveal thickness from baseline over time by spectral-domain optical coherence tomography. Ocular and systemic safety events also were evaluated through month 24. At month 24, the mean change from baseline in BCVA was (letters) +9.1 (0.5 mg monthly), +7.9 (0.5 mg PRN), +8.0 (2.0 mg monthly), and +7.6 (2.0 mg PRN). The change in mean BCVA from month 12 to 24 was (letters) -1.0, -0.3, -1.2, and -1.0, respectively. The proportion of patients who gained ≥ 15 letters from baseline in BCVA at month 24 was 34.5%, 33.1%, 37.6%, and 34.8%, respectively. The mean number of ranibizumab injections through month 24 was 21.4, 13.3, 21.6, and 11.2, respectively; 5.6 and 4.3 mean injections were required in year 2 in the 0.5 mg and 2.0 mg PRN groups, respectively. The average treatment interval in the 0.5 mg PRN group was 9.9 weeks after 3 monthly loading doses, and 93% of these patients did not require monthly dosing. Ocular and systemic safety profiles over 2 years were similar among all 4 treatment groups and were consistent with previous ranibizumab trials in AMD. At month 24, mean BCVA improvements were clinically meaningful and similar among all 4 ranibizumab treatment groups. The 0.5 mg PRN group achieved a mean gain of 7.9 letters at month 24 with an average of 13.3 injections (5.6 injections in year 2). No new safety events were identified over 24 months.

Stereotactic Radiotherapy for Neovascular Age-related Macular Degeneration: 52-Week Safety and Efficacy Results of the INTREPID Study

To determine the safety and efficacy of low-voltage, external-beam, stereotactic radiotherapy (SRT) for patients with neovascular age-related macular degeneration (nvAMD). Randomized, double-masked, sham-controlled, multicenter, clinical trial. Two hundred thirty patients with onset of nvAMD within 3 years who received 3 or more injections of ranibizumab or bevacizumab within the preceding year and who needed continuing ranibizumab or bevacizumab treatment. Participants were randomized 2:1:2:1 to 16 Gy plus pro re nata (PRN) ranibizumab, sham 16 Gy plus PRN ranibizumab, 24 Gy plus PRN ranibizumab, or sham 24 Gy plus PRN ranibizumab, respectively. The primary efficacy end point was the mean number of ranibizumab injections at 52 weeks. Secondary end points were change in mean best-corrected visual acuity (VA), loss of fewer than 15 Early Treatment Diabetic Retinopathy Study letters, gain of 0 or more and 15 or more letters, and change in angiographic total lesion size and choroidal neovascularization (CNV) lesion size. Both the 16-Gy and 24-Gy SRT arms received significantly fewer ranibizumab treatments compared with the sham arms: mean number of treatments, 2.64 (median, 2), 2.43 (median, 2), and 3.74 (median, 3.5), respectively (P = 0.013 and P = 0.004, respectively, vs. sham). Change in mean VA was -0.28, +0.40, and -1.57 letters for the 16-Gy, 24-Gy, and sham arms, respectively. The 16-Gy, 24-Gy, and sham arms lost fewer than 15 letters in 93%, 89%, and 91% of eyes, respectively, with 53%, 57%, and 56% gaining 0 or more letters, respectively, and 4% gaining 15 letters or more in all arms. Mean total angiographic lesion area changed by -1.15 mm(2), +0.49 mm(2), and +0.75 mm(2), respectively; mean CNV lesion area decreased by 0.16 mm(2), 0.18 mm(2), and 0.10 mm(2), respectively. Optical coherence tomography central subfield thickness decreased by 85.90 μm, 70.39 μm, and 33.51 μm, respectively. The number of adverse events (AEs) and number of serious AEs (SAEs) were similar across arms. No AEs were attributed to radiation. No SAEs occurred in the study eye. A single dose of SRT significantly reduces ranibizumab retreatment for patients with nvAMD, with a favorable safety profile at 1 year. Whereas chronic nvAMD typically results in loss of VA over time, SRT is associated with relatively well-preserved VA over 1 year. Proprietary or commercial disclosure may be found after the references.

RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH ADULT-ONSET FOVEOMACULAR VITELLIFORM DYSTROPHY

To evaluate the efficacy of intravitreal injections of ranibizumab for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy. Retrospective case series of 24 eyes affected with choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy treated by intravitreal injections of ranibizumab (0.5 mg/0.05 mL). Best-corrected visual acuity, fundus examination, spectral domain optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine green angiography were performed for the diagnosis of adult-onset foveomacular vitelliform dystrophy and choroidal neovascularization. After initial 3 monthly injections of ranibizumab, patients were followed up monthly and retreated if neovascular activity persisted. Outcome measure was the proportion of patients losing fewer than 3 lines of visual acuity from baseline to 12 months (final visit). At final visit, the mean number of ranibizumab injections was 4.5 ± 1.29. From baseline to final visit, 21 of 24 eyes (87.5%) lost fewer than 3 lines of visual acuity. Mean best-corrected visual acuity did not change significantly from baseline to final visit (0.37 ± 0.2 logarithm of the minimum angle of resolution vs. 0.30 ± 0.25 logarithm of the minimum angle of resolution, respectively; P = 0.115). Mean central macular thickness significantly decreased from baseline to final visit (327 ± 83 μm vs. 260 ± 57 μm, respectively; P = 0.001). In this series, ranibizumab succeeded in stabilizing best-corrected visual acuity in patients with choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy. Ranibizumab seems to be a reasonable therapeutic option in this condition.

Ranibizumab for Edema of the Macula in Diabetes Study

To assess the benefit of increased follow-up and treatment with ranibizumab between months 24 and 36 in the Ranibizumab for Edema of the Macula in Diabetes (READ-2) Study. Prospective, interventional, multicenter follow-up of a randomized clinical trial. Patients who agreed to participate between months 24 and 36 (ranibizumab, 28 patients; laser, 22; and ranibizumab + laser, 24) returned monthly and received ranibizumab, 0.5 mg, if foveal thickness (FTH, center subfield thickness) was 250 μm or greater. Main outcome measures were improvement in best-corrected visual acuity (BCVA) and reduction in FTH between months 24 and 36. Mean improvement from the baseline BCVA in the ranibizumab group was 10.3 letters at month 36 vs 7.2 letters at month 24 (ΔBCVA letters = 3.1, P = .009), and FTH at month 36 was 282 μm vs 352 μm at month 24 (ΔFTH = 70 μm, P = .006). Changes in BCVA and FTH in the laser group (-1.6 letters and -36 μm, respectively) and the ranibizumab + laser group (+2.0 letters and -24 μm) were not statistically significant. The mean number of ranibizumab injections was significantly greater in the ranibizumab group compared with the laser group (5.4 vs 2.3 injections, P = .008) but not compared with the ranibizumab + laser group (3.3, P = .11). More aggressive treatment with ranibizumab during year 3 resulted in a reduction in mean FTH and improvement in BCVA in the ranibizumab group. More extensive focal/grid laser therapy in the other 2 groups may have reduced the need for more frequent ranibizumab injections to control edema. Long-term visual outcomes for treatment of diabetic macular edema with ranibizumab are excellent, but many patients require frequent injections to optimally control edema and maximize vision. clinicaltrials.gov Identifier:NCT00407381

Twelve-Month Efficacy and Safety of 0.5 mg or 2.0 mg Ranibizumab in Patients with Subfoveal Neovascular Age-related Macular Degeneration

To evaluate the 12-month efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered monthly and on an as-needed (PRN) basis in treatment-naïve patients with subfoveal neovascular age-related macular degeneration (wet AMD). A 24-month, phase III, randomized, multicenter, double-masked, dose-response study. Patients aged ≥ 50 years with subfoveal wet AMD. Patients (n = 1098) were randomized to receive ranibizumab 0.5 mg or 2.0 mg intravitreal injections administered monthly or on a PRN basis after 3 monthly loading doses. The primary efficacy end point was the mean change from baseline in best-corrected visual acuity (BCVA) at month 12. Key secondary end points included the mean number of ranibizumab injections, the mean change from baseline in central foveal thickness (CFT) over time, and the proportion of patients who gained ≥ 15 letters of BCVA. Unless otherwise specified, end point analyses were performed using the last-observation-carried-forward method to impute missing data. At month 12, the mean change from baseline in BCVA for the 4 groups was +10.1 letters (0.5 mg monthly), +8.2 letters (0.5 mg PRN), +9.2 letters (2.0 mg monthly), and +8.6 letters (2.0 mg PRN). The proportion of patients who gained ≥ 15 letters from baseline at month 12 in the 4 groups was 34.5%, 30.2%, 36.1%, and 33.0%, respectively. The mean change from baseline in CFT at month 12 in the 4 groups was -172.0 μm, -161.2 μm, -163.3 μm, and -172.4 μm, respectively. The mean number of injections was 7.7 and 6.9 for the 0.5-mg PRN and 2.0-mg PRN groups, respectively. Ocular and systemic safety profiles were consistent with previous ranibizumab trials in AMD and comparable between groups. At month 12, the ranibizumab 2.0 mg monthly group did not meet the prespecified superiority comparison and the ranibizumab 0.5 mg and 2.0 mg PRN groups did not meet the prespecified noninferiority (NI) comparison. However, all treatment groups demonstrated clinically meaningful visual improvement (+8.2 to +10.1 letters) and improved anatomic outcomes, with the PRN groups requiring approximately 4 fewer injections (6.9-7.7) than the monthly groups (11.2-11.3). No new safety events were observed despite a 4-fold dose escalation in the study. The pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvasculaR age-related macular degeneration (HARBOR) study confirmed that ranibizumab 0.5 mg dosed monthly provides optimum results in patients with wet AMD. Proprietary or commercial disclosure may be found after the references.

TOPICAL BROMFENAC AS AN ADJUNCTIVE TREATMENT WITH INTRAVITREAL RANIBIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION

Intravitreal injection of ranibizumab is highly effective for wet age-related macular degeneration. Its limitation is that most patients require repeated intravitreal injections to achieve and maintain the visual gain. We assessed the effectiveness of adjunctive topical bromfenac, a nonsteroidal antiinflammatory drug, with ranibizumab. Patients with wet age-related macular degeneration with lesions smaller than 2 disk diameters were randomized 2:3 to adjunctive topical bromfenac (n = 16) or sham (n = 22) and a 0.5-mg ranibizumab injection in a double-masked fashion. Subjects were examined monthly, and ranibizumab was injected as needed from baseline. The primary endpoint was the comparison of the number of ranibizumab injections over 6 months. The visual and anatomic responses also were compared. The mean number of ranibizumab injections over 6 months was 2.2 in the bromfenac group and 3.2 in the sham, a difference that reached significance (P = 0.0274). The changes in visual acuity did not differ significantly (P = 0.3141) although the central retinal thickness was tended to decrease more in bromfenac group (P = 0.0604). Multivariate analysis showed that topical bromfenac is significantly associated with fewer ranibizumab injections. Topical bromfenac might reduce the frequency of ranibizumab over 6 months in eyes with relatively small age-related macular degeneration lesions.

Combination therapy with low-dose transpupillary thermotherapy and intravitreal ranibizumab for neovascular age-related macular degeneration: a 24-month prospective randomised clinical study

AimTo compare the effect of combined low-dose transpupillary thermotherapy (TTT) and intravitreal ranibizumab with sham TTT and intravitreal ranibizumab in patients with neovascular age-related macular degeneration (AMD).MethodsA 24-month, double-masked, randomised,...

A Pilot Study on the Combination Treatment of Reduced-Fluence Photodynamic Therapy, Intravitreal Ranibizumab, Intravitreal Dexamethasone and Oral Minocycline for Neovascular Age-Related Macular Degeneration

Aim: To assess the safety and efficacy of the combined treatment of reduced-fluence verteporfin photodynamic therapy (PDT), intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for choroidal neovascularisa- tion (CNV) secondary to age-related macular degeneration (AMD). Methods: Nineteen patients with subfoveal CNV secondary to AMD were recruited into the trial. All study eyes (n = 19) received a single cycle of reduced-fluence (25 mJ/cm²) PDT with verteporfin followed by an intravitreal injection of ranibizumab 0.3 mg/0.05 ml and dexamethasone 200 µg at baseline. Oral minocycline 100 mg daily was started the following day and continued for 3 months. Patients were followed up monthly for 12 months. Repeat intravitreal ranibizumab was given if best-corrected visual acuity (BCVA) deteriorated by >5 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or central retinal thickness (CRT) on ocular coherence tomography increased >100 µm. Results: Eighteen patients completed the 12-month study. Stable vision (loss of ≤15 ETDRS letters) was maintained in 89% eyes (16/18). The mean change in BCVA was –5.0 ± 10.5 ETDRS letters. The mean number of ranibizumab injections was 3.4 (range 2–6). The mean reduction in the CRT was 66.3 µm (±75). Conclusion: This open-label clinical trial has demonstrated the safety in terms of adverse effects and maintenance of stable vision of combination treatment with verteporfin, ranibizumab, dexamethasone and minocycline in exudative AMD. However, the outcomes with reduced-fluence PDT combination therapy does not differ significantly with outcomes of clinical trials on combination treatment with standard dose PDT and intravitreal ranibizumab in neovascular AMD.