Consecutive Monthly Intravitreal Ranibizumab Research Articles

Short-Term Outcomes following “Switching” to Monthly Ranibizumab in Neovascular Age-Related Macular Degeneration Showing Insufficient Response to Bimonthly Aflibercept

Results CRT and logMAR VA were 349.62 ± 223.51 μm and 0.50 ± 0.23 at the baseline and 274.69 ± 148.77 μm and 0.46 ± 0.24, 311.54 ± 192.90 μm and 0.45 ± 0.20 at 1 month after the first and third ranibizumab injections, respectively. The CRT decrease during three ranibizumab injections was statistically significant (38.08 ± 69.52 μm, p=0.033). Change in VA was not statistically significant. The percentage of eyes with SRF was 100% at baseline and 53.8%, 76.9%, and 69.2% one month after each ranibizumab injections. The percentage of eyes with IRF was 38.5% at baseline and 23.1%, 23.1%, and 15.4%, respectively, after switching. Conclusion Switching to monthly ranibizumab in nAMD showing an insufficient response to bimonthly aflibercept led to immediate anatomical improvement. It can be considered in countries where the healthcare insurance system limits the minimum injection interval of aflibercept.

Intravitreal Ranibizumab versus Intravitreal Ranibizumab Combined with Posterior Subtenon Triamcinolone Acetonide in Diabetic Macular Edema

Objectives:This is a retrospective, comparative evaluation of the short-term efficacy and safety of intravitreal ranibizumab (IVR) and IVR combined with posterior subtenon triamcinolone acetonide (STA) in the treatment of diabetic macular oedema (DME).Methods:A total of 79 pseudophakic eyes of 57 patients with DME who underwent IVR injection treatment were examined retrospectively. All of the patients were treatment-naive. In the study group (STA+IVR), consisting of 30 eyes of 39 patients, the STA and IVR were administered in the first treatment session simultaneously, followed by 2 consecutive monthly IVR injections. In the control group (IVR only) comprised 40 eyes of 27 patients, 3 consecutive monthly IVR injections were administered. Patients with serous retinal detachment (SRD) according to optical coherence tomography images were identified in both groups for subgroup analyses. The primary outcome measures were changes in central macular thickness (CMT), best corrected visual acuity (BCVA), and the intraocular pressure (IOP) at 1, 2, and 3 months post-injection.Results:There was no statistically significant difference between the demographic characteristics of the patients’ baseline BCVA and CMT measurements (p>0.05). For the IVR group, the mean pre-treatment CMT and BCVA was 421.20±89.10 μm and 0.42±0.24 logMAR, respectively. After the third injection, the mean was 308.12±59.07 μm and 0.20±0.12 logMAR, respectively. The combined treatment group baseline measurements were 454.50±122.52 μm and 0.54±0.29 logMAR, respectively. After the third injection, the mean was 294.22±50.33 μm and 0.27±0.21 logMAR, respectively. The decrease was statistically significant for both groups (p=0.001). Comparison of the CMT within groups revealed a statistically significant difference in favor of the combined group after the second injection (p=0.017). There was no statistically significant difference in the BCVA gains between groups (p>0.05). Patients with SRD were evaluated as a subgroup, and at the first month, the mean gain in CMT was -71.63±57.98 μm in the control group and -123.61±93.46 μm in the study group (p=0.048). The required anti-glaucomatous treatment was statistically significant in the combined group (p=0.008).Conclusion:Both treatments provided improvement in BCVA and CMT and can be considered functional and anatomically effective treatment options for DME.

THE CORRELATION BETWEEN AQUEOUS VASCULAR ENDOTHELIAL GROWTH FACTOR LEVEL AND CLINICAL ACTIVITY IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

The aim of the current study was to investigate the correlation between the pretreatment aqueous level of vascular endothelial growth factor (VEGF) and clinical activity in neovascular age-related macular degeneration. Patients with neovascular age-related macular degeneration treated by intravitreal ranibizumab injections and followed for 12 months were included in the current study. The treatment regimen consisted of three consecutive monthly intravitreal ranibizumab injections (loading treatment) followed by a pro re nata (PRN) treatment regimen. The aqueous VEGF levels were measured by enzyme-linked immunosorbent assay using aqueous humor samples obtained just before the first intravitreal ranibizumab injections. Sixty-four eyes of 64 patients were included in the current study. The mean number of intravitreal ranibizumab injections during 12 months was 4.6 ± 1.4, and 17 eyes had no recurrence after loading treatment. The mean aqueous VEGF level was significantly higher in eyes with recurrence after loading treatment than in eyes without recurrence (107.6 vs. 83.8 pg/mL, respectively; P = 0.04) and significantly higher in eyes with recurrence within 3 months after loading treatment than in other eyes (114.9 vs. 86.7 pg/mL, respectively; P < 0.01). Pretreatment aqueous VEGF level was significantly correlated with the likelihood of recurrence in neovascular age-related macular degeneration. The measurement of pretreatment aqueous VEGF level may be useful to determine the best treatment options for patients with neovascular age-related macular degeneration.

Dexamethasone implant as an adjuvant therapy to ranibizumab loading dose in persistent diabetic macular edema.

This study evaluates the effectiveness of a single-dose dexamethasone implant (DI) as an auxiliary therapy to continued intravitreal ranibizumab (IVR) treatment in patients with persistent diabetic macular edema (DME). Twenty-five pseudophakic eyes of 25 patients with DME who underwent a single injection of DI as an adjuvant therapy following an IVR loading dose were examined retrospectively. All patients were treatment naive and had a poor response to a loading dose of three consecutive monthly IVR injections. IVR treatments were continued pro re nata after the DI. The main outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 1, 3, 6 and 8 months post-DI treatment. After the IVR loading dose, the mean BCVA and CMT were 0.9 ± 0.6LogMAR and 478.2 ± 107.8µm, respectively. One month after the DI, the mean BCVA and CMT had improved to 0.6 ± 0.4LogMAR (p = 0.005) and 313.8 ± 62.7µm (p < 0.001), respectively. This improvement was maintained with mean 0.8 ± 0.8 IVR injections throughout the follow-up period. The final mean BCVA and CMT were 0.5 ± 0.5LogMAR and 298.4 ± 71.5µm. Subgroup analyses revealed that different DME types did not have any effect on CMT or BCVA improvement (p = 0.188, p = 0.136; respectively). Adding DI results in rapid anatomical and visual improvement in patients who respond poorly to an IVR loading dose. Improvements may be maintained with additional IVR in follow-up.

Inner nuclear layer cystoid spaces are a poor prognostic factor in typical age-related macular degeneration and polypoidal choroidal vasculopathy.

To investigate predictive factors for changes in best-corrected visual acuity (BCVA) at 24months after intravitreal ranibizumab (IVR) for neovascular age-related macular degeneration (nAMD). This retrospective study included 55 eyes of 55 consecutive patients (32 men and 23 women) with nAMD who received three consecutive monthly IVR injections and were re-treated as needed over a 24-month period. We used the mean changes in logarithm of the minimal angle of resolution (logMAR) BCVA at 24months as the dependent variable in regression analysis. The presence of intraretinal cystoid spaces in the inner nuclear layer (INLc, P=0.004) and baseline subfoveal choroidal thickness (SFCT, P=0.013) predicted BCVA changes from baseline to 24months. The presence of INLc and thinning of SFCT were associated with decreased BCVA at 24months. Thirty-five eyes without INLc showed improved logMAR BCVA, from 0.550±0.273 to 0.368±0.274 (P=0.045); however, 20 eyes with INLc showed decreased logMAR BCVA, from 0.708±0.347 to 0.971±0.523 (P<0.001) through the 24-month follow-up. The mean number of IVR injections during the follow-up period was 8.74±4.76 in eyes without INLc and 10.63±4.72 in eyes with INLc, without a statistically significant difference (P=0.144). Eyes with INLc or thinned SFCT showed worse visual outcomes compared with eyes without the INLc or with thick SFCT. Furthermore, eyes without INLc showed improved BCVA; however, eyes with INLc showed decreased BCVA with an as-needed regimen.

Prognostic factors of short-term outcomes of intravitreal ranibizumab in diabetic macular edema.

To evaluate the prognostic factors for short-term visual and anatomical improvement of intravitreal ranibizumab (IVR) for diabetic macular edema (DME). Fifty-one eyes from 35 patients that received three consecutive monthly IVR for DME with moderate visual loss were retrospectively recruited; all cases had their baseline best-corrected visual acuity (BCVA) between 20/400 and 20/40. BCVA and central subfield thickness (CST) at baseline and month 3 were collected. Linear mixed models were used to evaluate the prognostic factors for visual and anatomical improvement at month 3. Younger age, poorer baseline BCVA and proliferative diabetic retinopathy (PDR) were correlated with better visual improvement at month 3 (P=0.002, 0.0001 and 0.007, respectively). Thicker CST and the presence of subretinal fluid at baseline were correlated with a greater reduction in CST (P<0.0001 and P=0.018, respectively). The presence of epiretinal membrane or previous posterior subtenon injection of triamcinolone acetonide (PSTA) were associated with a smaller reduction in CST (P=0.029 and 0.018, respectively), but had no significant effects in visual improvement at month 3 (P>0.05 for both). For eyes with DME and moderate visual loss, those with younger age, poorer baseline BCVA or PDR tend to have better visual improvement after three consecutive monthly IVR. Epiretinal membrane or previous PSTA result in less resolution of CST, but do not significantly affect visual improvement.

Systemic Associations with Residual Subretinal Fluid after Ranibizumab in Diabetic Macular Edema.

Purpose To investigate the impact of systemic diseases on the occurrence of subretinal fluid (SRF) in diabetic macular edema (DME) and prognostic factors for residual SRF following three consecutive monthly intravitreal ranibizumab. Methods Ninety-seven eyes from 68 patients with DME who completed 3 consecutive monthly injections of ranibizumab were enrolled. Systemic parameters mainly included chronic kidney disease (CKD), hypertension, HbA1c, and insulin dependence. Renal parameters for CKD were serum creatinine, estimated glomerular filtration rate (eGFR), and serum albumin. Ocular factors were baseline central macular thickness (CMT), severity of diabetic retinopathy (DR), and status of panretinal photocoagulation (PRP). Results Chronic kidney disease had significant correlation with baseline SRF (R = 0.397, p < 0.001 after partial correlation with adjustment for age and DR severity). As for CKD, lower serum albumin, but not eGFR or serum creatinine, was associated with baseline presence of SRF (p = 0.026, p = 0.08 and p = 0.53, resp., after adjustment for age and DR severity). Overall, lower eGFR and lower HbA1c values, contrary to popular belief, predicted the presence of residual SRF following intravitreal injections (p = 0.016 and p < 0.001, resp.). Conclusions Tight sugar control and poorer baseline kidney function may slow the resorption of SRF after anti-VEGF injections in patients with DME in the short term.

Two-year results of combined intravitreal ranibizumab and photodynamic therapy for retinal angiomatous proliferation.

The aim of this study was clarify the efficacy of combination therapy of intravitreal ranibizumab (IVR) injections and photodynamic therapy (PDT) in patients with symptomatic retinal angiomatous proliferation (RAP) over 24 months. We retrospectively reviewed 37 naïve eyes of 31 patients treated with three consecutive monthly IVR injections (0.5 mg/0.05 ml) and PDT and followed for at least 24 months. The mean logarithm of the minimum angle of resolution best-corrected visual acuity levels improved significantly (P < 0.0001) from 0.63 at baseline to 0.39 at 24 months. Geographic atrophy (GA) involving the fovea developed in nine (24%) eyes, with a significant (P = 0.036) decrease in VA at 24 months and a high (100%) prevalence of reticular pseudodrusen (RPD) at baseline. Complete occlusion of the retinal–retinal anastomosis seen in 35 eyes was achieved in 33 eyes at month 24. The central retinal thickness decreased significantly (P < 0.0001) from 415 to 129 μm at 24 months. The mean number of treatments during 24 months was 2.5 PDT and 5.5 IVR injections. Combination therapy comprising IVR injections and PDT is generally effective in maintaining or improving VA and retinal morphology within 2 years in eyes with RAP, except for eyes with baseline RPD, which are likely to develop GA in the fovea resulting in reduced VA.

Comparison of intravitreal ranibizumab between phakic and pseudophakic neovascular age-related macular degeneration patients: Two-year results

Background and objectiveTo compare the efficacy of intravitreal ranibizumab (IVR) for the treatment of neovascular age-related macular degeneration (nAMD) between phakic and pseudophakic eyes after a follow-up of two years. Materials and methodsData were analyzed retrospectively. The newly diagnosed and treatment naïve nAMD patients were included in the study. The patients were divided into two subgroups: phakic group, and pseudophakic. All patients received 3 consecutive monthly IVR injections, and then the treatment was continued on an as-needed regimen. Patients were examined monthly, and the data at the baseline, at month 6, 12, 18, and 24 were evaluated. The changes in best corrected visual acuity (BCVA), central retinal thickness (CRT), and the number of injections were compared between the two groups. ResultsThe study included 92 eyes of 87 patients (58 phakic, 34 pseudophakic). Mean logarithm of the minimal angle of resolution (LogMAR) VA at the baseline, and at month 6, 12, 18, and 24 was 0.89, 0.74, 0.75, 0.73, and 0.75, in the phakic group; and 0.79, 0.71, 0.66, 0.70, and 0.70 in the pseudophakic group, respectively. The change in mean BCVA from the baseline to month 6, 12, 18, and 24 was not statistically different between the two groups (p=0.4, p=0.9, p=0.5, p=0.6, respectively). Mean injection number at month 24 was 7.9 and 8.1 in the phakic and pseudophakic group, respectively (p=0.7). ConclusionIntravitreal ranibizumab treatment on an as-needed treatment regimen is effective in preserving vision and improving central retinal thickness in both the phakic and pseudophakic group of nAMD patients. The functional and anatomical outcomes of the treatment, and the number of injections were similar in the phakic and pseudophakic nAMD patients after a follow-up time of 24months.

Optical coherence tomography-based ranibizumab monotherapy for retinal angiomatous proliferation in Korean patients.

To evaluate the visual outcome of optical coherence tomography-based ranibizumab monotherapy in Korean patients with retinal angiomatous proliferation and identify prognostic factors of visual outcome. A prospective single-arm clinical study of 31 retinal angiomatous proliferation patients who underwent 3 consecutive monthly intravitreal ranibizumab injections was conducted. Additional treatment was given based on optical coherence tomography at monthly follow-ups over 24 months. Best-corrected visual acuity improved from 48.7 ± 19.3 to 56.3 ± 19.1 letters at 24 months (P = 0.010). Total cumulative numbers of injection were 5.5 ± 2.2 and 7.7 ± 3.4 times at 12 and 24 months, respectively. Older age, larger choroidal neovascularization size, and poor initial best-corrected visual acuity were associated with poor visual outcome. Final best-corrected visual acuity was significantly worse with Stage 3 disease (70.4 ± 5.1, 62.3 ± 11.6, 46.2 ± 22.3 letters improved in each stage; P = 0.015). Among factors associated with poor visual outcome, only the stage of retinal angiomatous proliferation remained statistically significant on multiple linear regression analysis (P = 0.006). Although baseline best-corrected visual acuity was similar, Stage 3 patients exhibited limited visual improvement despite anatomical improvement, and more recurrences requiring more injections. Retinal angiomatous proliferation may be successfully managed with ranibizumab monotherapy in Korean patients, with the number of treatments required comparable to other forms of neovascular age-related macular degeneration. However, visual improvement was limited in late-stage RAP.

Switching to intravitreal aflibercept injection for polypoidal choroidal vasculopathy refractory to ranibizumab.

To clarify the efficacy of switching to intravitreal aflibercept injection to treat polypoidal choroidal vasculopathy refractory to ranibizumab. In this retrospective study, 43 eyes of 42 patients (mean age, 76.5 years) with polypoidal choroidal vasculopathy treated with aflibercept (2 mg/0.05 mL) were reviewed. A treatment history of 3 consecutive monthly intravitreal injections of ranibizumab as an induction phase followed by a pro re nata maintenance phase over 12 months was seen for all patients. All patients who were refractory to ranibizumab (defined as having persist subretinal or intraretinal fluid by optical coherence tomography and unchanged or decreased visual acuity compared with the time of the first ranibizumab injection, despite receiving the last 3 consecutive monthly intravitreal ranibizumab injections after 12 months). The mean logarithm of the minimum angle of resolution best-corrected visual acuity levels (Snellen equivalent) improved significantly (P = 0.0074) from 0.38 (20/48) at baseline to 0.34 (20/43) 3 months after switching to aflibercept (Month 3) (mean best-corrected visual acuity improvement, 0.47 line). The central retinal thickness decreased significantly (P < 0.0001) from 245 μm at baseline to 131 μm at Month 3. Of 30 eyes with polypoidal lesions at baseline, the polypoidal lesions regressed completely in 15 eyes (50%) at Month 3. Administering intravitreal aflibercept injection for patients with polypoidal choroidal vasculopathy refractory to ranibizumab maintained or improved visual acuity and reduced or eliminated exudative lesions and occluding polypoidal lesions without adverse events with short-term follow-up.

Fibrovascular pigment epithelial detachment is a risk factor for long-term visual decay in neovascular age-related macular degeneretion.

The individual outcome of anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration is variable. To investigate the prognostic value of spectral domain optical coherence tomography structures for best-corrected visual acuity (BCVA) outcome, volumetric analysis of spectral domain optical coherence tomography structures was performed in neovascular age-related macular degeneration correlated with BCVA after 24 months. At the Department of Ophthalmology, University of Cologne, Germany, 75 patients with neovascular age-related macular degeneration were analyzed prospectively over 24 months. Patients received three initial consecutive monthly intravitreal ranibizumab injections followed by monthly spectral domain optical coherence tomography controls. Therapy was continued as a pro re nata regimen. Volumetric analysis of spectral domain optical coherence tomography images was performed using commercially available software (3D-Doctor). Subretinal tissue, subretinal fluid, serous pigment epithelial detachment, and fibrovascular pigment epithelial detachment (FPED) were identified. By contrast to all other structures, FPED did not respond to ranibizumab therapy. Volume of FPED at baseline and after the loading phase correlated most with impaired BCVA after 24 months (r = -0.0215, P = 0.9263 [subretinal tissue]; r = -0.3120, P = 0.0216 [subretinal fluid]; r = -0.0757, P = 0.6470 [serous pigment epithelial detachment]; r = -0.4182, P = 0.0111 (FPED baseline); r = -0.4768; P = 0.0002 [FPED after loading phase]). Of all identified structures, FPED was most deleterious for BCVA after 24 months. The knowledge about possible BCVA course can influence the decision for more intense treatment regimens.

COMPARISON OF INTRAVITREAL RANIBIZUMAB IN PHAKIC AND PSEUDOPHAKIC NEOVASCULAR AGE-RELATED MACULAR DEGENERATION PATIENTS WITH GOOD BASELINE VISUAL ACUITY

To compare the efficacy of intravitreal ranibizumab for the treatment of neovascular age-related macular degeneration between phakic and pseudophakic eyes with visual acuity ≥0.5 Snellen equivalent. This was a retrospective, interventional, comparative study. The newly diagnosed neovascular age-related macular degeneration patients with visual acuity of ≥0.5 Snellen equivalent were included in the study. The patients were divided into two subgroups: phakic group and pseudophakic. All patients received three consecutive monthly intravitreal ranibizumab injections, and then, reinjection was performed as needed. Patients were examined monthly, and the data at the baseline, at Months 3, 6, 9, and 12 were evaluated. The changes in visual acuity, central retinal thickness, and the number of injections were compared between the groups. The study included 96 eyes of 96 patients (56 phakic and 40 pseudophakic). Mean Snellen visual acuity at the baseline, at Months 3, 6, 9, and 12 was 0.56 ± 0.09, 0.64 ± 0.15, 0.62 ± 0.21, 0.60 ± 0.22, and 0.61 ± 0.20 for the phakic group; and 0.55 ± 0.08, 0.63 ± 0.14, 0.60 ± 0.13, 0.58 ± 0.14, and 0.59 ± 0.13 for the pseudophakic group, respectively. The change in mean visual acuity and central retinal thickness at the study visits was not statistically significant between the 2 groups (P > 0.05 for all). Mean injection number at Month 12 was 4.5 and 4.3 in the phakic and pseudophakic group, respectively (P = 0.5). Intravitreal ranibizumab treatment on an as-needed treatment regimen is effective in preserving vision and improving central retinal thickness in both the phakic and pseudophakic group of neovascular age-related macular degeneration patients with good baseline visual acuity.

Three Consecutive Monthly Intravitreal Ranibizumab for Choroidal Neovascularization in Central Serous Choriorethinopathy: A Case Report

Purpose: The author report the result of three consecutive monthly intravitreal ranibizumab injection for choroidal neovascularization (CNV) after bevacizumab injection for chronic central serous rethinopathy (CSR). Methods: A 48 year old man with chronic CSR was treated with intravitreal single dose 2.5 mg bevacizumab. One year after CNV was occurred, and three consecutive monthly intravitreal ranibizumab injections were performed. Results: Four weeks later the first ranibizumab dose, best corrected visual acuity was improved 20/80 to 20/20 and remained stable within one year. Conclusion: Repeat intravitreal ranibizumab injection in CNV after bevacizumab injection for chronic CSR appeared to be an effective treatment option.

The 12-Month Outcome of Three Consecutive Monthly Intravitreal Injections of Ranibizumab for Myopic Choroidal Neovascularization

The aim of this study was to evaluate the 12-month outcomes, efficacy, and safety of three consecutive monthly intravitreal ranibizumab injections for myopic choroidal neovascularization (CNV). We retrospectively reviewed the medical records of 25 consecutive eyes that received a loading dose of three consecutive monthly intravitreal injections of ranibizumab for myopic CNV between February, 2008, and March, 2010, with a follow-up of 12 months. Eyes with persistent or recurrent CNV after 3 months received additional ranibizumab injections as needed. Patients' demographic data, best corrected visual acuity (BCVA), CNV findings on fluorescent angiography (FAG), central macular thickness (CMT) on optical coherence tomography (OCT), total number of treatments, and complications were recorded. Mean baseline BCVA was 0.73 logarithm of the minimum angle of resolution (logMAR) (standard deviation [SD] 0.63), and improved significantly to 0.42 logMAR (SD 0.43) at 1 month, 0.38 logMAR (SD 0.47) at 2 months, 0.34 logMAR (SD 0.43) at 3 months, and 0.34 logMAR (SD 0.40) at 12 months (all P<0.001, Wilcoxon signed-rank test). The average number of injections was 3.44 (SD 0.92). At 12 months, mean improvement was 2.88 lines (SD 2.35), and 20 eyes (80%) showed a gain of at least one line after treatment. At 3 months, OCT showed significant reduction in CMT (P=0.012, two-tailed t-test), and FAG showed significant reduction of mean CNV size from 0.3 (SD 0.16) to 0.19 (SD 0.12) disc area (P=0.007, two-tailed t-test). No angiographic leakage was evident at 3 months in 21 eyes (84%); four eyes (16%) required additional injections for persistent leakage. Two eyes (8%) had recurrent CNV during follow-up and required retreatment. No complications were noted after treatment. An initial loading dose of three ranibizumab injections is safe and effective in treating myopic CNV, with visual improvement maintained over 12 months.

Comparison of two intravitreal ranibizumab treatment schedules for neovascular age-related macular degeneration

IntroductionRanibizumab (Lucentis), a humanised antibody fragment that inhibits vascular endothelial growth factor (VEGF)-A, is widely used for the treatment of neovascular age-related macular degeneration (NV-AMD). The objective of this study...