Intravitreal Ranibizumab Treatment Research Articles

Effectiveness of Intravitreal Ranibizumab in Nonvitrectomized and Vitrectomized Eyes with Diabetic Macular Edema: A Two-Year Retrospective Analysis.

The aim of this study was to compare the effectiveness of intravitreal ranibizumab (IVR) injections for the treatment of diabetic macular edema (DME) in eyes with and without previous vitrectomy. The medical records of 28 eyes (11 vitrectomized and 17 nonvitrectomized) of 28 patients (mean age, 59.0 ± 9.6 years; male to female ratio 1 : 1) who were diagnosed with DME and had received IVR treatment were reviewed retrospectively. The indications of vitrectomy in 11 vitrectomized eyes were intravitreal hemorrhage (n = 8) and epiretinal membrane (n = 3). The best-corrected visual acuity (BCVA), central macular thickness (CMT), and total macular volume (TMV) were measured at baseline and at months 6, 12, 18, and 24 of the follow-up. The number of IVR injections, the duration between diagnosis of DME and IVR injection, and the hemoglobin A1c (HbA1c) level at baseline were also recorded. Baseline demographics, HbA1c, BCVA, CMT, and TMV values were similar between two groups (p > 0.05). The duration between diagnosis of DME and IVR injections was similar in both groups (16 ± 5 months vs. 13 ± 4 months, respectively; p=0.11). IVR injection was performed 6.3 times in vitrectomized eyes and 6.1 times in nonvitrectomized eyes during the 24-month period (p > 0.05). The mean BCVA improved significantly during the 24-month period in both groups. The improvements in BCVA, in CMT, and in TMV were more significant at month 6 (p=0.036) group, at month 12 (p=0.013), at month 12 (p=0.021), and month 24 (p=0.021) in nonvitrectomized eyes, respectively, while there was no difference in improvements of BCVA, CMT, and TMV in vitrectomized group at each visit. Treatment effected by time in terms of BCVA, CMT, and TMV values in all groups (p=0.0004, p < 0.0001, p < 0.0001, respectively), not by time-group interaction and group (all p values >0.05). In conclusion, IVR treatment for DME is equally effective in both groups. However, the response to treatment is seen earlier in nonvitrectomized eyes compared to vitrectomized eyes.

Can Vitreous Reflux Affect The Short-Term Treatment Response After Intravitreal Ranibizumab Injection?

ABSTRACT Purpose The aim of this study was to evaluate the effect of vitreous reflux (VR) on the short-term effect of intravitreal ranibizumab injection. Materials and Methods The study included 181 eyes of 81 age-related macular degeneration (AMD) and 100 diabetic macular edema (DME) patients. Treatment response was evaluated by measuring central macular thickness (CMT) as well as 1 mm and 3 mm central macular thicknesses (MT1 and MT3). Patients were grouped as; Group 1: no VR, Group 2: <3 mm VR, and Group 3: >3 mm VR according to conjunctival bleb diameters. The data were analyzed using variance, correlation and regression analyses. Results In AMD patients, reduction of CMT values following the treatment were 88.3 ± 110.6 µm in Group 1, 85.6 ± 158.7 µm in Group 2, and 93.1 ± 92.2 µm in Group 3. Likewise, in DME patients, it was 82.4 ± 88.4 µm, 72.9 ± 109.9 µm, and 73.7 ± 113.7 µm, respectively. Reduction of MT1 values after the treatment were 47.4 ± 72.6 µm, 36.0 ± 131.9 µm, and 36.7 ± 114.4 µm in AMD patients, and 33.3 ± 72.5 µm, 36.6 ± 90.2 µm, and 46.9 ± 83.4 µm in DME patients. In all comparisons among groups of VR, macular thickness (MT) change did not exhibit significant difference following an intravitreal ranibizumab treatment (p > .05). Conclusion We found that the increase in VR amount did not adversely affect the decrease in MT after intravitreal ranibizumab treatment in AMD and DME patients.

Microperimetry and mfERG as functional measurements in diabetic macular oedema undergoing intravitreal ranibizumab treatment.

To evaluate Microperimetry (MP) and multifocal electroretinogram (mfERG) as whole-macula functional markers of treatment response in naive diabetic macular oedema (DMO) patients undergoing ranibizumab treatment. An exploratory sub-analysis of a prospective study (NCT01947881-CHARTRES). Patients received three monthly ranibizumab injections (loading dose) followed by pro re nata (PRN) regimen during 1 year. At baseline, during and after treatment (Months 0, 3, 6 and 12), subjects were tested using BCVA, OCT, MP and mfERG. MP was performed in the central 12°, and retinal sensitivity was measured overall (mean sensitivity (MS)), and in three concentric rings (R1-R3). mfERG P1 amplitude and implicit time were measured over six concentric rings (R1-R6). Thirty-two eyes were included. MP mean and rings sensitivity were significantly lower in DMO (p < 0.001). After loading dose, a significant improvement in retina sensitivity was observed, particularly in good BCVA responders (MS = +2.28 dB; R1 = +2.33 dB, R2 = +2.20 dB, R3 = +2.25 dB; p = 0.049). Overall retinal sensitivity was significantly correlated with BCVA improvement (r = 0.54; p = 0.026) and inversely correlated with OCT central subfield thickness improvement (r = -0.39; p = 0.026). mfERG amplitude and implicit time were also lower in DMO (p < 0.011). An improvement of mfERG P1 amplitude and implicit time in R1 was noted in good responders after ranibizumab loading dose (+16.49 nV/deg2; p = 0.013 and -0.005 ms; p = 0.048, respectively). When changing to PRN treatment regimen, BCVA was maintained during the 12 months of follow-up but worsening of the visual function was detected by MP and mfERG. Microperimetry and mfERG were able to demonstrate DMO functional improvement after treatment loading dose, as well as early visual changes when treatment regimen was switched to PRN.

Relationship Between Final Visual Acuity and Optical Coherence Tomography Findings in Patients with Diabetic Macular Edema Undergoing Anti-VEGF Therapy

Objectives:To identify the prevalence of findings in optical coherence tomography (OCT) sections before intravitreal anti-VEGF treatment in patients with diabetic macular edema (DME), and to evaluate the relationship between these findings and final visual acuity and number of injections.Materials and Methods:This retrospective study included 296 eyes of 191 patients (104 male, 87 female) who started intravitreal ranibizumab treatment after being diagnosed with DME in the retina unit between January 2013 and April 2017 were included the study. Spectral domain OCT findings at the time of presentation such as presence of serous macular detachment (SD), vitreomacular traction (VMT), and epiretinal membrane (ERM) were recorded. In addition, the regularity of the ellipsoid zone (EZ) and inner retinal layers was also studied.Results:The mean central retinal thickness measured in SD-OCT was 449±81 μm before treatment and 350±96 μm after treatment (p<0.001). SD was detected in 155 eyes (52.4%), ERM in 67 eyes (22.6%), and VMT in 9 eyes (3%). Thirty eyes (10.1%) had disorganization of the retinal inner layers (DRIL) and 54 eyes (18.2%) had EZ deterioration. The presence of ERM, EZ irregularity, and DRIL were associated with significantly lower final visual acuity (p<0.0001), while there was no relationship between pre-treatment SD and final visual acuity (p=0.11). Injection number was higher in eyes with SD and ERM compared to those without, but this difference was statistically significant only in the presence of SD (p=0.01 and p=0.59, respectively). There was no difference in injection number according to EZ irregularity or presence of DRIL.Conclusion:The coexistence of SD with DME was associated with increased need for treatment but not with final visual acuity. EZ irregularities, DRIL, and ERM are findings that negatively affect visual acuity.

Association between the patterns of diabetic macular edema and photoreceptors' response after intravitreal ranibizumab treatment: a spectral-domain optical coherence tomography study.

To analyze photoreceptors' condition after intravitreal ranibizumab treatment according to the pattern of diabetic macular edema (DME) on spectral-domain optical coherence tomography (SD-OCT). Retrospective study includes 58 treatment naïve patients with DME, treated with intravitreal ranibizumab injections and followed up for at least 12months. Patients were classified based on DME morphology on SD-OCT into: diffuse macular edema, cystoid macular edema (CME) and serous retinal detachment with CME (SRD/CME). The DME morphology was analyzed, while quantitative measurement of ellipsoid zone (EZ) defect, as well as qualitative assessment of the condition of external limiting membrane (ELM) and interdigitation zone (IZ) at foveal area, was taken before and after treatment. Before treatment, patients with CME presented worse ELM and IZ condition and greater EZ defect than patients with diffuse macular edema or SRD/CME. After treatment, the restoration of EZ defect and IZ was more evident in patients with CME than in diffuse macular edema or SRD/CME. Patients with DME presented significant photoreceptors' restoration after intravitreal ranibizumab injections at the 12-month follow-up. The improvement in EZ defect size and IZ was dependent on the pattern of DME on SD-OCT.

Changes in Ocular Blood Flow after Ranibizumab Intravitreal Injection for Diabetic Macular Edema Measured Using Laser Speckle Flowgraphy.

Purpose To evaluate the effects of intravitreal ranibizumab (IVR) treatment on the blood flow of the optic nerve head (ONH) and of retinal vessels of the peripapillary region of eyes with diabetic macular edema (DME) assessed using laser speckle flowgraphy (LSFG). Methods Forty eyes of 30 patients treated with IVR for DME were included in this prospective clinical study. Mean blur rate (MBR) and relative flow volume (RFV) of the ONH and of a superior retinal artery and an inferior retinal vein of the peripapillary region were measured using LSFG at baseline, 2 weeks (T1), and 1 month (T2) after IVR injection. In addition, best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured in all cases. Results The BCVA improved and CRT decreased significantly during the follow-up period (p < 0.010). MBR-related parameters of the ONH such as MBR of all area (MA), MBR of vascular area (MV), and MBR of tissue area (MT) decreased significantly at 2 weeks after IVR compared to baseline values (MA, p < 0.010). MBR-related parameters of the ONH such as MBR of all area (MA), MBR of vascular area (MV), and MBR of tissue area (MT) decreased significantly at 2 weeks after IVR compared to baseline values (MA, p < 0.010). MBR-related parameters of the ONH such as MBR of all area (MA), MBR of vascular area (MV), and MBR of tissue area (MT) decreased significantly at 2 weeks after IVR compared to baseline values (MA, p < 0.010). MBR-related parameters of the ONH such as MBR of all area (MA), MBR of vascular area (MV), and MBR of tissue area (MT) decreased significantly at 2 weeks after IVR compared to baseline values (MA, p < 0.010). MBR-related parameters of the ONH such as MBR of all area (MA), MBR of vascular area (MV), and MBR of tissue area (MT) decreased significantly at 2 weeks after IVR compared to baseline values (MA, p < 0.010). MBR-related parameters of the ONH such as MBR of all area (MA), MBR of vascular area (MV), and MBR of tissue area (MT) decreased significantly at 2 weeks after IVR compared to baseline values (MA, p < 0.010). MBR-related parameters of the ONH such as MBR of all area (MA), MBR of vascular area (MV), and MBR of tissue area (MT) decreased significantly at 2 weeks after IVR compared to baseline values (MA, p < 0.010). MBR-related parameters of the ONH such as MBR of all area (MA), MBR of vascular area (MV), and MBR of tissue area (MT) decreased significantly at 2 weeks after IVR compared to baseline values (MA, p < 0.010). MBR-related parameters of the ONH such as MBR of all area (MA), MBR of vascular area (MV), and MBR of tissue area (MT) decreased significantly at 2 weeks after IVR compared to baseline values (MA, Conclusion IVR injection leads to a reduction of ocular blood flow both in the ONH and in the retinal peripapillary vessels associated with peripapillary vessel constriction. The reduction of CRT and related improvement of vision may be related to the changes in ocular blood flow.

Intravitreal ranibizumab versus vitrectomy for recurrent vitreous haemorrhage after pars plana vitrectomy for proliferative diabetic retinopathy: a prospective study.

To compare prospectively intravitreal ranibizumab treatment and pars plana vitrectomy (PPV) in patients with recurrent vitreous haemorrhage (VH) due to proliferative diabetic retinopathy (PDR), who were previously treated with PPV. Participants in this prospective study were 37 patients (37 eyes) with PDR, previously treated with PPV. All patients presented recurrent VH and were treated with either ranibizumab (n = 18) or PPV (n = 19). All participants were examined at week 2 post-treatment and every month thereafter for 1 year. Main outcomes were the need of PPV, the rate of recurrence of VH and the change in visual acuity by the end of the 12-month follow-up. At month 12, there was statistically significant improvement in visual acuity in both groups compared to baseline, but the two groups did not differ regarding the change in visual acuity. In ranibizumab group, two patients presented recurrent VH during the follow-up and one patient needed PPV to clear the VH by month 12. In PPV group, two patients had mild recurrent VH, which cleared itself. No statistically significant difference was noticed regarding the rate of recurrent VH and the need of PPV between the two groups. Intravitreal ranibizumab seems to be a safe and effective treatment alternative in patients with recurrent VH secondary to PDR, who had been previously treated with PPV.

RATES AND RISK FACTORS FOR RECURRENCE OF RETINOPATHY OF PREMATURITY AFTER LASER OR INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR MONOTHERAPY.

To determine the rates and risk factors of recurrent retinopathy of prematurity (ROP) treated by laser photocoagulation, intravitreal bevacizumab (IVB) monotherapy, or intravitreal ranibizumab (IVR) monotherapy. In this retrospective cohort study, consecutive infants with Type 1 ROP who received laser, IVB, or IVR treatments were followed for at least 75 weeks of postmenstrual age. Data analysis was performed between March 2010 and February 2017 in Chang Gung Memorial Hospital, Linkou, Taiwan. A total of 176 infants (340 eyes) were included in this study. The mean follow-up was 197.3 ± 110 weeks. All of the baseline demographic and ROP characteristics among the laser, IVB, and IVR groups were similar. The overall recurrence rate after treatment was 44 of 340 eyes (12.9%). The IVB group had a recurrence rate of 10.0%, followed by the laser group (18.0%) and the IVR group (20.8%); however, these rates were not significantly different (P = 0.0528). Compared with the laser group, the IVB and IVR groups exhibited recurrence at later ages (43.4 ± 3.5 weeks for the IVB group, 42.3 ± 2.0 weeks for the IVR group, and 39.5 ± 2.8 weeks for the laser group; P = 0.0058). The mean interval of recurrence from initial treatment in the laser group was 3.6 ± 1.4 weeks compared with 8.8 ± 3.9 weeks and 8.3 ± 1.6 weeks in the IVB and IVR groups, respectively (P = 0.0001). Overall, the independent risk factors of recurrence included an early postmenstrual age at initial treatment (P = 0.0160), Zone I (P = 0.0007), low Apgar score (P = 0.0297), and multiple births (P = 0.0285). There was no significant difference in progression to retinal detachment among the three groups (laser: 3/61, 4.9%; IVB: 2/231, 0.9%;and IVR: 1/48, 2.1%; P = 0.2701). Laser, IVR, and IVB are effective for Type 1 ROP. Retinopathy of prematurity recurrence requiring re-treatment was encountered as late as 50 weeks of postmenstrual age after IVB or IVR but earlier after laser. Longer follow-up for infants treated with anti-vascular endothelial growth factor is needed, especially in patients with significant risk factors such as an early postmenstrual age at initial treatment, Zone I ROP, low Apgar score, and multiple births.

Comparison of Intravitreal Aflibercept and Ranibizumab for Treatment of Myopic Choroidal Neovascularization: One-Year Results-A Retrospective, Comparative Study.

Purpose To compare one-year treatment outcomes of intravitreal aflibercept (IVA) and intravitreal ranibizumab (IVR) for treatment of myopic choroidal neovascularization (mCNV). Methods The medical records of a total of 30 eyes diagnosed with mCNV and underwent IVA or IVR treatment for a minimum one-year follow-up were studied retrospectively. All the subjects had an axial length >26 mm and received a 1 + PRN (pro re nata) regimen IVA or IVR. Best-corrected visual acuity (BCVA) and central macular thicknesses (CMT) on optical coherence tomography were evaluated before and after treatment. Results There were 12 eyes in IVA group, with a mean age of 60.0 ± 10.2 years. The mean BCVA significantly improved from baseline 1.54 ± 0.76 to 0.85 ± 0.61 and the mean CMT significantly decreased from baseline 384.3 ± 119.1 μm to 305.9 ± 75.4 μm to 305.9 ± 75.4 p : 0.024 and p : 0.024 and μm to 305.9 ± 75.4 μm to 305.9 ± 75.4 p : 0.024 and p : 0.024 and p : 0.024 and p : 0.024 and Conclusions Both IVA and IVR treatment modalities resulted in similar anatomical outcomes but IVA had better visual outcomes in treatment of mCNV.

The association of exudation pattern with anatomical and functional outcomes in patients with Neovascular Age-Related Macular Degeneration

Objective. To evaluate the correlation between visual outcomes and fluid configuration observed on spectral-domain optical coherence tomography (SD-OCT) in patients with wet age-related macular degeneration (AMD). Methods. Sixty-five eyes of 53 patients with AMD who were administered intravitreal ranibizumab treatment with 12 months of follow-up were included in this retrospective study. Presence of intraretinal cystoid fluid (IRC) and pigment epithelial detachment (PED), thickness of subretinal fluid (SRF), central macular thickness (CMT), and central macular volume (CMV) were assessed. Results. Subretinal fluid was observed in 29 eyes (45%), IRC in 36 eyes (55%), and PED in 39 eyes (60%). Baseline and final best-corrected visual acuity (BCVA) were 0.69±0.4 and 0.60±0.4 logMAR in the IRC negative group and 1.17±0.5 and 0.97±0.5 logMAR in the IRC positive group. BCVA was lower in IRC positive group (baseline p=0.001 and final=0.003); however, marked improvement was detected in both groups. Anatomic improvement and increased visual acuity were observed in groups with and without PED, IRC, and SRF. An inverse correlation was detected between pre-treatment CMT, IRC and post-treatment IRC, and final BCVA. Conclusion. Significant visual and anatomic improvement was observed after one-year of ranibizumab treatment regardless of fluid configuration. However, the presence of IRC was observed to be associated with worse visual acuity. Baseline retinal fluid configuration may have prognostic effects on functional success in patients treated with ranibizumab for wet AMD. Abbreviations. AMD = Age-related macular degeneration, VEGF = Vascular endothelial growth factor, IRC = intraretinal cystoid fluid, PED = pigment epithelial detachment, SRF = subretinal fluid, SD-OCT = spectral-domain ocular coherence tomography, IVR = intravitreal ranibizumab, BCVA = best-corrected visual acuity, FFA = fundus fluorescein angiography, CMT = central macular thickness, CMV = central macular volume.

One-Year Outcomes of 1 Dose versus 3 Loading Doses Followed by Pro Re Nata Regimen Using Ranibizumab for Neovascular Age-Related Macular Degeneration: The ARTIS Trial.

Purpose. To compare the functional and anatomical outcomes of one dose and three loading doses followed by the pro re nata (PRN) regimen in Chinese neovascular age-related macular degeneration (nvAMD) (including polypoidal choroidal vasculopathy (PCV)) patients. Methods. In this multicenter, prospective, open-label, controlled, 12-month study (ClinicalTrials.gov: NCT02810808), patients were randomized (1 : 1) to 1 dose + PRN (PRN group) or 3 loading doses + PRN (LD group) using intravitreal ranibizumab treatment. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were evaluated. The main outcome was the change in BCVA. The noninferiority limit was 5 letters. Results. Forty-five patients in the PRN group and 49 patients in the LD group finished 12-month follow-up. Each group included 4 PCV patients. The mean change in BCVA from baseline was 7.8 letters in the PRN group, compared with 10.9 letters in the LD group (P=0.344). There were no significant differences between two groups in the mean change of CRT (−159.3 μm vs. −120.5 μm) at month 12. The mean number of injections during the 12-month follow-up was 6.0 in the PRN group and 6.8 in the LD group. The proportion of patients who gained an improvement in visual acuity by 15 or more letters was 28.9% in the PRN group and 44.9% in the LD group (P=0.066). Conclusion. One dose + PRN showed noninferior visual gains than 3 loading doses + PRN regimen using ranibizumab in Chinese nvAMD and PCV patients. Number of injections in the PRN group was similar as that in the LD group but remained a potential risk of vision instability during one-year follow-up using OCT-guided retreatment criteria. This trial is registered with NCT02810808.

Pretreatment neutrophil-to-lymphocyte ratio predicts prognosis in patients with diabetic macular edema treated with ranibizumab

BackgroundTo investigate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients with diabetic macular edema (DME) treated monthly with ranibizumab.MethodsWe retrospectively analyzed the medical records of all patients who received intravitreal ranibizumab (IVR) treatment for DME at the First Affiliated Hospital of Nanchang University between December 2015 and December 2017. Clinicopathological parameters, including NLR, were evaluated to identify predictors of better outcomes of IVR monotherapy.ResultsNinety-one treatment-naïve eyes treated with IVR for DME were retrospectively analyzed in this study. Baseline best-corrected visual acuity (BCVA), neutrophils, NLR, monocyte-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were negatively correlated with the changes in BCVA at 24 weeks compared with the baseline, while baseline central retinal thickness and lymphocytes were positively correlated with the changes in BCVA at 24 weeks compared with the baseline. Multiple linear regression analysis revealed that NLR was independently associated with the mean change of BCVA between baseline and week 24. In addition, patients with NLR < 2.27 showed a better improvement in letter score than those with NLR > 2.27.ConclusionPretreatment NLR is independently associated with the BCVA in DME patients treated with IVR, and higher pretreatment NLR may contribute to inferior BCVA outcomes.

Influence of Baseline Macular Edema on Cost Evaluation of Panretinal Photocoagulation vs Intravitreal Ranibizumab for Proliferative Diabetic Retinopathy

Purpose: This article evaluates the influence of baseline diabetic macular edema (DME) on cost-utility analysis of treatment for proliferative diabetic retinopathy (PDR) based on 5-year Diabetic Retinopathy Clinical Research Network ( DRCR.net ) Protocol S results. Methods: A decision-analysis model calculated comparative cost utility of panretinal photocoagulation (PRP) and intravitreal ranibizumab (IVR) treatment for PDR with and without baseline DME. Centers for Medicare &amp; Medicaid Services data were used to calculate associated modeled costs in a hospital/facility-based and nonfacility setting. Cost utility was calculated based on the preserved visual utility and estimated life years remaining. Sensitivity analyses were performed to evaluate the impact of the model’s assumptions. Results: The modeled cost per quality-adjusted life year (QALY) of treatment for PDR with baseline DME for 5 years of utility in the facility (nonfacility) setting was $280,919 ($203,444) in the PRP group and $452,387 ($339,319) in the IVR group. The estimated lifetime cost per QALY in the facility (nonfacility) setting was calculated as $84,761 ($50,077) in the PRP group and $314,483 ($230,301) in the IVR group. The cost per QALY of IVR for the first 5 years of treatment was 1.6 to 1.7 times that of PRP, whereas lifetime cost per QALY was 3.7 to 4.6 times higher. When considering all patients regardless of baseline DME status, lifetime cost per QALY of PRP was 8% to 13% higher, whereas IVR was only 1% higher compared with the cost per QALY without baseline DME. Conclusions: When considering the subset of patients with PDR and baseline DME, PRP maintains a more favorable cost utility compared with IVR. This augments previous reports that PRP has a more favorable cost utility than IVR for PDR without DME, given the marginal visual benefit of IVR.

Outcome Predictors of SD-OCT-Driven Intravitreal Ranibizumab in Choroidal Neovascularization due to Myopia

Purpose: To analyze the efficacy and outcome predictors of SD-OCT (spectral-domain optical coherence tomography)-driven ranibizumab treatment in patients with choroidal neovascularization due to myopia (mCNV). Methods: This prospective investigator-initiated study includes 20 patients with treatment-naïve mCNV. Evaluation included best-corrected visual acuity (BCVA), morphological SD-OCT parameters, and treatment frequency. Results: From baseline to month 12, BCVA improved from 58.5 ± 16.9 to 66.1 ± 14.9 letters. Central retinal thickness (CRT) significantly decreased, and qualitative SD-OCT parameters improved. Better baseline visual acuity (VA), lower spherical equivalent, better inner/outer segment line and external limiting membrane integrity showed a significant positive effect on BCVA outcome. Less fluctuation in CRT (worst minus best CRT) indicated better BCVA at 12 months. No serious adverse events occurred. Conclusions: SD-OCT-guided intravitreal ranibizumab treatment in mCNV was efficient and safe. We determined useful predictive factors in regard to VA outcome after 12 months.

Retinal and Choroidal Changes after Anti Vascular Endothelial Growth Factor Therapy for Neovascular Age-related Macular Degeneration.

To investigate changes in retinal nerve fiber layer, ganglion cell-inner plexiform layer, and choroidal thickness in the macular area in patients with neovascular age-related macular degeneration who received repeated intravitreal ranibizumab and aflibercept treatments. This retrospective study included 90 eyes of 90 treatment-naive patients. Fifty eyes were treated with intravitreal injections of aflibercept, and 40 were treated with intravitreal injections of ranibizumab. Unaffected fellow eyes (71 eyes) were used as controls. The dosage was one injection per month for 3 consecutive months as an initial treatment. The patients were examined monthly for 6 months following the initial injection. Additional intravitreal injections were given reactively in an optical coherence tomography-guided "pro re nata" protocol. Measurements of the retinal nerve fiber layer, ganglion cell-inner plexiform layer, full retina, and choroidal thickness were simultaneously obtained via swept-source optical coherence tomography in the nine Early Treatment Diabetic Retinopathy Study subfields. The retinal nerve fiber layer thickness in the nine Early Treatment Diabetic Retinopathy Study subfields did not differ significantly among the three study groups (aflibercept vs. ranibizumab vs. control). The ganglion cell-inner plexiform layer thickness was significantly reduced in the aflibercept group, while the choroidal thickness was reduced in both the aflibercept and ranibizumab groups. Excessive long-term vascular endothelial growth factor inhibition by an anti-vascular endothelial growth factor agent that is trapped by neuronal and retinal pigment epithelium cells may adversely affect the function of physiological vascular endothelial growth factor and harm retinal cells and vessels.

Five-year treatment outcomes following intravitreal ranibizumab injections for neovascular age-related macular degeneration in Japanese patients.

To assess the real-world 5-year treatment outcomes of ranibizumab therapy in Japanese patients with neovascular age-related macular degeneration (AMD). This was a retrospective, observational, and open-label effectiveness study that included 295 eyes. The participants were patients with treatment-naïve neovascular AMD who received intravitreal ranibizumab (IVR) monthly injection at least three times as the loading phase, followed by further injections as needed (pro re nata (PRN)) and follow-up assessments for 5years. Outcomes were determined at least 5years after the first ranibizumab injection. Mean logMAR best-corrected visual acuity (BCVA) at baseline was 0.52. The mean BCVA significantly improved after three loading injections; however, it declined gradually. The BCVA at 1year was significantly better than the baseline BCVA, whereas the 3-year, 4-year, and 5-year BCVA values were significantly lower than the baseline values. The average central foveal thickness improved significantly from 366 ± 125μm to 268 ± 134μm (p < 0.0001). Macular atrophy was significantly more likely to occur in cases with classic choroidal neovascularization (CNV) than in cases with other AMD (p = 0.01). IVR is well tolerated in eyes with AMD. However, a PRN regimen for AMD may have limited real-world effectiveness for long-term maintenance of improved visual acuity. Macular atrophy may occur more frequently in classic CNV. To maintain good vision, IVR treatment should be started earlier and performed continuously.

A Systematic Review and Meta-Analysis of Clinical Outcomes of Intravitreal Anti-VEGF Agent Treatment Immediately after Cataract Surgery for Patients with Diabetic Retinopathy.

Aims To examine possible benefits of intravitreal anti-vascular endothelial growth factor (VEGF) agent treatment immediately after cataract surgery for patients with diabetic retinopathy (DR). Methods A comprehensive literature search was performed using the Cochrane collaboration methodology to identify randomized controlled trials (RCTs) and comparative studies of cataract surgery with or without anti-VEGF agent treatment for any diabetic retinopathy. Meta-analyses were performed for clinical outcome parameters including changes in macular thickness (MT), best-corrected visual acuity (BCVA), incidence of diabetic retinopathy and maculopathy progression, laser treatment rate, and other complications. Results Nine RCTs and 3 nonrandomized comparative studies were identified and used for comparing cataract surgery with intravitreal bevacizumab (IVB) or intravitreal ranibizumab (IVR) treatment (338 eyes, intervention group) to cataract surgery alone (329 eyes, control group). Analysis of all data showed that the mean BCVA at 1 week postoperatively had no statistically significant difference in the two groups, but at 1, 3, and 6 months postoperatively, the mean BCVA was statistically significantly better in the anti-VEGF treatment group than that in cataract surgery alone group. Analysis of all data showed that the mean MT was statistically significantly less in the anti-VEGF treatment group at 1 week and 1, 3, and 6 months postoperatively (P=0.05, P=0.006, P=0.0001, and P=0.0001, respectively); but postoperative clinical outcomes were differentiated from the type of anti-VEGF agents, IVB or IVR, and the existing macular edema preoperatively. Intravitreal anti-VEGF agent treatment statistically significantly reduced the incidence of diabetic retinopathy progression and maculopathy progression compared to the control group (P=0.0003, P < 0.00001, respectively). Conclusion IVB or IVR treatment immediately after cataract surgery may represent a safe and effective strategy to prevent postoperative macular thickening or reduce macular edema and result in greater mean improvements in visual acuity for diabetic patients.

Long-Term Changes in Submacular Choroidal Thickness after Intravitreal Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration: 14-Mo Follow-Up

ABSTRACTPurpose: To study (i) the long-term effects of intravitreal ranibizumab treatment on changes in submacular choroidal thickness and (ii) the relationship between any resulting changes in choroidal thickness and visual outcomes following such treatment in patients with neovascular age-related macular degeneration (n-AMD).Methods: Reviewed were medical records of 30 consecutive, treatment-naïve, patients with unilateral n-AMD (n = 30 eyes) and unaffected fellow eyes (n = 26 eyes) (controls). Monthly injections of 0.5 mg ranibizumab were administered until stabilization of n-AMD, with additional injections as needed over the following 14-mo. Choroidal thickness was determined using enhanced-depth imaging–optical coherence tomography (EDI–OCT) before and after initiation of ranibizumab therapy. Choroidal thickness measurements were generated via manual segmentation.Results: The mean age of patients was 71.9 ± 7.4 (56–83) years; the mean best-corrected visual acuity (BCVA) of affected eyes improved from 51.1 to 59.4 letters (p < 0.001); and the mean number of injections was 9.16 ± 1.75. Subfoveal choroidal thickness decreased from 208.3 ± 73.7 μm at baseline to 185.3 ± 70.1 μm at mo-14 (p < 0.001), with significant (p < 0.001) decreases at all measured time points. Choroidal thickness also tended to decline in fellow eyes but was only statistically significant nasally 1,000 μm (p =0.04). Mean changes in choroidal thickness did not correlate with BCVA at mo-14 (p = 0.76). Disciform scars and geographic atrophy (p = 0.017), and BCVA (p < 001) at baseline were predictive of visual outcome. Age (p = 0.001), reticular drusen (p = 0.004), and size of choroidal neovascularized area (p = 0.042) were predictive of decreases in choroidal thickness.Conclusions: Submacular choroidal thickness appeared to decrease significantly in eyes with n-AMD over a 14-mo period of ranibizumab treatment. No corresponding decrease in choroidal thickness occurred in fellow eyes.

Stereopsis after Intravitreal Ranibizumab Injections for Branch Retinal Vein Occlusion

To evaluate stereopsis before and after intravitreal ranibizumab (IVR) injections in patients with branch retinal vein occlusion (BRVO) and investigate the relationship between stereopsis and retinal microstructure. Prospective, observational, controlled study. Thirty-two eyes of 32 patients undergoing IVR treatment for BRVO and 28 eyes of age-matched healthy control participants. Stereopsis was measured using the Titmus stereo test (TST) and TNO stereo test before and 1, 2, 3, 4, 5, and 6 months after treatment. Stereopsis, best-corrected visual acuity (BCVA), duration of disease, central retinal thickness, status of the external limiting membrane, ellipsoid zone, and external limiting membrane, and serous retinal detachment (SRD) after treatment. Treatment with IVR significantly improved the TST (P < 0.001) and TNO stereo test (P < 0.05) scores as well as BCVA (P < 0.001) and central retinal thickness (P < 0.005). Stereopsis after IVR injection in eyes with BRVO was significantly worse than that in healthy control participants (TST, P < 0.001; TNO stereo test, P < 0.001). The TST and TNO stereo test scores were correlated significantly with BCVA and the presence of SRD at baseline. After 6 months of treatment, an association of TST and TNO stereo test scores with BCVA and status of the external limiting membrane and ellipsoid zone was observed. Stereopsis after treatment showed a significant relationship with BCVA and presence of SRD at baseline. Administration of IVR for BRVO improved early stereopsis, albeit not to a normal level. Presence of SRD and visual acuity were predictors of stereopsis after treatment in patients with BRVO.

Intravitreal Ranibizumab Treatment and Treatment Regimens in Macular Edema due to Branch Retinal Vein Occlusion

Branch retinal vein occlusion (BRVO) represents the second most common retinal vascular disorder. With an understanding of the role of VEGF in macular edema due to BRVO, intravitreal anti-VEGF agents are used as the most important therapeutic tool in the management of BRVO. In this review, we try to discuss intravitreal ranibizumab treatment and treatment regimens in macular edema due to branch retinal vein occlusion.