Intravitreal Aflibercept Injection Group Research Articles

Ocular and Systemic Risk Factors for Disease Worsening Among Patients with NPDR: Post Hoc Analysis of the PANORAMA Trial

PurposeIdentify baseline systemic and ocular characteristics associated with nonproliferative diabetic retinopathy (NPDR) worsening, and the impact of intravitreal aflibercept injection (IAI) on these associations. DesignPost hoc analysis of PANORAMA. ParticipantsPatients with moderately severe to severe NPDR enrolled in the prospective PANORAMA phase 3 trial. MethodsAssociations between baseline systemic and ocular factors with events indicative of NPDR worsening at Week 100 were evaluated by multivariable analysis in sham-treated eyes. NPDR worsening was defined as development of (1) vision-threatening complications (VTCs; comprising PDR and/or anterior segment neovascularization), (2) center-involved diabetic macular edema (CI-DME), or (3) ≥ 2-step Diabetic Retinopathy Severity Scale (DRSS) worsening. Impact of IAI on identified baseline factors was evaluated using univariable analysis in combined IAI groups. Main Outcomes MeasuresBaseline systemic and ocular factors associated with events indicative of NPDR worsening at Week 100. The cumulative incidence and risk of developing such events at Week 100 among sham versus IAI-treated eyes. ResultsUsing multivariable analyses among sham-treated eyes, 5 baseline factors associated with increased risk of NPDR worsening were identified: fluorescein leakage, retinal nonperfusion area, thicker central subfield thickness, eosinophil level, and proteinuria. Considering baseline fluorescein leakage area as a prognostic indicator in detail, the risk of developing VTCs alone, VTCs and/or CI-DME, or ≥ 2-step DRSS worsening increased with increasing fluorescein leakage area in the sham group (all P < 0.05). Considering baseline retinal nonperfusion area as a prognostic indicator in detail, the risk of developing VTCs alone, CI-DME alone, or VTCs and/or CI-DME increased with increasing baseline retinal nonperfusion area in the sham group (all P < 0.05). In contrast, among IAI-treated eyes, increasing baseline fluorescein leakage or retinal nonperfusion areas did not increase the risks of NPDR worsening. ConclusionsWithin the PANORAMA trial, increased areas of fluorescein leakage and retinal nonperfusion at baseline were identified as key ocular biomarkers associated with events indicative of NPDR worsening among sham-treated patients. IAI treatment appeared to mitigate the effect of these baseline risk factors and reduced the likelihood of NPDR worsening.

Complications, Compliance, and 3-Year Outcomes After Endolaserless Vitrectomy With Aflibercept Monotherapy for Proliferative Diabetic Retinopathy-Related Vitreous Hemorrhage

To report the 3-year outcomes for endolaserless vitrectomy with intravitreal aflibercept injection (IAI) monotherapy for proliferative diabetic retinopathy (PDR)-related vitreous hemorrhage (VH). Eyes underwent endolaserless vitrectomy and received one preoperative and intraoperative IAI followed by randomization to a q8week or q16week IAI group. Additional IAI was administered as needed. 31/40 eyes were randomized (14 q8week eyes, 17 q16week eyes). Through 152 weeks, q8week and q16week eyes received 18.6 and 12.1 IAI, respectively. Q8week eyes observed a 34 letter visual acuity (VA) increase (P = 0.003) compared to a 27 letter increase in the q16week group (P = 0.013). Endolaserless vitrectomy with aflibercept monotherapy for PDR-related VH provides significant long-term visual gains. Frequent IAI is required for fewer proliferative consequences. [Ophthalmic Surg Lasers Imaging Retina 2023;54:89-96.].

Intravitreal Nesvacumab (Anti-Angiopoietin-2) Plus Aflibercept in Neovascular AMD: Phase 2 ONYX Randomized Trial.

To compare intravitreal nesvacumab (anti-angiopoietin-2) + aflibercept vs intravitreal aflibercept injection (IAI) in neovascular age-related macular degeneration (nAMD). Eyes were randomized (1:2:3) to nesvacumab 3 mg + aflibercept 2 mg (LD combo), nesvacumab 6 mg + aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, week 4, and week 8. The LD combo was continued every 8 weeks (q8w). At week 12, the HD combo was re-randomized to q8w or every 12 weeks (q12w) and IAI was re-randomized to q8w, q12w, or HD combo q8w through week 32. The study comprised 365 eyes. At week 12, the mean best-corrected visual acuity (BCVA) gains from baseline were similar in the LD combo group, HD combo group, and IAI group (5.2 letters, 5.6 letters, and 5.4 letters, respectively); the mean central subfield thickness (CST) reductions were similar (182.2 µm, 200.0 µm, and 178.6 µm, respectively). The mean changes in BCVA and CST through week 36 were similar across groups. At week 12, complete retinal fluid resolution was observed in 49.1% (LD combo), 50.8% (HD combo), and 43.6% (IAI) of eyes; the proportions with a CST of 300 μm or less were similar across groups. Numerical trends at week 32 toward complete retinal fluid resolution with combination treatment were not maintained at week 36. Serious ocular adverse events were infrequent and comparable across groups. In nAMD, nesvacumab + aflibercept showed no additional BCVA or CST benefit over IAI monotherapy.

Time to Resolution of Diabetic Macular Edema after Treatment with Intravitreal Aflibercept Injection or Laser in VISTA and VIVID

To assess the relationship between baseline factors and time to diabetic macular edema (DME) resolution. Post hoc analysis of VISTA and VIVID. Eyes with baseline central subfield thickness (CST) of ≥ 290 μm. Eyes were treated with intravitreal aflibercept injection (IAI) 2 mg (n= 558; every 4 weeks or every 8 weeks after 5 monthly doses) or laser control (n= 274). The effect of baseline factors on the time to DME resolution (CST < 290 μm) was assessed in univariable and multivariable models and further evaluated by the Kaplan-Meier method. Time to and cumulative incidence of DME resolution. Eyes treated with IAI had a 2.5-fold higher DME resolution rate, with median time of 33.0 weeks (95% confidence interval [CI], 28.1-40.0), compared with DME resolution not being achieved in 50% of eyes treated with laser control. Multivariable analysis demonstrated that a lower DME resolution rate was associated with a thicker baseline CST (hazard ratio [HR] [95% CI] per 100-μm CST increase, 0.79 [0.72-0.86]) and better baseline best-corrected visual acuity (BCVA) (HR [95% CI] per 5-letter increase, 0.87 [0.83-0.92]) with IAI. Tertiles of increasing CST (T1CST ≤ 419 μm; T2CST > 419 to ≤ 541; T3CST > 541) were associated with longer median times to DME resolution (20.1, 39.1, and 49.1 weeks, respectively; P < 0.001 for T2CST and T3CST versus T1CST) and lower cumulative incidence of events (HR, 1.0, 0.6, and 0.6, respectively; P < 0.001 for T2CST and T3CST versus T1CST) with IAI. Tertiles of increasing BCVA (T1BCVA ≤ 57 letters; T2BCVA > 57 to ≤ 66; T3BCVA >66) were associated with longer median times to DME resolution (28.4, 31.7, and 44.1 weeks, respectively; P < 0.05 for T3BCVA versus T1BCVA) and lower cumulative incidence of events (HR, 1.0, 0.9, and 0.8, respectively; P < 0.05 for T3BCVA versus T1BCVA) with IAI. No other baseline factor was associated with the time to DME resolution. The median time to DME resolution was 33 weeks among IAI-treated eyes. A thicker baseline CST and better baseline BCVA in the IAI group were associated with a longer time to and a lower rate of DME resolution.

Proliferative Diabetic Retinopathy Events in Patients With Diabetic Macular Edema: Post Hoc Analysis of VISTA and VIVID Trials.

This work aimed to assess the incidence of proliferative diabetic retinopathy (PDR) events and improvement to mild non-PDR (NPDR) or better after intravitreal aflibercept injection (IAI) or laser treatment (control) in diabetic macular edema (DME). PDR events in the VISTA (NCT01363440) and VIVID (NCT01331681) phase 3 clinical trials were evaluated in a combined IAI-treated group (IAI 2 mg every 4 weeks or 2 mg every 8 weeks after 5 initial monthly doses; n = 475) and a macular laser control group (n = 235) through week 100 in eyes without PDR at baseline (Diabetic Retinopathy Severity Scale [DRSS] score ≤ 53). Improvement in the DRSS score to 35 or better was evaluated in those with a baseline DRSS score of 43 or greater. A lower proportion of eyes in the IAI group than in the laser group developed a PDR event through week 100 (4.4% vs 11.1%; adjusted difference, -6.7%; 97.5% CI, -11.7 to -1.6; nominal P = .0008). All PDR events occurred in eyes with a baseline DRSS score of 43, 47, or 53 and not in those with a score of 35 or less. A greater proportion of eyes in the IAI group than in the control group achieved a DRSS score of 35 or less (20.0% vs 3.8%; nominal P < .0001). Fewer eyes with NPDR and DME treated with IAI than eyes treated with a laser had a PDR event. More eyes treated with IAI improved to mild NPDR or better (DRSS score ≤ 35) through 100 weeks.

Intravitreal Aflibercept Injection vs Sham as Prophylaxis Against Conversion to Exudative Age-Related Macular Degeneration in High-risk Eyes

Anti-vascular endothelial growth factor (VEGF) agents may provide a prophylactic effect in high-risk eyes with intermediate dry age-related macular degeneration (AMD) against conversion to exudative AMD (eAMD), lowering the risk of vision loss. To evaluate intravitreal aflibercept injection (IAI) as prophylaxis against the conversion to eAMD in high-risk eyes at 24 months. This single-masked, sham-controlled, randomized clinical trial performed at 4 US clinical sites enrolled patients with intermediate AMD in 1 eye (study eye), defined as presence of more than 10 medium drusen (≥63 to <125 μm), at least 1 large druse (≥125 μm), and/or retinal pigmentary changes, and eAMD in the fellow eye. Patients were treated from June 23, 2015, to March 13, 2019. Intravitreal aflibercept injection (2 mg) or sham quarterly injection for 24 months (1:1 randomization). The primary end point was the proportion of patients with conversion to eAMD at month 24 characterized by development of choroidal neovascularization, as assessed by leakage on fluorescein angiography and fluid on spectral-domain optical coherence tomography by an independent masked reading center. Of 128 patients enrolled, 127 (63 in the IAI group and 64 in the sham group) were included in the primary analysis (68 men [53.5%]; mean [SD] age, 76.5 [8.1] years). Baseline demographic and clinical characteristics were balanced between the groups. By month 24, 6 patients (9.5%) in the IAI group and 7 (10.9%) in the sham group developed eAMD (P = .98). Patients with a history of eAMD for longer than 2 years in their fellow eye at baseline showed a lower rate of conversion to eAMD in the study eye compared with those with a history of eAMD for 2 years or less in the fellow eye. Safety was consistent with previous studies involving intravitreal anti-VEGF injections. In this evaluation of quarterly anti-VEGF exposure as prophylaxis to reduce conversion of eyes with high-risk dry AMD to eAMD, the rates of conversion were not lower in the IAI group compared with the sham treatment group at month 24. Understanding the mechanism of conversion to eAMD and therapies that could prevent this event remains an important unmet need. ClinicalTrials.gov Identifier: NCT02462889.

Chorioretinal response to intravitreal aflibercept injection in acute central serous chorioretinopathy.

To evaluate chorioretinal responses to intravitreal aflibercept injection (IAI) in patients with acute central serous chorioretinopathy (CSC). Seventy-one eyes from 71 patients with symptomatic CSC for less than six months were included. Thirty-five eyes received a single IAI and 36 eyes were observed without treatment. Best-corrected visual acuity (BCVA), central subfield foveal thickness (CSFT), and subfoveal choroidal thickness (SFCT) were assessed at baseline and at 1, 2, and 3mo. The mean SFCT in the IAI group decreased at 1mo, rebounded at 2mo and remained stable at 3mo compared to the baseline, while significant change was not noted in the observation group. The mean CSFT decreased significantly during the 3-month study period in both groups, and was significantly lower in the IAI group at 1mo (P<0.001). A rebound of CSFT between 1 and 2mo was noted in 14 eyes (40.0%) in the IAI group and in 1 eye (2.8%) in the observation group (P<0.001). The significant visual improvement was achieved from 1mo in the IAI group, and from 2mo in the observation group. The rate of complete absorption of subretinal fluid at 3mo did not differ between the two groups. (45.7% vs 41.7%, P=0.813). A single IAI for acute CSC induce a transient decrease in SFCT and CSFT, which implies that IAI may have a pharmacological effect on the underlying hyperpermeable choroid in acute CSC.

Outcomes in Patients with Diabetic Macular Edema Requiring Cataract Surgery in VISTA and VIVID Studies

To evaluate the impact of cataract surgery on visual and anatomic outcomes in patients with diabetic macular edema treated with intravitreal aflibercept injection (IAI) or laser control and who did not require rescue therapy. Post hoc analysis of 2 phase 3 trials, Study of Intravitreal Aflibercept Injection in Patients with Diabetic Macular Edema (VISTA) and Intravitreal Aflibercept Injection in Vision Impairment Due to DME (VIVID). Fifty-four patients (laser treatment, n= 11; IAI, n= 43) who underwent cataract surgery during the study period. In VISTA and VIVID, patients received IAI 2 mg every 4 weeks, IAI 2 mg every 8 weeks after 5 monthly doses, or laser control through week 100. Starting at week 24, if rescue treatment criteria were met, IAI patients received laser therapy, and laser therapy patients received IAI 2 mg every 8 weeks (after 5 monthly doses). Patients who received rescue treatment before cataract surgery were excluded. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in the laser control and pooled IAI groups before and after cataract surgery. The cumulative incidence of cataract surgery did not depend on treatment group assignment (rate ratio,= 1.517; 95% confidence interval, 0.782-2.944; P= 0.2174). At the last study visit before surgery, BCVA was 62.2 and 56.9 letters and CRT was 342 μm and 301 μm in the laser control and IAI groups, respectively. At the first study visit after cataract surgery, BCVA was improved significantly in both the laser control and IAI groups to 73.5 letters (P= 0.010 compared with last visit before surgery) and 67.2 letters (P < 0.001 compared with last visit before surgery), respectively. Corresponding change in CRT was a modest increase to 364 μm (P > 0.05 compared with last visit before surgery) and 359 μm (P= 0.013 compared with last visit before surgery), respectively. Incidence of cataract surgery was similar in both treatment groups. Despite a modest worsening in CRT after cataract surgery, BCVA was improved in both treatment groups.

Intravitreal Combined Aflibercept + Anti–Platelet-Derived Growth Factor Receptor β for Neovascular Age-Related Macular Degeneration: Results of the Phase 2 CAPELLA Trial

To compare the efficacy and safety of intravitreal aflibercept+ anti-platelet-derived growth factor receptor β (PDGFRβ) combination with intravitreal aflibercept injection (IAI) monotherapy in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). Phase 2, randomized, double-masked study. A total of 505 patients (eyes) with nAMD. Patients were randomized 1:2:2 to low-dose combination intravitreal anti-PDGFRβ 1 mg and aflibercept 2 mg (LD combo), high-dose combination intravitreal anti-PDGFRβ 3 mg and aflibercept 2 mg (HD combo), or IAI alone every 4 weeks through week 12. At week 12, patients in the HD combo and IAI groups were re-randomized to continue as assigned or switch to HD combo → IAI or IAI → HD combo and dosed every 4 weeks through week 28. During weeks 28 to 52, patients received treatment as needed per prespecified criteria. This report presents efficacy through week 28 and safety through week52. Mean best-corrected visual acuity (BCVA) change from baseline at week 12(primary end point). At week 12, mean BCVA gains from baseline were 5.8, 5.8, and 7.5 letters with LD combo, HD combo, and IAI, respectively (P= 0.21 for LD combo and P= 0.10 for HD combo vs. IAI). The corresponding proportions of eyes that gained ≥15 letters were 12%, 19%, and 22%, respectively. Mean reductions in central retinal thickness from baseline were 126.1, 127.1, and 126.9 μm, respectively. Proportions of eyes with complete resolution of fluid from baseline were 35%, 24%, and 42%, respectively. Vision and anatomic outcomes at week 28 were consistent with the week 12 results. Through week 52, the incidence of intraocular inflammation was 1.0%, 7.5%, 2.1%, 2.1%, and 0%, respectively. The incidence of Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events was 1.9%, 0.9%, 1.1%, 2.1%, and 1.9%, respectively. Intravitreal aflibercept+ anti-PDGFRβ did not improve BCVA over IAI alone. Anatomic outcomesevaluating complete fluid resolution favored IAI. Adverse events were consistent with the reported IAIsafety profile, except for a higher frequency of intraocular inflammation in the HD combo group.

Higher-Order Assessment of OCT in Diabetic Macular Edema from the VISTA Study: Ellipsoid Zone Dynamics and the Retinal Fluid Index

To investigate retinal fluid features and ellipsoid zone (EZ) integrity dynamics on spectral-domain OCT (SD-OCT) in eyes with diabetic macular edema (DME) treated with intravitreal aflibercept injection (IAI) in the VISTA-DME study. A post hoc subanalysis of a phase III, prospective clinical trial. Eyes received either IAI 2 mg every 4 weeks (2q4) or every 8 weeks after 5 initial monthly doses (2q8). All eyes from the VISTA Phase III study in the IAI groups imaged with the Cirrus HD-OCT system (Zeiss, Oberkochen, Germany) were included. The OCT macular cube datasets were evaluated using a novel software platform to generate retinal layer and fluid boundary lines that were manually corrected for assessment of change in EZ parameters and volumetric fluid parameters from baseline. The retinal fluid index (i.e., proportion of the retinal volume consisting of cystic fluid) was also calculated at each time point. The feasibility of volumetric assessment of higher-order OCT-based retinal parameters and its correlation with best-corrected visual acuity (BCVA). Overall, 106 eyes of 106 patients were included. Specifically, 52 eyes of 52 patients were included in the IAI 2q4 arm, and 54 eyes of 54 patients were included in the IAI 2q8 arm. Ellipsoid zone integrity metrics significantly improved from baseline to week 100, including central macular mean EZ to retinal pigment epithelium (RPE) thickness (2q4: 26.6 μm to 31.6 μm, P < 0.001; 2q8: 25.2 μm to 31.4 μm, P < 0.001). At week 100, central macular intraretinal fluid volume was reduced by >65% (P < 0.001) and central macular subretinal fluid volume was reduced by >99% in both arms (P < 0.001). Central macular retinal fluid index (RFI) significantly improved in both arms (2q4: 17.9% to 7.2%, P < 0.001; 2q8: 19.8% to 4.2%, P < 0.001). Central macular mean EZ-RPE thickness (i.e., a surrogate for photoreceptor outer segment length) and central RFI were independently correlated with BCVA at multiple follow-up visits. Intravitreal aflibercept injection resulted in significant improvement in EZ integrity and quantitative fluid metrics in both 2q4 and 2q8 arms and correlated with visual function.

Intravitreal aflibercept versus photodynamic therapy in Chinese patients with neovascular age-related macular degeneration: outcomes of the SIGHT study

Objective To assess the efficacy and safety of intravitreal aflibercept injection (IAI) compared with photodynamic therapy (PDT) in the treatment of Chinese patients with predominantly classic subfoveal choroidal neovascularization (CNV) lesions secondary to neovascular age-related macular degeneration (nAMD). Methods A randomized, double-blind, multi-center phase-3 clinical trial lasting for 52 weeks (from December 2011 to August 2014). Subjects were randomized in a 3:1 ratio to either IAI group or PDT-to-IAI group. Subjects in the IAI group received 2 mg IAI at baseline and at week 4, 8, 16, 24, 32, 40, 48, with sham injection at week 28, 36. Subjects in the PDT-to-IAI group were forced to receive PDT once at baseline and more time at week 12, 24 if PDT retreatment conditions were met. Sham injections were given in PDT-to-IAI group at baseline and at week 4, 8, 16 and 24, followed by 2 mg IAI at week 28, 32, 36, 40, 48. The primary outcome of efficacy were the change in mean Best Corrected Visual Acuity (BCVA) from baseline to week 28, and that of week 52. Safety evaluation included the percentage of subjects who suffered treatment emergent adverse events (TEAEs). Results Among the 304 subjects enrolled, there were 228 and 76 cases in IAI group and PDT-to-IAI group respectively. At week 28, the changes of mean BCVA in IAI group, PDT-to- IAI group compared to baseline were +14.0, +3.9 letters, respectively. At week 52, the changes of mean BCVA in two groups were +15.2, +8.9 letters respectively with the difference of +6.2 letters (95%CI 2.6−9.9, P=0.000 9). At week 52, the mean foveal retinal thickness in the two groups decreased by −189.6, −170.0 μm, respectively. Subjects with the most BCVA increase in IAI group were those aged <65, and those with active CNV lesion area <50% of total lesion area. The most common TEAEs in IAI group and PDT-to-IAI group are macular fibrosis [11.8% (27/228), 6.6% (5/76)] and BCVA decline [6.6% (15/228), 21.1% (16/76)]. There were 3 cases of arterial thromboembolic events defined in the antiplatelet experimental collaboration group, but all were considered unrelated to interventions. Conclusions The efficacy of aflibercept is superior to that of PDT in nAMD patients in China. The therapeutic effect of aflibercept persisted to week 52 in all subjects. The rate of adverse events was consistent with the safety data of aflibercept known before. Key words: Wet macular degeneration/drug therapy; Choroidal neovascularization/drug therapy; Angiogenesis inhibitors/therapeutic use; Antibodies, monoclonal/therapeutic use; Photochemotherapy

Comparing Cytokine Kinetics between Ranibizumab and Aflibercept in Central Retinal Vein Occlusion with Macular Edema

Purpose: To investigate dynamic changes in aqueous humor levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and inflammatory factors in patients receiving intravitreal ranibizumab injection (IRI) or intravitreal aflibercept injection (IAI) to treat central retinal vein occlusion (CRVO) with macular edema. Methods: In 22 CRVO patients scheduled to receive 3 doses of ranibizumab (11 eyes) or aflibercept (11 eyes) at monthly intervals, aqueous samples were collected at the time of intravitreal injection. The concentrations of VEGF, PlGF, soluble intercellular adhesion molecule-1, monocyte chemotactic protein (MCP)-1 (CCL2), platelet-derived growth factor-AA, interleukin (IL)-6, IL-8 (CXCL8), IL-12(p70) (IL12B), and IL-13 in aqueous samples were measured by the suspension array method. Results: Visual acuity and foveal thickness improved significantly in both the IRI group and the IAI group. In addition, aqueous levels of VEGF and PlGF as well as MCP-1 and IL-6 decreased significantly over time in both groups. These parameters did not significantly differ between both groups. Conclusions: In CRVO patients, both ranibizumab and aflibercept achieved similar improvement in clinical parameters and similar reductions in aqueous VEGF, PlGF, MCP-1, and IL-6 levels.

Endolaserless Vitrectomy With Intravitreal Aflibercept Injection for Proliferative Diabetic Retinopathy-Related Vitreous Hemorrhage (LASER LESS TRIAL)

Purpose: For proliferative diabetic retinopathy (PDR) eyes not requiring vitrectomy, Diabetic Retinopathy Clinical Research Protocol S and the CLARITY trial demonstrated better visual function and anatomical outcomes with less proliferative and diabetic macular edema consequences in the antivascular endothelial growth factor groups compared to the panretinal photocoagulation groups. Intravitreal aflibercept injection (IAI) may represent a useful therapy with vitrectomy for PDR-related vitreous hemorrhage (VH) as a viable alternative to intraoperative endolaser during vitrectomy. We will determine the safety and efficacy when aflibercept is used for PDR-related VH with endolaserless vitrectomy. Methods: Evaluation of endolaserless vitrectomy and 2 mg IAI for PDR-related VH. Eyes receive 1 preoperative and intraoperative IAI followed by randomization to a q8week group receiving 4 postoperative q4week IAI followed by q8week IAI or q16week group receiving 2 postoperative q4week IAI followed by q16week IAI. Main Outcome Measures: Herein, we present pooled safety and efficacy outcomes through 4 months. Results: Twenty-one of 24 eyes were randomized. Preoperative average visual acuity (VA) was 36 letters (20/200). At 4-month follow-up, 18 of 21 randomized eyes showed an average VA of 72 letters (20/40) with an average visual gain of 38 (range, 0-84 gain) letters. Average optical coherence tomography (OCT) central subfield thickness (CST) at 1-month postoperative follow-up was 311 µm. Average OCT CST at 4-month follow-up was 272 µm (average thinning of 38 µm). No significant short-term ocular or systemic adverse events were observed through 4 months. Conclusions: Endolaserless vitrectomy with IAI for PDR-related VH demonstrates short-term safety with significant VA improvement.

Outcomes of Diabetic Macular Edema Patients by Baseline Hemoglobin A1c: Analyses from VISTA and VIVID

To examine the relationship between glycemic control at baseline and response to anti-vascular endothelial growth factor treatment for diabetic macular edema (DME). Post hoc analysis of 2 similarly designed phase III trials, VISTA and VIVID. Patients with central-involved DME. Both VISTA and VIVID compared efficacy and safety of intravitreal aflibercept injection (IAI) with macular laser photocoagulation for DME. Current analysis focused on comparison within each treatment group in an integrated VISTA and VIVID dataset. Baseline hemoglobin A1c (HbA1c) was partitioned into 4 quartiles: 4.5% to <6.7% (n= 233), 6.7% to <7.4% (n= 206), 7.4% to <8.6% (n= 209), and 8.6% to <14.7% (n= 208). Outcomes were analyzed by mixed model for repeated measures. Intragroup differences were quantified by a regression model. Change from baseline best-corrected visual acuity (BCVA), central subfield thickness (CST), and HbA1c. In the IAI group, mean BCVA improvement from baseline did not depend on baseline HbA1c at week 52 (P= 0.1852), but seemed to be dependent at week 100 (P= 0.0425). The mean CST reduction from baseline was independent of baseline HbA1c at both weeks 52 (P= 0.1857) and 100 (P= 0.7346). Mean HbA1c change from baseline in IAI group was small across all HbA1c quartiles. In the laser group, the mean BCVA gain decreased with increasing baseline HbA1c at both weeks 52 (P= 0.0421) and 100 (P= 0.0001). Similarly, the mean CST decrease was greater with decreasing baseline HbA1c, at both weeks 52 (P= 0.0065) and 100 (P=0.0162). The mean HbA1c change from baseline in the laser group was minimal across HbA1c quartiles, although glycemic control tended to worsen in upper quartiles. The benefit of IAI in patients with DME was less dependent on their presenting glycemic status as opposed to laser.

Short-term focal macular electroretinogram of eyes treated by aflibercept & photodynamic therapy for polypoidal choroidal vasculopathy.

To compare short-term outcomes of intravitreal aflibercept injection (IAI) with or without initial photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV) using focal macular electroretinography (FMERG). Observation case series. Twelve patients (6 males, 6 females; 12 eyes) with naïve PCV received 3 initial IAIs and a single session of PDT 3days after the first IAI (combination group), and 13 patients (7 males, 6 females; 13 eyes) with naïve PCV received 3 initial IAIs only (IAI group) were retrospectively observed. Changes in visual acuity, central retinal thickness (CRT), central choroidal thickness (CCT), and FMERG parameters (FMERGs) were compared. The combination group showed improved visual acuity after the second and third IAI (P = 0.040, 0.019, respectively); both groups showed reduced CRT after the first IAI (P < 0.01, each). Only the combination group showed reduced CCT after the third IAI (P = 0.031). The FMERGs of the IAI group showed improved amplitudes of a-waves after the third IAI (P = 0.026) and of b-waves after the first and third IAI (P = 0.034, < 0.01, respectively); the combination group did not show improvement. The implicit times of the a- and b-waves were not changed in either group. Combination therapy and IAI monotherapy each improved visual acuity and retinal structure to a similar degree; combination therapy reduced choroidal thickness but did not improve FMERGs in the short term.

Intravitreal Aflibercept for Macular Edema Following Branch Retinal Vein Occlusion: 52-Week Results of the VIBRANT Study

To determine week 52 efficacy and safety outcomes in eyes with macular edema after branch retinal vein occlusion (BRVO) treated with 2 mg intravitreal aflibercept injection (IAI) compared with grid laser. VIBRANT was a double-masked, randomized, phase 3 trial. Eyes randomized and treated in VIBRANT were followed to week52. In the IAI group, eyes received IAI every 4 weeks through week 24 and IAI every 8 weeks through week 48 with rescue grid laser if needed at week 36. In the grid laser group, all eyes received grid laser at baseline and, if prespecified rescue criteria were met, 1 additional laser from week 12 to 20 and IAI every 8 weeks after 3 monthly doses from week 24 onward (the laser/IAI group). The primary outcome measure was percentage of eyes with improvement from baseline best-corrected visual acuity (BCVA) letter score ≥15 at week 24. All outcome measures at week 52 were exploratory, and P values are considered nominal. The percentage of eyes with improvement from baseline letter score ≥15 in the IAI and laser/IAI groups was 52.7% versus 26.7% (P= 0.0003) at week 24 and 57.1% versus 41.1% (P= 0.0296) at week 52. The corresponding mean change from baseline BCVA letter score was 17.0 versus 6.9 (P < 0.0001) at week 24 and 17.1 versus 12.2 (P= 0.0035) at week 52. The mean reduction from baseline central retinal thickness was 280.5 μm versus 128.0 μm (P < 0.0001) at week 24 and 283.9 μm versus 249.3 μm (P= 0.0218) at week 52. In the IAI group, 10.6% of eyes received rescue laser at week 36, and in the laser/IAI group, 80.7% received rescue IAI from week 24 to week 48. Traumatic cataract in 1 eye (1.1%) in the IAI group was the only ocular serious adverse event. After 6 monthly IAI, injections every 8 weeks maintained control of macular edema and visual benefits through week 52. In the laser group, rescue IAI given from week 24 onward resulted in substantial visual improvements at week52.

Intraocular Pressure in Patients with Neovascular Age-Related Macular Degeneration Receiving Intravitreal Aflibercept or Ranibizumab

To assess change in intraocular pressure (IOP) in patients with neovascular age-related macular degeneration (NVAMD) receiving intravitreal aflibercept injection (IAI) or ranibizumab in VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2 studies. Analyses from 2 randomized, active-controlled, phase III trials. A total of 2457 patients with NVAMD. Patients received IAI 2 mg every (q) 4 weeks (2q4), 0.5 mg q4 weeks (0.5q4), 2 mg q8 weeks (after 3 monthly doses; 2q8), or ranibizumab 0.5 mg q4 weeks (Rq4) for 52 weeks. At week 52, patients were switched to a variable regimen requiring at least quarterly dosing and allowing interim injections based on anatomic and visual assessment. Pre-injection IOP was analyzed in study and uninjected fellow eyes from baseline to week 96. Prespecified end points included mean change in IOP from baseline and prevalence of a >21 mmHg and >10 mmHg increase in IOP from baseline. Cumulative incidence of sustained (at 2 consecutive visits) IOP >21 mmHg, a single event of IOP >25 mmHg, and sustained IOP increase from baseline (≥5 mmHg) was also evaluated. Mean IOP change from baseline over 96 weeks in all IAI groups was consistently lower than in the Rq4 group, and this finding was replicated in both trials. In an analysis integrating both studies, the proportion of study eyes with IOP >21 mmHg at week 96 was 20.2%, 14.2%, 12.1%, and 12.5% in Rq4, 2q4, 2q8, and 0.5q4, respectively. Reduction in risk, relative to Rq4, of having sustained IOP >21 mmHg over 96 weeks was 62% (95% confidence interval [CI], 36%-78%), 50% (95% CI, 19%-70%), and 69% (95% CI, 45%-84%) for 2q4, 2q8, and 0.5q4, respectively. Risk reduction in the IAI groups for a sustained IOP increase ≥5 mmHg was 31% (95% CI, 8%-48%), 38% (95% CI, 17%-54%), and 47% (95% CI, 27%-61%), respectively. In uninjected fellow eyes, only sustained IOP >21 mmHg events were higher in the Rq4 group compared with all IAI groups. Incidence of elevated IOP in eyes with NVAMD was lower in all IAI groups than in the ranibizumab group.

Intravitreal Aflibercept for Macular Edema Following Branch Retinal Vein Occlusion: The 24-Week Results of the VIBRANT Study

To compare the efficacy and safety of intravitreal aflibercept injection (IAI) with macular grid laser photocoagulation for the treatment of macular edema after branch retinal vein occlusion (BRVO). The VIBRANT study was a double-masked, active-controlled, randomized, phase III trial. Treatment-naïve eyes with macular edema after BRVO were included in the study if the occlusion occurred within 12 months and best-corrected visual acuity (BCVA) was between ≤73 and ≥24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/40-20/320 Snellen equivalent). Eyes (1 eye per patient) received either IAI 2 mg every 4 weeks (n=91) from baseline to week 20 or grid laser (n=92) at baseline with a single grid laser rescue treatment, if needed, from weeks 12 through 20. The primary outcome measure was the proportion of eyes that gained ≥15 ETDRS letters from baseline BCVA at week 24. Secondary end points included mean change from baseline BCVA and central retinal thickness (CRT) at week 24. The proportion of eyes that gained ≥15 ETDRS letters from baseline at week 24 was 52.7% in the IAI group compared with 26.7% in the laser group (P=0.0003). The mean improvement from baseline BCVA at week 24 was 17.0 ETDRS letters in the IAI group and 6.9 ETDRS letters in the laser group (P<0.0001). The mean reduction in CRT from baseline at week 24 was 280.5 μm in the IAI group and 128.0 μm in the laser group (P<0.0001). Traumatic cataract in an IAI patient was the only ocular serious adverse event (SAE) that occurred. There were no cases of intraocular inflammation or endophthalmitis. The incidence of nonocular SAEs was 8.8% in the IAI group and 9.8% in the laser group. One Anti-Platelet Trialists' Collaboration-defined event of nonfatal stroke (1.1%) and 1 death (1.1%) due to pneumonia occurred during the 24 weeks of the study, both in patients in the laser group. Monthly IAI provided significantly greater visual benefit and reduction in CRT at 24 weeks than grid laser photocoagulation in eyes with macular edema after BRVO.