Aflibercept For Diabetic Macular Edema Research Articles

Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema

Biosimilars may be lower-cost alternatives to originator biologic products, potentially offering expanded access or reduced economic burden, but have not been evaluated with aflibercept in diabetic macular edema (DME). To compare efficacy and safety of MYL-1701P, an aflibercept biosimilar, with reference aflibercept (Eylea [Regeneron]) in DME. This was a double-masked, randomized clinical trial that included participants at 77 centers across the US, Europe, Japan, and India. Included in the analysis were individuals 18 years and older with type 1 or type 2 diabetes with central DME and best-corrected visual acuity (BCVA) letter score of 73 to 38 in the study eye using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Study data were analyzed from October to December 2021. Formulations of MYL-1701P (0.5-mg vial) or reference aflibercept every 4 weeks for 5 consecutive intravitreal injections, followed by every 8 weeks through week 52. The primary outcome was the adjusted difference in least squares mean (SE) change from baseline BCVA letter score at week 8 with an equivalence margin of -3 to +3 letters. Secondary outcomes included change in central subfield thickness (CST), BCVA, number of injections over 52 weeks, incidence of adverse events (AEs), and antidrug antibodies (ADAs). A total of 355 participants (mean [SD] age, 62.2 [9.2] years; 216 male [60.8%]) were randomized to MYL-1701P (179 participants [50.4%]) and aflibercept (176 participants [49.6%]). At week 8, mean (SE) change in BCVA was 6.60 (0.55) letters vs 6.56 (0.55) letters in the MYL-1701P vs aflibercept groups. The adjusted mean difference of 0.04 letters (90% CI, -1.16 to 1.24 letters) met the primary outcome. At week 8, mean (SE) change in CST was -112 (7) μm vs -124 (7) μm in the MYL-1701P vs aflibercept groups (adjusted mean difference, 12 μm; 90% CI, -3 to 26 μm). The incidence of treatment-emergent AEs in the MYL-1701P and aflibercept arms were ocular (30.9% [55 of 178] vs 29.5% [52 of 176]), serious ocular (0.6% [1 of 178] vs 1.1% [2 of 176]), nonocular (65.2% [116 of 178] vs 65.3% [115 of 176]), and serious nonocular (16.9% [30 of 178] vs 11.9% [21 of 176]). The mean (SD) total number of injections was 8.4 (2.1) vs 8.7 (1.8) in the MYL-1701P vs aflibercept groups. The incidence of treatment-induced or treatment-boosted ADAs was 2.8% (5 of 177) vs 5.7% (10 of 176) in the MYL-1701P vs aflibercept arms. MYL-1701P demonstrated clinical equivalence in regard to efficacy, with comparable safety and immunogenicity, to reference aflibercept. These findings support use of MLY-1701P as an alternative to reference aflibercept. ClinicalTrials.gov Identifier: NCT03610646.

Efficacy of Faricimab versus Aflibercept in Diabetic Macular Edema in the 20/50 or Worse Vision Subgroup in Phase III YOSEMITE and RHINE Trials

PurposeDRCR.net Protocol T data suggest the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME enrolled in faricimab phase 3 trials with baseline Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA ≤20/50. DesignYOSEMITE/RHINE were identically designed, multicenter, randomized, double-masked, active comparator–controlled, noninferiority trials. ParticipantsAdults aged ≥18 years with center-involving macular edema secondary to type 1 or 2 diabetes. MethodsPatients were randomized to faricimab every 8 weeks (Q8W), faricimab per a personalized treat-and-extend–based regimen (T&E), or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intent-to-treat population with baseline BCVA ≤20/50 (ETDRS letters <69). Main Outcome MeasuresChanges in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses. ResultsIn YOSEMITE/RHINE, 220/217 patients in the faricimab Q8W; 220/219, faricimab T&E; and 219/214, aflibercept Q8W arms had baseline BCVA ≤20/50. In both trials, mean change in ETDRS BCVA was comparable between treatments at years 1 and 2. In YOSEMITE, adjusted mean (95% CI) change from baseline in CST (μm) at year 1 was greater with faricimab Q8W (–232.8 [–243.5, –222.1]) and faricimab T&E (–217.4 [–227.9, –206.9]) versus aflibercept Q8W (–190.4 [–200.9, –179.8]; P<0.0001 and P=0.0004, respectively). The pattern was similar in RHINE: faricimab Q8W, –214.2 (–225.3, –203.1); faricimab T&E, –206.6 (–217.4, –195.7); aflibercept Q8W, –186.6 (–197.7, –175.5); P=0.0006 and P=0.0116 for faricimab arms versus aflibercept, respectively. In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. Median time to first CST <325 μm and first absence of intraretinal fluid was shorter in the faricimab arms versus aflibercept, with fewer injections on average. ConclusionsIn patients with DME and baseline ETDRS BCVA ≤20/50, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept over 2 years of treatment.

Long-Term Change in Renal Function After Intravitreal Anti-VEGF Treatment for Diabetic Macular Edema: A 2-Year Retrospective Cohort Study.

To investigate the longitudinal changes in renal function and associated factors after intravitreal anti-vascular endothelial growth factor (VEGF) administration in diabetic macular edema (DME). A total of 108 patients who had received intravitreal ranibizumab or aflibercept for DME and had follow-up visits for at least 2years in one hospital were retrospectively enrolled. The estimated glomerular filtration rate (eGFR) at baseline and during the follow-up period and receipt of any renal replacement therapy were recorded. Linear regression and Cox regression models were used to evaluate factors associated with eGFR decline and renal replacement therapy. After intravitreal anti-VEGF treatment, eGFR showed a mean decline of -10.4 ± 23.2% and -16.5 ± 26.4% at months 12 and 24, respectively. Patients in the eGFR > 120mL/min and 15-30mL/min groups had the greatest decline (-32.0 ± 20.6% and -37.4 ± 30.9%, respectively) while those in the 61-90mL/min group had the smallest decline (-4.3 ± 19.7%) in eGFR after the 2-year treatment. One out of 52 patients (1.9%) receiving ranibizumab and five out of 56 patients (8.9%) receiving aflibercept started hemodialysis or peritoneal dialysis within the 2-year follow-up period (P = 0.21). Baseline eGFR correlated with renal replacement therapy after intravitreal anti-VEGF treatment (hazard ratio = 0.879 per increase of 1 in eGFR, P = 0.018). In DME patients receiving intravitreal anti-VEGF treatment, a persistent decline in eGFR was observed during the 2-year treatment course. Patients with extremely high or low eGFR had greater eGFR decline, and those with poor baseline eGFR tended to require dialysis after intravitreal anti-VEGF treatment.

Aflibercept for Diabetic Macular Edema in Real-Life Practice in GREece: Three-Year Outcomes of the ADMIRE Study

ABSTRACT Purpose To evaluate the efficacy and safety of intravitreal aflibercept injections for diabetic macular edema (DME) treatment in a tertiary referral center in Greece. Methods ADMIRE was a prospective, observational cohort study of patients with DME. Efficacy was assessed by change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month 36 after treatment with intravitreal aflibercept in treatment-naive patients and previously treated patients. Safety was evaluated by recording any patients-reported events. Results Participants in the study were 94 patients with DME, 70 treatment naive and 24 previously treated with ranibizumab. At month 36 of the follow-up period, the mean change in BCVA was +7.4 letters compared to baseline (p < .001). The mean change in BCVA in treatment-naive patients was +8.9 letters and differed significantly compared to previously treated patients (+5.9 letters, p = .041). In addition, patients who received a loading dose of 5 monthly injections at the initiation of treatment provided better VA outcomes (+11.4 vs. +6.1 letters, p < .001). Accordingly, the mean CST at month 36 (369.6 ± 72.8 μm) was significantly decreased compared to baseline (479.2 ± 68.3 μm, p < .001). Overall, the mean number of injections at month 36 was 13.4. Safety analysis showed that the reported ocular adverse events during the 36-month study period were mild and not sight-threatening. Conclusion Intravitreal aflibercept was found to be safe and effective for the treatment of DME in real-life in a Greek population. Treatment-naive patients and those who received a loading dose of five consecutive monthly injections at initiation of treatment exhibited better outcomes, suggesting that early and effective treatment may prevent vision loss.

Angiographic biomarkers are significant predictors of treatment response to intravitreal aflibercept in diabetic macular edema

This prospective single-center study aims to identify biomarkers that predict improvement in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6 months, in 76 eyes with diabetic macular edema (DME) treated monthly with intravitreal aflibercept. At baseline, all patients underwent standardized imaging with color photography, optical coherence tomography (OCT), fluorescein angiography (FA) and OCT angiography (OCTA). Glycosylated hemoglobin, renal function, dyslipidemia, hypertension, cardiovascular disease and smoking were recorded. Retinal images were graded in a masked fashion. Baseline imaging, systemic and demographic variables were investigated to detect associations to BCVA and CRT change post aflibercept. Predictors of BCVA improvement included greater macular vessel density quantified using OCTA (p = 0.001) and low-density lipoprotein (LDL) ≥ 2.6 mmol/L (p = 0.017). Lower macular vessel density eyes showed a significant reduction in CRT but no BCVA improvement. Predictors of CRT reduction included peripheral non-perfusion seen on ultrawide-field FA (p = 0.005) and LDL ≥ 2.6 mmol/L (p < 0.001). Retinal angiographic biomarkers derived from OCTA and ultrawide-field FA may help predict functional and anatomic response to anti-vascular endothelial growth factor (VEGF) therapy in patients with DME. Elevated LDL is associated with treatment response in DME. These results may be used to better-select patients who will benefit from intravitreal aflibercept for treatment of DME.

Ultra-Wide-Field Fluorescein Angiography Assessment of Non-Perfusion in Patients with Diabetic Retinopathy Treated with Anti-Vascular Endothelial Growth Factor Therapy

Purpose: To follow the evolution of peripheral ischemia by fluorescein angiography (FA) on ultra-wide-field (UWF) images in diabetic patients treated with anti-vascular endothelial growth factor (anti-VEGF) for macular edema. Methods: Prospective, non-interventional cohort study analyzing UWF-FA images of 48 patients with diabetic retinopathy (48 eyes) treated for diabetic macular edema. UWF-FA was performed at baseline and after one year of anti-VEGF therapy (M12). The primary endpoint was the change in the non-perfusion index. Results: Of the 48 patients included in this study, 25 completed the one-year follow-up, and 20 had FA images of sufficient quality to be interpreted. The non-perfusion index did not significantly change from baseline after one year of anti-VEGF treatment (0.7% of the non-perfused area at baseline versus 0.5% at M12; p = 0.29). In contrast, the diabetic retinopathy severity score improved significantly between baseline and M12. Conclusions: Anti-VEGF treatment with aflibercept for diabetic macular edema had no impact on the retinal perfusion assessed by FA, but it allowed for artificially improving diabetic retinopathy severity scores.

Morphological and functional changes in the macular area in diabetic macular edema after a single intravitreal injection of aflibercept.

To evaluate the changes in macular morphology and function after a single intravitreal injection of aflibercept in diabetic macular edema (DME) using optical coherence tomography angiography (OCTA) and MP-3 microperimetry. Twenty-eight patients (42 eyes) diagnosed with DME were treated with intravitreal injection of aflibercept. The changes in best corrected visual acuity (BCVA), central retinal thickness (CRT), foveal avascular zone (FAZ) area, vessel density of superficial retinal capillary plexus (SVD), vessel density of deep retinal capillary plexus (DVD), mean light sensitivity (MLS), 2° fixation rate (P1), 4° fixation rate (P2), and other indicators 1mo after treatment were compared; of these, BCVA was converted into logarithm of the minimum angle of resolution (logMAR), and the correlation among the factors was analyzed. After treatment, logMAR BCVA was 0.47±0.24, which was significantly better than that before treatment (0.63±0.28, P<0.001). The CRT was 359.21±107.87 µm after treatment, which was significantly lower than before treatment (474.10±138.20 µm, P<0.001). The FAZ area, SVD, and DVD were not significantly changed after treatment compared with the baseline. MLS was 22.16±4.20 dB after treatment, which was significantly higher than before treatment (19.63±4.23 dB, P<0.001). P2 significantly increased after treatment than before treatment (P=0.007). P1 had no significant change after treatment than before treatment (P=0.086). A single intravitreal injection of aflibercept effectively reduces macular edema and improves retinal sensitivity, fixation stability, and visual acuity, possibly without causing significant changes in the retinal vascular condition in a short time.

Evaluating the Treatment of Diabetic Macular Edema with Aflibercept Based on a Regional Network of Ophthalmologic Care Givers.

In Austria, anti-VEGF therapies are reimbursed only in clinical settings. This study aimed to describe the outcome of a treat and extend regimen (TER) with aflibercept for diabetic macular edema (DME) in a network of practitioners. In a prospective study over 36 months, patients with DME were treated with a loading dose of aflibercept and further on with adjusted treatment intervals based on optical coherence tomography (OCT) findings. All patients were monitored in an outpatient setting by regional ophthalmologists, and the treatment was administered in the clinic. Main outcome parameters were best-corrected visual acuity (BCVA) from baseline to the last regular visit. Number of visits at the practitioner's office as well as the number of injections were secondary outcome parameters. Thirty-three patients completed the study at their final visit. BCVA improved significantly by 5.8 letters between baseline and the final visit from 70.4 letters at baseline (p=0.004). Patients visited the practitioner's office 12.8 times in the observation period of 36 months. 3.7, 5.1, and 3.9 visits were performed, respectively, in the first, second, and third years, and 25.5 ± 7.9 injections were performed. The mean interval of injections over the observation period was 6.2 ± 2.2 in weeks. The treat and extend regimen was valuable for treating patients with DME in this specific setting. The functional results of this study were comparable to those of other real-world evaluations. Adherence to the same treating institution seems to be important to avoid differences in therapeutic decision making and may also increase patient's compliance.

Renal thrombotic microangiopathy and nephrotic proteinuria induced by intravitreal injection of aflibercept for diabetic macular edema

BackgroundVascular endothelial growth factor inhibitors (VEGFIs) are used to treat malignant neoplasms and ocular diseases by inhibiting angiogenesis. Systemic use of VEGFIs has various side effects, including hypertension, proteinuria, and thrombotic microangiopathy, but adverse events due to intravitreal injection of VEGFIs have not been fully clarified. Although age-related macular degeneration was initially the most common target of intravitreal injection of VEGFIs, it has also been applied sporadically for diabetic macular edema in recent years. Proteinuria following intravitreal injection of VEGFIs would be reversible. In patients with diabetes mellitus (DM), however, it would be difficult to determine whether kidney damage arises from the clinical course of DM or from intravitreal injection of VEGFIs for diabetic macular edema.Case presentationA 55-year-old woman with a 20-year history of type 2 DM began intravitreal injection of VEGFI (aflibercept, 2 mg every 4 weeks) for treatment of diabetic macular edema 2 years previously. She presented with leg edema, hypertension, and nephrotic-range proteinuria 14 months after the first injection. Histological examination of renal biopsy specimens revealed diabetic nephropathy with renal thrombotic microangiopathy probably associated with intravitreal injection of VEGFI. The patient’s nephrotic syndrome completely improved at 6 months after simply discontinuing aflibercept.ConclusionsThis is a precious report of pathologically investigated renal thrombotic microangiopathy leading to nephrotic syndrome due to intravitreal injection of aflibercept for diabetic macular edema in a patient with type 2 DM. Renal function and proteinuria should be monitored in diabetic patients who receive intravitreal injection of a VEGFI. If kidney damage develops independent of the clinical course of DM during intravitreal injection of a VEGFI, renal biopsy should be performed and intravitreal VEGFI injection discontinued.

Intravitreal aflibercept for diabetic macular edema in real-world clinical practice in Japan: 24-month outcomes

PurposeTo report the safety and effectiveness of intravitreal aflibercept (IVT-AFL) for diabetic macular edema (DME) in the real-world clinical practice setting in Japan.MethodsIn this prospective, multicenter, observational, post-marketing surveillance, patients with DME newly receiving IVT-AFL were enrolled. During a 24-month follow-up, the primary outcome was the occurrence of safety events. Other pre-specified endpoints were effectiveness indicators, such as best-corrected visual acuity (BCVA), central retinal thickness, and injection frequency.ResultsIn total, 646 patients administered at least one IVT-AFL injection were included in the safety analysis. During the follow-up period, adverse events occurred in 42 patients (6.50%), whereas adverse drug reactions occurred in 12 (1.86%). In the 12 patients who had adverse drug reactions, seven events occurred in seven patients within the first month of the most recent injection. In addition, 622 patients were included in the effectiveness analysis set. The number of injections over 24 months was 3.6 ± 3.0 (mean ± standard deviation [SD]). BCVA (logarithm of the minimum angle of resolution) was 0.437 ± 0.362 (mean ± SD) (n = 622) at baseline and 0.321 ± 0.348 (n = 177) after 24 months of treatment with IVT-AFL. Central retinal thickness was 440.8 ± 134.2 μm (mean ± SD) (n = 444) at baseline and 355.5 ± 126.4 μm (n = 140) at 24 months.ConclusionRoutine administration of IVT-AFL for DME was not associated with new safety concerns, and BCVA outcomes were maintained over 24 months in the real-world setting. Nonetheless, patients in this real-world setting received fewer injections than those in clinical trials, suggesting that a margin for improvement exists in clinical practice.Trial registrationClinicalTrials.gov: NCT02425501.

Safety and Outcomes of Intravitreal Aflibercept in Diabetic Macular Edema - A Systematic Review.

Recent evidence on the role of vascular endothelial growth factor (VEGF) in the pathogenesis of ischemia and microvascular hyperpermeability leading to macular edema has brought anti-VEGF intravitreal therapy into the limelight. We performed a systematic literature review focusing on the outcomes and safety of the intravitreal use of aflibercept in diabetic macular edema. The studies documented cases with at least three consecutive intravitreal injections of aflibercept (IVA) repeated monthly with a follow-up period of at least one year. The outcomes were evaluated in terms of reported functional and anatomical improvement of the macula, as reflected by changes in visual acuity and macular thickness measured by Optical Coherence Tomography (OCT). In addition, for safety assessment, all reported local and general adverse effects were analyzed. All studies showed an overall significant anatomical and functional improvement. In patients with the 5 IVA monthly at the beginning of the therapy, the visual gain at 52 weeks varied widely between 5 and 18.9 EDRS letters, with a mean value of 9.48 letters. The higher gain was obtained in treatment naïve patients, with worse VA and increased CST at baseline. The lower gain was obtained in patients previously treated with anti- VEGF. Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events were not statistically different between the aflibercept group and the laser group. Intravitreal aflibercept therapy provides significant improvement in visual acuity and a good safety profile. Randomized studies are needed to document the optimal frequency of intravitreal injections for optimal treatment.

Исследование эффективности антиангиогенной терапии диабетического макулярного отека на авитреальных глазах в условиях реальной клинической практики

Despite the vitrectomy performed for diabetic macular edema (DME), some patients still have symptoms of the disease due to overproduction of VEGF by the ischemic retina, which requires regular administration of an antiangiogenic drug. Studies of the pharmacokinetics of antiangiogenic drugs after vitrectomy in humans have not been carried out. Data from the DRCR.net (Post-Hawk Protocol I) study and real-life clinical practice studies show similar results for anti-VEGF DMO therapy in vitreous eyes and after vitrectomy (2, 7). Purpose. To assess the effectiveness of antiangiogenic therapy with aflibercept for DMO in avitreal eyes in real clinical practice. Methods. The initial and after vitrectomy best corrected visual acuity (BCVA) and central retinal thickness (CRT) were determined according to OCT data, then these parameters were monitored by 1, 3, 6 and 12 months after the start of antiangiogenic therapy with aflibercept. 14 patients (14 eyes) with persistent DME underwent vitrectomy with removal of the internal limiting membrane, in 5 of them the epiretinal fibrosis was removed and 3 of them with a traction retinal detachment that was also removed with air tamponade. Results. Aflibercept intravitreal injections were started with 5 loading doses by 1-11 months after vitrectomy. On average, after 12 months, patients received 7.2 injections, while there was no need for laser surgery of the macular zone. By the end of the study, the CRT decreased by 255 ±86 µm, the BCVA was 0.35 ± 0.2 in comparison with the initial 0.07±0.03 (on a decimal scale). Conclusions. The effectiveness of the anti-VEGF therapy with aflibercept for DME in avitreal eyes was confirmed by an increase in functional (BCVA) and normalization of morphological (CRT on OCT) parameters after the first injections during the period of loading doses. Previous vitrectomies in patients with DMO do not affect the long-term favorable clinical outcomes of anti-VEGF therapy with aflibercept. Key words: vitrectomy, diabetic macular edema, aflibercept, anti-VEGF, OCT, best corrected visual acuity, central retinal thickness.

Aflibercept in clinical practice; visual acuity, injection numbers and adherence to treatment, for diabetic macular oedema in 21 UK hospitals over 3 years

IntroductionRandomised controlled trials provide evidence that a treatment works. Real world evidence is required to assess if proven treatments are effective in practice.MethodRetrospective data collection on patients given aflibercept for diabetic macular oedema over 3 years from 21 UK hospitals: visual acuity (VA); Index of multiple deprivation score (IMD); injection numbers; protocols used, compared as a cohort and between sites.ResultsComplete data: 1742 patients (from 2196 eligible) at 1 year, 860 (from 1270) at 2, 305 (from 506) at 3 years. The median VA improved from 65 to 71, 70, 70 (ETDRS letters) at 1, 2 and 3 years with 6, 9 and 12 injections, respectively. Loss to follow-up: 10% 1 year, 28.8% at 3. Centres varied: baseline: mean age 61–71 years (p < 0.0001); mean IMD score 15–37 (p < 0.0001); mean VA 49–68 (p < 0.0001). Only four centres provided a loading course of five injections at monthly intervals and one 6. This did not alter VA outcome at 1 year. Higher IMD was associated with younger age (p = 0.0023) and worse VA at baseline (p < 0.0001) not total number of injections or change in VA. Lower starting VA, higher IMD and older age were associated with lower adherence (p = 0.0010).ConclusionsThe data showed significant variation between treatment centres for starting age, VA and IMD which influenced adherence and chances of good VA. Once treatment was started IMD did not alter likelihood of improvement. Loading dose intensity did not alter outcome at one year.

Effect of switching treatment to ranibizumab or aflibercept for diabetic macular edema in patients refractory to bevacizumab

Effect of switching treatment to ranibizumab or aflibercept for diabetic macular edema in patients refractory to bevacizumab

Comparison of two-year treatment outcomes between subthreshold micropulse (577nm) laser and aflibercept for diabetic macular edema.

To compare two-year treatment outcomes of subthreshold micropulse (577nm) laser and aflibercept for diabetic macular edema (DME). Retrospective case-control study. A total 164 eyes in 164 DME patients treated with either micropulse laser (86 eyes) or intravitreal aflibercept monotherapy (78 eyes) were recruited. Main outcome measures included at least five Early Treatment Diabetic Retinopathy Study (ETDRS) letters' improvement from baseline at 6, 12 and 24months. Rescue aflibercept was initiated in 24% of eyes in micropulse laser group. At 6-month visit the aflibercept group achieved a higher percentage of eyes with at least 5-letter visual acuity improvement than micropulse laser group (56% vs 38%, P = 0.044), however, this was not the case at 12-month (45% vs 49%, P = 0.584) and 24-month visits (49% vs 57%, P = 0.227). At 6-month visit the aflibercept group achieved a higher percentage of eyes with at least 10% improvement of central macular thickness (73% vs 49%, P = 0.005), but this was not the case at 12-month (73% vs 70%, P = 0.995) and 24-month visits (85% vs 84%, P = 0.872). Aflibercept achieved faster and higher rates of anatomical and functional improvement than micropulse laser in DME patients. Long term efficacy of treatment did not result in significant differences between aflibercept monotherapy and micropulse laser in DME patients. Primary treatment of micropulse laser with deferred rescue aflibercept might be the treatment option without reducing the chance of visual improvement in DME eyes.

Intravitreal Ranibizumab Versus Aflibercept for Diabetic Macular Edema in Vitrectomized Eyes: 12 Month Results

ABSTRACT Purpose To evaluate and compare the effect of intravitreal ranibizumab and aflibercept on the treatment of diabetic macular edema in previously vitrectomized eyes. Materials and Methods A total of fifty-two vitrectomized eyes with diabetic macular edema were retrospectively evaluated. Patients were divided into two groups; Group 1 (n = 30 eyes) received 0.5 mg/0.05 mL intravitreal ranibizumab and Group 2 (n = 22 eyes) received 2 mg/0.05 mL intravitreal aflibercept for 3 monthly injections and thereafter as needed over 12 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT) and injection number of the drugs were the outcomes of the study. Results Fifty-two previously vitrectomized eyes were enrolled in this study. Thirty-eight of them (73.1%) were male and 14 (26.9%) were female. The mean age was 61.54 ± 7.33 year (range: 50–72 year). BCVA increased and CMT decreased significantly in both groups at the end of the follow-up period (p < .05). The change in BCVA and CMT was not statistically different between the groups (p > .05). However, there was a statistically significant difference between the groups in terms of the injection number (p < .05). Conclusion Both ranibizumab and aflibercept were found to be effective on diabetic macular edema in previously vitrectomized eyes. There was no difference between the groups in terms of visual acuity gain and CMT improvement. However, the number of injections was found to be lower in aflibercept group. Therefore, aflibercept may be preferred in the treatment of macular edema in previously vitrectomized eyes.

Outcomes of a 2-year treat-and-extend regimen with aflibercept for diabetic macular edema

This prospective, open-label, single-arm, non-randomized clinical trial, assessed the efficacy of a 2-year treat-and-extend (T&E) regimen involving intravitreal aflibercept injection (IAI), with the longest treatment interval set to 16 weeks, and adjunct focal/grid laser in diabetic macula edema (DME) patients. We examined 40 eyes (40 adults) with fovea-involving DME from 8 Japanese centers between April 2015 and February 2017. Participants received IAI with an induction period featuring monthly injections and a subsequent T&E period featuring 8–16-week injection interval, adjusted based on optical coherence tomography findings. The primary endpoints were mean changes in the best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Thirty patients (75%) completed the 2-year follow-up. The mean BCVA and CST changed from 60.5 ± 15.6 letters and 499.2 ± 105.6 µm at baseline to 66.6 ± 17.1 letters (P = 0.217) and 315.2 ± 79.0 µm (P < 0.001), respectively, after 2 years. The treatment interval was extended to 12 and 16 weeks in 6.7% and 66.7% of patients, respectively, at the end of 2 years. The T&E aflibercept regimen with the longest treatment interval set to 16 weeks, with adjunct focal/grid laser may be a rational 2-year treatment strategy for DME.

Treat-and-extend therapy with aflibercept for diabetic macular edema: a prospective clinical trial.

To investigate the efficacy and safety of a treat-and-extend (T&E) regimen using aflibercept (Eylea) for diabetic macular edema (DME). Prospective, open-label, multicenter, single-arm, nonblinded clinical study. Forty eyes of 40 patients with DME received a T&E regimen of intravitreal aflibercept injection (IAI) with the longest treatment interval set to 16weeks and adjunct focal/grid laser for 1year. An intent-to-treat analysis was performed using the same last-observation-carried-forward method. A per-protocol analysis was also performed for patients who completed a 1-year T&E regimen. The primary endpoints were mean changes in best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Secondary endpoints included IAI-interval extension and resultant IAI numbers and the association between an early response to IAI and final BCVA gain at 1year. Thirty-one patients (77.5%) completed the 1-year aflibercept T&E regimen. In these per-protocol participants, the mean CST improvement/reduction was 187.3 ± 145.0µm (P < .001), but the mean BCVA gain was limited to 4.3 ± 12.2 letters (P = .782). Subanalysis revealed that eyes that gained ≥ 4 letters (median at week 12) after the initial 3 consecutive IAIs (induction phase) achieved greater vision improvement (13.8 ± 9.5 letters) than did the residual eyes (- 4.3 ± 9.2 letters) at 1year (P < .001). Treatment intervals were extended to 12 and 16weeks in 16.1% (5/31) and 45.2% (14/31) of the patients, respectively. The mean IAI number was 7.0 ± 1.1. The results of this study suggest that although the BCVA improvement might be somewhat less than that of frequent treatment, a T&E aflibercept regimen with the longest treatment interval set to 16weeks is a realizable rational strategy for DME treatment over 1year.

Treat-and-extend vs pro re nata regimens of aflibercept in diabetic macular edema

Objective The aim of the present study was to compare between two regimens of intravitreal injection of aflibercept in diabetic macular edema (DME): treat-and-extend (T and E) vs pro re nata (PRN). Background T and E and PRN (as needed) regimens of intravitreal antivascular endothelial growth factor treatment have been found to reduce the injection burden on patients and improve the cost-effectiveness of the treatment of macular edema. Patients and methods This prospective randomized comparative study was conducted on patients with DME, who were randomly divided into two groups. Eyes in group I were treated with T and E regimen of intravitreal injection of aflibercept and eyes in group II were treated with PRN regimen of intravitreal injection of aflibercept. Results The mean baseline best-corrected visual acuity (BCVA) was 0.833 ± 0.159 logarithm of the minimum angle of resolution (logMAR) units in patients with T and E protocol and 0.880 ± 0.077 logMAR units in patients with PRN protocol; after the loading dose, the BCVA was improved to 0.673 ± 0.103 logMAR units in patients with T and E protocol and 0.700 ± 0.093 logMAR units in patients with PRN protocol; and after resolving edema, the BCVA was 0.353 ± 0.106 logMAR units in patients with T and E protocol and 0.407 ± 0.096 logMAR units in patients with PRN protocol, with no statistically significant differences between the groups. However, there was a highly statistically significant difference between the groups regarding number of injections (P = 0.005). Conclusion Overall, an individualized T and E regimen has the potential to reduce clinic burden and improve patient compliance, while still maintaining effectiveness and providing well-tolerated treatment for DME.

Comparison of 2-Year Outcomes between Intravitreal Ranibizumab and Intravitreal Aflibercept for Diabetic Macular Edema with "Treat-and-Extend" Regimen-Its Usefulness and Problems.

Background: To compare the effectiveness of intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) performed with the treat-and-extend (TAE) regimen on eyes with diabetic macular edema (DME). Patients and methods: This is a retrospective study of 125 eyes of 125 treatment-naïve DME patients who received anti-VEGF injections at three consecutive monthly intervals as the loading phase. The changes in the best-corrected visual acuity (BCVA), central retinal thickness (CRT), diabetic retinopathy severity scale (DRSS), and total injection numbers were compared between the two anti-VEGF agents. Results: Among 125 eyes, 26 eyes completed the treatment with the TAE regimen for 24 months (20.8%). Thirteen eyes of 13 patients (mean age, 70.9 ± 6.0 years) received intravitreal injections of 0.5 mg ranibizumab, and 13 eyes of 13 patients (65.9 ± 8.6 years) received 2 mg aflibercept. No significant differences were detected in the baseline demographics. At 24 months, BCVA was significantly improved in both groups; from 0.31 ± 0.19 to 0.10 ± 0.12 logMAR units for IVR and 0.41 ± 0.19 to 0.16 ± 0.28 logMAR units for IVA (p = 1.29 × 10−9). CRT was significantly reduced in both groups; 440.9 ± 69.3 to 307.5 ± 66.4 μm for IVR and 473.9 ± 71.5 to 317.8 ± 71.2 μm for IVA (p = 3.55 × 10−9). No significant differences were detected in the improvements of BCVA, CRT in both groups, and the total injection numbers for 24 months (11.0 ± 1.2 for the IVA group and 12.0 ± 1.0 the IVR group). DRSS was significantly improved in both groups (p = 0.0004 for IVR and p = 0.009 for IVA). Conclusion: No significant differences were detected in the improvements of BCVA or CRT and injection numbers between the IVR and IVA groups treated with the TAE regimen. These results indicate that the results of the treatment with both agents with the TAE regimen were equally effective, but only 20.8% of patients completed 24 months of continuous treatment with the TAE regimen. Synopsis: There are no significant differences regarding effectiveness between the IVR and IVA groups treated with the TAE regimen for DME eyes.