Menoufia Medical Journal

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 33  |  Issue : 2  |  Page : 599--603

Aflibercept vs ranibizumab in management of diabetic macular edema


Khaled E Ahmed, Ahmed I Basiony, Eman S Hamad 
 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Correspondence Address:
Eman S Hamad
Shebin El Kom, Menoufia
Egypt

Abstract

Objective The aim was to compare the efficacy of intravitreal injection of aflibercept and ranibizumab in the treatment of diabetic macular edema (DME). Background Diabetic retinopathy is a microangiopathy of the retina from which nearly all persons with diabetes eventually suffer. DME is one of its complications that threaten the patient's vision. Patients and methods This is a randomized prospective study. Fifty eyes with DME were divided into two groups (each containing 25 eyes). Eyes in group I were treated with intravitreal injection of aflibercept, and eyes in group II were treated with intravitreal injection of ranibizumab. All eyes had three successive injections. The outcomes were visual acuity and central subfield macular thickness. Results The mean baseline best-corrected visual acuity (BCVA) in group I was 0.65 ± 0.12 μm and in group II was 0.63 ± 0.19 μm (P = 0.72). After 3 months, the mean BCVA in group I improved to 0.34 ± 0.16 and in group II improved to 0.44 ± 0.21 (P = 0.10). At the end of sixth month, the BCVA was 0.42 ± 0.18 in group I and0.47 ± 0.18 in group II (P = 0.23). The mean baseline central subfield thickness (CST) of eyes in group I was 523.8 ± 105.3 μm and in group II was 477.4 ± 143.6 μm (P = 0.11). After 3 months, the mean CST in eyes of group I decreased to 348.04 ± 98.4 μm, whereas in eyes of group II, the mean CST decreased to 377.5 ± 115.7 μm (P = 0.031). After 6 months, the mean CST in the eyes of the group I became 373.6 ± 139.8 μm, whereas in eyes of group II became 371.7 ± 102.3 μm (P = 0.96). Conclusion Aflibercept and ranibizumab have the same efficacy in the treatment of DME.



How to cite this article:
Ahmed KE, Basiony AI, Hamad ES. Aflibercept vs ranibizumab in management of diabetic macular edema.Menoufia Med J 2020;33:599-603


How to cite this URL:
Ahmed KE, Basiony AI, Hamad ES. Aflibercept vs ranibizumab in management of diabetic macular edema. Menoufia Med J [serial online] 2020 [cited 2020 Aug 13 ];33:599-603
Available from: http://www.mmj.eg.net/text.asp?2020/33/2/599/287777


Full Text



 Introduction



Diabetic macular edema (DME) is one of the most common causes of moderate vision reduction in patients with diabetic retinopathy[1].

There are several therapies for DME such as focal/grid laser photocoagulation, corticosteroids, subthreshold micropulse diode laser photocoagulation, and pars plana vitrectomy. However, intravitreal injections of vascular endothelial growth factor (VEGF) antibodies have become the gold standard therapy for DME worldwide[2].

VEGF is the main cause of vascular growth and edema, which are present in many vascular retinal disorders such as diabetic retinopathy and DME[3]. There are three commonly used intravitreal anti-VEGF agents: aflibercept, bevacizumab, and ranibizumab. They are beneficial and safe for the treatment of DME. Only ranibizumab and aflibercept are approved by the Food and Drug Administration for this indication[4].

Ranibizumab is a recombinant humanized monoclonal antibody fragment that binds to all the isoforms of human VEGF-A and reduces DME with subsequent visual improvement; thus, it has replaced laser photocoagulation in the treatment of DME. Aflibercept is a recombinant fusion protein that binds all isoforms of VEGF-A, VEGF-B, and placental growth factor[5].

The aim of this study was to compare between the effectiveness of aflibercept and ranibizumab in the management of DME.

 Patients and Methods



After obtaining approval by the Ethics Committee at El-Menoufia University. A total of 50 eyes of 32 diabetic patients were included in this prospective randomized study, and they were recruited from the Ophthalmology Clinic of Menoufia University Hospital. All patients provided written informed consent to participate. The patients were randomly divided into two groups: patients in group I (25 eyes) were treated with intravitreal aflibercept injection and patients in group II (25 eyes) were treated with intravitreal ranibizumab injection.

Inclusion criteria were patients with type I or II diabetes, DME in eyes diagnosed clinically and with optical coherence tomography (OCT), best-corrected visual acuity (BCVA) in the range from 1 to 0.6 (moderate visual loss), and edema affecting central subfield thickness (CST) (detected with OCT).

Exclusion criteria were patient with central macular thickness less than 300 μm, presence of tractional membrane, presence of intraocular inflammation, glaucoma, and choroidal neovascularization.

All patients underwent a full ophthalmologic evaluation, including BCVA, Intraoccular pressure (IOP) measurement, slit-lamp examination, and dilated fundus examination. Macular examination with OCT (Heidelberg Engineering, Heidelberg, Germany) was done for all eyes. Macular thickness map with follow-up software was used to detect and measure the changes in CST.

The anti-VEGF agents were injected into the eyes in both groups at baseline and then every 1 month for three intravitreal injections. All eyes in group I received an injection of 2 mg/0.05 ml aflibercept and those in group II received an injection of 0.5 mg/0.05 ml ranibizumab. Topical anesthesia was induced by 0.4% Benoxinate eye drops, which were instilled before injection. After disinfection, draping, and proper topical anesthesia, the anti-VEGF agent was injected into the vitreous cavity. A 27 G needle was used in intravitreal injection, which was done at 4 mm from the limbs if the patient was phakic and at 3.5 mm if the patient was pseudophakic. Evaluation of vision was done at the end of the maneuver to ensure that the intraocular pressure was not excessively high.

BCVA and CST were recorded at baseline and follow-up visits (third and sixth month).

Data were collected, tabulated, and statistically analyzed using an IBM personal computer with Statistical Package for the Social Sciences (SPSS) version 20 (SPSS Inc., Chicago, Illinois, USA) and Epi Info 2000 programs (CDC, Atlanta, Georgia, USA), where the following statistics were applied. Data were presented in the form of the mean, SD, range, and qualitative data were presented in the form numbers and percentages.

χ2-test was used to study the association between two qualitative variables. Mann–Whitney test is a test of significance used for comparison between two groups not normally distributed having quantitative variables. Wilcoxon test was used for comparing nonparametric data. P value less than or equal to 0.05 was considered statistically significant.

 Results



A total of 50 eyes of 32 patients received intraocular injections of aflibercept (group I, 25 eyes) or intraocular injections of ranibizumab (group II, 25 eyes).

The mean age of the patients was 57.6 ± 5.8 years (range: 42–65 years) in the aflibercept group and 55.5 ± 5.5 years (range: 49–65 years) in the ranibizumab group. No significant difference was detected between the two groups (P = 0.10).

The mean baseline BCVA and CST of eyes treated with aflibercept were 0.65 ± 0.12 and 523.8 ± 105.3 μm, respectively, and of eyes treated with ranibizumab were 0.63 ± 0.19 and 477.5 ± 143.6 μm, respectively. These differences were not statistically significant (P = 0.72 and 0.11, respectively).

The BCVA was recorded before injection, after 3 months, and after 6 months. After 3 months of follow-up period, the mean BCVA in eyes treated with aflibercept improved to 0.34 ± 0.16 and that in eyes treated with ranibizumab improved to 0.44 ± 0.21, with no significant difference between the two groups (P = 0.10) [Figure 1] and [Figure 2]. At the end of the follow-up period, eyes in aflibercept group (25 eyes) showed improvement of vision in 18 (72%) eyes, worsening of vision in five (20%) eyes, and remained stationary in two (8%) eyes. Eyes in ranibizumab group (25 eyes) showed vision improvement in 17 (68%) eyes, worsening of vision in five (20%) eyes, and stationary vision in three (12%) eyes [Table 1].{Table 1}{Figure 1}{Figure 2}

The CST was measured before injection, after 3 months and after 6 months. After 3 months, the mean CST in eyes of group I (aflibercept) decreased to 348.04 ± 98.4 μm, whereas in eyes of group II (ranibizumab), the mean CST decreased to 377.5 ± 115.7 μm, with no significant difference between the two groups (P = 0.031). After 6 months of follow-up period, the mean CST in eyes of the group I (aflibercept) became 373.6 ± 139.8 μm, whereas in eyes of group II (ranibizumab) became 371.7 ± 102.3 μm, with no significant difference between the two groups (P = 0.96) ([Table 2] and [Figure 2]).{Table 2}

The drugs were injected into the study eyes at baseline and then every 1 month until the third month.

No serious complications such as retinal detachment or endophthalmitis were detected in any patient of both the groups during the follow-up period.

 Discussion



DME is a common complication of diabetic retinopathy and is known to be the leading cause for visual impairment for the diabetic patient[6]. VEGF is an important mediator of abnormal vascular permeability in DME[7].

Intravitreous injections of anti-VEGF agents are superior to laser photocoagulation of the macula, for initial management of vision loss from DME involving the macular center[8].

Three commonly used intravitreous VEGF inhibitors – aflibercept (Eylea; Regeneron Pharmaceuticals, Near Tarrytown, New York, USA), bevacizumab (Avastin; Genentech), and ranibizumab (Lucentis; Genentech) – have been shown to be beneficial and relatively safe for the treatment of DME, but only aflibercept and ranibizumab are approved by the Food and Drug Administration for this indication[9].

Ranibizumab is a Fab fragment of a monoclonal anti-VEGF. It inhibits the activity of VEGF-A by binding and antagonizing the receptor site for the active form of the glycoprotein[10]. Aflibercept is a recent anti-VEGF agent made of a recombinant fusion protein that binds both VEGF isoforms A and B, and placental growth factor[11]. This study compares intravitreal aflibercept and ranibizumab in the treatment of DME in eyes with moderate visual loss.

The baseline CST in both the groups did not differ significantly, and the results indicated that both aflibercept and ranibizumab showed the same degree of CST decrease at the end of the follow-up time (P = 0.96).

Wykoff and Hariprasad[12] studied the effect of aflibercept, bevacizumab, and ranibizumab for DME. They concluded that aflibercept and ranibizumab had similar anatomic efficacy with no statistically significant differences between the drugs, and both were significantly more effective anatomically than bevacizumab. In the present study, the baseline visual acuity was between 1 and 0.6.

The baseline BCVA in both groups did not differ significantly, and the results indicated that both aflibercept and ranibizumab showed the same degree of BCVA improvement at the end of the follow-up period (P = 0.23).

At the end of the follow-up period, this study failed to show a significant difference in BCVA between aflibercept and ranibizumab (P = 0.23). This could be explained by a smaller sample size.

Wells et al.[13], studied the effect of aflibercept, bevacizumab, and ranibizumab for DME. They concluded that the relative effect of these drugs depended on baseline visual acuity. When the initial visual acuity loss was mild, there were no apparent differences, on average, among the study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. In the present study, the baseline visual acuity was between 1 and 0.6.

Moreover, Cai and Bressler[14] studied the effect of aflibercept, bevacizumab, and ranibizumab for vision-impairing center-involved DME. At 1 year, all three anti-VEGF drugs, on average, improved visual acuity. There was no difference among drugs in mean change in visual acuity from baseline among eyes with baseline visual acuity of 20/32 to 20/40, whereas aflibercept yielded superior vision outcomes among eyes with baseline visual acuity of 20/50 to 20/320.

In addition, a double-crossover study was done by Vandekerckhove[15], where treatment was prospectively switched three times. The magnitude and consistency of the benefits observed with aflibercept was more. They suggest that the dramatic anatomical and functional success of aflibercept due to the superior VEGF-binding affinity of aflibercept. Moreover, the potential tachyphylaxis or tolerance to ranibizumab are common drawbacks of its use.

Fouda and Bahgat[16] also reported that both aflibercept and ranibizumab improved visual acuity and decreased CMT in eyes with DME and moderate visual loss, with no difference between the two drugs; however, aflibercept needs a number of re-injection less than that of ranibizumab.

Our study also showed that, regarding IOP, the two groups were similar at baseline, after the third injection, and after 6 months. Moreover, there was no statistically significant change of IOP at the end of the therapy for anyone.

No other serious complications such as retinal detachment or endophthalmitis were detected in any patients of both the groups during the follow-up period.

 Conclusion



Both intravitreal aflibercept and intravitreal ranibizumab were effective regarding anatomical and functional outcomes of patients with DME with no difference between them.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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