Intravitreal pegaptanib for the treatment of ischemic diabetic macular edema

Abstract

PurposePegaptanib has been shown to be effective in treating diabetic macular edema (DME). In the original Phase II/III trial, however, patients with macular ischemia were excluded. In this study, we treated patients with ischemic DME.MethodsMacular ischemia was defined as a 30% increase in the area of the foveal avascular zone (FAZ) at 45 seconds on fundus fluorescein angiography. In addition, the participants had diffuse foveal-involving DME with a central subfield thickness (CST) of >300 μm on spectral-domain optical coherence tomography. Five intravitreal pegaptanib injections were given 6 weeks apart. The final study visit was 6 weeks after the fifth injection. The primary outcome was change in the size of FAZ. Secondary outcomes were change in best-corrected visual acuity (BCVA) and the change in CST.ResultsThirty participants were enrolled. Three were unable to complete the full course of treatment. Their outcomes were carried forward for the first part of this analysis. There was no statistically significant change in the mean size of the FAZ from baseline to the final visit. Subclassifying participants as those with minimal/moderate ischemia (16 participants, FAZ area <1,000 pixels) and those with more severe ischemia (14 participants, FAZ area >1,000 pixels) also showed no statistically significant change in the mean area of the FAZ. On average, BCVA increased and CST decreased from baseline to the final visit, but these changes were not statistically significant. Using per protocol analysis on those participants who completed the full course of treatment, the mean BCVA increased from 49.2 to 53.9 letters (P=0.046).ConclusionIn this study, intravitreal injection of pegaptanib did not significantly alter the size of the FAZ in participants with varying degrees of ischemic DME. There was, however, a significant improvement in mean BCVA in those who completed the treatment course.

The Bioactivity of D-/L-Isonucleoside- and 2′-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression

“…It is worth noting that Macugen is chemically modified and contains both 2′-F and 2′-OMe modifications and the attachment of a 40-kDa polyethylene glycol. 49 Macugen is also lately explored for its application in diabetic macular edema, 50 ischemic diabetic macular edema 51 and myopic choroidal neovascularization. 52 Recently, a new monoclonal antibody (ranibizumab, Novartis) drug was approved by FDA in 2015 and is now in clinical use to compete with Macugen.…”

Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes

“…The common strategies in the chemical modifications of nucleic acid aptamers and their purposes. Among the modifications, such as modifications on the terminals of nucleic acids, modifications on the phosphodiester linkage, modifications on the sugar ring and modifications on the bases, the 3′ end capping with inverted thymidine [6,12] and PEGylation [13] have been the common strategies in the chemical modifications of nucleic acid aptamers for development clinical therapeutics [14][15][16][17].…”

“…Then, the chemical modification strategies of aptamers for resisting nuclease degradation [12,[20][21][22][23][24][25][26], improving target binding affinities [10,[27][28][29][30][31] and resisting renal clearance [32][33][34][35][36] will be summarized, sequentially. Among the modifications, such as modifications on the terminals of nucleic acids, modifications on the phosphodiester linkage, modifications on the sugar ring and modifications on the bases, the 3′ end capping with inverted thymidine [6,12] and PEGylation [13] have been the common strategies in the chemical modifications of nucleic acid aptamers for development clinical therapeutics (e.g., pegaptanib [14][15][16][17], etc.). More excitingly, aptamers with improved binding affinities are being generated with modifications on the bases [29] or substitutions of two non-bridging phosphate oxygen atoms in nucleic acids by sulfur replacement [10] (see "SOMAmers" and "PS2 walk" below).…”

Current and Novel Therapeutic Approaches for Treatment of Diabetic Macular Edema

“…Additional studies have also shown similar results, with improvements in visual or anatomical outcomes [ 73 , 74 , 75 , 76 ]. However, due to the drug’s low clinical efficacy in comparison to other anti-VEGF medications, it is utilized considerably less often in clinical practice [ 77 ].…”