Effect of repeated intravitreal anti-vascular endothelial growth factor drugs on corneal nerves

Abstract

To investigate the potential effect of repeated intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs on corneal nerves. A total of 64 patients were treated with intravitreal injection of anti-VEGF drugs. There were 19 cases of neovascular age-related macular degeneration (AMD), 20 cases of diabetic macular edema (DME) and 25 cases of retinal vein occlusion (RVO). Twenty-nine cases were treated with aflibercept (2 mg/0.05 mL) whereas 35 cases were managed with ranibizumab (0.5 mg/0.05 mL). A corneal confocal microscope was used to collect images of corneal subbasal nerve plexus, and Image J was used for image analysis. The changes in corneal nerve were compared between 1 month after each injection and before injection. There were no significant differences in the density and length of corneal nerve at specific time after the surgery in comparison with baseline in patients who were given 3 intravitreal injections. There was no significant correlation between the numbers of injections and the changes of the corneal nerves. After 3rd injection, the nerve length of the DME group was markedly lower than that of AMD and RVO groups, the difference was statistically significant (P < .05). The nerve density of the DME group was not significantly different from that of AMD and RVO groups, whereas the nerve length and nerve density of the AMD and RVO groups were not statistically significant between each other also. The corneal nerve length after the 2nd and 3rd injections of Aflibercept were lower than that before surgery, the difference was statistically significant. There were no significant differences in nerve density and nerve length at each time point after Ranibizumab injection. The length and density of the corneal nerve after multiple injections in contralateral eye displayed no significant changes compared with the baseline. Repeated intravitreal anti-VEGF drug can reduce the length of corneal nerves. For patients who need repeated intravitreal injections of anti-VEGF drugs, especially in DM, attention should be paid on the changes affecting the corneal nerves. It is also needed to strengthen the local anti-inflammatory therapy to avoid infection and to use artificial tears to protect the microenvironment of the ocular surface after the surgery.

Calreticulin accelerates corneal wound closure and mitigates fibrosis: Potential therapeutic applications

“…[42][43][44] As extensive data on the CALR fragment (amino acids 135-164) termed vasostatin and also, intact CALR, show inhibition of angiogenesis via suppression of endothelial cell proliferation and VEGF levels, the action of CALR in the posterior portion of the eye for the treatment of macular degeneration, currently treated with anti-VEGF Mabs, which have complications, should be investigated. [45][46][47] For support of this use, gene delivery of the vasostatin domain inhibited ocular neovascularization. 48 The numbers of myofibroblasts in a healing corneal wound is commensurate with the extent of fibrosis.…”

“…Other ophthalmic therapeutic applications of CALR for repair of corneal injury include CE defects, all types of PRK, corneal transplants, corneal abrasions from dry‐eye, post‐surgery involving the ocular surface and systemic disease affecting the eye such as diabetic keratopathy 42–44 . As extensive data on the CALR fragment (amino acids 135–164) termed vasostatin and also, intact CALR, show inhibition of angiogenesis via suppression of endothelial cell proliferation and VEGF levels, the action of CALR in the posterior portion of the eye for the treatment of macular degeneration, currently treated with anti‐VEGF Mabs, which have complications, should be investigated 45–47 . For support of this use, gene delivery of the vasostatin domain inhibited ocular neovascularization 48 …”