Date Published: January 13, 2017
Publisher: Public Library of Science
Author(s): Gulfidan Bitirgen, Selman Belviranli, Rayaz A. Malik, Hurkan Kerimoglu, Gunhal Satirtav, Nazmi Zengin, Friedemann Paul.
To evaluate the effects of repeated intravitreal ranibizumab injections on corneal sensitivity, corneal sub-basal nerve plexus (SBNP) and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with neovascular age-related macular degeneration (AMD).
Sixty-six eyes of 33 patients who had received unilateral repeated intravitreal ranibizumab injections (0.5 mg/0.05 ml) for the treatment of AMD and 25 eyes of 25 healthy subjects were included in the study. Central corneal sensation was measured using the contact Cochet-Bonnet esthesiometer. The laser scanning in vivo corneal confocal microscope was used to determine corneal SBNP parameters. The peripapillary RNFL thickness was assessed with spectral-domain optical coherence tomography. Data obtained from the ranibizumab-injected eyes were compared with those of the fellow non-treated eyes and the eyes of the healthy control subjects.
The mean number of ranibizumab injections per eye was 8.9±5.0 (range 3–20). There were no statistically significant differences in the central corneal sensitivity threshold and corneal SBNP parameters between the ranibizumab-injected eyes and the fellow untreated eyes or between those with neovascular AMD and the healthy control group (P>0.05 for all). The average peripapillary RNFL thickness of the treated eyes did not differ significantly to the fellow eyes (P = 0.237), and the eyes of healthy control subjects (P = 0.918). There were no significant correlations between the number of ranibizumab injections and any of the study parameters.
Multiple intravitreal injections of ranibizumab seem to have no harmful effects on corneal sensitivity, innervation and peripapillary RNFL thickness in patients with AMD.
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among elderly people in developed countries . Neovascular or exudative AMD, characterized by new formation of choroidal vessels into the sub-retinal space, is responsible for almost 90% of severe vision loss due to AMD . Although the age-related changes that stimulate pathologic neovascularization are not completely understood, vascular endothelial growth factor A (VEGF-A), which is a key regulator of angiogenesis and vascular permeability, has been implicated as an important factor in the pathogenesis of AMD [3,4].
Thirty-three patients (16 male, 17 female) with unilateral neovascular AMD who had received at least three injections of intravitreal ranibizumab (Lucentis; Novartis Pharma AG, Basel, Switzerland) and 25 healthy control subjects (14 male, 11 female) were enrolled in this cross-sectional study undertaken at a tertiary referral center. The study design fulfilled the tenets of the Declaration of Helsinki and was approved by the Clinical Research Ethics Committee of the Necmettin Erbakan University. Written informed consent was obtained from all patients after a detailed explanation of the nature and possible consequences of the study.
The mean ages of the patients and control group were 67.91±7.29 years (range 55–81 years) and 66.24±7.24 years (range 56–85 years), respectively. There were no statistically significant differences between patients with AMD and healthy controls for age (P = 0.391) and gender (P = 0.571). No significant differences were observed in central corneal sensitivity threshold, corneal SBNP parameters and peripapillary RNFL thickness between male and female genders in both the AMD and control groups (P>0.05 for all). The mean number of injections was 8.9±5.0 (range 3–20) and the mean time elapsed from the last intravitreal injection treatment was 2.7±1.7 months (range 1–6 months). The mean IOP of eyes receiving ranibizumab injections (14.79±2.58 mmHg) did not differ significantly from those of the fellow eyes (14.73±2.75 mmHg) and control eyes (13.56±2.66 mmHg) (P = 0.837 and P = 0.082, respectively).
The use of intravitreal injections of anti-VEGF agents for the treatment of retinal diseases, especially neovascular AMD, is now common practice. We found no significant change in corneal sensation or corneal nerve and retinal nerve fiber morphology in ranibizumab-injected eyes. This is reassuring given the theoretical concern of a potentially detrimental effect on nerves in the eye following anti-VEGF therapy, given that endogenous VEGF has neurotrophic and neuroprotective effects . Indeed, Matsuzaki et al . have demonstrated direct protective effects of VEGF-A on cultured neuronal cells. It has also been shown that a chronic decrease in endogenous VEGF-A levels is linked to an increased risk of motor neuron degeneration in amyotrophic lateral sclerosis . In a more recent study, Hulse et al . reported that VEGF-A165b, which is a splice isoform of VEGF-A, had neuroprotective and anti-nociceptive effects on epidermal sensory neurons in diabetic rats. In relation to neural changes there are experimental data showing the neuroprotective role of VEGF on retinal neural cells [8,24].