Anti‐vascular endothelial growth factors treatment of wet age‐related macular degeneration: from neurophysiology to cost‐effectiveness

Wet age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the Western world, causing suffering to the individual and high social and healthcare costs to society. During the last decade, anti-vascular endothelial growth factors (anti-VEGF) have become the first choice treatments for this previously devastating condition. Currently, there are three intravitreally injected anti-VEGF medications available: bevacizumab, ranibizumab and aflibercept. Clinical trials have shown that these three anti-VEGF medications exert similar effects on visual acuity and possess similar safety profiles, although aflibercept requires less frequent injections. In fact, the required frequency of repeated injections represents a major burden on ophthalmology clinics. Visual evoked potential (VEP) recording offers a non-invasive tool to investigate the function of the visual pathway. The aims of this study were to determine (1) how the VEP changes after bevacizumab injections, (2) if VEP is useful as a diagnostic or monitoring tool for wet AMD, (3) if the binocular face detection task improve after anti-VEGF injections, and (4) which anti-VEGF medication and injection protocol may be considered as most cost-effective. The publication I was a pilot study of six wet AMD-patients treated with anti-VEGF injections, where VEP revealed that its latency had shortened and amplitude increased after the treatment. The subsequent publications II and III were non-randomized cohort studies. A total of 16 patients with unilateral wet AMD and six healthy control subjects were included. The patients received three bevacizumab injections every 4–6 weeks. VEPs were performed before the first injection and 4–6 weeks after the last injection with a similar time interval used for the non-treated controls. In publication II, significant changes (p < 0.05) were found in the following parameters in the treated eyes: logMAR visual acuity decreased on average by 0.18 0.32 units, optical coherence tomography (OCT) retinal thickness decreased by 170 200 lm and VEP amplitude increased by 1.0 1.4 lV. There was a significant correlation between the relative changes of VEP amplitude and retinal thickness r = 0.630 (p < 0.05), and between visual acuity (logMAR) and retinal thickness r = 0.576 (p < 0.05). These results seem to indicate that the application of VEP does not confer any additional benefits in the diagnosis or monitoring of wet AMD. In publication III, face pictures elicited well-defined event-related components in occipital and parieto-occipital cortical areas at baseline and after treatment. The face-specific N170 component was pronounced in all subjects with longer peak latency in patients than in controls (p = 0.032). However patients did not experience any significant improvement in facespecific electrical potentials after the anti-VEGF treatment. In publication IV, the cost-effectiveness of the three anti-VEGF injections and two injection protocols (i.e. regular monthly and pro re nata) for wet AMD were compared. A two-eye Markov transition model was developed for this analysis and a sensitivity analysis of estimated model parameters was performed. Regular monthly injections of bevacizumab were superior in comparison to the other options, a result reinforced by the sensitivity analyses. National Library of Medicine Classification: W 74, WW 103, WW 166, WW 270 Medical Subject Headings: Wet Macular degeneration/drug therapy; Neurophysiology; Drug Costs; Treatment Outcome Vottonen, Pasi Silm€anpohjan kostean ik€arappeuman hoito anti-VEGF injektioilla: neurofysiologiasta kustannusvaikuttavuuteen It€a-Suomen yliopisto, terveystieteiden tiedekunta Publications of the University of Eastern Finland. Dissertations in Health Sciences Numero 374. 2016. 97 s. ISBN (print): 978-952-61-2253-3 ISBN (pdf): 978-952-61-2254-0 ISSN (print): 1798-5706 ISSN (pdf): 1798-5714 ISSN-L: 1798-5706