Anti–Vascular Endothelial Growth Factor Use and Atrophy in Neovascular Age-Related Macular Degeneration

Abstract

Topic: To summarize the rates of atrophy, risk factors, and atrophy-associated visual outcomes in patients with neovascular age-related macular degeneration (nAMD) who received antievascular endothelial growth factor (VEGF) treatment for macular neovascularization (MNV).Clinical Relevance: Age-related macular degeneration is a leading cause of vision loss worldwide, and VEGF inhibitors are the primary treatment for nAMD. However, atrophy is observed frequently in eyes treated with anti-VEGF therapy, prompting questions regarding a causative role for these therapies in atrophy development.Methods: PubMed was searched for articles published in the past 5 years (January 1, 2014, through January 10, 2019). Studies including atrophy outcome(s) in patients with age-related macular degeneration who received anti-VEGF treatment were included. Review articles, retrospective studies, case reports or studies, preclinical studies, prevalence data reports, and non-English studies were excluded. Randomization was not required.Results: Overall, 145 studies were identified; 29 publications were included, with cohorts ranging from 8 to 1185 eyes. Imaging methods used to assess atrophy varied across studies. All studies confirmed the occurrence of atrophy, and when available, longitudinal data from the included studies demonstrated an increase in atrophy incidence over time. Key risk factors or phenotypes associated with atrophy were fellow eye atrophy, reticular pseudodrusen, increased injections, and type 3 lesion. In addition, visual acuity loss was noted with foveal atrophy.Discussion: All studies demonstrated that atrophy occurs in the context of MNV treated with anti-VEGF therapy; however, it is not clear whether anti-VEGF treatment is causative of atrophy versus being associated with atrophy development. The included studies were not designed or powered to assess atrophy as a primary outcome. In addition, it is difficult to determine whether prognostic factors directly affect atrophy. Furthermore, patient populations in clinical trials do not necessarily represent real-world patients. Although phenotypes and risk factors may help to identify those at greater risk of atrophy developing, it is important to recognize that adequately treating exudative MNV remains the best option to optimize vision outcomes in patients with nAMD, particularly given the risk of vision loss with undertreatment observed in the real world. Ophthalmology 2020;127:648-659 ª

The long-term effects of anti-vascular endothelial growth factor therapy on the optical coherence tomography angiographic appearance of neovascularization in age-related macular degeneration

“…Finally, the association with the development of atrophy and anti-VEGF use has been hotly debated in recent years, but this study found no significant association between the development of atrophy and anti-VEGF exposure or MNV growth variables [46]. Though a clear correlation with the development of atrophy was not expected, it is possible that macular atrophy was under identified since, for some subjects, analysis was restricted to 3 × 3 mm images, the length of follow-up may not have been long enough to detect this effect, and the type and amount of anti-VEGF treatment may be different than other studies that have suggested this association.…”

<p>Trends in Real-World Neovascular AMD Treatment Outcomes in the UK</p>

“…56,57 Sadda et al reported that it is important to recognize that adequately treating nAMD remains the best option to optimize visual outcomes in patients, particularly given the risk of vision loss with under-treatment observed in the real-world. 59 Mones et al 60 suggest that better long-term visual outcomes could be achieved by changing the community mindset that contributes to under-treatment of this chronic disease. Other reasons initial gains may wane over time include loss of patient enthusiasm for frequent treatment and also the progressive onset of atrophic AMD.…”

Longitudinal Analysis of Structural and Functional Changes in Presence of Reticular Pseudodrusen Associated With Age-Related Macular Degeneration

“… 5 – 7 Distinctive clinical characteristics of RPD are the typical incomplete or complete ring-shaped pattern with initial sparing of the fovea in contrast to soft drusen, which are typically located in central retinal areas, as well as the higher associated risk of progression to late stages including atrophy development. 8 – 12 Moreover, a higher incidence of RPD and development of multifocal lesions of macular neovascularization type 3 (MNV 3) has been recently described, which were typically more likely distributed in the temporal perifoveal area corresponding to the predominant pattern of RPD distribution. 13 , 14 In this context Sadda and coworkers 12 demonstrated in a meta-analysis that atrophy development often occurred in context of MNV treated with anti-vascular endothelial growth factor (VEGF) therapy; however, at the same time it remained unclear whether anti-VEGF treatment is a causal reason for atrophy or rather associated with atrophy development.…”

“… 8 – 12 Moreover, a higher incidence of RPD and development of multifocal lesions of macular neovascularization type 3 (MNV 3) has been recently described, which were typically more likely distributed in the temporal perifoveal area corresponding to the predominant pattern of RPD distribution. 13 , 14 In this context Sadda and coworkers 12 demonstrated in a meta-analysis that atrophy development often occurred in context of MNV treated with anti-vascular endothelial growth factor (VEGF) therapy; however, at the same time it remained unclear whether anti-VEGF treatment is a causal reason for atrophy or rather associated with atrophy development. Besides RPD counting as a high-risk factor for retinal atrophy and corresponding progressive visual impairment, a putative association of RPD and systemic cardiovascular diseases has been suggested in previous studies.…”