Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population in developed countries. Severe visual loss in AMD usually occurs in patients with neovascular AMD (nAMD), which is caused by vascular endothelial growth factor A (VEGF-A) driven choroidal neovascularization (CNV).

Intravitreal therapy with VEGF-A inhibitors is the current standard treatment for nAMD. Optimization of current VEGF-A therapies includes finding a dosing regimen that maximizes visual acuity (VA) and minimizes the frequency of intravitreal injections and associated risks of treatment.

The "treat and extend" protocol is OCT guided with the primary aim of complete resolution of all retinal fluid, i.e. both intraretinal fluid (IRF) and subretinal fluid (SRF), both of which are considered to be a sign of disease activity. Once all fluid is resolved, an extension of the treatment interval by 2 weeks is mandated. If there is return of either SRF or IRF, the interval is shortened by one week. Currently, the relevance of both IRF and SRF in relation to best-corrected visual acuity (BCVA) outcomes is still being disputed. From the CATT and VIEW studies there is some reason to suspect that some SRF may be allowed to remain to extend the treatment interval without affecting BCVA. In contrast to IRF which has clearly been shown to correlate with poorer VA and is considered to be a sign of active disease, SRF may only be a sign of impaired pumping function of the RPE, similar to what is seen in central serous chorioretinopathy and as such may not be considered as an indication of ongoing disease activity. The consequence of insisting upon complete lack of SRF (strict approach) is more injections and therefore increased exposure of the retina to anti-VEGF agents. And there are recent reports that frequent intravitreal injections may lead to changes in the retinal nerve fiber layer and increased risk of geographic atrophy development. As a consequence, limiting the number of injections would be desirable if the same VA result could be achieved. From the pivotal anti-VEGF studies it has become apparent that patients show an individualised response to therapy. As such optimization of individualized treatment needs to be explored and understood. This study aims to explore further the "treat and extend" approach and will evaluate and compare two individualized aflibercept treatment regimens, differentiated by the definition of disease activity which determines the treatment interval until the next injection. The aim will be to determine whether small amounts of SRF may be tolerated using a "treat and extend" regimen in the treatment of nAMD and whether the presence and extent of both intra-retinal fluid and/or sub-retinal fluid (SRF) helps to decide on extension or reduction of treatment intervals in a "treat and extend" regimen. The results will be used to generate further recommendations about strict versus relaxed treatment approaches and how they can be utilised within a clinically practical "treat and extend" approach to maximize patient outcomes, while reducing the need for potentially unnecessary intravitreal injections.

Taking all together, the study aims for optimization of flexible patient treatment.