We thank Drs Huising and McGwin for commenting on our article. Although we acknowledge that defining the study as a prospective, case-control one may appear incorrect and apparently misleading, we contend that the 2 terms actually refer to 2 different phases of data analysis in the course of the study.

Case-control studies are used to identify factors that may contribute to a medical condition by comparing subjects who have that condition (the cases) with patients who do not have the condition, but are otherwise similar (the controls). At baseline, we wanted to test whether different aqueous levels of vascular endothelial growth factor (VEGF) were recordable in affected eyes (eyes with neovascular age-related macular degeneration [AMD]) versus unaffected eyes (eyes without evidence of neovascular AMD). This was the case-control phase of the study.

As shown in the Results, we found no statistically significant difference in the levels of VEGF in 2 forms of neovascular AMD (ie, type 1 and type 2) versus controls. This result was not unexpected. In fact, neovascular AMD is a complex and multifactorial process in which aging processes, genetic predisposition, and environmental factors cause an imbalance between proangiogenic and antiangiogenic factors, ultimately leading to the formation and proliferation of abnormal vessels. Among proangiogenic factors, VEGF is thought to be the most potent mediator of both choroidal and retinal angiogenesis; however, the simplistic approach that VEGF overexpression within the retina or the RPE would be sufficient to promote the development of new vessels does not apply.

The interesting, emerging result of our study was that levels of aqueous VEGF in patients with type 3 neovascularization were higher compared with those in both controls and eyes with type 1 or 2 neovascularization. This result is the answer to the hypothesis we clearly formulated in the Introduction: to evaluate whether a clinically more aggressive form of neovascular AMD (ie, the type 3) was associated to higher levels of VEGF. Therefore, we were not assuming that AMD is a risk factor for VEGF levels in comparison with healthy controls (as misinterpreted by Huising and McGwin).

In the second, prospective phase of the study, the group of patients with neovascular AMD was analyzed further on the basis of characteristic angiographic and optical coherence tomography features that account for the recognition of 3 subgroups (neovascularization types 1, 2, and 3). In this phase of the study, we wanted to test the impact of monthly intravitreal injections of bevacizumab (Avastin; Genentech, Inc, South San Francisco, California, USA) on aqueous VEGF levels in eyes with different baseline concentrations of VEGF.

We used nonparametric tests because of the nonnormal distribution of the data. Specifically, the Mann–Whitney U test was used to compare 2 groups, the Kruskal-Wallis test was used to compare multiple groups at some point in time, and the Friedman test was used to compare the changes over time in each single group.

We used the Spearman test taking advantage of the function “change from baseline,” which makes it suitable and appropriate for an analysis of the data over time. The Spearman coefficient is robust, has a higher power, and performs well in comparison with other statistical methods. Therefore, the data presented in Table 2 are correct and no reanalysis is needed.