Wnt Modulators in the Aqueous Humor Are Associated With Outer Retinal Damage Severity in Patients With Neovascular Age-Related Macular Degeneration

PURPOSE. To investigate the associations of the Wnt modulators Wnt inhibitory factor 1 (WIF-1) and Dickkopf 3 (DKK-3) in the aqueous humor with neovascular age-related macular degeneration (nAMD) and to determine their clinical implications. METHODS. Seventy-four nAMD patients initially treated with an intravitreal injection of ranibizumab (IVR) and 74 age- and sex- matched controls were studied. Aqueous humor WIF-1 and DKK- 3 levels were measured by Western blotting and an ELISA before and 1 month after two consecutive IVRs (pre- and post-IVR). Visual acuity assessments and spectral domain optical coherence tomography were performed pre- and post-IVR. RESULTS. Western blotting showed increased WIF-1 and DKK-3 in 12 nAMD patients compared with 12 controls. The ELISA analysis demonstrated elevated WIF-1 (pre) and DKK-3 (pre) in 62 patients compared with 62 controls (54.7 vs. 23.0 and 114.3 vs. 93.0 ng/mL, respectively). In multivariate analyses, high WIF-1 (pre) levels were associated with increased disruption in the photoreceptor junction's inner and outer segments (IS/OS) (pre and post) and high WIF-1 (post) levels. Interestingly, WIF-1 (pre) levels were significantly higher in type 3 neovascularization (NV) patients than in type 1 or 2 NV (90.5 +/- 36.7 vs. 48.3 +/- 22.5 and 41.3 +/- 28.8 ng/mL, respectively). However, choroidal thickness was not correlated with WIF-1 levels. CONCLUSIONS. We report, for the first time, the possibility of phenotypic, anatomic, and ocular proteomic correlations, demonstrating correlated WIF-1 and DKK-3 upregulation in nAMD patients' aqueous humor. Secreted WIF-1, reflecting the degree of retinal structure damage, may be a new biomarker for the retina's healthy and disease states.