Drusen are considered a characteristic feature of AMD and are one of its earliest findings. The contents of the deposits can initiate inflammation by causing an immune response. Inflammation is an important factor in the pathogenesis of both dry AMD and neovascular AMD (Stanton and Wright, 2014).

Lymphatics contribute to tissue homeostasis by facilitating the clearance of excess fluid and macromolecules from the interstitium. A body of evidence also shows that lymphangiogenesis plays important roles in the regulation of fluid homeostasis and the pathogenesis of diseases such as inflammation, tumor metastasis, lymphedema, atherosclerosis, obesity (Adams and Alitalo, 2007; Karaman et al., 2017; Norrmén et al., 2011; Yu et al., 2018). When lymphatic vessels are damaged (radiation therapy, etc.), blocked (due to infection and inflammation), or removed (surgery), lymphatic drainage becomes inadequate. This causes lymphedema and increased interstitial tissue pressure.(Alitalo and Carmeliet, 2002).

For many years, the eye was thought to lack lymphatic drainage, and the cornea, sclera, and uveal tissues were historically considered "alymphatic." (Freeman and Troutt, 1985). Various biomarkers have been reported in recent studies to facilitate histological identification of lymphatics. These proteins take part in the development of lymphatic vessels and the formation of new lymphatic vessels (lymphangiogenesis) (Karaman et al., 2017; Kong et al., 2017). Specific lymphatic markers are vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor (VEGFR) R-2 and R-3, Podoplanin (PDPLN) (transmembrane mucin-type glycoprotein), and lymphatic endothelial hyaluronan receptor-1 (LYVE-1)(Karpanen and Alitalo, 2008).

The recent discovery of specific lymphatic endothelial cell markers has stimulated the investigation of lymphatic channels in ocular pathologies. Yücel et al. (2009) in his study, observed that fluorescent antigens injected into the anterior chamber of the sheep eye were detected in the LYVE-1-positive channels in the ciliary body later. In the same study, it was shown that after intracameral Iodine-125 serum albumin injection, the fluid drained into the cervical, retropharyngeal, submandibular and preauricular lymph nodes in the head and neck region. In their animal experiments, Camelo S. et al. (2008) showed that intravitreally injected Rhodamine liposomes were found in the cervical lymph nodes 24 hours after the injection. Yücel et al. (2020) injected an intracameral infrared substance into mice, which were grouped as young and old, and imaged the ipsilateral cervical lymph nodes with photoacoustic tomography. In this study, it was found that lymphatic drainage from the eye was significantly reduced in the aged mouse group.

The role of lymphangiogenesis in most eye diseases, especially inflammatory disease, or edema, is unknown. Experimental studies on animals suggest that reduced lymphatic drainage of aqueous humor, proteins and antigens from the eye may be one of the causes of eye diseases such as glaucoma and inflammatory eye disease, which increase with age.

As a result of the etiopathogenesis of AMD and the biochemical structure of drusen, it is known that this disease is associated with inflammatory reactions. Therefore, the aim of this study was to evaluate the relationship between AMD and lymphangiogenesis by quantitatively analyzing lymphangiogenesis biomarkers such as LYVE-1, PDPLN, VEGF-C and VEGFR-3, VEGFR-2 in human vitreous, aqueous and serum. Our main purpose is to emphasize the relationship of these markers with the pathogenesis of the disease in AMD patients.

In literature Özgürtaş T. et al (2022) stated that the VEGF-C/VEGF-R ratio has a greater prognostic value than VEGF-C and/or VEGF-Rs alone. With prospective nature of current study, this ratio is selected as one of the main parameters analyzed here.