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Alessandro Finzi,1 Simone Ottoboni,1 Mauro Cellini,1 Beniamino Corcioni,2 Caterina Gaudiano,2 Luigi Fontana1 1Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 2Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyCorrespondence: Alessandro Finzi, Ophthalmology Unit, Department of Experimental, Diagnostic and Specialty Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Pelagio Palagi 9, Bologna, 40138, Italy, Tel +39 051 2142831, Email finzialessandro@gmail.comPurpose: Age-related macular degeneration (AMD) presents a multifaceted etiopathogenesis involving ischemic, inflammatory, and genetic components. This study investigates the correlation between ocular hemodynamics, scleral rigidity (SR), and plasma endothelin-1 (ET1) levels in treatment-naive patients with asymmetrical AMD.Patients and Methods: This study included 20 treatment-naive patients (12 females and 8 males) with an average age of 76.4 ± 3.7 years, who presented with AMD with neovascular membrane formation (nAMD) in one eye, and intermediate grade 2 AMD (iAMD) in the other eye. The control group consisted of 20 healthy subjects (13 females and 7 males) with a mean age of 74.7 ± 3.9 years. All patients and healthy controls underwent color Doppler imaging (i) of the ophthalmic artery (OA), short posterior ciliary arteries (SPCAs), and central retinal artery (CRA); Plasma ET-1 levels were measured for all patients and healthy subjects. Corneal biomechanics were assessed using an Ocular Response Analyzer and two indices were obtained: corneal hysteresis (CH) and corneal resistance factor (CRF).Results: Results showed reduced blood flow velocities and increased resistance indices in AMD eyes, particularly affecting the short posterior ciliary arteries. According to mechanical theory, ARMD eyes exhibited elevated scleral rigidity and corneal resistance factor compared to controls, with a notable rise in SR in neovascular AMD (nAMD) eyes. As per the chronic subacute inflammation theory, plasma ET-1 levels were significantly higher in AMD patients, correlating with abnormal SPCAs blood flow and increased resistance indices.Conclusion: Findings suggest a multifactorial etiology of AMD involving an increase of ET-1 plasma levels with biomechanic damages of corneal and scleral tissue in nAMD.Keywords: AMD, endothelin-1, corneal biomechanics, scleral rigidity, hemodynamics