*Article*

#### **The HYLAN M Study: <sup>E</sup>**ffi**cacy of 0.15% High Molecular Weight Hyaluronan Fluid in the Treatment of Severe Dry Eye Disease in a Multicenter Randomized Trial**

**Gysbert-Botho van Setten 1, Christophe Baudouin 2, Jutta Horwath-Winter 3, Daniel Böhringer 4, Oliver Stachs 5, Ebru Toker 6, Sultan Al-Zaaidi 7, Jose M. Benitez-del-Castillo 8, Ria Beck 5, Osama Al-Sheikh 9, Berthold Seitz 10, Stefano Barabino 11, Herbert A. Reitsamer 12 and Wolfgang G.K. Müller-Lierheim 13,\***


Received: 3 October 2020; Accepted: 31 October 2020; Published: 2 November 2020

**Abstract:** The aim of the HYLAN M study was to investigate if symptoms and/or signs of patients suffering from severe dry eye disease (DED) can be improved by substituting individually optimized artificial tear therapy by high molecular weight hyaluronan (HMWHA) eye drops. In this international, multicenter study, patients with symptoms of at least ocular surface disease index (OSDI) 33 and corneal fluorescein staining (CFS) of at least Oxford grade 3 were included. A total of 84 per-protocol patients were randomized in two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the week 8 visit, the average OSDI of the verum group had improved by 13.5 as compared to the control group (*p* = 0.001). The best corrected visual acuity (BCVA) had improved by 0.04 logMAR (*p* = 0.033). CFS, tear film break-up time (TBUT), Schirmer I, lid wiper epitheliopathy (LWE), mucocutaneous junction (Yamaguchi score), and tear osmolarity were not significantly different between the verum and control groups (*p* > 0.050). We conclude that for most patients with severe DED, 0.15% HMWHA eye drops provide excellent improvement of symptoms without impairment of dry eye signs.

**Keywords:** dry eye disease; severe keratitis; hyaluronan; hylan A; multicenter; randomized trial
