Addition of a Clinical Global Impression Questionnaire for both patient and Clinician at Day 28. Addition of Impression Cytology procedure at Day 0 and Day 28. Update of the inclusion criterion #10 Previous wording: “Corrected visual acuity ≥0.7 logMAR (20/100 Snellen or 50 ETDRS) in both eyes”. New wording: “Corrected visual acuity ≤ 0.7 logMAR (≥20/100 Snellen or ≥50 ETDRS) in both eyes” Update of the paragraph related to inclusion criteria for VAS. Previous wording: “Assessment of inclusion/non-inclusion criteria will be performed both at the Screening Visit (V0) and at the Baseline visit (V1). All inclusion criteria must be met in the eye with the highest VAS scoring. VAS must be ≥ 20 for the fellow eye. The eye with the highest VAS scoring at the Screening Visit (V0) is not necessarily the same eye with the highest VAS scoring at the Baseline Visit. […]” New wording: “Assessment of inclusion/non-inclusion criteria will be performed both at the Screening Visit (V0) and at the Baseline visit (V1). Since the allocated treatment will be administered in both eyes, a minimum level of 20 in the VAS scale for pain/discomfort is required in the two eyes. All inclusion criteria must be met in the eye with the highest VAS scoring. VAS must be ≥ 20 for the fellow eye. The eye with the highest VAS scoring at the Screening Visit (V0) is not necessarily the same eye with the highest VAS scoring at the Baseline Visit. […]” Update of the non-inclusion criterion #2 Previous wording: “[…] and documented use of condoms”. New wording: “[…] and documented use of condoms” Update of the non-inclusion criterion #9 Previous wording: “Use of contact lenses or punctual plugs during the treatment and the previous 7 days (prior to treatment initiation).” New wording: “Use of contact lenses or presence of punctual plugs during the treatment and the previous 7 days (prior to treatment initiation).”

Update of the non-inclusion criterion #11 Previous wording: “Previous refractive surgery, cornea transplant. Meibomian gland dysfunction or history of lid malposition (ectropion, entropion, ptosis), that may affect accurate assessment of the disease and/or mask the effects of the drug New wording: “ Previous refractive surgery, cornea transplant. Meibomian gland dysfunction or history of lid malposition (ectropion, entropion, ptosis), history of recurrent corneal herpes or history of recurrent corneal erosion or neurotrophic keratopathy that may affect accurate assessment of the disease and/or mask the effects of the drug” Paragraph 5.2. Randomization is more consistent: “Patients who meet all of the inclusion and none of the non-inclusion criteria at the Baseline visit will be randomized. Treatments will be allocated following a pre-established randomization list using a random design by blocks created by Linical Co. Ltd. The team ins charge of the randomization is located at a separate office from the main reporting team in order to preserve the masking of the investigational product. Numbers will consist of 5-digit identifiers which will act as both Subject Randomization Number and Medication Identifier. Drug packaging (Idifarma) will apply these 5-digit identifiers to the vials containing the investigational products. Once the investigator has confirmed that a subject is eligible for randomization, the eCRF will assign the next randomization number available at the site and this number medication will be used throughout the entire treatment period.

Drug packaging will retain a list of the mapping of 5-digit identifiers to investigational product which will be supplied to the reporting statistician only at the time of full study unmasking, post database lock, in order to determine the medication actually received. The information on this list will also be provided to the designated research personnel of each site in a sealed, tamper-proof format such that emergency unmasking of the contents of a single vial only can be performed if required.” Update of protocol titles 4.1 and 4.2. Previous wording: “4.1. Primary outcomes” & “4.2. Secondary outcomes” New wording: “4.1. Primary outcomes/objectives”& “4.2. Secondary outcomes/objectives” 7.4.1 Labelling distribution and storage Name of manufacturer of artificial tears was changed from “Theradis” to “Idifarma” 8.1 Detailed Study Plan The order of procedures has been updated 8.3.3 Ocular tests – IOP Previous wording: “The IOP measurement will be performed in both eyes between 9 a.m. and 12 p.m by contact tonometry.” New wording: “The IOP measurement will be performed in both eyes at the same time (± 1 h) at every visit between 9 a.m. and 12 p.m. by contact tonometry.” 10.2.8 Notifications of AEs Update of the email address to be used for notifications of AEs 12.4 Confidentiality of data; 14.1 Source documents; 14.3 Monitoring In these sections, addition that the direct access to the data by Monitors (access direct conditioned to the compliance of certain rules) and by Regulatory Authorities as well as Ethics Committee remains through the investigator