Significant changes included following: • Revision of a criterion to exclude subjects who had previously received latanoprostene bunod ophthalmic solution from participating in study; • Addition of a exclusion to exclude subjects with a current cancer diagnosis from participating in study; • Correction to exclusion criterion regarding the Best-Corrected Visual Acuity (BCVA); • Addition of the requirement of a visual fields assessment for eligibility; • Clarification that assessment of the primary objective after 3 months of treatment was to be done after 90 days of treatment; • Ophthalmoscopy was not required to be performed under dilation; • Revision of the order of performing pachymetry, slit-lamp examination, IOP measurements, installation of fluorescein agent, and visual fields for ease of performing assessments at study sites; • Revision that conjunctival hyperemia assessment did not have to be performed as part of the slit-lamp examination and should precede the slit-lamp examination; • Specification of which assessments had to be performed by an ophthalmologist; • Clarification that specular microscopy was to be performed only on the study eye; • Correction that mydriatic drugs were not to be used until after all vision testing was completed; • Revision of the instructions for AE and serious adverse event monitoring for increased subject safety; • Text revisions for clarification of the study endpoints, the timing of dosing, the inclusion and exclusion criteria, which subjects were required to undergo a washout period, the washout period required for different IOP-lowering medications (including addition of a tabular summary), the study schedule for subjects required to undergo a washout period, that study drug instillation was to be done by the subject, when subject dosing instructions should have been dispensed, that the pachymetry test was to be performed by a calibrated ultrasonic pachymeter, and the details of the statistical methods to be used.

Significant changes included the following: • Text revisions for clarification of exclusion criteria; • Updated the number of investigative sites participating in the study (increased from 30 to 45 sites); • Revision of the instructions for unmasking in the event of an emergency, to be in line with ICH guidance and standards of practice; • Clarification that specular microscopy was to be performed in the study eye and at select US sites only; • Clarification of period during which diclofenac was disallowed.

Significant changes included the following: • Clarification of the inclusion criterion regarding acceptable contraceptive methods for female subjects and male subjects with partners of childbearing potential.