Inclusion Criteria:  Be at least 18 years of age Provide written informed consent Be willing and able to comply with all study procedures Have a patient-reported history of dry eye Have a history of use or desire to use eye drops for dry eye symptoms Have a best corrected visual acuity (BCVA) of 0.7  Exclusion Criteria:  Have any clinically significant slit-lamp findings Be diagnosed with an ongoing ocular infection Have worn contact lenses within 7 days of Visit 1 Have used Restasis®, Xiidra®, Cequa®, or Eysuvis® Have had any ocular and/or lid surgeries Be currently taking any topical ophthalmic prescription Have an uncontrolled systemic disease Be a woman who is pregnant, nursing, or planning a pregnancy; Be a woman of childbearing potential who is not using an acceptable means of birth control Participated in a previous clinical study involving PL9643 Be unable or unwilling to follow instructions, including participation in all study assessments and visits