The purpose of this study is to determine whether Metformin could prevent the progression of glaucoma in a safe and effective manner.

Primary open-angle glaucoma (POAG) is a serious blinding disease characterized by irreversible damage to retinal ganglion cells (RGCs). At present, there is no effective treatment for the rescue of visual function loss caused by POAG.

Metformin is the classic first-line therapy for diabetes. Recently, it has been found that Metformin may have other beneficial effects such as promoting weight loss and reversing age-related neurodegeneration. Importantly, retrospective case-control studies found that there were associations between Metformin treatment and a reduction in the incidence of glaucoma. Specifically, diabetic patients treated by Metformin had a 25% lower risk to develop open-angle glaucoma. In addition, previous animal experiments have preliminarily shown that Metformin can play a neuroprotective role by activating AMPK kinase, regulating methylation levels and promoting ganglion cell survival. Therefore, the investigators hypothesize that Metformin can prevent visual function deterioration via rescuing retinal ganglion cells.

The main objective of this study is to assess the progression of visual field loss in patients with POAG after treatment with Metformin versus placebo. The secondary objectives include the followings: RNFL thickness, vision, cup/disk ratio, safety, and biochemical tests to determine the alteration of AMPK and methylation parameters associated to the use of Metformin.

Approximately 40 study subjects will be randomized in a 1:1 ratio to each treatment group. The treatment group will be assigned to the study intervention (oral Metformin) for 12 months while the placebo group will receive placebo containing fructose and starch for 12 months. Throughout the 12-month study period, progression of visual function and systematic safety examinations will be measured. At 18 months, there will be one additional follow up visit.

Inclusion Criteria:

• Age between 18-65 years old;

• The baseline value of intraocular pressure ≤ 21 mmHg in either eye whether untreated or treated by ≤ 2 eye drops (laser or filtering surgery should be performed over 3 months).

• Over two times of experience of visual field examination (24-2 or 30-2 visual field examinations) in the past two years, or false positive/false negative ratio less than 33%;

• Diagnosed POAG by Glaucoma specialists from Zhongshan Ophthalmic Center with open angle, and impairment in optic disc or visual field in one or both eyes.

• Patient is at risk of glaucomatous progression, as determined by the documented presence of optic disc hemorrhage within 12 months in either eye, OR ≥2 of the following risk factors:

• Vertical cup-to-disc ratio >0.8 in one or both eyes

• Mean deviation in visual field worse than <10 dB in either eye (verified by the reading center)

• Pseudoexfoliation in either eye

• Family history (parent or sibling) of glaucoma

• Hypertension

• Systemic hypertension requiring medical treatment Migraine (defined by the International Headache Society with or without aura, Raynaud's syndrome, or both:

• The main organs are functioning normally and meet the following criteria:

  1. Blood sample should meet the following criteria: (no blood transfusion within 14 days) A. Hemoglobin (> 90g/L); B. Platelet count (>105*10e9/L)
  2. Biochemical and urinary examinations should meet the following criteria:
  1. . Urine bilirubin < 1.25 times ULN (Upper Limit of Normal);
  2. . ALT and AST < 2.5 times ULN;
  3. . CREA ≤ ULN;

Exclusion criteria:

• Secondary open-angle glaucoma (such as pigmentation syndrome, trauma, etc.) or angle-closure glaucoma.
• The best corrected visual acuity of either eye is less than 6/36;
• The mean derivation of visual field in either eye is less than - 22dB.
• Use of >2 topical (or any oral) IOP-lowering products at the baseline visit.
• Any ocular pathology in either eye that may have interfered with the ability to obtain visual field, disc imaging, or accurate IOP readings such as uveitis, refractive opacification;
• Eye drops such as neuroprotective therapies have been used in the past three weeks might affect this clinical study, for inclusion need 8 weeks of wash period.
• Pregnant or nursing women;
• Diabetes mellitus, definite impairment of liver and kidney function, or severe heart, liver or kidney diseases;
• In the last three months, ophthalmic surgery (including cataract surgery) has been performed
• Enrolled in other clinical study at the same time.
• Could not complete the study according to the requirements in this research .
• History of epilepsy or severe mental illness, including schizophrenia, bipolar disorder or severe depression

Participants and researchers are double-blind. After signing informed consent, subjects who meet the inclusion criteria will be randomly divided into the oral Metformin experimental group or the oral placebo control group at a ratio of 1:1. Random lists will be generated by independent statisticians. Randomized group will be sealed in a separate opaque envelope, showing only the research identification number. Participants and researchers (medical evaluators, outcome evaluators and data analysts) will be unaware of the grouping.

During the period of treatment, if patient suffers from lactic acidosis, excessive ventilation, myalgia, the masking should be unveiled and his/her systematic and eye conditions should be assessed to choose the best treatment. The choice of remedial treatment plan is based on the consensus of doctors and patients. The changes of treatment methods and curative effect should be recorded in detail for future analysis