The goal of this observational study is to evaluate whether prostaglandin analogue eye drops have a direct neuroprotective effect on retinal ganglion cells - beyond their intraocular pressure (IOP)-lowering effect - in adult patients with glaucoma or ocular hypertension. The study includes individuals diagnosed with glaucoma (any sex/gender, adult age groups) undergoing standard clinical treatment. The main questions it aims to answer are:

• Do prostaglandin analogues provide a neuroprotective effect on retinal ganglion cells that is independent of their IOP-lowering properties?
• Should prostaglandin analogues be promoted/favoured over other IOP-lowering compounds for long-term glaucoma management?

Researchers will compare an interventional group, which consist of 750 eyes treated with prostaglandin analogues (e.g., latanoprost, travoprost, tafluprost, bimatoprost, unoprostone), with a control group, which consist of 750 eyes treated with non-prostaglandin IOP-lowering compounds (e.g., timolol, dorzolamide, brimonidine, netarsudil) to see if treatment with prostaglandin analogues is associated with better retinal ganglion cell survival over a period of 3 years (36 months).

Data will be collected from individuals who had at least 36 months of documented follow-up, with clinical data available at approximately 3, 6, 12, 24, and 36 months. Eligible individuals must have been treated with either prostaglandin analogues or other intraocular pressure (IOP)-lowering agents as part of routine clinical care. The data to be obtained from medical records will include at least:

• Intraocular pressure readings
• Visual field testing
• OCT measures
• Visual acuity
• Adverse events
• Treatment adherence/compliance
• Additional glaucoma interventions

Glaucoma is among the most prevalent causes of irreversible blindness and is characterized by a progressive, irreversible degeneration of the retinal ganglion cells. Elevated intraocular pressure (IOP) is the most important glaucoma risk factor and the only risk factor that is readily modifiable with established treatment options, which include pharmacological approaches, laser treatment, and surgery. However, in many patients the disease progresses even after IOP is effectively lowered. Hence, neuroprotective treatment approaches that go beyond IOP lowering are needed.

Prostaglandin analogue eye drops reduce IOP by increasing uveoscleral outflow and are a well-established treatment option in ocular hypertension and glaucoma. Animal studies suggest that prostaglandin analogues may have a direct neuroprotective effect on retinal ganglion cells in addition to the effect mediated by IOP lowering. Proposed mechanisms of action include inhibiting of caspase-3 and cyclooxygenase as well as activation of polypeptide 2B1 and Klotho protein. However, this proposed additional, direct neuroprotective effect has not yet been tested in human patients. The viability and functional status of the retinal ganglion cells in glaucoma can be assessed by morphological readings, the standard nowadays being various optical coherence tomography modalities, and by visual field testing. Detection of Apoptosing Retinal Cells (DARC) is another, relatively novel technology that allows for quantification of retinal ganglion cell death, presumably on a much shorter time scale.

This is an observational, retrospective and longitudinal clinical study, according to the normal clinical practice.

This study aims to evaluate prostaglandin analogues neuroprotective effect on retinal ganglion cells apart from intraocular pressure (IOP)-lowering over a period of 3 years (36 months) and whether treatment of ocular hypertension and glaucoma participants with prostaglandin analogues should be promoted/ favoured over other IOP-lowering compounds. It will have a follow-up at 3, 6, 12, 24, and 36 months in eyes with glaucoma treated with prostaglandin analogues or a different topically applied compound.

Inclusion Criteria:

• Age 18+ years
• Established glaucoma diagnosis (primary open-angle glaucoma, normal tension Glaucoma, pseudoexfoliation glaucoma, pigmentary dispersion glaucoma) in either eye
• Visual field mean deviation (MD; location-weighted mean difference from average age-corrected visual field sensitivity) of 2 visual fields differing by no more than 3 dB, for a mean deviation of better than -6.0 dB, or by no more than 4 dB, for a mean deviation worse than -6.0 dB, as measured using Humphrey perimetry (or equivalent Haag-Streit / Octopus; in at least one eye; analogous to The United Kingdom Glaucoma Treatment Study)
• Treatment with either prostaglandin analogues only or another topically applied IOP-lowering compound only for at least 3 years
• Documented follow-up period of at least 3 years
• At least 6 patient visits documented over the follow-up period with readings of IOP, visual field, OCT
• No additional glaucoma intervention apart from laser trabeculoplasty and/or cataract surgery during the observational period

Exclusion Criteria:

• Follow-up period < 3 years
• Number of patient visits <6 visits
• Number of OCT, visual field readings during the observation period < 6
• Low compliance/therapy interruption
• Beginning of combination therapy of prostaglandin analogues and other IOP lowering eye drops during the observation period
• In case of glaucoma diagnosis in both eyes: different topical IOP-lowering treatment regimes (e.g. prostaglandin analogues in one eye and beta-adrenergic blocking agents in the fellow eye)
• Additional glaucoma intervention during the observational period other than laser trabeculoplasty and/or cataract surgery

1500 eyes (750 treated with prostaglandin analogues and 750 treated with a different IOP-lowering compound)