Maximum Tolerated Medical Therapy for Glaucoma: Fixed-Dose Combinations of Timolol, Dorzolamide, Brimonidine with Latanoprost Versus Timolol, Dorzolamide with Latanoprost.

Purpose: Maximal medical therapy involves using three or more classes of topical anti-glaucoma agents to achieve the target intraocular pressure (IOP). This study compared the effectiveness, tolerability, and safety of a fixed combination of timolol, dorzolamide, brimonidine, and latanoprost (TDB-L) versus a fixed combination of timolol, dorzolamide, and latanoprost (TD-L) for uncontrolled IOP in patients with primary open-angle glaucoma.

Methods: In this randomized, double-masked Phase IV trial, 47 eyes from 26 patients were assigned to TDB-Lor TD-L for 60 days, with follow-ups on days 14, 30, and 60. IOP was measured at 9:00 and 11:00 a.m. Follow-ups assessed tolerability via the Ocular Comfort Index (OCI) and conjunctival hyperemia (CH). Safety evaluations included chemosis, fluorescein conjunctival staining (FCS), visual acuity, corneal and retinal nerve fiber layer thickness, ganglion cell layer, and adverse events (AEs).

Results: By day 60, both treatment groups achieved a significant reduction in IOP, with TDB-L decreasing from 20.1 ± 1.6 mmHg to 14.0 ± 2.2 mmHg and TD-L from 20.8 ± 1.8 mmHg to 16.8 ± 2.0 mmHg (between groups, p = 0.042). In the TDB-L group, the reduction in IOP by day 60 was 6.3 mmHg, compared to 4.5 mmHg in the TD-L group. OCI scores did not significantly change. By day 60, 15% of eyes exhibited moderate CH (all in TD-L, p = 0.002). The safety of both groups was similar, as neither presented drug-related AEs nor showed differences in safety parameters, with differences being found only in FCS (between groups, p = 0.001).

Conclusion: Both TDB-L and TD-L achieved significant IOP reductions after two months, were well tolerated, and safe. Adding a fourth hypotensive agent may offer an effective option for patients needing more IOP reduction beyond TD-L, highlighting their role in managing glaucoma in regions with high socioeconomic burdens and limited treatment access.

Trial registration: ClinicalTrials.gov identifier NCT04702789, registered on 21 October 2019.