Over the Last 25 Years, Latanoprost Has Changed the Paradigm of Glaucoma Treatment
An important milestone in the treatment of glaucoma was the introduction of latanoprost with an entirely new mechanism of action compared to previously used antiglaucoma medications. Prostaglandin analogs (PGAs) have become the first-line treatment for primary open-angle glaucoma (POAG) primarily due to their efficacy, once-daily dosing, and minimal systemic side effects. The following recent review briefly summarizes the impact of the introduction of PGAs 25 years ago on current clinical practice in the treatment of glaucoma.
Lowering IOP as the Basis of Glaucoma Treatment
Glaucoma is one of the leading causes of irreversible blindness worldwide. In 2020, it was responsible for moderate to severe visual impairment in 4.1 million and blindness in 3.6 million people. Approximately two-thirds of cases are POAG.
The pathogenesis of glaucoma is multifactorial, and major risk factors include elevated intraocular pressure (IOP), positive family history, and age. The primary approach to preserving vision in patients with glaucoma is to address the only modifiable risk factor – IOP. Significant limitation of glaucoma progression is achieved by reducing IOP by 20–40%. Treatment options include pharmacotherapy and laser or surgical intervention.
Pharmacotherapy for Glaucoma
In most patients, the first step in glaucoma treatment is pharmacotherapy. IOP is the result of a balance between the production of aqueous humor by the ciliary body and its drainage via the trabecular or uveoscleral pathway. It has been demonstrated that lower IOP can be achieved primarily by enhancing uveoscleral outflow.
In the EU, several classes of IOP-lowering drugs are currently available, differing in their mechanisms of action: PGAs, beta-blockers (BBs), carbonic anhydrase inhibitors, alpha2 agonists, and parasympathomimetics. PGAs are considered first-line drugs due to their efficacy, minimal systemic side effects, and once-daily dosing. Latanoprost, the first topical PGA for glaucoma treatment, entered the market 25 years ago, completely changing the treatment paradigm at that time.
PGAs in Glaucoma Treatment
Mechanism of Action
PGAs bind to receptors on the ciliary muscle, inducing its relaxation and increased outflow of aqueous humor. Another effect of PGAs is increased remodeling of the extracellular matrix in the ciliary muscle, iris root, and sclera, thereby reducing resistance to aqueous humor outflow.
Efficacy
Currently available drugs in this group include 0.005% latanoprost, 0.004% travoprost, 0.03% and 0.01% bimatoprost, and 0.0015% tafluprost. PGAs have been shown to result in greater IOP reduction than BBs, with a lower risk of side effects. Their IOP-lowering effect begins 2–4 hours after administration, with a peak effect at 8–12 hours. They also minimize IOP fluctuations. Topical application of PGAs results in a 25–32% reduction in IOP, lasting for 24 hours. PGAs are the first-line therapy for ocular hypertension, POAG, and pseudoexfoliative glaucoma. They may be indicated for angle recession glaucoma and are considered a last resort for elevated IOP due to trauma, inflammatory glaucoma, or active macular edema.
If PGA monotherapy is well-tolerated but does not achieve sufficient IOP reduction, they can be combined with other drugs with different mechanisms of action. More than one drug is used by about half of glaucoma patients.
Safety
PGAs are generally well-tolerated and associated with mild to moderate ocular and periocular symptoms, mostly cosmetic in nature: conjunctival hyperemia, eyelash changes, eyelid pigmentation, iris pigmentation, periocular hypertrichosis, corneal epithelial disorder, iritis. Special attention is given to the potential for cystoid macular edema and deepening of the upper eyelid sulcus.
PGAs should not be administered to patients at risk of cystoid macular edema, and it should be noted that the deepening of the upper eyelid sulcus is an independent factor in the failure of surgical glaucoma treatment.
Impact of PGAs on Glaucoma Surgery
When topical glaucoma treatment is insufficient, laser or surgical intervention is indicated. The gold standard for surgical treatment is trabeculectomy. However, the introduction of PGAs significantly reduced the number of trabeculectomies performed. For example, the number of trabeculectomies among Medicare beneficiaries in the US decreased from 59,645 in 1995 to 24,178 in 2004. The number of laser trabeculoplasties dropped from 148,816 in 1996 to 75,647 in 2001.
Previous concerns about whether the introduction of PGAs would adversely affect the success of invasive treatments were dispelled by results showing that using latanoprost during the 6 months before trabeculectomy had no significant impact on surgical outcomes or postoperative IOP.
Conclusion
Prostaglandin analogs, particularly latanoprost, have been an integral part of glaucoma pharmacotherapy for 25 years. Numerous studies have been published during this time, demonstrating their efficacy and favorable safety profile. PGAs are now first-line therapy in many indications. Due to their effectiveness, minimal systemic effects, and once-daily dosing, these drugs have changed the paradigm of glaucoma therapy, as evidenced by the significant decline in trabeculectomies and laser procedures since their introduction into clinical practice.
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Source: Cordeiro M. F., Gandolfi S., Gugleta K. et al. How latanoprost changed glaucoma management. Acta Ophthalmol 2024 Mar; 102 (2): e140−e155, doi: 10.1111/aos.15725.
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