Pharmacotherapy of Glaucoma in a Nutshell According to the Latest Recommendations of the European Glaucoma Society

Introduction

Glaucoma, also known as green cataract, is a disease characterized by increased intraocular pressure (IOP) along with changes in the internal structures of the eye and damage to the optic nerve, which can lead to visual impairments. The essence of therapy is to reduce IOP to an optimal level, usually through medication in the form of eye drops. In addition to pharmacotherapy, patients are advised to maintain a healthy lifestyle (without alcohol and smoking) and pay attention to the treatment of any additional conditions (such as hypertension, hypotension, or diabetes).

Basic Principles of Glaucoma Pharmacotherapy

Treatment is considered effective if the reduction in IOP is comparable with published results for the given medication on a similar population. The highest reduction in IOP is achieved with prostaglandin analogs (PGAs), followed by non-selective beta-blockers, rho kinase inhibitors, alpha-adrenergic agonists, selective beta-blockers, and local carbonic anhydrase inhibitors.

According to the mechanism of action, preparations indicated for the treatment of glaucoma are divided into three groups: substances that reduce the production of intraocular fluid, substances that influence the outflow of intraocular fluid, and substances that act osmotically.

Initiating Treatment with Monotherapy

To minimize the occurrence of side effects, the smallest amount of medication necessary to achieve the desired therapeutic response should be administered. Monotherapy is recommended as the initial approach. When choosing a medication, consider not only the effectiveness of the preparation and target IOP but also systemic contraindications (allergies, respiratory diseases, arrhythmias, concomitant medication), the eye surface (with a possible preference for preservative-free preparations), associated eye diseases, and also estimated patient adherence to treatment, quality of life, and medication cost. The effect of therapy depends on the untreated IOP; a greater reduction occurs in patients with higher untreated IOP values.

After successful reduction of IOP levels, regular examinations of the fundus, intraocular pressure, visual field, and attention to possible symptoms of decompensation and overall patient quality of life (blurred vision, perception of colored halos around point light sources, eye or head pain, the presence of nausea or vomiting) are recommended.

Medication Swap in Monotherapy

If the initial treatment is not effective or the medication is not tolerated, another monotherapy (from the same or different group of drugs) should be considered. Switching monotherapy is preferred over adding a second drug. Laser trabeculoplasty is also an option.

Combination Therapy

In selected cases, such as advanced glaucoma or very high IOP, where the target IOP is not achieved with a single drug or it is unlikely to be achieved, combination therapy can be recommended. Fixed combination therapy is preferred as it helps maintain adherence to treatment and limits exposure to preservatives.

If adequate compensation is not achieved with two medications, considering the addition of a third, or surgery might be necessary. Laser and surgical procedures are part of the treatment for advanced glaucoma, with non-penetrating surgeries (sclerectomy, trabeculotomy) generally being sufficiently effective and safer than penetrating trabeculectomy, which, however, can achieve a more significant reduction in IOP.

In cases of uncertainty regarding treatment efficacy, medication can be temporarily discontinued, and therapy re-evaluated based on untreated IOP. The goal is always to achieve the therapeutic response with the smallest amount of medication and associated side effects, complications, costs, and impacts on the patient's life.

The Impact of Preservatives on Local Toxicity

Preservatives in topical medications can cause or worsen existing ocular surface diseases (OSDs) which have high prevalence in adults, such as dry eye syndrome or Meibomian gland dysfunction. The most common preservative is benzalkonium chloride (BAC). OSD symptoms often subside after substituting a BAC-containing preparation with a preservative-free one. Other ways to mitigate OSDs include reducing the number of applied eye drops (using fixed combinations), treating the eye surface with preservative-free artificial tears, or surgical procedures.

The European Medicines Agency (EMA) suggests limiting the use of preparations with preservatives in long-term treated glaucoma patients and those who do not tolerate them. Alternatively, preparations with minimal preservatives ensuring adequate antimicrobial efficacy but without mercury-based preservatives may be considered.

Summary and Conclusion

Glaucoma treatment begins with monotherapy, using the smallest amount of medication necessary to achieve the desired therapeutic response. If adequate compensation is not achieved, various anti-glaucoma medications can be tried. When monotherapy does not sufficiently reduce IOP, treatment is escalated to two or three medications, ideally in fixed combination form and preferably without preservatives or with minimal amounts, thus reducing the risk of negative effects on the ocular surface.

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Sources:
1. European Glaucoma Society Terminology and guidelines for glaucoma, 5^th edition. Br J Ophthalmol 2021; 105 (Suppl. 1): 1–169, doi: 10.1136/bjophthalmol-2021-egsguidelines.
2. Treatment of glaucoma. Czech Glaucoma Society, 2014. Available at: http://glaukom.cz/lecba-glaukomu
3. Complications of surgical treatment of glaucoma. proLékaře.cz, 9 Nov 2008. Available at: www.prolekare.cz/tema/glaukom/detail/komplikace-chirurgicke-meu-glaukomu-3351