From Ocular Hypertension to Primary Open-Angle Glaucoma: European Approaches to Treatment (EGS, 2014–2018)

It has been proven that glaucoma belongs to a group of neurodegenerative diseases that affect the visual system. Today, glaucoma is the leading cause of irreversible blindness worldwide.

In the 2014 European Glaucoma Society (EGS) Guidelines on Glaucoma, translated into Ukrainian, prepared for publication, and published by us in collaboration with the EGS, glaucoma is defined as follows: “Primary open-angle glaucoma (POAG) is a chronic, progressive optic nerve neuropathy with characteristic morphological changes in the optic nerve head and in the retinal nerve fiber layer in the absence of other ophthalmic diseases or congenital anomalies. These changes are associated with progressive loss of retinal ganglion cells and narrowing of the visual field.” A shortcoming of this definition is undoubtedly the lack of reference to the role of intraocular pressure (IOP) in the development and course of the disease. This point is significant and will therefore be addressed in the next edition of these guidelines, scheduled for 2020.
Currently, elevated IOP is considered the primary modifiable risk factor for the development and progression of glaucoma. However, glaucoma sometimes progresses with relatively low or normal IOP, i.e., normal-tension or low-tension glaucoma occurs. At the same time, in some cases with sufficiently high IOP (ocular hypertension—OH), visual function remains stable.
In the past, OHT was considered a diagnosis, but now this condition is interpreted as a persistent elevation of IOP above the mean normal value by 2 or 3 standard deviations. The etiology and pathogenesis of OHT remain unknown.
Clinical signs and symptoms of OH include:

• IOP >21 mm Hg without treatment;
• normal visual field; • normal optic disc and retinal nerve fiber layer;
• gonioscopy: open anterior chamber angle (to rule out intermittent anterior chamber angle block);
• no signs or history of other ophthalmic diseases or steroid use.

Until recently, OHT was not considered a disease or a threat to vision. Today, influenced by the results of multicenter studies outlined in the EGS protocols, attitudes toward OHT are shifting somewhat, and the question of whether to treat OHT is becoming more pressing for ophthalmologists. In the Ocular Hypertension Treatment Study (OHTS), which investigated the possibility of OHT progressing to primary open-angle glaucoma (POAG), evidence was obtained confirming the definite existence of such a risk. In this study, over 1,500 patients with OHT were observed and divided into two groups: participants in one group received a topical medication to lower IOP, while in the other group, no IOP-lowering treatment was administered. The aim of this large-scale study was to reduce IOP to <24 mm Hg or by at least 20% from baseline and, after a certain period, to follow up on the participants to identify cases of OAG. The latter was established based on two positive results of computerized perimetry and optical coherence tomography in the presence of visual field defects or deterioration of the optic nerve head. Patients in the control group with a newly diagnosed PVRG based on the aforementioned manifestations were prescribed antihypertensive eye drops. In the treatment group, the mean IOP in individuals with OGC was within 22.5 mm Hg. It is important to note that over a 5-year follow-up period, signs of glaucomatous damage were detected in 4.4% of participants in the treatment group who were taking antiglaucoma medications, whereas in the control group, OAG was diagnosed in 9% of patients (p<0.0001). These data reliably indicate a 50% reduction in the risk of OAG progressing to glaucoma during treatment. Kass et al. in 2002 also demonstrated similar results (Fig. 1).
Thus, IOP control is of great importance in individuals with OAG. Given the prevalence of OAG among various segments of the population aged over 40, the risk of a progressive increase in the incidence of glaucoma has every reason to rise. For example, according to a survey of an independent cohort of Kyiv residents (n=1000) aged 35 and older, conducted in 2010–2011 by staff of the Department of Ophthalmology at the Kyiv Medical University of the Ukrainian Academy of Medical Sciences and the Kyiv City Ophthalmological Center of Kyiv City Clinical Hospital No. 1, elevated IOP was found in 29.0% of cases. Further ophthalmological examination revealed signs of primary open-angle glaucoma (POAG) in nearly one-third of individuals with elevated IOP.
Further randomized follow-up over 5 years showed that in over 90% of untreated patients, glaucoma did not develop as a result of elevated IOP. However, after 13 years, glaucoma developed in 22% of those who initially received no treatment and in 16% of the group that received therapy. It is important to note that the transformation of OGC into PGCG was first detected in approximately 50% of patients on optic nerve head images and in about 40% of patients based on perimetry results.

In addition, the following risk factors for progression were identified: thinner central corneal thickness (CCT), higher IOP, optic disc hemorrhages (Fig. 2), age, increased ratio of cup diameter to optic disc diameter in the vertical and horizontal meridians (Fig. 3), and increased standard deviation of the central visual field pattern (PSD). Regarding disc hemorrhages, the rate of glaucoma progression was higher in eyes with their presence.

Given that visual function directly affects quality of life, the primary goal of glaucoma treatment is to preserve the patient’s vision and relative quality of life at an acceptable cost. The assessment of treatment costs must take into account the associated inconveniences and side effects, as well as the financial costs to the individual and society as a whole. For the most part, patients with early- and moderate-stage glaucoma retain good vision and experience only a slight decline in quality of life; however, progressive loss of visual function in both eyes severely impairs quality of life (EGS, 2014–2018, 4th edition).
Thus, based on the presented data, it is advisable to recommend the use of hypotensive eye drops in cases of elevated IOP when two of the aforementioned risk factors for PAG are present. According to the European protocol “Terminology and Guidelines on Glaucoma,” to lower IOP, it is advisable to prescribe first-line medications, starting with the prostaglandin analog (PGA) group, which not only reduces IOP by 20–25% with a single instillation but also adequately controls it throughout the day, preventing fluctuations during nighttime hours (Fig. 4).

Given that OGC and POCD are conditions requiring reliable 24-hour IOP control throughout life, the preferred options in personalized treatment remain original APG, preferably without preservatives, and the prescription of medications to prevent the development of ocular surface diseases in accordance with the provisions of the latest DEWS-II (2017).
It should be noted that the following risk factors and prognostic factors for the progression of OAG in PAG have been established to date:

• age (a 26% increase in risk for every 10 years of life);
• IOP (a 1 mmHg increase in IOP above normal corresponds to a 9% increase in risk);
• the ratio of the excavation diameter to the optic disc diameter in the vertical and horizontal meridians (a 19% increase in risk for every 0.1 increase in the ratio);
• PSD (a 13% increase in risk with a 0.2 dB increase in PSD);
• CTR (a 2.04-fold increase in risk with a 40 μm decrease in CTR).

This list draws physicians’ attention to certain important factors that may play a significant role in determining the risk and prognosis of PAVK progression in individuals with elevated IOP. Based on the combined OHTS-EGPS prognostic model, a calculator was developed to quantitatively assess the 5-year risk of OI progression in PAVK. This tool, available to every specialist, helps determine the optimal frequency of patient visits to the doctor and select a possible treatment (Fig. 5); however, existing limitations must be taken into account. Since the calculator was developed based on data from the OHTS and EGPS studies, its results are not valid for individuals under 40 years of age, patients with untreated IOP <22 mm Hg, and members of ethnic groups other than Caucasian and African American. The calculator also does not account for factors associated with an increased risk of glaucoma, such as a family history of glaucoma and pseudoexfoliation. Additionally, the patient’s life expectancy must be taken into account.

Regarding the frequency of examinations, once OAG has been diagnosed, it is recommended to conduct them once every 12–24 months. The following should be performed:

• examination of the optic disc;
• visual field testing;
• IOP measurement;
• photography of the retinal nerve fiber layer and the optic disc at the start of follow-up and subsequently every 2–3 years.

If the results of these examinations are normal, the intervals between visits can be extended.
Researchers have found that in the absence of treatment, the risk of developing glaucoma increased by 9.5% in individuals with OHT over a 5-year follow-up period. It has been proven that the higher the IOP, the greater the risk of developing glaucoma. In the presence of risk factors, the advisability of prophylactic IOP reduction is considered in individual patients.
Moderate and intermittent increases in IOP are not sufficient grounds for prescribing therapy, but in cases of chronic IOP elevation above 20 mm Hg, treatment may be advisable even in the absence of risk factors. Treatment options are consistent with the OAG treatment algorithm (EGS, 4th edition, 2014–2018).

Thus, the current view on the problem of OGL, based on the results of large-scale global studies in recent years, indicates that under certain circumstances, there are real conditions for the transformation of OGL into PVR. This should change our approach to this problem and lead to corresponding changes in the tactics of monitoring and treating patients with OGL. If OG progresses to PVR, there is a real risk of vision loss and, consequently, blindness. It is important to note that treatment decisions for each individual patient must be made on a case-by-case basis; in other words, therapy must be personalized.