Primary open-angle glaucoma: clinical guidelines

List of Abbreviations

AGO – antiglaucoma surgery

IOP – intraocular pressure

AQH – aqueous humor

ONH — optic nerve head

LDG — low-pressure glaucoma

GON – glaucomatous optic neuropathy

ONH – optic nerve head

CI – confidence interval

LI — laser iridectomy

Med – medication

LDGP — laser descetomegoniopuncture

LTP – laser trabeculoplasty

ICD-10 – International Classification of Diseases 10th Revision

INN – International Nonproprietary Name

NPDS — non-penetrating deep sclerectomy

NRR – neuroretinal rim

OCT – optical coherence tomography

PG — pigmentary glaucoma

VF – visual field

POAG – primary open-angle glaucoma

PEG — pseudoexfoliative glaucoma

PERG – pattern electroretinogram

PES — pseudoexfoliation syndrome

SAP – standard automated perimetry

SLT — selective laser trabeculoplasty

RNFL – retinal nerve fiber layer

ACA – anterior chamber angle

PCC – phacoemulsification of cataract

COPD – chronic obstructive pulmonary disease

CCT – central corneal thickness

C/D – ratio of the maximum cup diameter to the OD diameter

ISNT (inferior, superior, nasal, temporal) – rule for ophthalmoscopic assessment of the neuroretinal rim in glaucoma diagnosis

P₀ – true intraocular pressure level

Pt – tonometry reading when measuring IOP with a contact Maklakov tonometer using a 10 g weight

Terms and Definitions

Ocular biomicroscopy is an in vivo visual examination method of the optical media and ocular tissues based on creating contrast between illuminated and non-illuminated areas, performed using a slit lamp and additional diagnostic lenses (specifically, for fundus biomicroscopy).

Intraocular pressure – the pressure of the fluid inside the eye resulting from the balance between aqueous humor production, trabecular and uveoscleral outflow, and episcleral venous pressure; it maintains the shape of the eye, ensures a constant supply of circulating nutrients, and provides normal trophism of intraocular tissues.

Glaucomatous optic neuropathy (GON) – acquired optic nerve pathology characterized by progressive loss of retinal ganglion cells and their axons, leading to structural and functional damage to the optic nerve, visual impairment, and blindness.

Gonioscopy – a method of visual examination (inspection) of the iridocorneal angle (ICA) performed using a slit lamp and a goniolens (gonioscope).

Optic disc – the site where retinal ganglion cell axons exit the eyeball.

Neuroretinal rim (NRR) ‒ the area between the margin of the optic disc and the edge of the cup where the majority of retinal ganglion cell axons are projected.

Needling is a surgical technique for mechanical revision of a filtering bleb using a hypodermic needle on a syringe.

Normal (a), moderately elevated (b), high (c) IOP – levels of IOP elevation according to the glaucoma classification.

Optical coherence tomography (OCT) ‒ a non-invasive, non-contact method for in vivo visualization, qualitative and quantitative analysis of the morphological features of fundus structures, based on the principle of light interferometry.

Ocular hypertension – elevated IOP in the absence of characteristic glaucomatous changes in the optic disc, retinal nerve fiber layer, and visual field defects.

Ophthalmoscopy – an instrumental method for examining the fundus and its structures.

Tonometry – an instrumental method for measuring IOP level, the value of which is determined by analyzing eye deformation data caused by a tonometer and expressed in millimeters of mercury (mmHg).

Perimetry – a method for examining the visual field.

Visual field – the totality of points in space simultaneously visible by the eye with a fixed gaze.

Refractory glaucoma – a form of the disease characterized by a severe, stubborn course, persistence, and often resistance to standard treatment methods.

Scotoma – a visual field defect not connected to the peripheral boundaries.

Retinal nerve fiber layer – the retinal layer formed by the axons of retinal ganglion cells.

Stabilized and unstabilized glaucoma are terms indicating the absence or presence of negative dynamics in the condition of the optic disc and visual field of the patient during follow-up examinations. When assessing the dynamics of the glaucomatous process, the IOP level and its compliance with the “target” value are also taken into account.

Standard automated perimetry is computerized threshold static perimetry in which the central visual field is examined using a white stimulus on a white background.

Iridocorneal angle – the space between the corneoscleral region and the anterior surface of the iris.

Phacodonesis – “trembling” of the lens during eye movement caused by the rupture of some fibers of the suspensory ligament (zonules of Zinn).

“Target” intraocular pressure – the maximum acceptable pressure at which glaucoma progresses slowly enough that vision-related quality of life remains reasonably stable over subsequent years.

Electrophysiological studies – methods for examining the function of the optic nerve, retina, and visual cortex of the brain.

MD, mean deviation – a perimetric index determined in static perimetry, representing the average difference between age-adjusted normal retinal sensitivity values and the measured threshold values at all test points.

PSD, pattern standard deviation – a perimetric index characterizing the severity of localized visual field defects.

GHT, Glaucoma Hemifield Test – a test comparing the upper and lower halves of the visual field across 5 (five) corresponding zones.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Primary open-angle glaucoma (POAG) is a chronic progressive optic neuropathy that encompasses a group of diseases with characteristic features:

• periodic or constant elevation of IOP above the individual's normal range;

• structural pathological changes of the optic disc and retinal nerve fiber layer;

• typical visual field defects corresponding to damage to the optic disc and retinal nerve fiber layer;

• open iridocorneal angle (confirmed by gonioscopy) [1-3].

POAG includes four clinical and pathogenetic forms: pseudoexfoliative glaucoma (PEG), chronic (simple), normal-tension glaucoma (NTG), and pigmentary glaucoma (PG).

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The etiology of POAG is not yet fully understood. Its onset and development are predominantly explained by a multifactorial concept involving various genetic and non-genetic factors [4-9].

Currently, several dozen genes related to the onset and development of POAG have been described [10]. Among the most studied are the myocilin (MYOC), optineurin (OPTN), and WD repeat domain 36 (WDR36) genes, which account for up to 10-15% of all cases [9, 11]. In a number of populations, a strong correlation has been established between the occurrence of PEG and polymorphisms of the lysyl oxidase-like 1 (LOXL1) gene [12].

Risk factors for the onset and progression of the disease include:

• age: POAG predominantly develops in patients over 40 years of age, and its prevalence increases with age (95% CI 2.5–4.0) [13–19].

• race/ethnicity: the prevalence of POAG is several times higher in African Americans than in Caucasians (95% CI 3.83–9.13) [20–23].

• gender: data on the relationship between gender and POAG are contradictory [24–27].

• family history: the prevalence of glaucoma among blood relatives of patients with POAG is 4–9 times higher than in the general population [9, 28–31].

• elevated IOP level: directly correlates with an increase in the prevalence and incidence of POAG. The risk of developing glaucoma increases by 10% for every 1 mm Hg increase in IOP above the population-average normal limit [32–40].

• pseudoexfoliation syndrome: the presence of pseudoexfoliations increases the risk of POAG by 9–11 times. Within 10 years, glaucoma develops in every third patient with PEX [41–45].

• pigment dispersion syndrome: the risk of developing pigmentary glaucoma in patients with pigment dispersion syndrome was approximately 10% at 5 years and 15% at 15 years [46–49].

• central corneal thickness (CCT): an increased risk of developing POAG by 30–41% has been established for every 40 µm of CCT thinning below the population average [50–53].

• myopia: high myopia (>6.0 diopters) increases the incidence of POAG [54–59].

• ocular perfusion pressure: a link has been found between low ocular perfusion pressure and an increased incidence of POAG. Since perfusion pressure represents the difference between diastolic blood pressure and IOP, treatment of arterial hypertension in patients with POAG can lead to systemic hypotension and, consequently, impaired blood supply to the optic disc [60–65].

• optic disc hemorrhages: In the Collaborative Normal Tension Glaucoma Study (CNTGS), the presence of hemorrhages in the optic disc area significantly correlated with glaucoma progression [66].

• other factors: there are reports of other factors that may be associated with an increased risk of onset and progression of POAG (cardiovascular pathology, including systemic arterial hypotension, systemic atherosclerosis; vasospastic syndrome, including Raynaud's disease, migraine and migraine-like conditions; sleep apnea and syncopal episodes of unclear origin; diabetes mellitus (95% CI 1.20–1.57)). However, literature data remain controversial [67–81].

The pathogenesis of glaucomatous optic neuropathy is not fully understood. Among the numerous theories of glaucomatous damage, the most common are the mechanical, vascular, and metabolic theories [4–7, 68, 82–87].

Comment: The multifactorial cascade of POAG pathogenesis includes [4–5, 82–91]:

• development of retention and impaired outflow of intraocular fluid due to trabeculopathy;

• instability and elevation of IOP above the individual's normal range;

• progressive deformation and partial collapse of the glial portion of the lamina cribrosa in the prelaminar region of the optic nerve head;

• posterior displacement of the scleral lamina cribrosa with deformation of the channels through which nerve fiber bundles pass, leading to compression of the exiting nerve fiber bundles and impaired axoplasmic flow. In addition, bowing may be facilitated by changes in the biomechanical properties of the lamina cribrosa, which deteriorate due to age-related dystrophic remodeling of the matrix of the lamina itself and the surrounding sclera resulting from changes in collagen composition and/or the structure of collagen structures;

• release of cytotoxic factors by damaged cells (reactive oxygen species, hydroperoxides, lipid peroxidation products, NO, Ca2+, etc.), damaging neighboring cells with the generation of an excessive concentration of glutamate;

• accelerated apoptosis of retinal ganglion cells, initially in the paramacular structures and subsequently in the peripheral ones, up to the complete disappearance of the retinal nerve fiber layer.

Hemodynamic disturbances are present in POAG at all levels: central, regional, and microcirculatory.

1.3 Epidemiology of the Disease or Condition

According to official Federal statistics in the Russian Federation as of January 1, 2022, there were 1 million 249 thousand 617 registered patients with glaucoma aged 18 years and older, which accounts for 1077.8 per 100 thousand of the adult population of the Russian Federation [99, 100]. Of these, 106,763 adult patients were diagnosed for the first time in their lives, which accounts for 92.2 per 100 thousand of the corresponding population of the Russian Federation [99, 100].

In the Russian Federation, global trends of rising glaucoma incidence are observed [26].

Analyzing the absolute figures of morbidity or total prevalence of glaucoma in the population of the Russian Federation, an increase of 17.6% over 10 years (from 2008 to 2019) can be noted. Such an increase may be associated with overall population aging, increased life expectancy, and improved registration of glaucoma patients. The decline in the indicator in 2020 reflects changes in the operation of all levels of ophthalmological care delivery to the population amid the fight against the novel coronavirus infection.

Thus, in 2008, 1,047,755 glaucoma patients were registered in the Russian Federation; in 2010 – 1,104,279; in 2012 – 1,144,045; in 2013 – 1,182,231; in 2015 – 1,281,566; in 2017 – 1,330,597; in 2019 – 1,338,242; in 2020 – 1,246,546 [101].

Moreover, a diagnosis of glaucoma was newly registered annually in the Russian Federation in 2008 in 120,598 patients; in 2010 – in 124,623; in 2012 – in 127,527; in 2013 – in 132,604; in 2015 – in 142,278; in 2017 – in 133,703; in 2019 – in 131,903; in 2020 – in 101,858 [101].

The expected global prevalence of glaucoma in 2020 was about 80 million people [25, 102, 103]; the expected prevalence of glaucoma in the Russian Federation, according to some authors, for the period from 2023 to 2025 will range from 1,202.1 to 1,408.5 thousand (minimum and maximum forecasts) per 100 thousand of the adult population [104–106].

Over the past 10 years, glaucoma has consistently ranked first among the causes of primary and accumulated visual disability [107–109]. As of January 1, 2022, there were 101,224 registered individuals with disabilities due to glaucoma in Russia, of whom 5,592 received disability status in 2021 [107].

The number of disabled individuals with glaucoma has been decreasing over the past 3 years. The primary disability rate per 10,000 adult population in 2021 decreased by 20% compared to 2019 (2019: 0.6; 2020: 0.44; 2021: 0.48). Accumulated disability due to glaucoma decreased by 7.2% in 2021 compared to 2019 (2019: 9.42; 2020: 9.01; 2021: 8.74). However, following the downward trend in the number of disabled individuals due to glaucoma, a certain increase in the number of newly recognized disabled individuals was noted in 2021, likely as a result of limited availability of scheduled ophthalmological care during quarantine measures aimed at preventing the spread of coronavirus infection.

Rates of primary disability vary significantly across different regions of the Russian Federation. The majority of visually impaired individuals due to glaucoma are specifically diagnosed with POAG (80.9%). Among the disabled population, men account for 58.2% and women for 41.8%. Upon initial disability assessment, 35.4% of glaucoma patients were classified as group I, 45.8% as group II, and 18.8% as group III disabled [108-111].

According to some epidemiological studies in the Russian Federation, glaucoma is diagnosed at advanced stages in 40-80% of cases, and in 50% of cases, patients are unaware of their condition and do not receive proper treatment [3, 110, 111].

The age of patients with newly diagnosed glaucoma predominantly ranges from 35 to 90 years. The incidence rate increases in older age groups: from 40 to 49 years – 0.55-0.88 (per 1,000 population), from 50 to 59 years – 1.5-2.5; from 60 to 69 years – 6.44-7.45; from 70 to 79 years – about 15.7 individuals; from 80 to 89 years – about 17.5 individuals. Thus, the number of POAG patients grows exponentially with age, increasing almost 20-fold in the oldest age group [3]. Open-angle glaucoma accounts for 72.3 to 96.1% of all forms of glaucoma. POAG is more common in women (56.6%) and slightly less common in men (43.4%), which correlates with established life expectancy [3, 26, 109-111].

1.4 Features of Coding the Disease or Condition

H.40.1 - Primary open-angle glaucoma [112, 113].

1.5 Classification of the disease or condition

Based on clinical and pathogenetic forms, POAG is subdivided into [112, 113]:

1. pseudoexfoliative glaucoma;

2. primary simple glaucoma;

3. low-tension glaucoma;

4. pigmentary glaucoma;

According to the IOP level, POAG is subdivided into:

Table 2 - Classification scheme for IOP levels in glaucoma [3, 114]

According to the disease course and clinical characteristics, POAG is subdivided into:

Table 3 - Classification scheme of glaucoma by disease course [114]

When assessing the dynamics of the glaucomatous process, the level of IOP and its compliance with "target" values are also taken into account.

According to the severity of the pathological process, POAG is subdivided into:

Table 4 - Classification scheme of glaucoma stages [114].

The division of the continuous glaucomatous process into 4 (four) stages is conventional. When determining the stage, the state of the visual fields and optic disc is taken into consideration. A number of alternative classification schemes have been proposed, which have not yet found wide application in domestic ophthalmological practice [115-118].

When discussing glaucoma stages, it is important not only to determine the transition from one stage to another, but also to identify and quantify disease progression. For this purpose, classifications are required that use functional (perimetric cumulative indices obtained using standard automated perimetry) and/or structural (optic nerve head status) parameters.

Thus, when using static perimetry, the modified classification by E. Hodapp, R. Parrish, and D. Anderson is applied [119].

Table 5 - Glaucoma classification according to static perimetry data

Examples of diagnosis:

Uncontrolled primary open-angle glaucoma of the left eye, moderate stage with moderately elevated IOP level (II b).

Controlled primary open-angle glaucoma of the right eye, advanced stage with normal IOP level (III a).

Uncontrolled pseudoexfoliative primary open-angle glaucoma of the right eye, advanced stage with high IOP level (III c).

Controlled low-tension primary open-angle glaucoma of the left eye, moderate stage with normal IOP level (II a).

Uncontrolled pigmentary primary open-angle glaucoma of the left eye, moderate stage with moderately elevated IOP level (II b).

1.6 Clinical presentation of the disease or condition

Glaucoma typically runs asymptomatically and in most cases is detected at moderate and/or advanced stages (e.g., during routine check-ups, prescription of glasses, fundus examination, etc.). Certain atypical complaints of glaucoma patients that should be noted may include: periodic blurring of vision, seeing halos around light sources, eye and head aches, flashing «floaters», rapid fatigue, frequent changes of presbyopic glasses, apparent eye moisture, lacrimation, etc. [120, 121]. The duration of the preclinical and initial stages is roughly 1 to 5 years. In some cases, the disease progresses through all stages up to complete blindness within 3-5 years [3].

POAG predominantly develops in patients over 40 years of age. The process is bilateral, but in most cases asymmetric [15, 122].

The disease is characterized by periodic or constant elevation of IOP above the individual norm. Asymmetry of ophthalmotonus between fellow eyes of >2-3 mmHg is detected, and the range of IOP fluctuations during the day may exceed 5 mmHg [123].

POAG is characterized by structural pathological changes of the optic disc and retinal nerve fiber layer: progressive thinning of the neuroretinal rim, widening and deepening of the cupping, followed by its deepening and vertical «stretching» with «breakthrough» to the disc margin, most frequently in the inferotemporal quadrant. In the final stage of the disease, the cupping becomes total and deep. Local or diffuse thinning of the retinal nerve fiber layer and progressive peripapillary atrophy in the β-zone (beta-zone) occur [124-126].

The disease causes typical visual field defects corresponding to damage of the optic disc and retinal nerve fiber layer. POAG is characterized by both diffuse and focal visual field changes. In the initial stage of the disease, enlargement of the blind spot, focal lesions (scotomas) in the paracentral section, especially frequently in Bjerrum's area, are typical; in rare cases, defects may occur in the periphery of the temporal half of the visual field. With the progression of the disease, arcuate scotomas merging with the blind spot, nasal step, and constriction of peripheral boundaries to tubular and residual visual fields may appear. Progression of visual field defects is characterized by: the presence of a new defect in a previously normal area, deepening of a pre-existing defect, expansion of a pre-existing scotoma to adjacent points, and a general decrease in sensitivity. In the final stage, a residual «island» of light perception on the temporal side or complete blindness is determined [3, 127].

Features of clinical and pathogenetic forms of POAG.

XFG is associated with pseudoexfoliation syndrome, a systemic pathology characterized by the accumulation of extracellular material in extra- and intraocular structures, including the trabecular meshwork, which leads to impaired aqueous humor outflow. It manifests as elevated IOP, pronounced dystrophic changes in the anterior segment of the eye, pseudoexfoliant deposits along the pupillary margin, on the anterior lens capsule, in the iridocorneal angle, as well as atrophy of the iris stroma and pigment ruff, and is accompanied by zonular weakness, phacodonesis, and lens subluxation. The iridocorneal angle is more frequently open. The degree of pigmentation is more pronounced compared to primary open-angle glaucoma. In most cases, asymmetry of symptoms between fellow eyes is detected. XFG is characterized by higher IOP levels accompanied by pronounced daily fluctuations, which ultimately increases the rate of disease progression [3, 43, 44].

PG is associated with pigment dispersion syndrome (usually bilateral), which may be inherited as an autosomal dominant trait with variable penetrance. PG occurs at the age of 15 to 68 years, more frequently in males with myopic refraction, and typically affects both eyes. A number of patients complain of blurred vision or seeing halos around lights upon sudden pupil dilation or a significant pigment release with the blockage of outflow pathways during strenuous physical activity. PG is characterized by the washout of pigment from the iris pigment epithelium caused by mechanical friction and its redistribution within the structures of the anterior eye segment, including the iridocorneal angle. The increase in IOP is caused by intratrabecular pigment blockade, secondary trabecular damage, collapse and sclerosis of the scleral venous sinus, as well as an increased pressure in the anterior chamber (relative to the posterior chamber) due to permanent contact of the lens zonules with the posterior surface of the iris, resembling a complete pupillary block. Biomicroscopy typically reveals pigment deposition on the corneal endothelium (Krukenberg spindle), on the lens periphery, and on the iris with focal depigmentation. Gonioscopy shows an open iridocorneal angle with a wide profile and hyperpigmentation of structures. The anterior chamber is deep with concavity (prolapse) of the peripheral iris. Areas of lattice retinal degeneration are common, increasing the risk of more severe changes. The severity of pigmentation does not always correlate with the clinical presentation of the disease [47–49].

NTG is characterized by IOP values not exceeding 21 mmHg (Po) and a daily IOP fluctuation volume not exceeding 5 mmHg. In European countries, NTG occurs in individuals over 35 years of age with a frequency of 11–30%, more frequently in women. NTG is characterized by optic disc changes typical of primary open-angle glaucoma, but with a relatively frequent occurrence of disc hemorrhage (splinter hemorrhages) in the optic disc area (0.2–2%), as well as more pronounced peripapillary atrophy. Visual field testing in patients with NTG more often reveals deep localized defects in the paracentral/central visual field. NTG is associated with systemic manifestations of vascular dysregulation: migraine, Raynaud's phenomenon, systemic arterial hypotension, ischemic vascular diseases, as well as autoimmune diseases and coagulopathies. When diagnosing NTG, non-glaucomatous optic neuropathies must be ruled out [3, 36].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the disease or condition

• periodic or permanent increase in IOP above the individual norm;

• structural pathological changes of the optic disc and RNFL;

• typical visual field defects corresponding to damage to the optic disc and RNFL;

• open iridocorneal angle (confirmed by gonioscopy).

2.1 Complaints and Anamnesis

Comments: When taking the medical history and assessing symptoms in ocular pathology, it is recommended to pay attention to the presence of risk factors for the onset and progression of POAG (see section 1.2), as well as family history features, general and ophthalmic status, presence/absence of allergic reactions and drug intolerance, frequency and duration of medications used with review of relevant medical documentation and assessment of the impact of visual functions on daily life and activities) [1, 3].

2.2 Physical Examination

There are no specific signs of POAG that can be detected during a physical examination. General propaedeutic principles of patient examination must be followed.

2.3 Laboratory Diagnostics

There are no diagnostic criteria for POAG based on clinical laboratory test data.

2.4 Instrumental Diagnostics

Comments: the examination is performed with correction of refractive errors using glasses or contact lenses (to achieve the best corrected visual acuity); an age-appropriate presbyopic addition is provided by placing a trial lens from a trial lens set (with a clear rim to eliminate errors) into a special holding device included in the perimeter design, or using the patient's own near-vision glasses. Correction of any refractive error is critical for the accuracy of perimetry.

Comment: The baseline method for measuring IOP accepted in the Russian Federation is Maklakov tonometry (Pt) using a 10 g weight. Tonography is used to determine the true IOP (Po). Goldmann tonometry (Po) is the universally accepted practice worldwide, and its results differ from tonometric values. To compare the two types of tonometry, the Nesterov-Egorov conversion ruler for intraocular pressure (Maklakov) tonometry with a 10 g weight may be used. In the Russian Federation, an induction tonometer, a dynamic contour tonometer, and an ocular response analyzer measuring via bidirectional corneal applanation (a device that allows, among other things, the interpretation of Goldmann tonometry values) and a transpalpebral tonometer are also registered (the latter measurement method has a number of advantages, in particular, it significantly reduces the risk of contamination due to the absence of direct contact with the eyeball, and can also be used in the postoperative period). Non-contact tonometry (pneumotonometry) should be considered as a screening method for determining IOP. During follow-up, it is recommended to use a single baseline tonometry method for the correct comparison of results [127, 128, 130-133]. In individual cases, a transpalpebral bimanual palpatory method of tonometry may be used to reduce the risk of potential complications (e.g., in the early stages after surgical and/or laser treatment, as well as in individuals with concomitant acute and chronic inflammatory eye diseases in the acute phase).

When analyzing tonometry data, absolute IOP values, diurnal fluctuations, the difference in ophthalmotonus between the eyes, and the characteristics of orthostatic fluctuations are taken into account [134-141].

The statistical norm for true IOP ($P₀$) in a healthy person ranges from 10 to 21 mm Hg, and for tonometric IOP (Pt) from 15 to 25 mm Hg. The mean IOP (Pt) in healthy individuals is 19.9±0.03 mm Hg, and the entire range of the statistical norm can be divided into three zones: the high-normal zone (23 to 25 mm Hg, 6.5% of people), the mid-normal zone (19-22 mm Hg, 72.2%), and the low-normal zone (<18 mm Hg, 20.3%) [134, 135, 140].

Diurnal IOP fluctuations, as well as asymmetry between the eyes in healthy individuals, generally remain within 2-3 mm Hg, and only in extremely rare cases reach 4-6 mm Hg. The higher the initial mean IOP level, the greater the diurnal fluctuations in ophthalmotonus may be. Patients with exfoliation glaucoma are characterized by a greater range of diurnal fluctuations (up to 8-13 mm Hg), whereas in patients with normal-tension glaucoma it may remain within average statistical values (up to 5 mm Hg) [138, 139].

Normal orthostatic fluctuations rarely exceed 4 mm Hg, whereas in glaucoma they range from 5 to 13 mm Hg [136, 137, 141].

IOP monitoring is also necessary when selecting topical hypotensive therapy, taking into account the onset of the drug's action, its peak effect, and the washout period [145-150].

IOP measurement must be performed prior to gonioscopy and pupillary dilation [3].

Comment: Measurement of the peripheral anterior chamber depth using the van Herick method is part of biomicroscopy and helps to approximately determine the degree of closure/opening of the iridocorneal angle. Additional criteria to be considered during biomicroscopy include: uneven arteriolar narrowing and venular dilation, ampullary vascular dilation, microaneurysm formation, increased capillary permeability, small hemorrhages, granular blood flow upon conjunctival examination; detection of asymmetry in anterior segment changes, determination of the degree of pigmentation on the endothelium (e.g., Krukenberg spindle, characteristic of pigmentary glaucoma), deposition of pseudoexfoliations along the pupillary margin of the iris and on the anterior lens capsule (characteristic of the pseudoexfoliative form of the disease), presence of iris heterochromia, stromal atrophy and its pigment border [151, 152].

Comment: Gonioscopy allows for differential diagnosis between angle-closure and open-angle forms of glaucoma; detection of signs of goniodysgenesis and iridocorneal angle malformations; deciding on the feasibility of laser surgery on the structures of the iridocorneal angle and performing these procedures; detecting interocular asymmetry of the gonioscopic picture; determining the sites of aqueous retention; searching for the causes of insufficient efficacy of hypotensive surgeries

Gonioscopy is based on the identification of angle landmarks and should include the evaluation of the following features: angle width (i.e., the distance between the corneal endothelium and the iris root), level of iris insertion; contour of the peripheral iris; degree of trabecular pigmentation; areas of iridotrabecular apposition or synechiae.

To systematize the results of the gonioscopic examination, it is advisable to use the classifications of E.G.A. van Beuningen, G. Spaeth, or R. Shaffer [153-155].

In addition to gonioscopy, ultrasound biomicroscopy and/or anterior segment OCT can be used to assess iridocorneal angle changes [156, 157].

The study is not indicated in patients with ocular surface inflammatory processes and cannot be performed correctly in patients with significant corneal opacities and/or hyphema.

Comment: Ophthalmoscopy is performed using various models of ophthalmoscopes; fundus biomicroscopy under medical mydriasis utilizes non-contact lenses for indirect fundus ophthalmoscopy (to obtain a stereoscopic image). Ophthalmoscopy requires both quantitative and qualitative characterization of parameters.

Qualitative characteristics:

• Neuroretinal rim (NRR). To determine the characteristics of the NRR, it is recommended to use the ISNT rule (Inferior, Superior, Nasalis, Temporalis). In eyes with early or moderately advanced glaucomatous damage, NRR tissue loss is observed predominantly in the infero- and superotemporal sectors of the optic disc. In eyes with advanced glaucomatous atrophy, NRR damage is more noticeable temporally along the horizontal meridian. In far-advanced glaucoma, the thinned NRR is located mainly in the nasal sector, with its better-preserved part located in the superonasal quadrant rather than the inferonasal one. When evaluating the NRR, the ISNT rule can only be used for standard optic disc sizes; in large and small sizes, as well as in myopia with tilted optic disc insertion, NRR evaluation is difficult and requires follow-up examinations to detect disease progression. The sensitivity and specificity of the method do not exceed 80% [159-161].

• Retinal nerve fiber layer (RNFL). Local or diffuse thinning (defects), which are better visualized in red-free light

• optic disc hemorrhage — presence

• peripapillary atrophy - presence and area

Quantitative characteristics:

• Optic disc (size and shape: small, medium, large)

• excavation (size and shape)

• ratio of the maximum excavation size to the optic disc diameter (C/D)

When examining the fundus, attention should also be paid to: the size and shape of the optic disc; the size, shape, and degree of pallor (pink or decolored) of the NRR; the size of the cup relative to the optic disc size, configuration (nature of the temporal margin: sloping, steep, undermined) and depth of the cup (shallow, medium, deep); the cup-to-disc (C/D) ratio; the severity of peripapillary chorioretinal atrophy; the location of the vascular trunk and associated 'bean-pot' ('bayonet') and boxcar phenomena of the so-called circumlinear vessel of the optic disc; hemorrhages on the optic disc; the diameter of retinal arterioles and the state of the RNFL [162-165].

To assess glaucomatous optic disc damage and its dynamics during glaucoma progression, one can sketch the disc and/or use the Disk Damage Likelihood Scale (DDLS). The scale and the diagram for its application are presented in Appendix G3 [162, 166].

Changes in the optic disc and RNFL characteristic of POAG are described in section 1.6.

Comment: In modern POAG diagnostics, perimetry remains the baseline investigation method for the detection, subsequent follow-up, and treatment of this category of patients.

Threshold central visual field perimetry (10⁰, 24⁰ and 30⁰) white-on-white is the preferred method for early detection of visual field defects [167-169]. To evaluate SAP results, various indices are used, such as mean defect or mean deviation (MD), pattern standard deviation (PSD, LV), as well as various diagnostic tests confirming the results of computerized progression analysis during serial examinations. SAP is difficult to reproduce in patients with low visual acuity and cognitive impairment. In the far-advanced stage, Goldmann perimetry to determine peripheral visual field boundaries, or the use of low-vision tests with a stimulus larger than the standard size, can be an acceptable alternative. It is advisable to take into account the degree of asymmetry of the above-mentioned parameters for making a diagnosis. The frequency of perimetry depends on the rate of disease progression.

During follow-up, it is recommended to use a single baseline perimetry method for accurate comparison of the obtained results.

2.5 Other Procedures

In the absence of conclusive data for establishing a diagnosis or determining disease progression, a number of additional (confirmatory) diagnostic methods may be performed in an ophthalmology office (consultative and diagnostic department), ophthalmology department, or Medical Ophthalmology Center.

Structural and functional techniques (tests) are continuously improving, becoming increasingly sensitive to the earliest changes. The gap between observed functional losses and preceding structural changes, from the perspective of comparing these two types of monitoring strategies, is steadily narrowing. Structural changes predominate early in the disease (glaucoma suspect, early stage). In the advanced stage of the disease, morphofunctional damage and its dynamics are in approximate equilibrium. In the far-advanced stage, functional changes predominate and serve as the target for glaucoma monitoring.

Comment: The normal distribution of central corneal thickness (CCT) in the adult population is 473-597 µm (mean - 540±30 µm). Significant deviations from mean CCT values (±50 µm) can affect tonometry results. To date, no consensus has been reached regarding the use of tonometry correction algorithms based on CCT data. It is advisable to divide corneas into thin (481-520 µm), medium (521-560 µm), and thick (>561 µm), and to take into account the associated risk [158, 170-176].

Comments: Data obtained using OCT should not be interpreted as a definitive diagnosis.

These are statistical data, the results of comparing the patient's parameters with the device's normative database. The obtained results must be correlated with the clinical picture to avoid false conclusions, especially in cases of atypical optic disc variants whose parameters are absent from the database. The initial examination is of key importance during OCT; its high quality is essential, since subsequent progression assessment is performed by comparing with the baseline image. The frequency of repeat examinations depends on the rate of POAG progression.

The method can also detect glaucoma progression at any stage when interpreted jointly with perimetry data [177].

Comments: the decision to prescribe additional diagnostic tests is made by the physician based on the results of the baseline examination. Pattern electroretinography (PERG) has the highest specificity and sensitivity in glaucoma; it reflects the activity of retinal ganglion cells themselves and can serve as a predictor of structural retinal changes. To assess the functional state of the retinal macular area, the PERG P50 component is taken into account, while the PERG N95 component is used to assess the functional state of the optic nerve.

To verify the diagnosis and perform differential diagnosis of POAG, other additional examination methods can be used: tonography, water-drinking and provocative tests to study IOP regulation [3, 6].

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

Comment: The goal of glaucoma treatment is to maintain the patient's visual functions and related quality of life.

Treatment should be initiated when all diagnostic data confirming the disease have been collected. The IOP level can be lowered using topical hypotensive therapy, laser treatment, or surgical methods (either as a single method or in combination). The benefits and risks of each treatment method must be discussed with the patient. Efforts should be made to ensure that the patient uses the minimum number of medicinal products (MPs) with the possibility of a pathogenetically substantiated choice of drugs, based primarily on data regarding their clinical efficacy [3].

Prolonged use of MPs leads to a decrease in the hypotensive effect, which requires timely adjustment of the ongoing therapy if signs of ophthalmotonus subcompensation are detected [178, 183, 184].

Before prescribing treatment, the expected "target" pressure level should be determined, taking into account the baseline ophthalmotonus values, the stage of the disease, its potential rate of progression, the patient's age and expected life expectancy, as well as additional risk factors. The "target" pressure cannot be determined with any certainty in a specific patient; there is no approved algorithm for establishing it, but this does not negate its application in clinical practice [150, 158, 173]. A strategy for determining the "target" pressure based on the percentage reduction of ophthalmotonus from the baseline is used [3, 150]. In all patients with POAG, one should strive for the maximum possible reduction in IOP, based on the stage of the disease. As an optimal characteristic of the upper limit of ophthalmotonus during treatment, one can use its values indicated below, taking into account the baseline normal ranges (see section 2.4) (Table 6) [3].

Table 6 - Optimal values of the upper limit of ophthalmotonus during treatment

An individualized approach to glaucoma treatment consists of adapting it to the needs of a specific patient. Patients with marked reduction in visual functions or young patients with disease manifestation should receive more aggressive treatment and be monitored more closely than patients with a low risk of visual function deterioration [38, 151].

It is necessary to revise the "target" pressure level upon confirmation of GON progression, implying the need for an additional 20% reduction in IOP from the previously achieved level [3, 32, 34, 36]. The use of MPs from the group of "antiglaucoma drugs and miotics" is possible in combination with each other, as well as in combination with laser and surgical treatment methods.

3.1 Medical treatment

Comments: although laser and surgical treatment can effectively reduce IOP, treatment with medicinal products from the group of "antiglaucoma drugs and miotics" remains the preferred starting treatment worldwide due to its favorable risk-benefit profile. When choosing drugs, it is necessary to consider their efficacy, potential side effects, dosing schedule, required percentage of IOP reduction from the baseline level, potential cost, availability, and patient preferences [3, 150, 184, 185].

Comment: prostaglandin analogues, beta-blockers, topical carbonic anhydrase inhibitors, and sympathomimetics for glaucoma treatment are used as first-choice drugs. Prostaglandin analogues possess maximum hypotensive activity. Comparisons of original prostaglandin analogue drugs and generic drugs showed no clinically significant difference in the IOP-lowering effect and their tolerability. At the same time, further studies are needed to confirm complete equivalence.

Drugs of other pharmacological groups (carbonic anhydrase inhibitors, sympathomimetics for glaucoma treatment, selective beta-blockers) are used less frequently as starting therapy drugs due to their lower hypotensive efficacy. The use of parasympathomimetics in patients with POAG is possible in certain clinical situations (pigmentary form of POAG, preparation for laser and surgical interventions) [185-189].

The use of antiglaucoma medications and miotics is associated with contraindications and side effects that must be taken into account when choosing a drug class. The main pharmacological classes of antiglaucoma drugs and miotics and their mechanism of action are presented in Table 7.

Table 7 - Main pharmacological classes of antiglaucoma drugs and miotics and their mechanism of action

** belongs to the drugs from the «List of Vital and Essential Drugs for Medical Use for 2024»

Comment: indications for the use of preservative-free formulations of antiglaucoma medications and miotics, both as monotherapy and within fixed combinations, may be expanded on an individual basis, taking into account documented changes in the ocular surface that significantly worsen surgical outcomes in patients who have received preservative-containing antiglaucoma medications and miotics for a long time.

· poor tolerability of first-line drugs;

· good tolerability, but failure to achieve the "target" intraocular pressure level [3, 32, 150].

GCP CLEL 5Grade of Recommendation – C (Level of Evidence – 5)

Comment: when prostaglandin analogues are used as "first-line" therapy, replacing the drug within the same group is possible, whereas switching to a drug from another pharmacological group is inappropriate [187, 188, 190, 206, 207].

Comment: It is advisable to combine drugs with different mechanisms of action: those that improve outflow and those that reduce aqueous humor secretion. To increase the hypotensive efficacy and patient adherence to medical glaucoma treatment, medications are used in the form of fixed combinations containing substances that, having different mechanisms of hypotensive action, exhibit an additive effect when combined (Table 8). In patients with advanced and far-advanced stages of POAG and/or a baseline very high pressure level, a more rapid transition or "starting" with combination treatment is possible [3, 210, 211]. The prescription of drugs belonging to the same pharmacological group should be avoided (for example, two different beta-blockers or two representatives of the prostaglandin analogue group must not be combined) [1-3, 190].

Table 8 - Fixed combinations of eye drops from the group of «Anti-glaucoma preparations and miotics»

Comment: Components of antiglaucoma combinations may be substituted if the "target" IOP level is not reached. The simultaneous use of more than 3 (three) medications is not recommended. Increasing the frequency of instillation of antiglaucoma medications and miotics leads to decreased treatment adherence, reduced therapeutic efficacy, and an increased number of adverse effects [213, 214].

The reduction of IOP during medical treatment in patients with NTG is less pronounced compared to other clinical and pathogenetic forms of POAG. In this regard, treatment often requires the use of maximally tolerated medical therapy, as well as more active application of laser and surgical treatment methods [214-217].

XFG is more resistant to conventional medical therapy and is often characterized by a higher baseline IOP level with pronounced diurnal fluctuations, accompanied by a higher rate of disease progression. Therefore, to achieve the "target" IOP level, usually more drugs and an earlier transition to laser and surgical treatment stages are employed [218, 219].

Variability in treatment adherence among glaucoma patients has been noted, ranging from 5 to 80%. Factors negatively affecting regimen compliance may be related to the prescribed medications (their cost, adverse effects, complex dosing regimen, inconvenience of instillations in certain situations – e.g., frequent business trips); to the patient themselves – forgetfulness, presence of comorbidities, insufficient understanding of the disease, demographic characteristics (e.g., gender – men are more frequently non-compliant); to the disease (e.g., patients with early stages are less compliant due to the absence of subjective symptoms); to the attending physician (lack of communication, insufficient information about the disease status). Lack of adherence to treatment can become one of the causes of disease progression. Although comprehensive approaches consisting of patient education combined with individual recommendations, including daily routine adaptation and simplified instillation regimens, may improve treatment adherence, overall there is insufficient evidence for their practical application.

Comment: none of the antiglaucoma drugs and miotics are classified as safe or completely contraindicated during pregnancy. Topical medications for POAG are prescribed only when the potential benefit of treatment outweighs the potential risk to the fetus. General principles for prescribing drugs include: using the minimum number of drugs sufficient to achieve target IOP, discussing treatment with an obstetrician-gynecologist and pediatrician, and reducing systemic absorption of the drug (by gentle pressing on the medial canthal area by the patient or using punctal occlusion). The first trimester of pregnancy is the most sensitive period due to potential teratogenic effects on the fetus from systematically used antiglaucoma drugs and miotics. Given the possible decrease in IOP during pregnancy in some patients, temporary cessation of topical hypotensive therapy under close monitoring may be considered. During pregnancy, beta-blockers, sympathomimetics for glaucoma treatment, and/or carbonic anhydrase inhibitors may be prescribed. Prostaglandin analogues should be used with caution due to their effect on uterine tone. Therefore, if signs of uterine hypertonus appear, their use must be discontinued. At the 9th month of pregnancy, beta-blockers and sympathomimetics for glaucoma treatment should be discontinued to avoid complications in the newborn. The use of topical carbonic anhydrase inhibitors can be continued. During lactation, topical carbonic anhydrase inhibitors and prostaglandin analogues are preferred. Laser trabeculoplasty can be an initial or adjunctive intervention in pregnant and lactating women. In some cases, antiglaucoma surgery may be considered [183, 220].

3.2 Laser Treatment

Laser interventions are subdivided into:

1) aimed at restoring aqueous humor outflow:

• laser trabeculoplasty (LTP);

• selective laser trabeculoplasty (SLT);

• laser iridotomy;

• laser descemetogoniopuncture (LDGP);

• hydrodynamic outflow activation (laser goniotrabeculopuncture);

• YAG laser trabecular activation

• aimed at reducing aqueous humor production:

• laser transscleral cyclophotocoagulation.

• micropulse laser cyclocoagulation

• endoscopic laser cyclodestruction

The advantages of laser interventions are:

• low invasiveness of procedures;

• absence of serious intra- and postoperative complications;

• ability to perform the intervention on an outpatient basis;

• the possibility of repeated laser interventions if the hypotensive effect decreases in the long-term postoperative period.

• It is recommended to perform laser trabeculoplasty (LTP) in patients with POAG to reduce IOP in the initial and moderate stages of the disease with a moderately elevated IOP level as an alternative strategy to medical therapy; in advanced stages, when surgical treatment is contraindicated; when hypotensive medical therapy is ineffective; when there is a need to optimize the hypotensive regimen (to reduce the number of used antiglaucoma drugs and miotics); in the presence of systemic and local adverse events caused by antiglaucoma drugs and miotics, and contraindications to their use; in case of potential non-compliance with the medical regimen [221-227].

Level of recommendation B (LoR B)Level of evidence 2 (LoE 2)Level of recommendation – B (Level of evidentiary validity – 2)

Comments: The expected average IOP reduction can be 20-25% (6-9 mm Hg). According to the Advanced Glaucoma Intervention Study (AGIS), LTP is often ineffective in young patients (under 40 years old) [32]. The hypotensive effect of LTP is evaluated 1-2 months after the procedure. Low efficacy of repeated LTP procedures is characteristic. The efficacy of IOP reduction does not differ significantly between argon/diode and selective laser trabeculoplasty (SLT), but the invasiveness and complication rate of SLT are significantly lower [221, 228]. Repeat LTP is possible after 1 year if the effect of the first procedure was prolonged and sufficient to reduce IOP. Performing SLT is advisable in cases of marked pigmentation of the trabecular meshwork (grades II-IV), with repeated procedures showing efficacy comparable to the initial surgery. LTP and SLT are not recommended for advanced glaucoma, high IOP levels, or poor visualization of the anterior chamber angle structures [221-227].

IOP control is necessary 30 minutes and 2 hours after LTP in patients with POAG to determine the severity of reactive hypertension, the magnitude of which can exceed 10 mm Hg [227]. The administration of local anti-inflammatory therapy for 4-7 days after LTP reduces the likelihood of postoperative complications (reactive hypertension, post-coagulation uveitis, peripheral goniosynechiae) [150].

As an alternative to LTP and SLT, YAG laser trabecular activation, laser goniotrabeculopuncture, and hydrodynamic outflow activation are proposed, which are performed in both pronounced and mild degrees of pigmentation of the anterior chamber angle drainage zone structures [229, 230].

Comments: LI is performed using an Nd:YAG and/or argon laser. Systematic reviews published to date indicate a lack of convincing evidence regarding the efficacy of LI in pigmentary POAG [231].

Comments: The timing of LDGP depends on the specific clinical situation and ranges on average from several days to several months after NPDS. LDGP in the early postoperative period is an effective and safe option that significantly increases the long-term hypotensive efficacy of non-penetrating deep sclerectomy. Ultrasound biomicroscopy of the anterior segment allows for the evaluation of the internal fistula and helps determine the timing and indications for laser goniodescemetopuncture after NPDS [229].

Comment: Two types of laser cyclophotocoagulation are used: transscleral and endoscopic. During the procedure, it is necessary to assess potential risks of complications, including postoperative inflammation, vision loss, hypotony, and subatrophy of the eyeball [232-235]. Endoscopic cyclophotocoagulation can be performed as a primary procedure in patients with subcompensated or compensated POAG (if it is necessary to reduce the medical regimen) simultaneously with cataract extraction or in an aphakic/pseudophakic eye [236-238]. Micropulse cyclophotocoagulation is used in patients with refractory and/or terminal glaucoma [239].

3.3 Surgical Treatment

• an elevated IOP level that cannot be normalized by any other treatment method;

• progressive deterioration of visual functions with an IOP level that does not exceed the upper limit of the statistical average norm, but exceeds its target values;

• the impossibility of implementing other treatment methods (including non-compliance with medical recommendations, pronounced side effects, or unavailability of appropriate drug therapy);

• the impossibility of adequate medical monitoring of the glaucoma process and patient compliance with treatment [240].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment:

The choice of surgical intervention method is determined by [241]:

• initial and target IOP levels;

• history (documented duration of the disease and available data on previous drug therapy and surgery),

• glaucoma stage, rate of disease progression;

• risk profile (only eye, occupation, refraction, comorbidities);

• surgeon's preferences and experience;

• patient's opinion and expectations, expected postoperative compliance;

• lens status and need for cataract surgery;

• individual characteristics not listed above.

All surgical interventions can be classified into several types [151, 241-249]:

• operations enhancing aqueous humor outflow (by creating new or activating existing pathways) of penetrating (trabeculectomy and its modifications) and non-penetrating (deep sclerectomy, viscocanalostomy) types, including those with the implantation of various devices;

• aqueous humor production-reducing cryo- or laser (transscleral or endoscopic) cyclodestruction.

Trabeculectomy remains the gold standard of surgical treatment for glaucoma uncontrolled by hypotensive therapy and laser treatment, especially in its advanced and far-advanced stages with high IOP values [241, 243, 245, 246, 250, 251], as it allows to achieve a pronounced and sustained IOP reduction and subsequently ensures a lower need for medical treatment. However, trabeculectomy is accompanied by a certain risk of intra- and early postoperative complications, necessitating patient monitoring during the first three months after the intervention.

Non-penetrating surgeries, in addition to technical complexity, have a less pronounced hypotensive effect compared to trabeculectomy; due to insufficient IOP reduction, laser goniopuncture is often required [247]. Therefore, such interventions are recommended for initial and advanced stages of glaucoma uncontrolled by hypotensive therapy and laser treatment with a moderate increase in IOP [261]. The advantage of non-penetrating techniques is a favorable safety profile, which, however, does not exempt from the need for postoperative monitoring and treatment, the main goal of which is to preserve subconjunctival filtration [246, 247, 252].

• prescription of the most effective and at the same time safe hypotensive therapy combining a preservative-free fixed combination of prostaglandin analogs and beta-blockers with topical carbonic anhydrase inhibitors; prescription of moisturizing eye drops without preservatives [253].

• four weeks prior to surgery, instillation of #fluorometholone 0.1% solution 1 drop 4 times daily [3,254,255] or 2 weeks prior, #dexamethasone 0.1% solution 1 drop 4 times daily [3,255]; supplementing therapy with #bromfenac 0.09% solution 1–2 times daily in case of pronounced symptoms and clinical signs of ocular surface disease [3,255];

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comment:

A combination of two or more of the listed risk factors for filtration loss is an indication for extending glucocorticoid therapy to 2–3 months [257].

If there is a threat of filtration loss in the early postoperative period (hypervascularization and flattening of the filtering bleb), revision (needling) of the filtering bleb or subscleral needling is indicated. In addition, off-label subconjunctival injections of #fluorouracil 5 mg/0.1 ml – 7.5 mg/0.15 ml with a maximum cumulative dose of 105 mg [258-261], and anti-angiogenic agents (angiogenesis inhibitors) [262, 263] may be used; however, universally accepted algorithms for their use do not yet exist [261, 263-265].

Unsuccessful attempts to restore lost filtration within 4–6 months are an indication for repeat intervention [3, 4, 243, 254, 266-268].

Comment: anti-glaucoma drainage implantation is recommended in the most complex cases. The choice of the drainage device depends on the technical capabilities and the surgeon's preferences. As a rule, glaucoma valve insertion is a fallback intervention when risk factors for insufficient efficacy of trabeculectomy with antimetabolites are present, although recent studies have demonstrated that their implantation is effective and safe as a primary surgical procedure [272].

An anti-glaucoma drainage device is a non-hollow linear implant that prevents adhesion of the superficial scleral flap to the bed and thereby maintains an intrascleral slit-like space for aqueous humor outflow. Anti-glaucoma drainage devices are divided into auto-, allo-, and explant drainages depending on the material.

1) Autodrainages are autologous scleral flaps (or other autologous tissue). Their disadvantages are rapid scarring and gradual blockade of outflow pathways created by the surgery.

2) Allodrainages are biomaterials from donor tissues.

3) Explant drainages are synthetic, made of polymeric and other materials. The most common and frequently used are hydrogel, composite drainages based on polylactide and polyethylene glycol, and silicone drainages. According to most researchers, the main cause of elevated IOP when using silicone drainages is the formation of a connective tissue capsule around the outer end of the drainage tube.

An anti-glaucoma filtration device is a tube (mini-shunt) providing passive and uncontrolled outflow of aqueous humor into the anterior (preequatorial) subconjunctival space. Advantages include design simplicity and ease of implantation, as well as a more pronounced immediate effect of the surgery compared to drainage devices. Disadvantages include early hypotonia and late obliteration of outflow pathways. An indication for mini-shunt implantation is stage I–III primary open-angle glaucoma uncontrolled by hypotensive therapy and laser treatment in patients under 60 years of age with their relatively high regenerative potential of the eyeball integumentary tissues.

There are devices that provide passive and uncontrolled outflow of aqueous humor into an equatorially located anti-glaucoma drainage implant that prevents cicatricial obliteration of the distal edge. Advantages include a substantial and prolonged IOP reduction; disadvantages include pronounced hypotonia in the early postoperative period. They are used in cases where filtering surgery is likely to be ineffective due to excessive scarring in the surgical area, with pre-existing excessive scarring and pronounced conjunctival pathology resulting from previous attempts at surgical IOP normalization, etc.

A glaucoma valve is a device that maintains unidirectional aqueous humor flow at certain IOP values, thereby preventing excessive filtration in the early postoperative period and minimizing the incidence of shallow anterior chamber syndrome. A glaucoma valve is usually used in patients for whom fistulizing surgery is likely to be ineffective. These are patients at risk of excessive scarring in the surgical area, with pre-existing excessive scarring and pronounced conjunctival pathology due to prior surgeries, active neovascularization, aphakia, and others.

Drainage surgery makes it possible to prolong the hypotensive effect of operations and establish a relatively controlled IOP level that helps slow down the progression of optic neuropathy.

Comments: Currently, the results on the comparative efficacy of combined versus staged cataract and glaucoma surgery are insufficient to justify the superiority of a combined procedure over trabeculectomy as the primary stage of surgery. The choice of the type and scope of surgical treatment should be determined individually by the surgeon and the patient, taking into account all potential risks and expected benefits of the operation. In cases of coexisting cataract and glaucoma, management tactics may change. Performing glaucoma surgery increases the risk of cataract progression and the need for phacoemulsification (phaco). Furthermore, the sequence of glaucoma surgery and phaco significantly affects the disease prognosis: phaco performed after glaucoma surgery reduces the duration of the latter's hypotensive effect. In coexisting cataract and advanced glaucoma with subcompensated IOP, a combined procedure or primary glaucoma surgery followed by cataract surgery may be performed. In far-advanced glaucoma or progressive disease, performing glaucoma surgery as the first stage is advisable [259, 260, 262].

Comments: in modern glaucoma surgery, laser cycloddestruction methods are preferred over cyclocryotherapy (see Section 3.2). Due to the risks of complications such as postoperative inflammation, visual acuity loss, hypotony, and globe subatrophy, cyclodestruction is indicated when a hypotensive surgery cannot be performed due to severe general condition, pronounced anterior segment changes, or patient refusal of surgical treatment [273].

3.4 Diet therapy, pain management, and other treatments

There is no specific diet for POAG. Analgesic methods are used during the surgical treatment stage of POAG and are not employed as an independent therapy.

To date, no reliable clinical studies have been conducted to confirm the efficacy of diet therapy and dietary supplements in glaucoma [274].

Alternative strategies for glaucoma optic neuropathy (GON) treatment (neuroprotection) are a subject of ongoing research and discussion [275]. According to multicenter studies CNTGS, 1998; AGIS, 2000; EMGT, 2002; OHTS, 2002, guaranteeing long-term complete stabilization of the glaucomatous process is extremely difficult, even with strict adherence to medical recommendations. It is evident that a treatment strategy aimed solely at normalizing intraocular pressure is unable to fully provide the desired effect, which has led to the search for new directions in pharmacotherapy for glaucoma. The most promising of these has been neuroretinoprotection, designed to protect retinal neurons and optic nerve fibers from the damaging effects of various factors [276-278].

Currently, it is customary to distinguish two directions of neuroprotection: direct and indirect. Direct neuroprotection directly protects retinal neurons and optic nerve fibers by blocking direct cell-damage factors. Indirect neuroprotection exerts an indirect protective effect by influencing various pathophysiological mechanisms, increasing the resilience of functional systems through the improvement of microcirculatory and hemorheological properties, antioxidant action, etc.

The role of certain agents from groups S01XA (other ophthalmological drugs) and N07XX (other drugs for disorders of the nervous system) in neutralizing glutamate receptors—a retinal neurotransmitter whose excess triggers a cascade of irreversible biochemical and ionic reactions leading to accelerated retinal ganglion cell death—has been proven [279, 280]. Data from meta-analyses and clinical studies confirm the neuroprotective effect of S01XA (other ophthalmological drugs, viz. bovine retinal polypeptides) [281-289] and N07XX (other drugs for disorders of the nervous system, viz. ethylmethylhydroxypyridine succinate**) [290-293] in patients with POAG.

Comments: Medicinal products are recommended to be prescribed in courses, the frequency of which is determined by the attending physician. A prerequisite for prescription is the presence of the indication "primary open-angle glaucoma" in the drug's package leaflet, which guarantees its safety and efficacy for this disease.

Table 9.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Medical rehabilitation is provided on a scheduled basis within the framework of primary health care and specialized, including high-tech, medical care.

Medical rehabilitation is carried out under the following conditions:

• outpatient (in settings not providing round-the-clock medical monitoring and treatment);

• day hospital (in settings providing medical monitoring and treatment during daytime hours, but not requiring round-the-clock medical monitoring and treatment);

• inpatient (in settings providing round-the-clock medical observation and treatment).

• It is recommended to carry out medical rehabilitation of patients with POAG in order to prevent disability, which can be achieved by diagnosing the disease at an early stage and prescribing treatment with its timely correction if necessary, alongside regular follow-up dispensary observation by an ophthalmologist [3].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: organizing schools for patients and their relatives, and psychological counseling when necessary, will help improve the quality of rehabilitation measures [295-297].

Comment: The frequency of ophthalmological examinations and the scope of tests and procedures after surgery are determined individually. Rehabilitation improves vision-related quality of life in patients with POAG. A multidisciplinary approach increases the efficacy of treatment and rehabilitation in patients with POAG.

Comment: Therapeutic exercise sessions, the frequency and types of sanatorium-resort treatment using natural therapeutic factors are determined individually by a general practitioner, taking into account concomitant somatic diseases after consultation with an ophthalmologist. Uncompensated IOP, as well as the early postoperative period, are absolute contraindications.

5. Prevention and Dispensary Observation

There is no specific prevention of glaucoma. Research results regarding the medical and economic efficacy of screening, prevention, and dispensary follow-up are contradictory and cannot be of a recommendatory nature. Prevention of blindness and low vision due to glaucoma does exist [3].

Comments: The first stage of health screening (dispensary observation) is carried out to identify signs of POAG, risk factors (especially with a burdened family history) in citizens, and to determine medical indications for additional examinations and evaluations by an ophthalmologist to clarify the diagnosis of glaucoma [3].

Comments: in patients receiving medical therapy, the efficacy and any side effects of treatment are determined; changes and new prescriptions from other specialists for systemic indications that may affect glaucoma treatment are identified; the patient's compliance with the hypotensive therapy regimen for glaucoma is monitored. In patients after surgical interventions, the functional and hypotensive effects of the surgery are evaluated, postoperative treatment (antimicrobial, anti-inflammatory, reparative, etc.) is adjusted, and monitoring and treatment of other ophthalmic pathologies (cataract, uveitis, diabetic retinopathy, dry eye syndrome, etc.) are carried out. In patients with a filtration bleb, its height, width, presence of wall thinning, vascularization, encapsulation, active filtration, and infection must be assessed.

Each patient visit is accompanied by an assessment of the patient's subjective well-being, visual functions (driving difficulties, impaired dark adaptation, problems with contrast sensitivity, reading fine print, and estimating distance to objects), quality of life, and patient adherence to the prescribed treatment. Reassessment of risk factors is carried out at each patient visit.

Ophthalmodynamometry / tonometry is performed using the same method at each patient examination (taking into account the time of day) with an assessment of whether the target pressure level has been achieved or not. If the target pressure is not reached or measurements fluctuate, tonometry at different times of the day may be required.

Gonioscopy is performed in POAG patients at least once a year, and more frequently if there is a risk of angle closure. Ophthalmoscopy to assess the state of the optic nerve and retina is performed under conditions of medicinal mydriasis [301]. Progression usually occurs over a long period of time. Signs of glaucomatous optic neuropathy (GON) progression regarding the optic disc in POAG patients are described in section 1.6. In perimetry, visual field changes must be confirmed by at least one repeat test. Poor concentration, cataract progression, changes in pupil size, retinal diseases, and various artifacts (lens rims, ptosis, deep-set eyes), as well as deterioration of general health, can affect the study results [151, 302]. Signs of GON progression during perimetry in POAG patients are described in section 2.4.

The frequency of ophthalmologist visits and the scope of necessary examinations for an established diagnosis are determined based on the specific tasks of current monitoring (see sections 1.2; 1.6; 2.1-2.5; 3.1-3.3). Regular monitoring of compliance with medical prescriptions helps to increase the effectiveness of the measures taken.

In stabilized POAG, it is necessary to perform visometry, tonometry, ophthalmoscopy, and perimetry at least once every 3–6 months, and gonioscopy at least once a year. Patients with an unstabilized course of the disease require individual follow-up schedules, depending on the characteristics of the glaucomatous process, the presence of comorbid conditions, and the medications used [3, 151].

If technically feasible, perform OCT once every 6–12 months.

When assessing a patient's quality of life, it is possible to use quality of life questionnaires with an assessment of the disease burden and treatment burden of POAG (see Appendix G2).

6. Organization of Medical Care

Primary specialized health care for POAG is provided by an ophthalmologist in the outpatient department of a medical organization.

Treatment (laser interventions, conservative medical therapy, or physiotherapy) is carried out in outpatient settings, day-care settings, or inpatient settings.

Indications for hospital admission of patients with POAG to a medical organization are:

Planned (elective):

• the need for surgical treatment of POAG and/or laser treatment and/or medical treatment when outpatient or day-hospital treatment is not feasible;

• conducting an in-depth examination, medical and/or laser treatment (if they cannot be performed in outpatient or day-care settings).

Emergency:

• the need for surgical treatment of POAG and/or laser treatment and/or medical treatment in the presence of a high ("c") intraocular pressure level and the impossibility of treatment in outpatient or day-hospital settings in the presence of a threat of rapid loss of visual functions

Indications for discharging a patient from a medical organization [3]:

• completion of a course of treatment or one of the stages of specialized, including high-tech, medical care in a 24-hour or day hospital in the absence of treatment complications requiring drug correction and/or medical interventions in a hospital setting (including the achieved normalization of IOP levels or relief of pain syndrome in absolute painful glaucoma);

• refusal of the patient or their legal representative from specialized, including high-tech, medical care in a 24-hour or day hospital, established by a medical organization's conciliar decision, in the absence of complications of the underlying disease and/or treatment requiring drug correction and/or medical interventions in a hospital setting;

• the need to transfer the patient to another medical organization according to the relevant medical profile. The conclusion on the feasibility of transferring the patient to a specialized medical organization is made after a preliminary consultation based on the provided medical documents and/or a preliminary examination of the patient by specialist doctors of the medical organization to which the transfer is planned.

7. Additional Information

The risk of disease progression is higher in patients who do not comply with the regimen of instilling antiglaucoma drugs and miotics.

Preservation of visual functions in POAG depends on the timely initiation of treatment and adherence to the optimal hypotensive therapy regimen in accordance with the drug instructions and clinical guidelines based on regular monitoring data.

In patients with initial and moderate stages of glaucoma, visual functions are preserved and quality of life deteriorates moderately, whereas advanced disease (due to loss of visual functions) leads to a significant deterioration in quality of life. Therefore, early detection of the disease is most important for preserving vision and preventing glaucoma blindness.

According to epidemiological studies, elderly people are characterized by the coexistence of two or more chronic diseases, which requires correction of the diagnostic and treatment process carried out for each pathology.

Local factors affecting disease outcome

Keratorefractive surgery alters the thickness, curvature, and biomechanical properties of the cornea, leading to an inaccurate assessment of IOP [171, 303, 304].

High myopia often makes early detection of POAG difficult, as glaucomatous optic disc changes can be masked by myopic optic disc features (myopic conus, tilted optic disc), while visual field defects and retinal nerve fiber layer thinning are indistinguishable from those found in glaucoma patients. Therefore, it is advisable to perform repeat diagnostic evaluations of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL). It should also be borne in mind that altered biomechanical properties of the myopic cornea lead to inaccurate intraocular pressure (IOP) measurements using traditional methods [305-308].

Systemic factors affecting disease outcome

Glaucoma is frequently associated with a number of systemic diseases, such as essential hypertension, coronary artery disease, diabetes mellitus, thyroid disorders, and asthma. Comorbidity (the presence of two or more concurrent diseases in a single patient) leads to a decline in quality of life, health self-assessment, mobility, and functional capacity, as well as an increase in hospital admissions, healthcare resource utilization, treatment costs, and mortality. The presence of multiple chronic conditions increases the complexity of management for both healthcare providers and patients, and negatively impacts treatment outcomes. Furthermore, the risk of side effects and harm caused by multiple factors, including drug-drug interactions, increases with the number of medications required to treat each of the patient's pathologies [309, 310].

Comment: Medications used for various conditions can influence the progression and development of glaucoma. Thus, systemic corticosteroids increase IOP regardless of the route of administration in 25–33% of patients, with an IOP elevation ≥32 mmHg possible in 5%, which undoubtedly increases the risk of developing or progressing glaucoma. In contrast, metformin**, beta-blockers, and HMG-CoA reductase inhibitors (statins) reduce these risks. Concomitant systemic and topical beta-blocker administration (often prescribed as monotherapy in glaucoma patients with concomitant cardiovascular disease, respectively) leads to a significant decrease in the hypotensive effect of topical beta-blockers compared to patients not receiving systemic beta-blockers. In addition, this patient population demonstrates significantly greater systolic blood pressure values and higher vascular risks [191].

Criteria for Evaluating the Quality of Medical Care

Quality criteria are used to assess the timeliness of medical care provision, the correctness of the choice of prevention, diagnostic, treatment, and rehabilitation methods, and the degree to which the planned outcome is achieved. Quality criteria are applied by disease (condition) groups and by conditions of medical care provision.

Table 10.1 - Quality of care assessment criteria for primary health care provided to adults with primary open-angle glaucoma (ICD-10 codes: H40.1), levels of evidence certainty, and recommendation grades

Table 10.2 - Quality of care assessment criteria for specialized medical care provided to adults with primary open-angle glaucoma (ICD-10 codes: H40.1), levels of evidence certainty, and recommendation grades

References

Appendix A1. Working Group Composition

1. Antonov A.A., PhD in Medical Sciences, Leading Researcher, Glaucoma Department, FSBSI "M.M. Krasnov Research Institute of Eye Diseases", Association of Ophthalmologists, Moscow

2. Astakhov S.Yu., MD, Professor, Head of the Department of Ophthalmology, First Saint Petersburg State Pavlov Medical University, Association of Ophthalmologists, Saint Petersburg

3. Borzunov O.I., MD, Associate Professor. Associate Professor at the Department of Ophthalmology, Ural State Medical University of the Russian Ministry of Health, Yekaterinburg.

4. Borzunova N.S., Candidate of Medical Sciences, Associate Professor. Associate Professor at the Department of Propaedeutics of Internal Diseases, Ural State Medical University of the Russian Ministry of Health, Yekaterinburg.

5. Brezhnev A.Yu., PhD in Medical Sciences, Associate Professor, Kursk State Medical University of the Russian Ministry of Health, Ophthalmological Clinical Hospital – Ophthalmological Center, Russian Glaucoma Society, The Society of Ophthalmologists of Russia, Kursk

6. Brzheskiy V.V., MD, Professor, Head of the Department of Ophthalmology, Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health, Russian Glaucoma Society, The Society of Ophthalmologists of Russia, Saint Petersburg

7. Gazizova I.R., MD, Institute of Experimental Medicine "Medical Research Center", Russian Glaucoma Society, The Society of Ophthalmologists of Russia, Saint Petersburg

8. Golubev S.Yu., PhD in Medical Sciences, Senior Researcher, State Research Center of the Russian Federation – Institute of Biomedical Problems of the RAS, Association of Ophthalmologists, Moscow

9. Dogadova L.P., PhD in Medical Sciences, Professor of the Department of Ophthalmology, Pacific State Medical University of the Russian Ministry of Health, Chief Ophthalmologist of the Far Eastern Federal District, Russian Glaucoma Society, The Society of Ophthalmologists of Russia, Vladivostok

10. Egorov E.A., MD, Professor of the Academician A.P. Nesterov Department of Ophthalmology, Faculty of General Medicine, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Russian Glaucoma Society, The Society of Ophthalmologists of Russia, Moscow

11. Erichev V.P., MD, Professor, Russian Glaucoma Society, The Society of Ophthalmologists of Russia, Moscow

12. Ivanova N.V., MD, Professor, Head of the Department of Eye Diseases, S.I. Georgievsky Medical Academy of Vernadsky Crimean Federal University, Russian Glaucoma Society, The Society of Ophthalmologists of Russia, Simferopol

13. Zhuravleva A.N., PhD in Medical Sciences, Researcher, Glaucoma Department, National Medical Research Center of Eye Diseases named after Helmholtz of the Russian Ministry of Health, Association of Ophthalmologists, Moscow

14. Zolotarev A.V., MD, Associate Professor, Head of the Department of Ophthalmology, Samara State Medical University of the Russian Ministry of Health, Chief Physician of the T.I. Eroshevsky Samara Regional Clinical Ophthalmological Hospital, Association of Ophthalmologists, Samara

15. Karlova E.V., MD, Assistant Professor of the Department of Ophthalmology, Samara State Medical University of the Russian Ministry of Health, Head of the Ophthalmological Department, T.I. Eroshevsky Samara Regional Clinical Ophthalmological Hospital, Association of Ophthalmologists, Samara

16. Kovlen D.V., MD, Associate Professor, Head of the Department of Physical and Rehabilitation Medicine, Military Medical Academy, Saint Petersburg; Chief Specialist in Sanatorium-Resort Treatment of the Russian Ministry of Defense.

17. Konoplyankin I.V., Instructor at the Department of Physical and Rehabilitation Medicine, Military Medical Academy, Saint Petersburg.

18. Konchugova T.V., Chief Researcher at the Department of Physiotherapy and Reflexology, National Medical Research Center for Rehabilitation and Balneology of the Russian Ministry of Health; Member of the National Association of Experts in Sanatorium-Resort Treatment.

19. Kosakyan S.M., PhD in Medical Sciences, Ophthalmologist, Glaucoma Department, National Medical Research Center of Eye Diseases named after Helmholtz of the Russian Ministry of Health, Association of Ophthalmologists, Moscow

20. Konovalova O.S., PhD in Medical Sciences, Head of the Tyumen Branch of the Ekaterinburg Eye Microsurgery MDC JSC, Associate Professor of the Department of Surgical Diseases with a Course in Ophthalmology, Tyumen State Medical University, Association of Ophthalmologists, Tyumen

21. Kulikov A.N., MD, Professor, Head of the Prof. V.V. Volkov Department and Clinic of Ophthalmology, Kirov Military Medical Academy of the Ministry of Defense of the Russian Federation, Chief Ophthalmologist of the Ministry of Defense of the Russian Federation, Chief freelance ophthalmologist of Saint Petersburg, Russian Glaucoma Society, The Society of Ophthalmologists of Russia, Saint Petersburg

22. Kulchitskaya Detelina Borisovna, Chief Researcher at the Department of Physiotherapy and Reflexology, National Medical Research Center for Rehabilitation and Balneology of the Russian Ministry of Health; Member of the National Association of Experts in Sanatorium-Resort Treatment.

23. Kuroedov A.V., MD, DSc, Head of the Ophthalmological Center, Mandryk Central Military Clinical Hospital of the Ministry of Defense of the Russian Federation, Head of the Department of Ophthalmology named after Academician A.P. Nesterov, Faculty of General Medicine, Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Russian Glaucoma Society, Russian Ophthalmological Society, Moscow

24. Lebedev O.I., MD, DSc, Professor, Head of the Department of Ophthalmology, Omsk State Medical University of the Russian Ministry of Health, Association of Ophthalmologists, Omsk

25. Lovpache J.N., Cand. Sc. (Med.), Independent Expert, 3Z-MSK Eye Clinic, Russian Glaucoma Society, Russian Ophthalmological Society, Moscow

26. Malishevskaya T.N., MD, DSc, Head of the Analytical Work Department, Helmholtz National Medical Research Center of Eye Diseases of the Ministry of Health of the Russian Federation, Associate Professor at the Department of Continuing Medical Education, Helmholtz National Medical Research Center of Eye Diseases of the Ministry of Health of the Russian Federation, Association of Ophthalmologists, Moscow

27. Malyugin B.E., MD, DSc, Corresponding Member of the RAS, Professor, Deputy General Director for Research, S. Fyodorov Eye Microsurgery Federal State Institution, Russian Ophthalmological Society, Moscow

28. Nikolaenko V.P., MD, DSc, Professor at the Department of Otorhinolaryngology and Ophthalmology, Saint Petersburg State University, Deputy Chief Medical Officer for Ophthalmology, City Multidisciplinary Hospital No. 2, Association of Ophthalmologists, Russian Glaucoma Society, Saint Petersburg

29. Onufriychuk O.N., Cand. Sc. (Med.), Ophthalmologist, Turner National Medical Research Center for Children's Orthopedics and Trauma of the Ministry of Health of the Russian Federation, Pirogov Clinic of High Medical Technologies of Saint Petersburg State University, Russian Glaucoma Society, Russian Ophthalmological Society, Saint Petersburg

30. Petrov S.Yu., MD, DSc, Head of the Glaucoma Department, Helmholtz National Medical Research Center of Eye Diseases of the Ministry of Health of the Russian Federation, Professor at the Department of Continuing Medical Education, Helmholtz National Medical Research Center of Eye Diseases of the Russian Ministry of Health, Association of Ophthalmologists, Moscow

31. Ryabtseva A.A., MD, DSc, Professor, Ophthalmologist at the Treatment and Rehabilitation Center of the Ministry of Foreign Affairs of Russia, Chief Freelance Ophthalmologist of the Central Federal District, Professor at the Department of Eye Diseases, Semashko National Research Institute of Public Health, Association of Ophthalmologists, Moscow

32. Seleznev A.V., Cand. Sc. (Med.), Associate Professor, Ivanovo State Medical Academy of the Ministry of Health of the Russian Federation, Russian Glaucoma Society, Russian Ophthalmological Society, Ivanovo

33. Simonova S.V., Cand. Sc. (Med.), City Clinical Hospital No. 15 named after O.M. Filatova of the Moscow Healthcare Department, Russian Glaucoma Society, Moscow

34. Sokolovskaya T.V., Cand. Sc. (Med.), Leading Researcher at the Department of Surgical Glaucoma Treatment, S. Fyodorov Eye Microsurgery Federal State Institution, Russian Ophthalmological Society, Moscow

35. Fursova A.Zh., MD, DSc, Honored Doctor of the Russian Federation, Head of the Ophthalmological Department, State Novosibirsk Regional Clinical Hospital, Association of Ophthalmologists, Novosibirsk

36. Yuryeva T.N., MD, DSc, Professor, Deputy Director for Research, Irkutsk Branch of the S. Fyodorov Eye Microsurgery Federal State Institution, Association of Ophthalmologists, Irkutsk

37. Yakubova L.V., Cand. Sc. (Med.), Senior Researcher at the Glaucoma Department, Helmholtz National Medical Research Center of Eye Diseases of the Ministry of Health of the Russian Federation, Association of Ophthalmologists, Moscow

No conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Methods used for evidence collection/selection: electronic database search, library resources. Description of methods used for evidence collection/selection: the evidence base for the recommendations includes publications included in the Cochrane library, EMBASE and MEDLINE databases, as well as monographs and articles in leading specialized peer-reviewed domestic and foreign medical journals on the subject with a search depth of at least 10 years. (In Russ.)

Levels of evidence certainty are presented in accordance with the methodological recommendations for the development and updating of clinical guidelines. (In Russ.)

Methods used to assess the quality and strength of evidence: expert consensus, significance assessment in accordance with the rating scheme.

The preliminary version of these recommendations was peer-reviewed by independent experts in order to ensure accessibility for understanding and interpreting the evidence underlying the recommendations. Comments received from experts were systematized and discussed by members of the working groups of the Association "Russian Glaucoma Society", Association "Society of Ophthalmologists of Russia" and Association "Association of Ophthalmologists", and the changes made were recorded. If no changes were made, the reasons for refusal were taken into account. (In Russ.)

Comments were received from primary care ophthalmologists regarding the clarity of the presentation of the recommendations and their assessment of the significance of the recommendations as a working tool in daily clinical practice. (In Russ.)

For the final edition and quality control of the implementation of the recommendations, they were re-analyzed by the working group members, who concluded that all expert comments and feedback were taken into account, and the risk of bias in the development of the recommendations was minimized. (In Russ.)

Economic analysis.

Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.

Target audience for these clinical guidelines:

1. Ophthalmologists

2. Healthcare and public health organization specialists

3. Residents in the specialty "Ophthalmology" (31.08.59) and scientific and pedagogical staff (postgraduate students) in the field of study "Clinical Medicine" (31.06.01), profile – "Eye Diseases" (14.01.07)

4. Students of higher medical educational institutions

Table A1 – Scale for assessing levels of evidence certainty.

Table A2 – Scale for assessing grades of recommendation (GoR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions).

Procedure for updating clinical guidelines

The mechanism for updating clinical guidelines provides for their systematic updating – clinical guidelines are reviewed at least once every 3 years, as well as when new data emerge from the perspective of evidence-based medicine regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or if there are justified additions/comments to the previously approved clinical guidelines, but no more than once every 6 months. The decision to update is made by the Russian Ministry of Health based on proposals submitted by medical non-profit professional organizations. The formulated proposals must take into account the results of a comprehensive assessment of medicines, medical devices, and the results of clinical approbation. (In Russ.)

Appendix A3. Reference Materials

These clinical guidelines were developed taking into account the following documents:

1. International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) (adopted by the 43rd World Health Assembly, 1990).

2. "On the transition of healthcare bodies and institutions of the Russian Federation to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision" (as amended by the Order of the Ministry of Health of the Russian Federation dated January 12, 1998, No. 3). Order of the Ministry of Health of the Russian Federation dated May 27, 1997, No. 170. (In Russ.)

3. "On sending the list of added and excluded ICD-10 categories". Letter of the Ministry of Health of the Russian Federation dated December 5, 2014, No. 13-2/1664. (In Russ.)

4. ICD-10 updates by 2022. URL: https://mkb-10.com/updates/ (accessed: August 29, 2022).

5. Federal Law No. 323-FZ dated November 21, 2011, «On the Fundamentals of Protecting Citizens' Health in the Russian Federation» (as amended on July 13, 2022).

6. Federal Law "On Amendments to Article 40 of the Federal Law 'On Compulsory Medical Insurance in the Russian Federation' and the Federal Law 'On the Basics of Protecting the Health of Citizens in the Russian Federation' regarding clinical guidelines" (as amended on June 11, 2021) dated December 25, 2018, No. 489-FZ. (In Russ.)

7. Order of the Russian Ministry of Health No. 114n dated February 25, 2022 "On Approval of the Standard of Medical Care for Adults with Primary Open-Angle Glaucoma (Diagnosis, Treatment, and Dispensary Observation)" (Registered with the Ministry of Justice of Russia on April 4, 2022, No. 68043)

8. "On approval of the Procedure for assigning certain functions of the attending physician to a paramedic or midwife by the head of a medical organization when organizing the provision of primary health care and emergency medical care for the direct provision of medical care to a patient during the period of observation and treatment, including the prescription and use of medicines, including narcotic and psychotropic drugs" (as amended on October 31, 2017). Order of the Ministry of Health of the Russian Federation dated March 23, 2012, No. 252n. (In Russ.)

9. "On approval of the Procedure for providing medical care to the adult population for diseases of the eye, its adnexa and orbit" (as amended on February 1, 2022). Order of the Ministry of Health of the Russian Federation dated November 12, 2012, No. 902n. (In Russ.)

10. "On approval of the Regulation on the organization of specialized, including high-tech, medical care" (as amended on August 27, 2015). Order of the Ministry of Health of the Russian Federation dated December 2, 2014, No. 796n. (In Russ.)

11. "On approval of criteria for assessing the quality of medical care". Order of the Ministry of Health of the Russian Federation dated May 10, 2017, No. 203n. (In Russ.)

12. "On approval of the professional standard 'Ophthalmologist'". Order of the Ministry of Labor and Social Protection of the Russian Federation dated June 5, 2017, No. 470n. (In Russ.)

13. "On the Approval of the Nomenclature of Medical Services" (as amended on September 24, 2020). Order of the Ministry of Health of the Russian Federation No. 804n dated October 13, 2017.

14. «On Approval of the List of Medical Devices Implantable into the Human Body upon Provision of Medical Care, and the List of Medical Devices Dispensed on Prescription for Medical Devices upon Provision of a Set of Social Services» (as amended on January 14, 2022). Decree of the Government of the Russian Federation No. 3053-r dated December 31, 2018.

15. "On the Approval of Criteria for the Formation of the List of Diseases, Conditions (Groups of Diseases, Conditions) for Which Clinical Guidelines Are Developed." Order of the Ministry of Health of the Russian Federation No. 101n dated February 28, 2019.

16. "On the Approval of the Procedure and Deadlines for the Development of Clinical Guidelines, Their Revision, the Standard Form of Clinical Guidelines and Requirements for Their Structure, Composition, and Scientific Validity of Information Included in Clinical Guidelines" (as amended on June 23, 2020). Order of the Ministry of Health of the Russian Federation No. 103n dated February 28, 2019.

17. "On the Approval of the Procedure and Deadlines for the Approval and Endorsement of Clinical Guidelines, Criteria for the Scientific and Practical Council's Decision to Approve, Reject, or Send Clinical Guidelines for Revision, or the Decision to Revise Them." Order of the Ministry of Health of the Russian Federation No. 104n dated February 28, 2019.

18. "On the Approval of the Procedure for Organizing the Provision of High-Tech Medical Care Using the Unified State Health Information System." Order of the Ministry of Health of the Russian Federation No. 824n dated October 2, 2019.

19. «On Approval of the List of Vital and Essential Medicines for Medical Use for 2020, the List of Medicines for Medical Use, Including Medicines for Medical Use Prescribed by Decisions of Medical Commissions of Medical Organizations, the List of Medicines Intended for Persons with Hemophilia, Cystic Fibrosis, Pituitary Dwarfism, Gaucher Disease, Malignant Neoplasms of Lymphoid, Hematopoietic and Related Tissues, Multiple Sclerosis, Hemolytic-Uremic Syndrome, Systemic-Onset Juvenile Arthritis, Mucopolysaccharidosis Types I, II and VI, Persons after Organ and/or Tissue Transplantation, and the Minimum Range of Medicines Necessary for the Provision of Medical Care» (as amended on March 30, 2022). Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019.

20. "On the Program of State Guarantees of Free Medical Care to Citizens for 2024 and for the Planning Period of 2025 and 2026." Decree of the Government of the Russian Federation No. 2353 dated December 28, 2023.

21. "On Approval of the Procedure for Conducting Dispensary Observation of Adults." Order of the Ministry of Health of the Russian Federation No. 168n dated March 15, 2022.

22. "On the List of Diseases or Conditions (Groups of Diseases or Conditions) in Which the Use of a Medicinal Product is Permitted in Accordance with Indicators (Characteristics) of the Medicinal Product Not Specified in Its Instructions for Use." Decree of the Government of the Russian Federation No. 1180-r dated May 16, 2022.

23. "On Approval of the Procedure for Conducting Preventive Medical Examinations and Medical Check-ups (Dispensary Profiling) of Certain Groups of the Adult Population" (as amended by Order of the Russian Ministry of Health No. 44n dated February 1, 2022). Order of the Ministry of Health of the Russian Federation No. 404น dated April 27, 2021.

24. "On Approval of Lists of Medical Indications and Contraindications for Sanatorium-Resort Treatment" Order of the Russian Ministry of Health No. 1029n dated September 28, 2020 (as amended on April 26, 2023).

25. "On Approval of the Standard of Sanatorium-Resort Care for Patients with Diseases of the Eye and Its Adnexa." Order of the Ministry of Health and Social Development of the Russian Federation No. 215 dated November 22, 2004.

26. "On Approval of the Standard of Medical Care for Adults with Suspected Glaucoma (Diagnosis, Treatment, and Dispensary Observation)." Order of the Ministry of Health of the Russian Federation No. 115n dated February 25, 2022.

27. "On Approval of Accounting Form of Medical Documentation No. 131/u 'Card for Accounting of Preventive Medical Examination (Dispensary Profiling)', the Procedure for Its Maintenance and the Form of Industry Statistical Reporting No. 131/o 'Information on Conducting Preventive Medical Examinations and Dispensary Profiling of Certain Groups of the Adult Population', the Procedure for Its Completion and Submission Deadlines." Order of the Ministry of Health of the Russian Federation No. 1207n dated November 10, 2020.

28. "On Approval of Lists of Medical Indications and Contraindications for Sanatorium-Resort Treatment." Order of the Ministry of Health of the Russian Federation No. 1029n dated September 28, 2020 (as amended by Orders of the Russian Ministry of Health No. 664n dated October 13, 2022, No. 193n dated April 26, 2023).

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Patients with POAG must be informed that an accurate diagnosis, as well as the ability to determine disease progression, will be established using a set of modern diagnostic methods. The benefits and risks of each treatment method must be discussed with the patient.

Below is a patient information leaflet for individuals diagnosed with POAG.

What is GLAUCOMA?

GLAUCOMA is a group of chronic eye diseases occurring predominantly in individuals over 40–50 years of age, whose main manifestation is an elevation in intraocular pressure, leading to gradual damage to the optic nerve and, consequently, to visual field defects («side» vision) and decreased visual acuity down to complete blindness.

How does GLAUCOMA manifest? What are the symptoms of the disease?

GLAUCOMA develops gradually, often proceeding without any symptoms, and this is precisely what makes it dangerous. Sometimes signs of GLAUCOMA may include: periodic "blurring" of vision; appearance of rainbow halos around light sources that do not disappear upon forced blinking or wiping the eye; loss of clear contours when viewing various objects; sensation of "heaviness" or pain in the eye; appearance of a "grid" or "veil" before the eye; difficulty with close-range work (e.g., reading); need for frequent changes of glasses; difficulty orienting in the dark. Headaches are also possible, mainly in the superciliary arches and temporal regions. In later stages, visual field constriction appears on the nasal side. These symptoms may also be observed in other diseases not related to GLAUCOMA, but their occurrence should always serve as a reason for an urgent visit to an ophthalmologist.

If I see well, does that mean I do not have GLAUCOMA?

GLAUCOMA is an insidious disease that is asymptomatic in its early stages. Therefore, regardless of whether you have complaints or not, you must undergo a routine annual preventive examination by an ophthalmologist as part of medical check-ups (dispensary profiling), with mandatory measurement of IOP and fundus examination. The scope of examinations is determined by the physician.

What are the risk factors that increase the likelihood of developing GLAUCOMA?

Risk factors are not the direct cause of GLAUCOMA, but they increase the likelihood of its occurrence. These include: age: GLAUCOMA usually develops in people over 40 years of age; hereditary predisposition: if family members or close relatives have already been diagnosed with GLAUCOMA; myopia exceeding 6 diopters; diabetes mellitus; migraine.

What treatment will the doctor prescribe for me in case of GLAUCOMA?

The main goal of treatment is to lower the IOP level, which helps stabilize the process or slow down its rate of progression while maintaining an acceptable quality of life. If you are diagnosed with GLAUCOMA, the doctor typically prescribes eye drops to lower IOP. If medical treatment and adherence to the prescribed regimen fail to lower the eye pressure or lower it insufficiently, laser surgery or incisional surgery will be offered. The choice of GLAUCOMA treatment method is determined individually, depending on the course of the disease and other concomitant factors, and falls within the competence of the attending physician.

What is the prognosis for the course of GLAUCOMA?

The primary condition for preserving satisfactory visual functions and the associated quality of life is timely detection of the disease and its adequate treatment. At the same time, GLAUCOMA is a severe chronic progressive disease that remains to this day one of the leading causes of irreversible blindness and low vision worldwide.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Glaucoma Risk Calculator

Russian title: Glaucoma Risk Calculator for Individuals with Ocular Hypertension

Original title (if applicable): S.T.A.R II (The Scoring Tool for Assessing Risk) Glaucoma Risk Calculator

Source (official developer website, validation publication): Medeiros F.A., Weinreb R.N., Sample P.A. et al. Validation of a predictive model to estimate the risk of conversion from ocular hypertension to glaucoma. Arch Ophthalmol. 2005;123:1351-1360.

Type (underline): disease risk calculator

Purpose: determining the 5-year risk of developing glaucoma in patients with ocular hypertension

Content (template): parameters used: age, IOP level, CCT, vertical cup-to-disc ratio, visual field PSD index.

Key (interpretation): Based on the results obtained, the 5-year risk of developing glaucoma is estimated as:

A) Low (result below 5%). Recommended strategy: observation without treatment.

B) Moderate (result between 5-15%). Recommended strategy: decision on medical treatment is made individually, taking into account the patient's preference.

C) High (result above 15%). Recommended strategy: treatment aimed at lowering IOP.

Notes. An electronic version of the calculator is available for download on smartphones and tablets (http://www.pocket.md/80/star-ii.html). Currently, this is the most widely used glaucoma risk calculator for patients with ocular hypertension (Ameen S., Javaid F., Cordeiro M.F. Risk calculators in glaucoma // Exp Rev Ophthalmol. 2016; 11(1): 21-27. DOI: 10.1586/17469899.2016.1136213).

Appendix G2. Quality of life in glaucoma patients.

Russian title: The Glaucoma Quality of Life – 15 (GQL-15) Questionnaire

Original title (if applicable): The Glaucoma Quality of Life – 15 (GQL-15) questionnaire

Source (official developer website, validation publication): Nelson P., Aspinall P., Papasouliotis O., Worton B., O'Brien C. Quality of life in glaucoma and its relationship with visual function // J Glaucoma. 2003; 12(2): 139-150.

Type (underline): questionnaire

Purpose: assessment of quality of life in glaucoma patients

Content (template):

Patient instructions:

Please indicate the correct answer on a scale from 1 to 5, where [1] means "no difficulty", [2] – "slight difficulty", [3] – "moderate difficulty", [4] – "great difficulty", and [5] – "severe difficulty". If you do not perform certain activities for other reasons unrelated to your vision, please select answer [0].

Does your vision condition cause difficulty when performing the following activities?

Key (interpretation): The GQL-15 questionnaire consists of 15 items evaluating 4 main visual quality characteristics: (1) central and near vision; (2) peripheral vision; (3) dark adaptation; (4) out-of-home mobility. The total score characterizes the quality of life of a glaucoma patient. The higher the score, the lower the quality of life.

Notes. Currently, a significant number of questionnaires dedicated to studying the quality of life of glaucoma patients have been developed and are available (Glau-QoL, NEI-VFQ, TSS-IOP, and others). Varying degrees of validation and complexity for patients determine the nuances of their use in clinical practice. The presented questionnaire is user-friendly due to its conciseness and has received positive feedback from ophthalmologists and patients.

Appendix G3. Disk Damage Likelihood Scale (DDLS) for assessing and sketching optic disc changes during glaucoma patient follow-up

Russian title: Disk Damage Likelihood Scale for assessing and sketching optic disc changes in glaucoma patients

Original title (if available): DDLS, Disk Damage Likelihood Scale

Source (official developer website, validation study): Spaeth G.L., Henderer J., Liu C. et al. The disc damage likelihood scale: reproducibility of a new method of estimating the amount of optic nerve damage caused by glaucoma. Trans Am Ophthalmol Soc. 2002;100:181-5; Cheng K., Tatham A.J. Spotlight on the Disc-Damage Likelihood Scale (DDLS). Clin Ophthalmol. 2021;15:4059-4071.

Type (underline): rating scale

Purpose: assessment of optic disc changes in the monitoring of glaucoma patients

Content (template): parameters used: optic disc size, neuroretinal rim (NRR) to optic disc size ratio

Key (interpretation): first, the size of the optic disc is determined (using a slit lamp scale with special conversion factors: for a +60 D lens magnification, the obtained result is multiplied by 0.88; for a +78 D lens, by 1.2; for a +90 D lens magnification, by 1.63), then the size and configuration of the neuroretinal rim are determined.

Optic discs corresponding to stage 4 and above on the DDLS scale are considered pathological.

Notes. Clinical examination of the optic disc remains an essential component of glaucoma diagnosis and monitoring. The DDLS provides a reliable method for clinical grading of glaucomatous optic disc changes, with a higher degree of reproducibility compared to the classic cup-to-disc ratio measurement.