Secondary glaucomas: clinical guidelines

List of Abbreviations

AGO – antiglaucoma surgery

ALT – alanine aminotransferase

AST – aspartate aminotransferase

VG – secondary glaucoma

IOP – intraocular pressure

AQH – aqueous humor

HIV – human immunodeficiency virus

GON – glaucomatous optic neuropathy

ONH – optic nerve head

CAI – carbonic anhydrase inhibitors

EIA – enzyme immunoassay

CME – cystoid macular edema

LI – laser iridotomy/iridectomy

Med – medication

ICD-10 – International Classification of Diseases 10th Revision

INN – International Nonproprietary Name

NVG – neovascular glaucoma

NRR – neuroretinal rim

OCT – optical coherence tomography (optical examination of the optic nerve head and retinal nerve fiber layer using a computerized analyzer)

PGA – prostaglandin analogues

PDR – proliferative diabetic retinopathy

VF – visual field

PRP – panretinal laser photocoagulation

POAG – primary open-angle glaucoma

PERG – pattern electroretinogram

SAP – standard automated perimetry

RNFL – retinal nerve fiber layer

ESR – erythrocyte sedimentation rate

UG – uveal glaucoma

US – ultrasound examination

ACA – anterior chamber angle

PhG – phacogenic glaucoma

PhG – phlebohypertensive glaucoma

EGD – esophagogastroduodenoscopy

PCC – phacoemulsification of cataract

COPD – chronic obstructive pulmonary disease

CRV – central retinal vein

CRV – central retinal vein

CCT – central corneal thickness

C/D – cup-to-disc ratio (ratio of the maximum cup diameter to the optic disc diameter)

ECG – electrocardiography

Echocardiography – echocardiography of the heart

HBsAg – hepatitis B surface antigen

HCV – hepatitis C virus

IL-1 – interleukin 1

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

MD – mean deviation (Humphrey scale)

PSD – pattern standard deviation

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

Po – true intraocular pressure level

TGF-β – transforming growth factor beta

VEGF – vascular endothelial growth factor

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.

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 – terms denoting 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 level of IOP and its compliance with the “target” value are also taken into account.

Standard automated perimetry – threshold static perimetry evaluating the central visual field 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 during static perimetry, representing the average difference between age-corrected normal retinal light sensitivity values and

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

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Secondary glaucomas (SG) – a term combining a group of progressive optic neuropathies in which the elevation of intraocular pressure is secondary to an underlying disease.

SGs result from eye injuries, ophthalmic conditions, and systemic diseases. The pathogenetic mechanisms of the glaucomatous process depend on the course of the underlying disease causing the glaucoma. Unlike primary glaucoma, the process is not always bilateral. Depending on the nature of the iridocorneal angle block, it can clinically present as open-angle or angle-closure [1, 2].

SGs include six main clinico-pathogenetic forms: inflammatory, neovascular, phlebohypertensive, phacogenic, drug-induced, and post-traumatic. Depending on the form of SG, approaches to diagnosis, medical therapy, and surgical treatment will correspondingly differ [3, 2].

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

1.1.1. Etiology and pathogenesis of inflammatory (uveitic) glaucoma

Inflammatory or uveal glaucoma (UG) develops during or after inflammation in keratitis, recurrent episcleritis, scleritis, and uveitis.

Intraocular pressure elevation may be caused by impaired aqueous humor outflow due to the effect of inflammatory cells, cytokines, iris pigment, corticosteroids from ongoing therapy on the trabecular meshwork, as well as closure of the iridocorneal angle (ICA) by peripheral anterior synechiae and/or ICA closure due to pupillary block.

Factors affecting intraocular pressure (IOP) [4-7]:

1. Reduced trabecular outflow:

- pro-inflammatory effects of cytokines IL-1, TGF-β on trabecular meshwork cells;

- trabeculitis (trabecular edema, accumulation of fibrin and inflammatory cells in outflow channels);

- deposition of pigment and pro-inflammatory cells in the trabecular meshwork;

- high viscosity of aqueous humor due to elevated protein levels;

- trabeculopathy secondary to steroid therapy;

2. Closure of the iridocorneal angle:

- blockade by peripheral anterior synechiae;

- due to pupillary block;

- neovascularization;

1.1.2. Etiology and pathogenesis of neovascular glaucoma

Neovascular glaucoma (NVG) develops as a result of elevated intraocular pressure (IOP) due to the blockade of anterior chamber angle structures by newly formed vessels and a fibrovascular membrane [134].

Retinal ischemia induces the production of vascular endothelial growth factor (VEGF), which triggers neovascularization processes in the posterior segment of the eye, as well as the release of VEGF from the non-pigmented epithelium of the ciliary body, causing the formation of new blood vessels in the anterior segment of the eye. Histologically, newly formed vessels are found on the surface of the iris and rarely in its stroma. They are formed by the sprouting of endothelial cells from capillaries, originating from vessels above the iris root or from the major arterial circle of the iris. They can block the trabecular meshwork zone by positioning themselves perpendicularly over it, which distinguishes them from the iris's own vessels that run along the iris root. The fibrovascular membrane consists of myofibroblasts and proliferating smooth muscle tissue and can extend onto the surface of the iris and the anterior chamber angle. Together with the supporting fibrovascular membrane, the vessels block the trabecular meshwork, contributing to the formation of peripheral anterior synechiae with secondary closure of the anterior chamber angle [135, 134].

Nosologies accompanied by the development of NVG [1]:

- central retinal vein occlusion;

- proliferative diabetic retinopathy;

- ocular ischemic syndrome in chronic carotid artery obstruction;

- central retinal artery occlusion;

- choroidal melanomas, uveal melanoma, and retinoblastoma [136-138];

Cases of NVG have been described in lymphoma with metastases in the ciliary body [139], Fanconi anemia [140], cryoglobulinemia [141], and sarcoidosis [142].

1.1.3. Etiology and pathogenesis of phlebotensive glaucoma

Phlebohypertensive glaucoma (PHG) develops as a result of impaired aqueous humor outflow due to elevated venous pressure in the vessels draining blood from the eyeball [2]. Episodic pressure elevation in episcleral veins does not reduce aqueous humor outflow and does not cause an increase in intraocular pressure. However, with chronically elevated episcleral venous pressure, outflow deterioration is possible, leading to the development of ocular hypertension and glaucoma-type optic neuropathy [1].

Nosologies accompanied by the development of PHG [1, 2]:

Venous compression/obstruction:

- thyroid eye disease;

- superior vena cava syndrome;

- retrobulbar tumors;

- cavernous sinus thrombosis.

Arteriovenous disorders:

- carotid-cavernous fistula;

- orbital varices.

Idiopathic dilation of episcleral veins

Thyroid eye disease is an organ-specific progressive disorder of the soft tissues of the orbit and eye, developing against the background of autoimmune thyroid pathology. It arises as a result of orbital tissue infiltration, including extraocular muscles, by lymphocytes, mast cells, and plasma cells. Elevated episcleral venous pressure may be observed in severe cases due to venous outflow obstruction [167]. Superior vena cava syndrome (cava syndrome) is a symptom complex developing as a result of circulatory disorders in the superior vena cava system and impaired venous blood drainage from the upper parts of the body. Other conditions associated with venous outflow obstruction and elevated episcleral venous pressure include local amyloidosis, retrobulbar tumors, and cavernous sinus thrombosis.

Carotid-cavernous fistulas are the most common cause of PHG and are classified into traumatic and spontaneous [168]. Traumatic fistulas are characterized by the formation of a high-flow communication between the internal carotid artery and the surrounding venous plexus of the cavernous sinus. The spontaneous type is more common in middle-aged and elderly women, representing small low-flow connections between the cavernous sinus and meningeal branches of the carotid arteries. The mixing of arterial and venous blood lowers arterial pressure and increases episcleral venous pressure [169].

Proposed mechanisms of idiopathic episcleral vein dilation include the existence of direct anastomoses between the arterial and venous systems in the anterior sclera, local venous obstruction in the area of extrabulbar muscles, and familial predisposition [1, 170].

1.1.4. Etiology and pathogenesis of phacogenic glaucoma

Phacogenic glaucomas refer to a group of ophthalmological nosologies associated with secondary IOP elevation due to changes in the shape, position, or integrity of the lens. Accordingly, phacotopic, phacomorphic, and phacolytic glaucomas are distinguished. Given the differences in etiology and treatment approaches, each form will be considered separately.

1.1.4.1. Etiology and pathogenesis of phacotopic glaucoma

Phacotopic glaucoma develops as a result of lens subluxation or dislocation in pseudoexfoliation syndrome or blunt eye trauma into the vitreous cavity or anterior chamber; in the latter case, it proceeds as angle-closure glaucoma. With rarer anterior displacement of the lens, pupillary block may develop with subsequent closure of the anterior chamber angle. With posterior lens dislocation, vitreous prolapse may occur, which can also lead to pupillary block [1, 173-176].

1.1.4.2. Etiology and pathogenesis of phacomorphic glaucoma

Phacomorphic glaucoma develops as a result of lens enlargement due to hydration and swelling of lens fibers in age-related or traumatic cataracts, or drug idiosyncrasy. In rare cases, lens swelling has been described as an idiosyncratic reaction to sulfonamides, carbonic anhydrase inhibitors, diuretics, acetylsalicylic acid, etc. The equatorial zone, regulated by the zonular apparatus, allows the lens to move forward and, together with the increase in anteroposterior dimension, creates a risk of iridolenticular contact, potential pupillary block, and iris bombe. A key risk factor is short hyperopic eyes. A complex clinical combination of phacomorphic glaucoma and angle-closure glaucoma arises, with difficult differentiation between these conditions. With lens enlargement, there is a possibility of developing a pupillary block, and with a narrow anterior chamber angle, an acute/subacute attack of secondary angle-closure glaucoma [173-175, 179, 180, 176].

1.1.4.3. Etiology and pathogenesis of phacolytic glaucoma

Phacolytic glaucoma develops as a result of a toxic-inflammatory reaction of ocular tissues to various lens components and includes three mechanisms that may develop separately or simultaneously: phacolytic, phacoanaphylactic (phacoantigenic), and phacofragmentary [189-196].

The phacolytic mechanism of IOP elevation consists of the imbibition of the trabecular meshwork by high-molecular-weight lens proteins and macrophages that leak through an intact capsule into the aqueous humor in hypermature cataracts [189, 190, 193, 194, 196].

Phacoanaphylactic (phacoantigenic) uveitis is a rare, severe granulomatous uveitis that develops after traumatic or surgical destruction of the lens as a result of immune complex formation following sensitization to lens proteins and loss of normal tolerance to these lens proteins [191, 197, 193, 198].

The phacofragmentary mechanism consists of the blockade of trabecular outflow by cortical and/or capsular lens material during phacoemulsification, penetrating eye trauma, or laser capsulotomy [199-202].

1.1.5. Etiology and pathogenesis of drug-induced (steroid) glaucoma

Systemic and topical corticosteroids (S01BA) have a pathological effect on the trabecular meshwork, causing microstructural changes in the trabeculae, initiating the deposition of extracellular material (glycosaminoglycan, elastin, and fibronectin), and inhibiting protease and phagocytic activity. In addition, trabecular meshwork cultures treated with dexamethasone** in experiments demonstrate decreased levels of tissue plasminogen activator, stromelysin, and metalloproteinases, as well as reduced arachidonic acid metabolism and phagocytic activity. These changes lead to an increased accumulation of cellular metabolic products in the trabecular tissue. The ultimate effect is a decrease in the aqueous humor outflow rate with the development of ocular hypertension [1, 207-209].

Glucocorticoids bind to several receptors throughout the body, including the glucocorticoid receptor alpha (GRalpha) and glucocorticoid receptor beta (GRbeta), which are ligand-activated transcription factors. GRbeta is thought to play a role in steroid resistance and has been shown to block the glucocorticoid response in trabecular cells, thereby suppressing phagocytic activity. This can lead to increased deposition of material, such as debris and pigment, in the juxtacanalicular meshwork in steroid-induced glaucoma.

Risk factors for steroid-induced ocular hypertension/glaucoma [210-212, 207, 213]:

- primary open-angle glaucoma

- glaucoma suspect

- family history of glaucoma in parents

- advanced age

- systemic connective tissue pathology

- high myopia

- type 1 diabetes mellitus

- genetic predisposition to steroid-induced ocular hypertension

Approximately one-third of patients receiving topical corticosteroids (S01BA) experience an IOP elevation of 6–15 mm Hg, and the percentage of such patients correlates with the duration of steroid therapy [214]. The development and severity of the hypertensive effect are influenced by the type and potency of the corticosteroid, the frequency, and the route of administration. The higher the potency of the corticosteroid, the greater the risk of IOP elevation. For example, dexamethasone** and prednisolone** are more potent steroids and raise IOP more frequently than less potent steroids such as fluorometholone and hydrocortisone** [215]. IOP elevation is more common with topical administration than with systemic administration and typically occurs within 1 to 4 weeks. Following cessation of steroid therapy, IOP normalization most commonly occurs within 1 to 4 weeks as well. Subconjunctival, sub-Tenon's, and retrobulbar corticosteroid injections (S01BA) can also cause IOP elevation. The proportion of patients who develop ocular hypertension from periocular corticosteroids (S01BA) is significantly higher than from topical ophthalmic corticosteroids (S01BA). IOP elevation following periocular administration of sustained-release corticosteroids (S01BA) usually occurs after several months, although in some cases it may be observed within a week and may return to baseline at six to nine months post-injection. In cases of significant IOP elevation following periocular corticosteroid administration (S01BA), excision of the corticosteroid depot may be required.

In approximately half of the patients who received systemic corticosteroids (triamcinolone) intravitreally, IOP elevation developed within two to four weeks post-injection. In pseudophakic eyes or those that have undergone anterior vitrectomy, IOP elevation may occur more rapidly.

1.1.6. Etiology and pathogenesis of post-traumatic glaucoma

Post-traumatic glaucomas represent a heterogeneous group of conditions resulting from multiple pathophysiological mechanisms that elevate IOP in the early or late stages following blunt or penetrating eye trauma.

Eye trauma accounts for 2–6% of annual hospital admissions for trauma patients [222, 223]. The risk of developing glaucoma after blunt trauma is approximately 19%, and after a penetrating injury, about 3% [224, 225]. Approximately 60% of patients with eye trauma are under 30 years of age [226]. The gender ratio ranges from 3 to 14 males to 1 female [227, 228, 226]. The causes and circumstances of eye trauma can vary widely depending on geographical, socioeconomic, and cultural factors. While in the past the majority of eye injuries occurred in the workplace or in violent conflict settings, in recent years there has been an increase in eye injuries resulting from leisure activities and motor vehicle accidents [229, 226].

1.1.6.1. Etiology and pathogenesis of early-onset post-traumatic glaucoma following blunt eye trauma

The cause of a closed globe injury is the direct impact of a large-area, high-kinetic-energy object on the eye, or the effect of a blast wave and/or concussion of individual body parts. The pathogenesis of closed globe injury is complex, diverse, and comprises several stages: tissue alteration, impaired neurovascular regulation, changes in biochemical parameters within the ocular fluid media, and the development of a general and local adaptation syndrome (stress response).

The impact of a blunt object leads to structural changes in the anterior segment of the eyeball, which compresses along the anteroposterior axis with an equatorial expansion, during which expansion and deformation of seven annular structures (according to D. Campbell, 1991) occur [230]:

- pupillary sphincter – deformation/rupture;

- iris root – iridodialysis;

- anterior part of the ciliary body – rupture between the longitudinal and circular muscles of the ciliary body;

- site of attachment of the ciliary body to the scleral spur – cyclodialysis;

- trabecular meshwork – rupture of the anterior part of the network;

- zonule fibers – subluxation/dislocation of the lens;

- site of attachment of the retina to the ora serrata – retinal detachment.

The conditions described can lead to acute or chronic IOP elevation [224].

In the early post-traumatic period, a slight decrease in IOP may be noted as a result of inflammatory processes, reduced aqueous humor production, and structural disorders in the iridocorneal angle with increased aqueous humor outflow. In some cases, IOP may be elevated due to blockage of the trabecular meshwork by erythrocytes, inflammatory cells, and cell breakdown products. In such cases, IOP normalizes within a few days or weeks.

Hemorrhage from the ciliary body vessels usually stops spontaneously as a result of IOP elevation, vasospasm, and thrombus formation. Final clot organization occurs on days 4 to 7. Uncomplicated hyphemas resolve within 1 week. Evaluating the grade of hyphema is important: Grade I – filling of the anterior chamber by less than one-third, Grade II – from one-third to half, Grade III – from half to nearly complete filling, Grade IV – complete filling of the anterior chamber with blood. The risk of developing glaucoma depends on the grade, duration of elevated IOP, and rebleeding. In the presence of hyphema, the probability of post-traumatic glaucoma is 13% with Grade II hyphema, 27% with Grade III hyphema, and 52% with total hyphema [231].

A hyphema up to 3 mm in height typically does not cause vision loss or increased tonometry. Hyphemas greater than 3 mm can significantly reduce vision due to pupillary blockage and lead to a significant IOP elevation (up to an acute attack) due to mechanical blockage of the iridocorneal angle. In addition, the hyphema may obscure the iridocorneal area of dialysis. Total hyphema filling the entire anterior chamber, in addition to vision loss and tonometry disturbances, may eventually lead to bloodstaining of the cornea – persistent corneal opacity due to infiltration of its stroma by formed blood elements. Preventing this complication is an important treatment objective, for which both conservative treatment (primarily enzymolysis) and surgical treatment (anterior chamber paracentesis, blood aspiration, anterior chamber tamponade with air or ophthalmic viscoelastic) can be used.

Inflammation is one of the primary responses to trauma and can cause IOP elevation both as a result of trabecular obstruction by inflammatory cells and cell breakdown products, and inflammation of the trabecular meshwork itself [224]. The severity of the inflammatory reaction depends on the extent of damage and ranges from asymptomatic iritis to severe uveitis with the deposition of precipitates in the anterior chamber and the formation of goniosynechiae.

1.1.6.2. Etiology and pathogenesis of late-onset post-traumatic glaucoma following blunt eye trauma

The development of late-onset post-traumatic glaucoma occurs as a result of iridocorneal angle recession, functional blockade of the trabecular meshwork by degenerated erythrocytes and/or hemolysis products, as well as lens dislocation and disruption of its integrity.

The cause of post-traumatic glaucoma associated with iridocorneal angle recession is the formation of micro-tears between the longitudinal and circular muscle portions of the ciliary body, triggering delayed inflammation and degeneration of the aqueous humor outflow zone. Post-traumatic glaucoma associated with angle recession can develop several years after the trauma. It is believed that glaucoma develops in 7–9% of patients with angle recession [244–246, 233].

Ghost cell glaucoma, described by D. Campbell, develops several weeks after trauma and is caused by the imbibition of the trabecular meshwork by degenerated erythrocytes (ghost cells). Young, elastic erythrocytes are normally capable of passing through the trabecular meshwork, whereas stiffer, aging erythrocytes are unable to pass into Schlemm's canal, leading to IOP elevation. This form of glaucoma occurs in the presence of long-standing hyphema/vitreous hemorrhage [247–255].

Hemolytic glaucoma develops several days or weeks after intraocular hemorrhage due to functional blockade of the trabecular meshwork by hemoglobin-engorged macrophages, free hemoglobin, and remnants of lysed erythrocytes.

Hemosiderotic glaucoma is a rare condition associated with a history of prolonged intraocular hemorrhage, leading to erythrocyte degeneration and the release of their contained hemoglobin, which can also cause retinal degeneration, cataract, iris discoloration, and corneal staining. Hemoglobin released from lysed erythrocytes is cleared from the eye by macrophages as free hemoglobin or its breakdown products – globin, bilirubin, and iron, which is taken up by the endothelial cells of the trabecular meshwork. Toxic inorganic iron granules accumulate inside the cells, causing hemosiderosis accompanied by sclerosis and obliteration of the intertrabecular spaces [256–258].

Blunt trauma to the eyeball can cause a number of post-traumatic glaucomas associated with lens pathology, the etiology, clinical presentation, and treatment of which are described in subsection 1.6.6.2:

- rupture of the zonule of Zinn fibers with lens subluxation and dislocation – phacotopic glaucoma;

- rupture of the lens capsule and/or lens fibers with hydration and lens enlargement followed by angle-closure – phacomorphic glaucoma;

- rupture of the lens capsule with release of its particles into the anterior chamber cavity – phacolytic glaucoma;

- rupture of the lens capsule with the development of an immunological reaction to the lens protein – phacoanaphylactic glaucoma.

1.1.6.3. Etiology and pathogenesis of post-traumatic glaucoma due to open globe injury

Penetrating injuries of the eyeball can be caused by blunt or sharp objects. The most common cause of post-traumatic glaucoma with a penetrating eye injury is secondary angle closure due to peripheral goniosynechiae following a prolonged flattening of the anterior chamber against the background of an inflammatory process. Another cause is the formation of posterior synechiae due to inflammation and pupillary block, which leads to iris bombe with secondary angle closure. The development of the previously described phacomorphic, phacolytic, and ghost cell glaucomas is also possible. In the presence of a metallic foreign body (iron, copper), secondary glaucoma may develop due to the toxic effect of metal oxides on the trabecular meshwork (siderosis, chalcosis) [262, 263, 225, 264, 233].

1.3 Epidemiology of the Disease or Condition

1.1.1. Epidemiology of inflammatory (uveitic) glaucoma

The prevalence of glaucoma in inflammatory diseases of the eyeball ranges from 10% to 20% [8-10, 109]. An important factor influencing this is the duration of the inflammatory pathology: the incidence of glaucoma in uveitis after 1 and 5 years is 6% and 11%, respectively, increasing to 22% after 10 years [11]. The prevalence of inflammatory glaucoma correlates with age, as well as with the etiology and clinical course of the inflammatory process. It is believed that uveitis is less common in very young and elderly individuals, but these very groups are more prone to IOP elevation [12, 13]. Among patients with uveitis older than 60 years, the increase in intraocular pressure can reach up to 30% [14]. Other factors, such as the chronic course of uveitis and predominant involvement of the anterior segment, also contribute to an increased risk of the ocular hypertension symptom [11, 15].

1.1.2. Epidemiology of neovascular glaucoma

The prevalence of neovascular glaucoma is approximately 3.9%, although exact data on overall incidence and prevalence are lacking [143]. The most common conditions associated with neovascular glaucoma are central retinal vein occlusion (CRVO), proliferative diabetic retinopathy (PDR), and a number of other conditions including ocular ischemic syndrome and tumors. Approximately 36% of neovascular glaucoma cases occur after CRVO, 32% in PDR, and 13% after carotid artery obstruction [144, 145]. Considering retinal ischemia as the leading etiological component, neovascular glaucoma is more prevalent in elderly patients with significant cardiovascular risk factors such as a history of hypertension, diabetes, dyslipidemia, and smoking.

Unlike CRVO, in which typical neovascular glaucoma occurs within 3 months of the onset of ischemic occlusion (the so-called "100-day glaucoma"), the development of hypoxia and ischemia in diabetic retinopathy occurs relatively slowly. The main factors causing vascular complications in diabetes mellitus are chronic hyperglycemia and ischemia-reperfusion, the production of large amounts of neovascular factors, and an imbalance between pro-angiogenic and anti-angiogenic processes. Under conditions of hypoxia and ischemia, this balance is disrupted, shifting towards unbalanced VEGF activation, accompanied by the activation, proliferation, and migration of endothelial cells, perocytes, and immune cells, which stimulates angiogenesis and promotes the formation of a neovascular network and neovascular membranes on the fundus, iris, and in the anterior chamber angle.

1.1.3. Epidemiology of phlebotensive glaucoma

Elevated episcleral venous pressure is an important cause of ocular hypertension and secondary glaucoma. The most common conditions associated with phlebohypertensive glaucoma are venous compression, arteriovenous shunts/malformations, and idiopathic dilation of episcleral veins. The prevalence of this form of glaucoma is considered low due to the rare occurrence of these systemic nosologies [270].

1.1.4. Epidemiology of phacogenic glaucomas

The epidemiology of phacogenic glaucomas differs between developed and developing countries. In developing countries with more limited healthcare resources and a high percentage of cataracts, the incidence of phacogenic glaucomas is up to 2.4% at the presentation of senile cataract, with a female predominance [269].

1.1.5. Epidemiology of drug-induced (steroid) glaucoma

Ocular hypertension has been described during local, periocular, intraocular, and inhalation corticosteroid therapy. Approximately one-third of patients treated with topical steroids experience a 6–15 mmHg increase in IOP, and the percentage of patients with steroid-induced ocular hypertension continues to increase with the duration of steroid therapy [214].

1.1.6. Epidemiology of post-traumatic glaucoma

The prevalence of eye trauma is 19.8% [223]. Among hospitalized trauma patients, eye injury is recorded in 2–6%, with blunt trauma being the most common [222]. The risk of developing glaucoma after blunt trauma, particularly closed globe contusion, is 19% [224]. The corresponding risk in penetrating eye injury is about 3% [225].

1.4 Features of Coding the Disease or Condition

H40.3 Secondary post-traumatic glaucoma

H40.4 Secondary glaucoma secondary to eye inflammation

H40.5 Secondary glaucoma secondary to other eye disorders

H40.8 Other glaucoma

H40.9 Unspecified glaucoma

H42.8 Glaucoma in other diseases classified elsewhere

1.5 Classification of the disease or condition

1.5.1. Classification of inflammatory (uveitic) glaucoma

Inflammatory glaucoma, as a chronic progressive optic neuropathy, meets the classical classification criteria characteristic of primary open-angle glaucoma.

Depending on the IOP level, inflammatory glaucoma is subdivided into:

Table 1 – Classification scheme of IOP levels in glaucoma [2, 16]

Depending on the clinical course and characteristics, inflammatory glaucoma is subdivided into:

Table 2 – Classification scheme of glaucoma by clinical course [16]

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

Depending on the severity of the pathological process, inflammatory glaucoma is subdivided into:

Table 4 – Classification scheme of glaucoma stages [16]

The division of the continuous glaucomatous process into 4 (four) stages is conventional. The status of the visual field and optic nerve head is taken into account when determining the stage.

In glaucoma developing as a result of secondary ocular hypertension against the background of an inflammatory process, diagnostic difficulties are associated with the inconstant nature of IOP elevation during exacerbations of inflammation, as well as reduced transparency of the optical media, which hinders functional testing and visualization of fundus structures. In such cases, the diagnosis of glaucoma may be established without additional examinations, and the stage of glaucoma optic neuropathy is not specified [1, 17].

1.5.2. Classification of neovascular glaucoma

Neovascular glaucoma, as a chronic progressive optic neuropathy, meets the classification criteria characteristic of primary open-angle glaucoma.

Depending on the IOP level, neovascular glaucoma is subdivided into:

Table 1 – Classification scheme of IOP levels in glaucoma [2, 16]

Depending on the clinical course and characteristics, neovascular glaucoma is subdivided into

Table 2 – Classification scheme of glaucoma by clinical course [16]

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

Depending on the severity of the pathological process, neovascular glaucoma is subdivided into:

Table 4 – Classification scheme of glaucoma stages [16]

The division of the continuous glaucomatous process into 4 (four) stages is conventional. The status of the visual field and optic nerve head is taken into account when determining the stage.

1.5.3. Classification of phlebohypertensive glaucoma

Phacogenic glaucoma, as a chronic progressive optic neuropathy, meets all classification criteria characteristic of glaucoma, including stage and level of IOP compensation (see section 3.3).

1.5.4. Classification of phacogenic glaucomas

1.5.4.1. Phacotopic glaucoma

1.5.4.2. Phacomorphic glaucoma

1.5.4.3. Phacolytic glaucoma

1.5.5. Classification of drug-induced (steroid) glaucoma

Steroid glaucoma, as a chronic progressive optic neuropathy, meets all classification criteria characteristic of glaucoma, including stage and level of IOP compensation (see section 3.3) [1, 216].

1.5.6. Classification of post-traumatic glaucomas

1.5.6.1. Early-onset post-traumatic glaucoma due to blunt ocular trauma

1.5.6.2. Late-onset post-traumatic glaucoma due to blunt ocular trauma

1.5.6.3. Post-traumatic glaucoma due to open ocular trauma

1.6 Clinical presentation of the disease or condition

1.6.1. Clinical presentation of inflammatory (uveitic) glaucoma

Changes in intraocular pressure associated with inflammation can range from hypotony to hypertension. The elevation of IOP in uveitis differs from IOP elevation in other diseases in that it may be short-term in some patients and chronic in others. Increased IOP is observed during an acute episode of uveitis, against the background of a chronic, sluggish inflammatory process, or in the long-term period due to steroid therapy. Glaucomatous optic neuropathy can develop either due to chronic IOP elevation or due to a high frequency of recurring short-term episodes of ocular hypertension [18, 19, 1, 14].

Clinical manifestations of the underlying disease (uveitis) depend on the localization of inflammation, morphological characteristics, degree of activity, course, as well as the clinical form of the systemic disease [20].

Patients may complain of blurred or decreased vision, and floaters in front of the eye. In acute inflammation, they may report eye redness, photophobia, lacrimation, eye pain, changes in iris color, and pupil size and shape. In intermediate and posterior uveitis, complaints may include flashes, visual field defects, micro- and macropsia, distorted vision, and color vision impairment.

The clinical manifestations of the underlying inflammatory process are characterized by pericorneal/mixed injection, endothelial "fogging", and precipitates on the posterior surface of the cornea (small "dust-like" in non-granulomatous inflammation, medium and large "mutton-fat" in granulomatous inflammation). As the inflammatory process subsides, the precipitates decrease in diameter, acquire clear margins, undergo pigment deposition, or resorb [20, 21]. Attention should also be paid to exudative cellular effusion into the anterior chamber, hypopyon, hyphema, and changes in the iris (stromal edema, dilation of its own vessels, and the development of newly formed vessels). In granulomatous inflammation, Koeppe nodules (at the pupillary margin) and Busacca nodules (in the mid-zone of the iris and the anterior chamber angle) may form [22-24]. Formation of anterior synechiae in the iridocorneal angle (during the organization of fibrinous exudate) and posterior synechiae between the iris and the lens is possible, up to seclusion of the pupil with the formation of a pupillary membrane. Cellular and exudative reactions may appear in the anterior vitreous (in patients with iridocyclitis), along with the development of macular edema and/or papillitis.

The incidence and structure of uveitis complications depend on the localization of the inflammatory process, the etiological form, the duration and severity of uveitis, and the adequacy of diagnosis and treatment. It should be borne in mind that, in addition to secondary glaucoma, complications of uveitis also include scleral and corneal perforation, secondary keratopathies, complicated cataract, vitreous fibrosis, retinal vessel and/or optic disc occlusion, proliferative vitreoretinopathy, optic disc atrophy, ischemic neuropathy and maculopathy, epiretinal membrane, retinal detachment (rhegmatogenous, tractional, exudative), retinoschisis, as well as persistent hypotony and subatrophy of the eyeball [23-26, 20, 27].

1.6.2. Clinical presentation of neovascular glaucoma

Depending on the degree of IOP elevation, the stage of glaucomatous optic neuropathy, and the volume and localization of neovascularization, the symptoms of neovascular glaucoma include decreased vision, corneal edema, photophobia, conjunctival injection, rubeosis, hyphema, and hemophthalmos. With significant ocular hypertension, the patient may experience pain in the eyeball, headache, nausea, and/or vomiting.

The clinical presentation of neovascular glaucoma is divided into three consecutive stages:

1. rubeosis of the iris;

2. stage of open-angle glaucoma;

3. stage of angle-closure glaucoma.

At the rubeosis stage, newly formed vessels are visualized at the pupillary margin and/or in the iridocorneal angle. As a rule, primary neovascularization develops in the pupillary area; however, in some cases, rubeosis may debut in the iridocorneal angle. Intraocular pressure may be normal or moderately elevated. At this stage, patients usually have no pronounced complaints, except for those related to the underlying disease (hyphema in proliferative diabetic retinopathy, visual field defects in central retinal vein occlusion).

At the open-angle glaucoma stage, IOP is decompensated, and rubeosis is clearly visualized in the pupillary zone as well as in the iridocorneal angle; hyphema is noted in some cases.

At the angle-closure glaucoma stage, the contraction of the fibrovascular membrane causes progressive closure of the iridocorneal angle and the formation of goniosynechiae. Patients often complain of photophobia, decreased visual acuity, severe eye pain, headache, nausea, and/or vomiting. Rubeosis is significantly pronounced, the pupil is rigid, ectropion is present, hyphema, moderate inflammation, and IOP up to 60–70 mm Hg are possible. Conjunctival injection and diffuse hypertensive corneal edema are frequently observed.

1.6.3. Clinical presentation of phlebohypertensive glaucoma

The biomicroscopic picture of elevated episcleral venous pressure glaucoma is characterized by pronounced dilation and tortuosity of episcleral veins, an open iridocorneal angle profile with blood filling Schlemm's canal, and increased IOP with an increased ocular pulse amplitude. In the early stage of the disease, the elevation of IOP is often combined with a normal outflow facility coefficient, but with chronic elevation of venous pressure, outflow may decrease and fail to recover even after normalization of venous pressure.

With significant increases in venous pressure, conjunctival chemosis, pulsating exophthalmos, and restriction of extraocular motility are noted.

1.6.4. Clinical presentation of phacogenic glaucomas

1.6.4.1. Clinical presentation of phacotopic glaucoma

Lens subluxation is characterized by decreased visual acuity, acquired myopia, asymmetry of the anterior chamber depth, episodic or constant elevation of intraocular pressure, a closed iridocorneal angle upon gonioscopy, phakodonesis, and partial displacement of the lens relative to the optical axis of the eye [176]. The clinical picture of anterior lens dislocation may be supplemented by a sharp increase in IOP; the anterior chamber is shallower than in the fellow eye, and the iridocorneal angle is closed upon gonioscopy. When the lens luxates into the anterior chamber, the condition is complicated by corneal decompensation due to iridolenticular contact. Posterior lens dislocation may be accompanied by vitreous prolapse into the anterior chamber. The iridocorneal angle is usually open, but pupillary block with secondary angle closure may develop [173-175, 177].

1.6.4.2. Clinical presentation of phacomorphic glaucoma

An increase in lens size is accompanied by progressive myopization, a shallow anterior chamber, and narrowing of the iridocorneal angle. Biomicroscopy reveals uneven lens opacification, fluid clefts in immature cataracts, a pearly color of the lens, anterior shift of the iridolenticular diaphragm, and a dull red reflex from the fundus. These signs may be unilateral. The clinical course resembles an acute attack of angle-closure glaucoma. Examination of the fellow eye reveals a deeper anterior chamber and a thinner lens, which rules out an acute attack of primary angle-closure glaucoma. Measurement of the anteroposterior axis and determination of refraction are useful for comparison with the fellow eye [173, 174, 179, 181, 180, 176].

1.6.4.3. Clinical presentation of phacolytic glaucoma

The phacolytic mechanism is accompanied by the development of a pronounced pain syndrome, hyperemia of the eyeball, and a high level of IOP. The difference from an acute attack of angle-closure glaucoma is a deep anterior chamber, absence of pupillary block, and an open iridocorneal angle. Examination reveals diffuse corneal edema and a white hypermature cataract [189, 203, 190, 191, 194, 196].

In phacoanaphylactic uveitis, conjunctival hyperemia, corneal edema with endothelial precipitates, and hypopyon are noted. IOP may be normal or elevated due to the effect of inflammatory cells and high-molecular-weight proteins on the trabecular meshwork [191, 197, 198].

In the phacotoxic/phacoflytic mechanism, white particles of lens matter, which may have a dense consistency and form a pseudohypopyon, are visualized in the anterior chamber aqueous humor [199-202].

1.6.5. Clinical presentation of drug-induced (steroid) glaucoma

The clinical picture of steroid-induced glaucoma is similar to that of primary open-angle glaucoma [1, 216].

1.6.6. Clinical presentation of post-traumatic glaucoma

1.6.6.1. Clinical picture of post-traumatic glaucoma due to blunt ocular trauma in the early period

Clinical signs indicating the possibility of glaucoma development in the early period after blunt eye trauma may include hyphema, deformation and/or rupture of the pupillary sphincter, iridodialysis and/or cyclodialysis, lens subluxation or dislocation, as well as retinal detachment. In the early post-traumatic period, a slight decrease in IOP may be noted as a result of inflammatory processes, reduced aqueous humor production, and structural disorders in the iridocorneal angle with increased aqueous humor outflow. In some cases, IOP may be elevated due to blockade of the trabecular meshwork by red blood cells, inflammatory cells, and cell breakdown products. In such cases, IOP normalizes within a few days or weeks.

1.6.6.2. Clinical picture of post-traumatic glaucoma due to blunt ocular trauma in the late period

Clinical signs of angle recession may include hyphema, iridodialysis, exposure of a wide ciliary body band, and an abnormally white scleral spur.

In ghost cell glaucoma, small khaki-colored ghost cells are visualized in the anterior chamber. The term "ghost cell" is used because the cells appear empty except for the presence of denatured hemoglobin visible on histopathology (Heinz bodies). Precipitation of these cells forms a yellowish-brown pseudohypopyon. The "candy stripe" sign appears when layers of fresh red blood cells and ghost cells overlap.

In hemolytic glaucoma, gonioscopy reveals an open iridocorneal angle with a reddish-brown trabecular meshwork band.

1.6.6.3. Clinical presentation of post-traumatic glaucoma due to open ocular trauma

Penetrating eye injuries may not be diagnosed on visual inspection alone; therefore, any history of facial trauma should raise suspicion of a penetrating globe injury. Attention should be paid to pupillary distortion, lens opacification, uveal prolapse, and vitreous hemorrhage. Intraocular pressure after a penetrating injury is typically low due to the open wound [262, 263, 225, 264, 233].

Depending on the mechanism and extent of the trauma, open globe injuries are classified into 5 types:

- Type A – contusion rupture of the eyewall (full-thickness wound caused by a blunt object);

- Type B – penetrating injuries – local full-thickness injuries to the eyewall without intraocular foreign body retention, typically caused by a sharp wounding projectile;

- Type C – local full-thickness (penetrating) injuries to the eyewall with intraocular foreign body retention;

- Type D – perforating injuries with double (entry and exit) full-thickness penetration of the eyewall;

- Type E – mixed, difficult-to-classify cases of severe polytrauma combining injuries to both intraocular contents and the eyewall (with perforation) or globe rupture.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the disease or condition

Criteria for diagnosing inflammatory (uveitic) glaucoma

- periodic or permanent elevation of intraocular pressure above the individual's normal range;

- structural pathological changes of the optic nerve head and retinal nerve fiber layer;

- typical visual field defects corresponding to optic nerve head and retinal nerve fiber layer damage;

- presence of an inflammatory process or its consequences that caused the intraocular pressure elevation and characteristic structural and functional glaucomatous changes.

Criteria for diagnosing neovascular glaucoma

- periodic or permanent elevation of intraocular pressure above the individual's normal range;

- structural pathological changes of the optic nerve head and retinal nerve fiber layer;

- typical visual field defects corresponding to optic nerve head and retinal nerve fiber layer damage;

- rubeosis iridis, new vessels in the iridocorneal angle, presence of a fibrovascular membrane on the iris surface and in the iridocorneal angle;

- presence of signs of retinal ischemia – hemorrhages, cotton-wool spots, neovascularization of the optic disc and retina, non-perfusion areas according to OCT angiography and fluorescein angiography of the eye;

- presence of a systemic or ophthalmic disease initiating retinal ischemia (diabetes mellitus, central retinal vein occlusion, etc.);

Criteria for diagnosing phlebotensive glaucoma

- marked dilation and tortuosity of episcleral veins, open iridocorneal angle profile with blood filling Schlemm's canal;

- periodic or permanent elevation of intraocular pressure above the individual's normal range;

- structural pathological changes of the optic nerve head and retinal nerve fiber layer;

- typical visual field defects corresponding to optic nerve head and retinal nerve fiber layer damage;

Criteria for diagnosing phacogenic glaucoma

- presence of lens pathology combined with signs of dislocation, increased size, or compromised integrity characteristic of the respective phacogenic glaucoma subtype;

- periodic or permanent elevation of intraocular pressure above the individual's normal range;

- structural pathological changes of the optic nerve head and retinal nerve fiber layer;

- typical visual field defects corresponding to optic nerve head and retinal nerve fiber layer damage.

Criteria for diagnosing drug-induced (steroid) glaucoma

- periodic or permanent elevation of intraocular pressure above the individual's normal range;

- structural pathological changes of the optic nerve head and retinal nerve fiber layer;

- typical visual field defects corresponding to optic nerve head and retinal nerve fiber layer damage;

- history of topical, periocular, intraocular, or inhalation corticosteroid therapy.

Criteria for diagnosing post-traumatic glaucoma

- history of ocular trauma with characteristic biomicroscopic signs.

- periodic or permanent elevation of intraocular pressure above the individual's normal range;

- structural pathological changes of the optic nerve head and retinal nerve fiber layer;

- typical visual field defects corresponding to optic nerve head and retinal nerve fiber layer damage.

2.1 Complaints and Anamnesis

2.1.1. Inflammatory (uveitic) glaucoma. History and symptoms.

Comments:

1. During history taking and symptom assessment, it is recommended to pay attention to risk factors for the onset and progression of the inflammatory process of the eyeball, as well as family history, general and ophthalmic status, presence/absence of systemic and infectious diseases, allergic reactions and drug intolerance, frequency and duration of medications used, with a review of relevant medical documentation and assessment of the impact of visual functions on daily life and activities [3, 2].

2. Potential visual symptoms associated with the underlying inflammatory disease: redness, photophobia, pain, accommodation disorders, decreased and/or blurred vision, floaters, flashes of light, lightning, line distortion, visual field loss, color perception disorders, changes in iris color, pupil size, and shape.

3. During questioning, attention should be paid to joint, muscle, and back pain, skin rashes, nail lesions, oral and/or genital ulcers, finger numbness, headaches and their characteristics, tinnitus and/or ringing in the ears, hearing impairment, cough (not caused by smoking or colds), graying and hair loss, vitiligo, nocturia, low-grade fever, and presence of thrombophlebitis.

4. Presence/absence of surgeries and trauma to the visual organ

5. The presence of general diseases diagnosed by specialists should be clarified.

2.1.2. Neovascular glaucoma. History and symptoms.

Comments:

1. During history taking and symptom assessment, it is recommended to pay attention to risk factors for retinal ischemia in neovascular glaucoma, as well as family history, general and ophthalmic status [3, 2].

2. Presence/absence of surgeries and trauma to the visual organ

3. The presence of general diseases diagnosed by specialists should be clarified.

2.1.3. Phlebotensive glaucoma. History and symptoms.

2.1.4. Phacogenic glaucomas. History and symptoms.

See section 2.4. Instrumental diagnostic procedures

2.1.5. Drug-induced (steroid) glaucoma. History and symptoms.

See section 2.4. Instrumental diagnostic procedures

2.1.6. Post-traumatic glaucoma. History and symptoms.

See section 2.4. Instrumental diagnostic procedures

2.2 Physical Examination

2.2.1. Inflammatory (uveitic) glaucoma. Physical examination.

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

Comments: the choice of specialist profile (rheumatologist, neurologist, dermatovenereologist, pulmonologist, hematologist, general practitioner, cardiologist, otorhinolaryngologist, urologist, obstetrician-gynecologist, gastroenterologist, pediatrician, dentist) is determined depending on whether the patient has a suspected systemic disease and the risk of systemic complications.

2.2.2. Neovascular glaucoma. Physical examination.

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

2.2.3. Phlebotensive glaucoma. Physical examination.

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

2.2.4. Phacogenic glaucomas. Physical examination.

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

2.2.5. Drug-induced (steroid) glaucoma. Physical examination.

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

2.2.6. Post-traumatic glaucoma. Physical examination.

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

2.3 Laboratory Diagnostics

2.3.1. Inflammatory (uveitic) glaucoma. Laboratory diagnostic examinations.

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

2.3.2. Neovascular glaucoma. Laboratory diagnostic examinations.

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

2.3.3. Phlebotensive glaucoma. Laboratory diagnostic examinations.

There are no diagnostic criteria for phlebotensive glaucoma based on clinical laboratory test data. In endocrine ophthalmopathy, there may be an increase or decrease in serum thyroid hormone levels and elevated anti-thyroperoxidase antibodies.

2.3.4. Phacogenic glaucomas. Laboratory diagnostic examinations.

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

2.3.5. Drug-induced (steroid) glaucoma. Laboratory diagnostic examinations.

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

2.3.6. Post-traumatic glaucoma. Laboratory diagnostic examinations.

There are no diagnostic criteria for post-traumatic glaucoma based on clinical laboratory test data.

2.4 Instrumental Diagnostics

2.4.1. Inflammatory (uveitic) glaucoma. Instrumental diagnostic examinations.

Comments: The examination is performed with refractive correction using glasses or contact lenses (if the anterior segment of the eye is intact), applying an age-appropriate presbyopic correction using a lens from a trial lens set (with a clear rim to eliminate errors) placed in a special holder integrated into the perimeter design or in the patient's own near-vision glasses. Correction of any refractive error is critical for perimetry accuracy.

Comment: The baseline IOP measurement method adopted in the Russian Federation is Maklakov tonometry (Pt) using a 10 g weight (TGD-01 intraocular pressure tonometer). Measuring IOP using the Goldmann tonometer (Po) is standard practice worldwide, and its results differ from tonometric values. To compare the two tonometry methods, the Nesterov-Egorov conversion ruler for the Maklakov intraocular pressure tonometer (10 g weight) can be used. Non-contact tonometry (pneumotonometry) should be considered as a screening method for determining IOP levels. During follow-up, it is recommended to use a single baseline tonometry method for accurate comparison of results [19, 38-42]. Transpalpebral bimanual palpation tonometry may be used during acute inflammatory eye diseases.

IOP monitoring is also necessary when selecting topical hypotensive therapy, taking into account the onset of drug action, peak effect, and washout period [43-48].

IOP measurement must be performed prior to gonioscopy and pupillary dilation [2].

Comment: Measuring the depth of the peripheral anterior chamber using the van Herick method is part of biomicroscopy and helps roughly estimate the degree of angle closure/opening. Additional criteria to consider during biomicroscopy include: uneven arteriolar narrowing and venular dilation, ampullary vascular dilation, microaneurysms, small hemorrhages, asymmetry in anterior segment changes, degree of endothelial pigmentation, keratic precipitates, neovascularization, inflammatory Koeppe/Busacca nodules, iris heterochromia, and stromal/pigment border atrophy [49, 24, 25, 20, 50].

Comment: Gonioscopy is based on identifying 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), iris insertion level, iris contour, trabecular pigmentation degree, areas of iridocorneal adhesions or synechiae, and presence of neovascularization. To systematize gonioscopic findings, it is advisable to use the classifications of E.G.A. van Beuningen, G. Spaeth, or R. Shaffer [51-53]. Ultrasound biomicroscopy and/or anterior segment OCT can be used in addition to gonioscopy to assess anterior chamber angle changes [54, 55].

The examination is contraindicated in patients with inflammatory conditions of the ocular surface and cannot be performed accurately in patients with severe corneal opacities and/or hyphema.

Comment: Ophthalmoscopy is performed using various models of ophthalmoscopes; fundus biomicroscopy under pharmacologic mydriasis employs non-contact lenses for indirect ophthalmoscopy (to obtain a stereoscopic image). Ophthalmoscopy requires quantitative and qualitative characterization of parameters (Appendix G1).

In cases of primary angle-closure without iridectomy, fundus examination with a dilated pupil (using short-acting mydriatics) is possible under medical supervision to rule out the potential risk of an acute glaucoma attack.

Qualitative characteristics:

- NRR. To determine the characteristics of the neuroretinal rim (NRR), it is recommended to use the ISNT rule (Inferior, Superior, Nasalis, Temporalis). In eyes with initial 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 on the temporal side along the horizontal meridian. In far-advanced glaucoma, the thinned NRR is located mainly in the nasal sector, with its better-preserved part situated in the superonasal quadrant rather than the inferonasal one. When assessing the NRR, the ISNT rule can only be used for standard optic disc sizes; for large and small sizes, as well as in myopia with tilted disc insertion, NRR assessment is difficult and requires follow-up over time to detect disease progression. The sensitivity and specificity of the method do not exceed 80% [56-58]. In patients with active uveitis, hyperemia and edema of the optic disc may occur, which prevents correct interpretation of the degree of glaucomatous changes.

- RNFL. Local or diffuse thinning (defects) best visualized in red-free light

- optic disc hemorrhage - presence

- peripapillary atrophy - presence and area

Quantitative characteristics:

● optic disc (size and shape, small, medium, large)

● cup (size and shape)

● ratio of the maximum cup size to the optic disc diameter (C/D ratio)

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 decolorized) 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 C/D ratio; the severity of peripapillary chorioretinal atrophy; the location of the vascular bundle and associated symptoms of "drilling" ("bayoneting") and attenuation 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 [59-62].

Comment: White-on-white threshold central visual field perimetry (10^°, 24^° and 30^°) is the preferred method for early detection of visual field defects [63, 64]. To evaluate standard automated perimetry (SAP) results, various indices are used, such as mean defect or mean deviation (MD), pattern standard deviation (PSD), as well as various diagnostic tests confirming the results of computer-based progression analysis during dynamic follow-up. 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 tests designed for low visual acuity using a stimulus larger than the standard size, can be an acceptable alternative. It is advisable to consider the degree of asymmetry of the parameters mentioned above to establish 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.

When interpreting perimetry results, it is necessary to account for the presence of inflammatory and atrophic foci in the fundus, macular or peripapillary edema, and the degree of vitreous and lens opacification. To diagnose glaucoma, perimetry is best performed during periods of uveitis remission.

2.4.2. Neovascular glaucoma. Instrumental diagnostic examinations.

Intraocular pressure (IOP) monitoring is also necessary when selecting local hypotensive therapy, taking into account the onset of drug action, its peak effect, and the washout period [19].

IOP measurement must be performed prior to gonioscopy and pupil dilation [2, 143].

Comment: The examination is contraindicated in patients with inflammatory conditions of the ocular surface and cannot be performed correctly in patients with pronounced 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.

If pupillary rubeosis is present, the decision to perform medical mydriasis should be made after assessing the risk of hyphema from newly formed vessels.

Comment: changes in perimetry data depend not only on the stage of the glaucomatous process but also on the underlying disease—the severity of post-thrombotic retinopathy, manifestations of proliferative diabetic retinopathy, etc.

2.4.3. Phlebohypertensive glaucoma. Instrumental diagnostic examinations.

Comments: Pronounced eyeball proptosis and conjunctival chemosis in carotid-cavernous fistula may hinder gonioscopy.

Comments: detected visual field changes may be caused not only by glaucoma but also by the underlying cause of venous outflow impairment: endocrine compressive optic neuropathy, cerebral blood flow disorders, etc.

2.4.4. Phacogenic glaucomas. Instrumental diagnostic examinations.

Comment: when performing gonioscopy in phacomorphic glaucoma, the anterior chamber angle is closed, and Forbes compression test is negative.

2.4.5. Drug-induced (steroid) glaucoma. Instrumental diagnostic examinations.

Comment: when taking anamnesis, it is recommended to pay attention to the presence of systemic or ophthalmological diseases (uveitis, vasculitis, asthma, dermatitis). Biomicroscopy may reveal other signs of corticosteroid use (thickening and/or of the cornea, posterior subcapsular cataract, ptosis, eyelid skin atrophy) [1, 212, 209, 216].

2.4.6. Post-traumatic glaucoma. Instrumental diagnostic examinations.

2.4.6.1. Post-traumatic glaucoma due to blunt eye trauma in the early period. Instrumental diagnostic examinations.

Comment:

The presence of hemorrhage in the anterior chamber reduces the likelihood of performing visometry, refractometry, static perimetry, gonioscopy, and ophthalmoscopy. Among additional diagnostic methods, ultrasound biomicroscopy should be preferred to assess the state of the anterior segment structures of the eye [234].

2.4.6.2. Post-traumatic glaucoma due to blunt eye trauma in the late period. Instrumental diagnostic examinations.

Comment:

The presence of hemorrhage in the anterior chamber reduces the likelihood of performing visometry, refractometry, static perimetry, gonioscopy, and ophthalmoscopy. Among additional diagnostic methods, ultrasound biomicroscopy should be preferred to assess the state of ocular structures [234].

2.4.6.3. Post-traumatic glaucoma due to open eye trauma. Instrumental diagnostic examinations.

2.5 Other Procedures

2.5.1. Inflammatory (uveitic) glaucoma. Other diagnostic examinations.

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. From the perspective of comparing these two types of monitoring strategies, the gap between observed functional losses and their preceding structural changes is steadily narrowing. Structural changes prevail at the beginning of the disease (suspected glaucoma, initial stage). At the advanced stage of the disease, morphofunctional lesions and their dynamics are in approximate equilibrium. At the far-advanced stage, functional changes predominate and serve as the target for monitoring glaucoma optic neuropathy (GON).

Comment: The normal distribution of central corneal thickness (CCT) in the adult population is 473-597 µm (mean - 540±30 µm). Significant deviations from average 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 the associated risk into account [66-68]. The test is not indicated for patients with ocular surface inflammatory processes and cannot be performed correctly in patients with pronounced corneal changes.

Comments: The results of OCT examinations during periods of active inflammation are difficult to interpret. During these periods, an increase in retinal nerve fiber layer (RNFL) thickness is noted compared to healthy individuals.

2.5.2. Neovascular glaucoma. Other diagnostic examinations.

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. From the perspective of comparing these two types of monitoring strategies, the gap between observed functional losses and their preceding structural changes is steadily narrowing. Structural changes prevail at the beginning of the disease (suspected glaucoma, initial stage). At the advanced stage of the disease, morphofunctional lesions and their dynamics are in approximate equilibrium. At the far-advanced stage, functional changes predominate and serve as the target for monitoring glaucoma optic neuropathy (GON).

Comment: The normal distribution of central corneal thickness (CCT) in the adult population is 473-597 µm (mean – 540±30 µm). Significant deviations from average 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 the associated risk into account [66-68].

2.5.2.1. Differential diagnosis of neovascular glaucoma

Neovascular glaucoma at the open-angle stage should be differentiated from uveitic glaucoma, which would be ruled out by a characteristic sign of neovascular glaucoma – neovascularization on the iris surface and in the iridocorneal angle. At the secondary angle-closure stage, in addition to angle-closure glaucoma, the differential diagnosis should include other causes of peripheral anterior synechiae formation (prior eye trauma and iridocorneal endothelial syndrome).

2.5.3. Phlebohypertensive glaucoma. Other diagnostic examinations.

Color Doppler imaging of the ocular vessels may be indicated to differentiate patients with idiopathic episcleral venous dilation from those with carotid-cavernous fistula, who may require invasive catheter angiography. Patients with carotid-cavernous fistula exhibit a characteristic reverse blood flow in the dilated superior ophthalmic vein, whereas in idiopathic episcleral venous dilation, orbital color Doppler imaging demonstrates normal retrograde blood flow through the superior ophthalmic vein [171]. Computed tomography of the orbits and brain is used when intracranial hemorrhage, compression of neural structures, and other complications of the disease are suspected.

2.5.3.1. Differential diagnosis of phlebohypertensive glaucoma

Phacolytic glaucoma should be differentiated from inflammatory diseases of the anterior segment of the eye accompanied by pronounced conjunctival hyperemia. Visual examination of the eyeball may reveal exophthalmos, incomplete eyelid closure, ciliary injection, dilated and tortuous veins, impaired ocular mobility, and impaired eyeball reposition. In carotid-cavernous fistula, a pulsing bruit is noted upon auscultation in the orbital region. Ophthalmoscopy reveals venous dilation and edema, optic disc edema, and punctate retinal hemorrhages.

2.5.4. Phacogenic glaucomas. Other diagnostic procedures.

Comment: in phacomorphic glaucoma, a convex volcano-like iris profile may be determined, with tight contact of the posterior surface of the iris with the anterior surface of the lens throughout, anterior shift of the lens-iris diaphragm, a large lens, and a slit-like or non-visualized posterior chamber of the eye.

2.5.4.1. Differential diagnosis of phacogenic glaucomas

Phacogenic glaucomas should be differentiated from post-traumatic glaucoma, in which subluxation or dislocation of the lens may also be observed; however, there will be a history of trauma, as well as characteristic clinical signs of injury: hyphema, deformation and/or rupture of the pupillary sphincter, iridodialysis and/or cyclodialysis, and retinal detachment.

2.5.5. Drug-induced (steroid) glaucoma. Other diagnostic procedures.

2.5.5.1. Differential diagnosis of drug-induced (steroid) glaucoma

This form of glaucoma should be differentiated from primary open-angle glaucoma, from which the steroid form will differ by the systemic or local use of corticosteroids.

2.5.6. Post-traumatic glaucoma. Other diagnostic procedures.

2.5.6.1. Differential diagnosis of post-traumatic glaucoma

Post-traumatic glaucoma has characteristic clinical signs, including a history of trauma, as well as hyphema, deformation and/or rupture of the pupillary sphincter, iridodialysis and/or cyclodialysis, subluxation or dislocation of the lens, and retinal detachment

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

3.1. Treatment of inflammatory (uveitic) glaucoma, including medical, laser, and surgical treatment

Successful treatment of uveitic glaucoma requires adequate simultaneous therapy for both the inflammatory process and intraocular pressure lowering. As a rule, the main goal should be the suppression of inflammation. Inadequate therapy for uveitis to avoid the development of steroid-induced hypertension can lead to inflammatory trabeculopathy with an even greater increase in intraocular pressure.

In acute uveitis with elevated IOP only during exacerbation periods, intraocular pressure can often be normalized with a course of local hypotensive therapy. In cases of a chronic inflammatory process requiring therapy with high doses of systemic corticosteroids (H02A), the addition of immunosuppressants (L04A) is recommended, which will control inflammation and allow the use of lower doses of systemic corticosteroids (H02A).

Long-acting corticosteroids in the form of injections or implants (S01BA) should be used with caution due to the potential development of prolonged uncontrolled steroid-induced ocular hypertension. At the same time, the treatment of uveitis should be aggressive, aimed at the prompt relief of inflammation and the achievement of remission, since inadequate therapy aimed at avoiding a steroid-induced increase in IOP may exacerbate the adverse symptoms of prolonged inflammation and worsen the outcome of the disease (6, 27).

When treating uveitic glaucoma, a number of features should be taken into account: drugs used for primary glaucoma may demonstrate varying efficacy if IOP decreases against the background of an inflammatory reaction. Currently, there are no reliable studies comparing the hypotensive efficacy of various agents in uveitic glaucoma; however, relative contraindications to their use have been described.

Comment:

When choosing drugs, it is necessary to consider their efficacy, potential side effects, dosing schedule, the required percentage of IOP reduction from baseline, potential cost, availability, and patient preference [2].

Before prescribing treatment, the expected "target" pressure level should be determined, taking into account baseline intraocular pressure 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, and there is no approved algorithm for establishing it; however, this does not negate its use in clinical practice [3, 18, 1, 2].

In all glaucoma patients, one should strive for the maximum reduction in IOP based on the stage of the disease. As an optimal characteristic of the upper limit of intraocular pressure during treatment, the values indicated below can be used taking into account the baseline normal ranges (Table 6) [2].

Table 6 – Optimal values of the upper limit of intraocular pressure during treatment

The personalized approach to glaucoma treatment consists of adapting it to the needs of a specific patient. Patients with marked visual impairment or young patients with disease manifestation should receive more aggressive treatment and be monitored more closely than patients at low risk of visual function deterioration [49, 76].

It is necessary to revise the "target" pressure level upon confirmation of glaucoma optic neuropathy progression, implying the need for an additional 20% IOP reduction from the previously achieved level [36, 2, 77, 78]. The use of drugs from the antiglaucoma medication and miotic groups is possible in combination with each other, as well as in combination with laser and surgical treatment methods.

3.1.1 Medical treatment of inflammatory (uveitic) glaucoma

Comments: treatment with medicinal products from the group of "antiglaucoma preparations and miotics" is the preferred initial therapy given its favorable risk-benefit profile based on the characteristics of the glaucomatous process against the background of inflammatory processes. When choosing drugs, it is necessary to take into account their efficacy, potential side effects, dosage regimen, required percentage reduction in IOP from baseline, potential cost, availability, and patient preferences [79, 2, 80, 81].

Beta-blockers are the first-line drugs of choice in patients with uveitic glaucoma in the absence of relevant systemic contraindications (asthma or bradycardia) [1,49, 271].

Carbonic anhydrase inhibitors are widely used in the hypotensive therapy of uveitic glaucoma both as monotherapy and as part of the fixed combination dorzolamide + timolol.

Sympathomimetics for the treatment of glaucoma in uveitic glaucoma are classified as second-line drugs in combination with beta-blockers and carbonic anhydrase inhibitors [1,49, 271].

The use of prostaglandin analogues in uveitic glaucoma is limited by data on their variable hypotensive efficacy, the potential for enhancement and/or reactivation of uveitis, and the development of cystoid macular edema (CME). According to the literature, an unpredictable high as well as low hypotensive effect of prostaglandins in the treatment of uveitis is noted, especially during the use of topical corticosteroids (S01BA) [82-84]. Data regarding the potential for enhancement or reactivation of the inflammatory process by prostaglandin analogues vary and are debatable, but since such cases have been described, it is recommended to preferentially select other drugs from the group of antiglaucoma preparations and miotics whenever possible [85-87]. There is some evidence regarding the reactivation of herpetic keratouveitis with the use of prostaglandin analogues, and therefore their prescription for this nosology is not recommended [88-90]. It is believed that the risk of CME development during prostaglandin analogue therapy is significantly higher in pseudophakia, aphakia, and retinopathies than in uveitis; however, the presence of this information requires prescribing prostaglandins with caution in this situation [91, 86].

The use of miotics (from the group of antiglaucoma preparations and miotics, S01E) is contraindicated due to their tendency to disrupt the blood-aqueous barrier and exacerbate inflammation. In addition, pupillary constriction in uveitis contributes to the development of posterior synechiae.

Mydriatics and cycloplegics (S01F) are frequently used in uveitis to prevent the formation of posterior synechiae, but caution should be exercised as they may also exacerbate angle closure.

The main pharmacological groups of antiglaucoma preparations and miotics and their mechanism of action are presented in Table 7.

Table 7 – Main pharmacological groups of antiglaucoma preparations and miotics and their mechanism of action

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

- poor tolerability of the starting therapy drug;

- good tolerability, but failure to achieve the «target» level of ophthalmotonus [36, 2, 80].

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

Comment: to increase the hypotensive efficacy and patient adherence to medical treatment for glaucoma, fixed combination drops are used containing substances that, having different hypotensive mechanisms of action, exhibit an additive effect when combined (Table 8). In patients with moderate and advanced stages and/or initially high pressure levels, a faster transition or «starting» with combination therapy is possible [2, 99, 100].

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

Comment: It is possible to replace components of antiglaucoma combinations if the "target" IOP level is not achieved. The use of more than 3 (three) medicinal products simultaneously is not recommended. Increasing the frequency of instillation of antiglaucoma preparations and miotics leads to reduced treatment adherence, decreased therapeutic efficacy, and an increased number of side effects [102, 103].

Variability in treatment adherence among glaucoma patients has been noted, ranging from 5 to 80%. Factors negatively affecting adherence may be related to the prescribed medicinal products (their cost, side effects, complex dosing regimen, inconvenience of instillations in certain situations – e.g., frequent business trips); to the patient themselves (forgetfulness, concomitant pathology, insufficient understanding of the disease, demographic characteristics – e.g., gender, as men are often less adherent); to the diseases (e.g., patients with early stages are less adherent due to the absence of subjective symptoms); to the attending physician (lack of communication, insufficient information about the disease state). Lack of treatment adherence can be one of the reasons for disease progression. Although comprehensive approaches consisting of patient education combined with individual recommendations, including adaptation of the daily routine and simplified instillation regimens, can improve treatment adherence, there is generally insufficient evidence for their practical application.

Comment: none of the antiglaucoma preparations and miotics is classified as safe or completely contraindicated during pregnancy. Topical glaucoma medications are prescribed only when the potential benefit of treatment outweighs the potential risk to the fetus. Basic principles for prescribing drugs: use the minimum number of drugs sufficient to achieve the "target" pressure, discuss treatment with an obstetrician-gynecologist and pediatrician, and reduce systemic absorption of the drug (by gently pressing on the medial canthal area or using punctal occlusion). The most sensitive period is the first trimester of pregnancy due to the potential teratogenic effect on the fetus of systemically administered antiglaucoma preparations and miotics. Considering the possible decrease in IOP during pregnancy in some patients, temporary cessation of topical hypotensive therapy under close observation may be considered. Beta-blockers, sympathomimetics for glaucoma treatment, and/or topical carbonic anhydrase inhibitors may be prescribed during pregnancy. Prostaglandin analogues should be used with caution due to their effect on uterine tone. Therefore, if signs of uterine hypertonus appear, their administration must be discontinued. In 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 may be continued. During lactation, it is preferable to prescribe topical carbonic anhydrase inhibitors and prostaglandin analogues. In some cases, antiglaucoma surgery may be considered [104, 105].

3.1.2 Laser treatment of inflammatory (uveitic) glaucoma

Comment: in uveitic glaucoma, the efficacy and safety of LI are lower than in primary angle-closure glaucoma for the following reasons:

- in uveitic glaucoma with pupillary block, the posterior chamber may not be a single continuous space, but rather a multi-chamber system with posterior iridolenticular synechiae acting as partitions. Therefore, performing LI will not be able to ensure the opening of the iridocorneal angle throughout its extent.

- if there are adhesions between the iris and the cornea, LI can lead to corneal endothelial injury and fail to form an adequate pathway for aqueous humor outflow between the posterior and anterior chambers due to iridocorneal contact.

- in uveitic glaucoma, there is a high probability of LI closure due to the ongoing inflammatory process; therefore, it is recommended to perform at least two iridotomies and intensive treatment with topical corticosteroids (S01BA) and mydriatic and cycloplegic agents (S01F).

- if LI fails to eliminate the pupillary block, surgical intervention including iridectomy with goniosynechiolysis is recommended [1].

Comment: cyclocoagulation in uveitic glaucoma can lead to a higher level of hypotony than in other types of glaucoma. The efficacy and safety of laser transscleral cyclophotocoagulation are currently under investigation [107, 108].

3.1.3 Surgical treatment of inflammatory (uveitic) glaucoma

- elevated IOP levels that cannot be normalized by any other treatment method;

- progressive deterioration of visual functions at an IOP level that does not exceed the upper limit of the normal statistical range, 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 pharmacotherapy);

- the impossibility of adequate medical monitoring of the glaucomatous process and patient adherence to treatment [1-3].

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

Comment:

The choice of surgical intervention method is determined by [3, 110, 109]:

- the baseline and "target" IOP levels;

- the stage of glaucoma, the rate of disease progression;

- medical history (documented duration of the disease and available data on previous drug therapy and surgery);

- characteristics of the uveal process (severity, localization, etc.);

- pathoanatomical characteristics of the anterior segment of the eye (anterior chamber depth, state of the iridocorneal angle, presence of anterior/posterior synechiae, presence of cataract).

- risk profile (only eye, profession, refraction, comorbid conditions);

- state of the lens and the need for cataract surgery;

- the patient's opinion and expectations, their expected adherence to treatment in the postoperative period;

- surgeon's preferences and experience.

Surgical interventions performed for uveitic glaucoma include:

- A16.26.070 Trabeculectomy (sinustrabeculectomy);

- A16.26.117 Non-penetrating deep sclerectomy;

- A16.26.130 Antiglaucoma drainage implantation;

- A16.26.093.002 Phacoemulsification with intraocular lens implantation.

Antiglaucoma surgery is recommended to be performed during the period of remission of the inflammatory process, at least 3 months after the end of the acute phase; however, in practice, this is not always feasible due to the need to reduce high IOP that is refractory to local and systemic hypotensive therapy [3, 111, 109].

Preoperative use of topical agents (S01BA) is intended to reduce the severity of the postoperative inflammatory response [272, 273].

Comment:

- It is believed that trabeculectomy without antimetabolites has low efficacy in uveitic glaucoma [116-120]. Off-label use may include #mitomycin as an intraoperative application on cellulose sponges of a 0.1-0.5 mg/ml solution for 1-5 minutes, #fluorouracil as subconjunctival injections into the area adjacent to the filtering bleb of 0.1 ml of a 50 mg/ml solution [1, 116, 117, 120-127, 274].

- As an adjunct to trabeculectomy, antiglaucoma drainage devices (collagen antiglaucoma drainage, resorbable antiglaucoma drainage) can be used to prevent adhesion of the superficial scleral flap to the bed and thereby maintain the intrascleral slit-like space for aqueous humor outflow [128, 129]. The choice of drainage device depends on the technical capabilities and preferences of the surgeon.

- If there is a threat of filtration failure in the early postoperative period (hypervascularization and flattening of the filtering bleb), revision (needling) of the filtering bleb and subscleral needling are advisable [130].

- Unsuccessful attempts to restore lost filtration over 4-6 months are an indication for repeat intervention [114, 130].

- Non-penetrating deep sclerectomy is not the surgery of choice in uveitic glaucoma due to the uncertain duration of its hypotensive effect. Non-penetrating deep sclerectomy may be performed if it is necessary to avoid prolonged postoperative hypotony with the development of maculopathy, the risk of which is significantly higher in uveitic glaucoma when performing full fistulizing interventions [1, 32, 116, 120].

Comment: in persistent postoperative hypotony due to excessive aqueous humor drainage, steroid therapy is discontinued faster than usual.

Comments:

- Trabeculectomy accelerates cataract progression; however, cataract surgery increases the risk of failure of a previously performed trabeculectomy [133, 75].

3.2. Treatment of neovascular glaucoma, including medical, laser, and surgical treatment

The treatment of neovascular glaucoma should be correlated with the stage of the disease and the transparency of the media. The treatment strategy focuses on combating retinal ischemia and neovascularization, as well as reducing IOP.

3.2.1. Treatment of neovascularization

Comment:

- PRP does not immediately reduce neovascularization, but has a longer-lasting therapeutic effect compared to intravitreal injections of VEGF/VEGFR (vascular endothelial growth factor) inhibitors (L01FG). An adequate volume of PRP must be chosen, from 1200 to 1600 burns per session, if 2 sessions are planned. Usually, PRP is performed in 2 or 3 sessions at five-day intervals [147];

- The combination of PRP with intravitreal administration of VEGF/VEGFR (vascular endothelial growth factor) inhibitors (L01FG) before or after laser treatment reduces the risks of hemorrhagic complications of PRP and improves the efficacy of laser treatment [148-151];

- The presence of media opacities, including cataract and vitreous hemorrhage, precludes the performance of PRP.

Comment: laser coagulating procedures in neovascular glaucoma are accompanied by a higher risk of postoperative hypotony.

3.2.2. Hypotensive treatment of neovascular glaucoma

Comments: the preferred therapy is treatment with drugs from the groups of carbonic anhydrase inhibitors (local or systemic), topical beta-blockers, and sympathomimetics for glaucoma treatment . The use of prostaglandin analogues is not recommended due to the potential potentiation of the inflammatory response and low efficacy resulting from difficult access to the uveoscleral pathway through the fibrovascular membrane [1, 154, 145, 134].

3.2.3. Laser treatment of neovascular glaucoma

Comment:

Performing transscleral laser cyclophotocoagulation in neovascular glaucoma can lead to a higher level of hypotony than observed with cyclophotocoagulation in other types of glaucoma.

Currently, a standardized protocol for transscleral laser cyclophotocoagulation in neovascular glaucoma has not been developed; the long-term hypotensive efficacy of transscleral laser cyclophotocoagulation in neovascular glaucoma is 35-65% [157].

3.2.4. Surgical treatment of neovascular glaucoma

During long-term follow-up, the majority of glaucoma patients (up to 80%) require surgical intervention regardless of prior treatment [154].

Comment: The long-term hypotensive efficacy of trabeculectomy with antimetabolites in neovascular glaucoma is 52-67% [158-160].

A history of panretinal laser photocoagulation of the retina and/or intravitreal administration of VEGF/VEGFR (vascular endothelial growth factor) inhibitors (L01FG) is necessary for the regression of new vessels and suppression of pathological neovascularization, and allows increasing the long-term hypotensive efficacy of trabeculectomy up to 80% [161, 162].

Comment: The long-term hypotensive efficacy of tube shunt implantation in neovascular glaucoma is 29-79% [165, 166]. A history of panretinal laser photocoagulation of the retina and/or intravitreal administration of VEGF/VEGFR (vascular endothelial growth factor) inhibitors (L01FG) is necessary for the regression of new vessels and suppression of pathological neovascularization, and allows increasing the long-term hypotensive efficacy of tube shunt implantation in neovascular glaucoma.

3.3. Treatment of phlebohypertensive glaucoma, including medical, laser, and surgical treatment

Treatment of SGF should include therapy for the underlying somatic nosology, which is the cause of elevated venous pressure [1, 169]. And while spontaneous carotid-cavernous fistulas may resolve spontaneously or close after diagnostic angiography, in a number of other conditions curing the root cause may prove impossible; for instance, embolization of carotid-cavernous fistulas is risky and may be unsuccessful.

3.3.1. Medical treatment of phlebohypertensive glaucoma

Comments:

The preferred hypotensive therapy in the initial stages of the disease is treatment with medicinal products from the groups of carbonic anhydrase inhibitors (topical or systemic), topical beta-blockers, and sympathomimetics for glaucoma treatment [1]. The use of prostaglandin analogs is of low efficacy in the early stages due to the normal rate of aqueous humor outflow. However, with prolonged chronic IOP elevation, when it cannot be normalized after normalizing episcleral venous pressure, a delayed impairment of aqueous humor outflow may occur, in which prescribing prostaglandin analogs will be sufficiently effective [1, 2, 172].

A number of conditions, such as orbital varices, in the initial stages are not accompanied by a significant prolonged IOP elevation and resolve with systemic conservative therapy. In such cases, if elevated ophthalmotonus is present, its temporary correction is possible using drugs from the groups of carbonic anhydrase inhibitors, topical beta-blockers, and sympathomimetics for glaucoma treatment [1, 2, 172].

3.3.2. Laser treatment of phlebohypertensive glaucoma

3.3.3. Surgical treatment of phlebohypertensive glaucoma

Comment: Trabeculectomy (sinustrabeculectomy) or implantation of antiglaucoma drains (tubular drainage devices) may be the surgery of choice. During surgical treatment of patients with SGF, hypotonia, shallow anterior chamber syndrome, choroidal detachment, and suprachoroidal hemorrhage occur more frequently; therefore, it is recommended to use systemic carbonic anhydrase inhibitors before surgery, perform preventive sclerotomy, and maintain the anterior chamber volume using viscoelastic materials. When implanting tubular drainage devices, it is recommended to implant a glaucoma valve or glaucoma shunt***, diverting aqueous humor from the anterior chamber to the equator of the eyeball) [1, 2, 3].

3.4. Treatment of phacogenic glaucomas

3.4.1. Treatment of phacotopic glaucoma, including medical, laser, and surgical treatment

Closure of the iridocorneal angle in lens subluxation or dislocation often does not respond to medical treatment.

Comment: posterior displacement of the lens without pupillary block by the vitreous body is not an emergency condition and should be considered as open-angle glaucoma. Lens removal should be performed in grade 2 and 3 subluxation or in complete lens dislocation according to the classification by N.P. Pashtayev (1986), upon the development of a pupillary block or open-angle phacotopic glaucoma [173, 174].

3.4.2. Treatment of phacomorphic glaucoma, including medical, laser, and surgical treatment

The goal of treatment for phacomorphic glaucoma is to lower IOP, open the iridocorneal angle, and prevent its re-closure [173, 174, 179, 180].

Comment:

The preferred therapy is treatment with medications from the groups of carbonic anhydrase inhibitors (topical or systemic), topical beta-blockers, and sympathomimetics for the management of glaucoma. In the event of an acute/subacute attack of secondary angle-closure glaucoma, systemic carbonic anhydrase inhibitors are preferred, as topical carbonic anhydrase inhibitors may worsen corneal edema. Prostaglandin analogs are effective only in patients with incomplete or partial angle closure. The use of miotics (from the group of antiglaucoma preparations and miotics, S01E) in the presence of a pupillary block may be accompanied by a certain hypotensive effect due to pulling the peripheral part of the iris away from the trabecular meshwork; however, in the presence of ciliary block or pronounced lens swelling, the use of pilocarpine** can lead to contraction of the circular portion of the ciliary muscle, which may result in anterior displacement of the lens and further angle closure [173, 174, 183, 175].

Prostaglandin analogs are effective in patients with partial angle closure [175]. Secondary angle closure due to drug-induced lens swelling generally responds to medical therapy and rarely requires surgical intervention. Lens swelling may resolve spontaneously after discontinuation of the offending drugs. However, in many cases, a filtering procedure and cataract extraction are necessary for long-term IOP control. Performing trabeculectomy without cataract surgery increases the risk of a flat anterior chamber and aqueous misdirection [170, 173, 175, 177].

Comment: if, after iridotomy, the IOP has decreased and gonioscopy shows that the iridocorneal angle has widened, pupillary block was likely the primary mechanism causing the IOP elevation. Residual angle closure after laser iridotomy can be eliminated using argon laser peripheral iridoplasty. If the IOP remains high and the angle is closed, the cause is lens swelling or anterior displacement, and the patient requires lens extraction.

Comment: cataract surgery in patients with phacomorphic glaucoma presents certain challenges. Corneal edema due to high IOP reduces the surgical view. A shallow anterior chamber and tension of the lens capsule can pose technical difficulties during capsulorhexis and be accompanied by trauma to the corneal endothelium. High preoperative IOP may increase the likelihood of choroidal hemorrhage during or after surgery. Extraction of a clear lens may be necessary in eyes with recurrent attacks of secondary angle closure or when medical and laser therapy fails [186–188].

3.4.3. Treatment of phacolytic glaucoma, including medical and surgical treatment

Comment: preferred preoperative therapy is treatment with medications from the groups of carbonic anhydrase inhibitors (topical or systemic), topical beta-blockers, and sympathomimetics for the management of glaucoma, as well as the use of topical corticosteroids (S01BA) [203].

Comment: if lens remnants persist, topical corticosteroid therapy will not provide a significant anti-inflammatory effect in phacoanaphylactic uveitis and may lead to a steroid-induced increase in IOP [197, 198].

Comment: therapy with topical corticosteroids (S01BA) is also recommended to control the inflammatory response. If there is a significant amount of cortical material, its surgical removal is necessary [199–202].

3.5. Treatment of drug-induced (steroid) glaucoma, including medical, laser, and surgical treatment

The management of clinically significant IOP elevation induced by corticosteroids and associated glaucoma is similar to the treatment of primary open-angle glaucoma or ocular hypertension.

Comment:

In patients with deposited intraocular corticosteroids (S01BA) who do not respond to hypotensive therapy, surgical removal of the deposited implant is recommended. In patients with Cushing's syndrome, normalization of IOP is usually observed after excision of the corticosteroid-producing tumor or hyperplastic tissue. If topical corticosteroid therapy (S01BA) is necessary, it can be switched to nonsteroidal anti-inflammatory drugs. Transitioning from topical corticosteroid therapy (S01BA) to systemic therapy (H02A) may also reduce the ocular hypertensive effect. Patients requiring systemic corticosteroid therapy can be switched to immunosuppressive therapy [1, 212, 207, 213, 209, 218, 216].

Comments: Preferred initial therapy consists of non-selective topical beta-blockers and carbonic anhydrase inhibitors [1, 207, 216].

The use of prostaglandin analogs has demonstrated high hypotensive efficacy in steroid glaucoma; however, their use may be limited by the presence of a local inflammatory disease that is the cause of corticosteroid therapy [1].

After initiating hypotensive therapy, tonometry should be performed every 2 weeks for the first month, monthly for 2–3 months, and every 3–6 months thereafter during long-term corticosteroid therapy. It is important to note that patients receiving a single intravitreal dose of triamcinolone should be monitored for several months, as some patients experience a significant increase in IOP more than 3 months after the injection [219].

3.6. Treatment of post-traumatic glaucoma

3.6.1. Treatment of post-traumatic glaucoma secondary to blunt eye trauma in the early period, including medical, laser, and surgical treatment

Medical treatment aims to normalize IOP, prevent secondary hemorrhage, and reduce the inflammatory response.

Comment:

Preferred initial therapy consists of topical beta-blockers and carbonic anhydrase inhibitors [232].

The use of miotics (from the group of antiglaucoma preparations and miotics, S01E) and prostaglandin analogues is not recommended due to the potential exacerbation of the inflammatory response.

Systemic carbonic anhydrase inhibitors are an alternative to topical hypotensive therapy in cases of uncontrolled IOP.

The use of mydriatic and cycloplegic agents (S01F) is recommended to relieve pain and prevent the formation of posterior synechiae [232, 238, 239].

The use of topical corticosteroids (S01BA) and non-steroidal anti-inflammatory drugs (S01BC) can reduce the risk of recurrent hemorrhage, the severity of uveitis, and the formation of posterior synechiae [240, 232, 235, 241, 242, 239].

3.6.2. Long-term management of post-traumatic glaucoma secondary to blunt eye trauma, including medical, laser, and surgical treatment

Comment:

Non-selective topical beta-blockers, carbonic anhydrase inhibitors, and sympathomimetics are the preferred starting therapy for glaucoma. The use of miotics (from the group of antiglaucoma preparations and miotics, S01E) and prostaglandin analogues is not recommended due to the potential exacerbation of the inflammatory response. Systemic carbonic anhydrase inhibitors are an alternative to topical hypotensive therapy in cases of uncontrolled IOP [1-3].

3.6.3. Management of post-traumatic glaucoma secondary to open globe injury, including medical, laser, and surgical treatment

Comment: postoperative therapy involves the administration of topical antimicrobials (S01A), mydriatics and cycloplegics (S01F), corticosteroids (S01BA), and non-steroidal anti-inflammatory drugs (S01BC) [263, 265, 225, 264].

The principles of surgical treatment for open globe injuries aimed at normalizing IOP include: removal of a swelling traumatic cataract—performed during an acute attack of phacomorphic ocular hypertension refractory to conservative management; removal of the lens from the anterior chamber—performed in case of lens dislocation into the anterior chamber to prevent an acute attack of secondary ocular hypertension and loss of corneal endothelial cells; anterior chamber paracentesis—performed in total hyphema to evacuate blood and blood clots for the prevention or treatment of an acute attack of ocular hypertension. If hyphema recurs during this procedure, completion of surgery with anterior chamber tamponade using air or a viscoelastic agent may be used to prevent blood staining of the cornea (corneal blood staining).

Comment: non-selective topical beta-blockers, carbonic anhydrase inhibitors, and sympathomimetics are the preferred therapy. The use of miotics (from clones of antiglaucoma preparations and miotics, S01E) and prostaglandin analogues is not recommended due to the potential exacerbation of the inflammatory response. Systemic carbonic anhydrase inhibitors are an alternative to topical hypotensive therapy in cases of uncontrolled IOP [265, 225, 233].

3.7. Diet therapy, analgesia, and other treatment methods

There is no special diet for secondary glaucoma. Anesthesia methods are applied at the stage of laser or surgical treatment of secondary glaucoma and are not used as an independent therapy.

Alternative treatment strategies for glaucomatous optic neuropathy (neuroprotection) are a subject of research and discussion [266]. 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. No studies have been conducted on the feasibility of neuroprotection in uveitic glaucoma.

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.

Comment: The frequency of ophthalmologic examinations and the scope of examinations and manipulations after surgery are determined individually. Rehabilitation improves vision-related quality of life in patients with secondary glaucoma. A multidisciplinary approach increases the efficacy of treatment and rehabilitation in these patients.

5. Prevention and Dispensary Observation

Comments: in patients receiving medical therapy, the efficacy and any side effects of the treatment are evaluated; changes and new prescriptions made by other specialists for systemic indications that may affect glaucoma treatment are identified; compliance with the regimen of hypotensive glaucoma therapy is monitored. In patients after surgical interventions, the functional and hypotensive effects of the surgery are assessed, postoperative treatment (antimicrobial, anti-inflammatory, reparative, etc.) is adjusted, and other ophthalmological pathology is monitored and treated. In patients with a filtering bleb, its height, width, presence of wall thinning, vascularization, encapsulation, active filtration, and infection must be evaluated.

Each patient visit is accompanied by an assessment of the patient's subjective well-being, visual functions (difficulties with driving, impaired dark adaptation, contrast sensitivity problems, small print reading, and distance estimation), quality of life, and treatment adherence.

The frequency of examinations depends on the etiology, severity, and potential course of the systemic inflammatory process or trauma, the presence and risk of complications, and the ongoing treatment. After achieving the target IOP, an ophthalmological examination is performed 1 time per month for 3 months, then, if the condition is stable, 1 time every 3 months for a year, and thereafter every 6 months. After discontinuing systemic therapy, monitoring should be performed at least 1 time every 3 months for at least 3 years, as most recurrences of the inflammatory process are observed during this period.

6. Organization of Medical Care

Primary specialized health care for secondary glaucoma 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 hospitalization of patients with secondary glaucoma in a medical organization are:

Planned (elective):

• the need for surgical treatment of secondary glaucoma and/or laser treatment and/or medical treatment to compensate for elevated IOP when treatment cannot be performed in outpatient or day-care settings;

• 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 secondary glaucoma and/or laser treatment and/or medical treatment in the presence of a high ("c") level of intraocular pressure and the inability to perform treatment in outpatient or day-care settings when there is a threat of rapid loss of visual functions.

Indications for patient discharge from a medical organization:

• 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 prognosis is largely determined by the etiopathogenetic form of the disease. Predictors of a good functional prognosis are a mild course of the inflammatory process in the eye, as well as the timely administration of local and systemic therapy.

Predictors of a poor functional prognosis are: a severe course or persistent activity and the development of uveitis complications, resistance to ongoing therapy, and a prolonged course of the disease.

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 assessment criteria for primary health care provided to adults with secondary glaucoma

Table 10.2 – Quality assessment criteria for specialized medical care provided to adults with secondary glaucoma

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. 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

4. 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

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

6. 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

7. 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

8. 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

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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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 P1 – Scale for assessing levels of evidence certainty.

Table P2 – Scale for assessing grades of recommendation (GoR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation 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 for 2024. URL: https://mkb-10.com/updates/ (accessed August 29, 2022).

5. Federal Law "On the Basics of Protecting the Health of Citizens in the Russian Federation" (as amended on August 8, 2024) dated November 21, 2011, No. 323-FZ. (In Russ.)

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 the Approval of the List of Medical Devices Implanted into the Human Body Upon Provision of Medical Care, and the List of Medical Devices Dispensed by Prescription upon Provision of a Set of Social Services" (as amended on February 20, 2024). 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 the Approval of the List of Vital and Essential Medicines for Medical Use for 2020, the List of Medicines for Medical Use, Including Medicines 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 Assortment of Medicines Necessary for the Provision of Medical Care" (as amended on April 16, 2024). 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" (as amended on March 23, 2024). Resolution of the Government of the Russian Federation No. 2353 dated December 28, 2023.

21. "On the Approval of the Procedure for Conducting Dispensary Observation of Adults" (as amended on February 28, 2024). 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 Indications (Characteristics) of the Medicinal Product Not Specified in its Instructions for Use" (as amended on August 1, 2023). Decree of the Government of the Russian Federation No. 1180-r dated May 16, 2022.

23. "On the Approval of the Procedure for Conducting Preventive Medical Examinations and Health Check-ups of Certain Groups of the Adult Population" (as amended by Order of the Ministry of Health of the Russian Federation No. 44n dated February 1, 2022) (as amended on July 19, 2024). Order of the Ministry of Health of the Russian Federation No. 404n dated April 27, 2021.

24. "On the 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 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.

Appendix B. Physician Action Algorithms

Fig. Algorithm for managing a patient with primary open-angle glaucoma (Cited from: National Guidelines for Glaucoma for Practicing Physicians // Moscow: "GEOTAR-Media"; 2019: 384)

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, the main manifestation of which is an increase in intraocular pressure, leading to progressive damage to the optic nerve and, consequently, the appearance of 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 the early stages. Therefore, regardless of whether you have complaints or not, you must undergo an annual preventive examination by an ophthalmologist as part of routine health checks, with obligatory measurement of IOP levels 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 stabilizes the process or slows down its progression while maintaining an acceptable quality of life. If you are diagnosed with GLAUCOMA, the doctor usually prescribes IOP-lowering eye drops. If medical treatment and adherence to the prescribed regimen do not lower the eye pressure or lower it insufficiently, laser or surgical intervention will be offered. The choice of GLAUCOMA treatment method is determined individually, depending on the course of the disease, 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. Disk Damage Likelihood Scale (DDLS) for assessing and sketching optic disc changes during the monitoring of glaucoma patients

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.