Congenital glaucoma: clinical guidelines

List of Abbreviations

CG – congenital glaucoma

IOP – intraocular pressure

AQH – aqueous humor

ONH – optic nerve head

VEP – visual evoked potentials

ICD-10 – International Classification of Diseases 10th Revision

NRR – neuroretinal rim

OCT – optical coherence tomography

VF – visual field

APLD – anteroposterior linear dimension of the eyeball

RNFL – retinal nerve fiber layer

ACA – anterior chamber angle

CCDS – ciliochoroidal detachment

TENS – transcutaneous electrical nerve stimulation

ERG – electroretinography

EP – electrophysiological studies

C/D – cup-to-disc ratio

AD – autosomal dominant inheritance pattern

AR – autosomal recessive inheritance pattern

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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 (IOP) – the pressure of fluid inside the eye resulting from the balance between aqueous humor production, trabecular and uveoscleral outflow, and episcleral venous pressure, which maintains the eye's shape and ensures a constant supply of circulating nutrients and normal trophism of intraocular tissues.

Congenital glaucoma (CG) – a group of heterogeneous conditions characterized by IOP elevation above the tolerable level in the first months/years of life due to embryogenesis disorders (anomalies of the iridocorneal angle and drainage system), accompanied by corneal opacity, deformation and enlargement of the eye in the first years of life, optic neuropathy, and subsequent optic atrophy and decreased retinal electrogenesis (in progressive cases).

Aniridic keratopathy – a peculiar disorder of corneal transparency arising from primary limbal stem cell deficiency and progressively spreading from the periphery to the center of the cornea as a vascularized pannus (disorder of normal corneal development and regeneration).

Hydrophthalmos ("watery eye") or buphthalmos ("ox eye") – a classic form of congenital glaucoma accompanied by changes in the anterior chamber angle (ACA).

Glaucomatous optic neuropathy (GON) – pathology of the optic nerve caused by elevated IOP, 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.

Goniodysgenesis – congenital anomalies of the ACA and drainage system of the eye resulting from delayed development and differentiation of these structures.

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

Goniotomy – a surgical intervention in which tissues obstructing aqueous humor outflow are removed under visual control (using a goniolens) within the ACA area to restore the anterior outflow pathway.

Goniosynechia – an adhesion in the iridocorneal angle of the eye between the iris root and the cornea.

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

Neuroretinal rim (NRR) – the area between the optic disc margin and the cup margin where the bulk of retinal ganglion cell axons is projected.

Needling – a surgical technique for mechanical revision of a filtration bleb using a hypodermic needle on a syringe.

Optical coherence tomography (OCT) – a non-invasive, non-contact diagnostic 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 levels in the absence of characteristic glaucomatous changes in the optic disc, RNFL, and visual field defects.

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

Tonometry – an instrumental method for measuring IOP levels, determined by analyzing eye deformation data using a tonometer and expressed in millimeters of mercury (mmHg).

Perimetry – a method for examining the visual field (VF).

Visual field – the set of spatial points simultaneously visible to the eye with a fixed gaze.

Refractory glaucoma – a severe, stubborn form of the disease characterized by resistance and often unresponsiveness to standard treatments.

Sinulectomy / trabeculectomy – a surgical intervention aimed at creating an additional outflow pathway for aqueous humor from the eyeball directed beneath the sclera and conjunctiva.

Scotoma – a visual field defect independent of peripheral boundaries.

Retinal nerve fiber layer (RNFL) – the retinal layer consisting of retinal ganglion cell axons.

Stabilized and unstabilized glaucoma – terms denoting the absence or presence of negative dynamics in the condition of the optic disc and visual field, anteroposterior linear dimension (APLD), and patient refraction during repeat examinations. When evaluating the dynamics of the glaucomatous process, the IOP level and its compliance with the "target" value are also taken into account.

Standard automated perimetry – automated threshold static perimetry evaluating the visual field using a white stimulus on a white background.

Anterior chamber angle (ACA, iridocorneal angle) – the space between the corneoscleral region and the anterior surface of the iris.

"Target" intraocular pressure – the maximum permissible pressure at which glaucoma does not progress: visual functions do not decline, GON does not progress, and the eyeball does not stretch.

Optic disc cupping (excavation) – a depression of varying shape and size in the optic disc, normally not exceeding 0.3 of the disc diameter (physiological cup).

Electrophysiological studies – methods for investigating the function of the optic nerve, retina, and visual areas in the cerebral cortex.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Congenital glaucoma (CG) is a group of heterogeneous conditions characterized by IOP elevation above the tolerable level in the first months/years of life due to embryogenesis disorders (anomalies of the iridocorneal angle and drainage system), accompanied by corneal opacity, deformation and enlargement of the eye in the first years of life, optic neuropathy, and subsequent optic atrophy and decreased retinal electrogenesis (in progressive cases) [1-5].

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

Most authors lean toward the multifactorial nature of CG. CG may occur either as a consequence of hereditary anomalies of the visual organ or as a result of exposure of the embryo or fetus to various intrauterine pathological agents between 7 and 36 weeks of gestation.

Primary CG is hereditary in 15-40% of cases, featuring an autosomal recessive inheritance pattern [Cyp1B1 (2p21), GLC3B (1p36), and GLC3C (14q24.3)] or an autosomal dominant inheritance pattern [GLC1A TIGR, MYOC], with variable penetrance from 40 to 100%. Numerous mutations in the Cyp1B1 gene have been identified, including missense mutations, nonsense mutations, frameshift mutations, deletions, and insertions with significant heterogeneity. Genetic assessment of pediatric glaucoma is particularly important in types of glaucoma with genotype-phenotype correlations (Table 1) [4,7,10,11].

In most cases, the etiology of CG involves multifactorial inheritance combined with non-genetic factors – maternal infectious diseases during pregnancy (influenza, mumps, poliomyelitis, toxoplasmosis), viral diseases (rubella, cytomegalovirus), endocrine and metabolic disorders, intoxications, drug administration, dietary factors (hypo- and avitaminosis), and environmental factors (physical, chemical).

Table 1. Glaucoma-associated syndromes and associated genes

Etiological diagnosis of congenital glaucoma is based on a thorough history-taking (condition and diseases of the pregnant woman) and the results of immunological, virological, and genetic studies.

1.3 Epidemiology of the Disease or Condition

Congenital eye diseases are currently a major cause of blindness and low vision in children [3-6,12-18]. Congenital glaucoma is relatively rare—1 case per 10,000–70,000 newborns, but its specific weight among the causes of blindness is up to 11%. In 60% of children, congenital glaucoma manifests in the first 6 months, and in 80% in the first year of life. In 75% of children, the disease is bilateral. Boys are affected more often. The success of treatment in children with congenital glaucoma largely depends on early diagnosis of the disease. If treatment is not started in a timely manner, the disease rapidly progresses and leads to irreversible changes in all structures of the eyeball. The complexity of diagnosing such diseases is determined by the clinical diversity and age-specific behavioral characteristics of the child.

1.4 Features of Coding the Disease or Condition

Q 15.0. Congenital glaucoma

1.5 Classification of the disease or condition

Classifications of congenital glaucoma are quite numerous, based on etiopathogenetic features, severity of clinical manifestations, and timing of the glaucomatous process. For modern nomenclature unification and systematic approach, it is advisable to use the international classification of childhood glaucomas agreed upon in 2013 by the World Glaucoma Association [16,19], according to which primary childhood glaucoma is subdivided into primary congenital glaucoma (with congenital anomalies of the anterior chamber angle structures) and juvenile open-angle glaucoma (manifesting between 3 and 35 years of age). Primary congenital glaucoma is most often divided by manifestation timing into neonatal (neonatal glaucoma)—from birth to 1 month of life, infantile—from 1 month to 2 years, and late-onset glaucoma—older than 2 years. Secondary childhood glaucoma is divided into 4 groups: associated with congenital anomalies of the eyeball (such as Axenfeld-Rieger anomaly, Peters anomaly, aniridia, lens ectopia, primary congenital glaucoma with systemic findings, etc.); secondary glaucoma with congenital systemic diseases or syndromes (Recklinghausen, Marfan, Weill-Marchesani, Stickler, Lowe syndromes, homocystinuria, mucopolysaccharidosis, juvenile xanthogranuloma, etc.); and secondary glaucoma associated with congenital infections, intoxications (congenital rubella, herpetic infection) and acquired conditions (consequences of trauma, uveitis, retinopathy of prematurity, cataract removal separately, tumor).

Russian classifications of the disease in question are also known, including those by T.I. Eroshevsky and B.A. Tokareva (1971), E.I. Kovalevsky (1969; 1986), E.S. Avetisov et al. (1987), E.G. Sidorov and M.G. Mirzoyants (1991), E.I. Sidorenko (2000), E.E. Somov (1992, 2016) and others. The clinical classification proposed by E.S. Avetisov, E.I. Kovalevsky, and A.V. Khvatova in 1987 [1] has become the most widespread in our country. According to it, the main criterion for the progression of the glaucomatous process is the stage of the disease, which, unlike glaucoma in adult patients, is determined not by perimetry data, but by the increase in corneal diameter and axial length of children's eyes, considering that in the majority of children, congenital glaucoma proceeds with an increase in these parameters—"stretching" of the cornea and eyeball, especially in the first 3 years of life (Table 2)

Table 2. Classification of congenital glaucoma (Avetisov E.S., Kovalevsky E.I., Khvatova A.V., 1987)

*- refers to tonometric IOP (Pt)

Somov E.E. (1992) [17-18] proposed, in order to assess the severity of the process, in addition to taking into account the corneal diameter, to add the size of the optic disc cupping and the state of visual functions; therefore, the United Clinical-Pathogenetic Classification of Congenital Glaucoma by Stages (Table 3) [20] remains very much in demand, although in practice it is often difficult to assign congenital glaucoma to a particular stage due to the mismatch of various indicators and difficulties in assessing visual functions.

Table 3. United clinical-pathogenetic classification of congenital glaucoma by stages (Katargina L.A. et al., 2016)

* When perimetry is unfeasible.

Currently, due to the development of modern highly informative imaging methods and the emergence of new data, approaches and diagnostic criteria are being improved.

1.6 Clinical presentation of the disease or condition

Clinical forms of congenital glaucoma

Congenital glaucoma is considered as a group of diseases, each of which is characterized by peculiar clinical and pathohistological manifestations [1-6,17-20].

There are 3 forms of congenital glaucoma distinguished:

Form I – simple CG (hydrophthalmos proper);

Form II – glaucoma combined with developmental anomalies of the anterior segment of the eye (microphthalmos, microcornea, Rieger anomaly/syndrome, Axenfeld anomaly, Peters anomaly, sclerocornea, aniridia, essential mesodermal atrophy of the iris, iris coloboma, Frank-Kamenetsky syndrome, Marfan syndrome, Marchesani syndrome);

Form III – glaucoma combined with phakomatoses, angiomatoses (Sturge-Weber-Krabbe syndrome and Recklinghausen's disease).

The main clinical signs of CG (classic course of hydrophthalmos) are:

1. increase in IOP above the tolerant level;

2. increase in the sagittal axis of the eyeball compared to age norms;

3. increase in corneal and limbal diameter;

4. development of corneal edema and opacity of varying degrees, ruptures and cracks of Descemet's membrane, endothelial defects;

5. deepening of the anterior chamber (>3–3.5 mm);

6. development of subatrophy and atrophy of the iris, iridodonesis;

7. development of glaucomatous optic nerve atrophy (with excavation);

8. formation of scleral thinning, bulging as staphylomas;

An important diagnostic sign is also the asymmetry in the severity of the listed signs (sagittal size length, corneal diameter, increased refraction, optic disc excavation).

Complaints are associated with the features of the clinical picture (in young children – reported by parents):

1. photophobia, lacrimation, blepharospasm (corneal syndrome);

2. increase in eye and cornea size;

3. periodic corneal clouding (edema phenomena), followed by persistent corneal opacity;

4. decreased vision (can be detected in older children);

5. when eye pain occurs, the child's behavior changes (sleeps poorly, is cranky, restless, loses appetite).

There are differences in the timing of the appearance of clinical signs in various forms of glaucoma. In Form I, the disease manifests at an early age up to 1 year (80% of cases), while in Forms II and III, it manifests at a later stage. The stage of the disease is determined by the "worst" clinical sign at the time of the child's examination (Tab. 3), although not all clinical and morphological signs of the disease always precisely correlate with its stage. Optical coherence tomography (OCT) of the retina and optic nerve (thinning of the peripapillary retinal nerve fiber layer, reduction in the width of the neuroretinal rim, and thickness of the ganglion cell layer in the macula) reliably assesses the presence and severity of glaucoma progression.

Ocular pathology associated with congenital glaucoma

CG can be one of the manifestations of a number of syndromes and systemic diseases (Forms II and III) [1-6,11,17,20,21-23,24]. In Forms II and III of congenital glaucoma, ophthalmotonus typically increases at an older age (in the second decade of life). Due to the increased strength characteristics of the eye tunics by this age, the clinical picture in these forms of glaucoma differs from classic hydrophthalmos (stretching of the eyeball, corneal syndrome), which is often the cause of delayed diagnosis of the disease.

At the same time, the development of glaucomatous changes in the optic nerve with a characteristic decrease in visual functions is also typical. At the same time, the absence of complaints from the child about vision loss does not always contribute to timely diagnosis and treatment.

Below are the developmental anomalies and syndromes most frequently encountered by clinicians.

Congenital aniridia is a rare genetically mediated panocular pathology. The most striking symptom of the disease is the congenital absence of the iris or its hypoplasia. Other frequently encountered manifestations include keratopathy caused by congenital limbal stem cell deficiency, cataract, glaucoma, hypoplasia of the fovea centralis and optic nerve, and nystagmus. In 75% of cases, an autosomal dominant inheritance pattern with high penetrance is observed.

Mutations of the PAX6 gene on the short arm of the 11th chromosome (locus 11p13) are responsible for "classic" congenital aniridia (nonsyndromic isolated with dominant inheritance) and familial aniridia. PAX6-associated aniridia is termed "aniridia syndrome" or PAX6 syndrome. Elevated IOP is noted in 50–70% of children. In addition, aniridia may be accompanied by pathology of other organs and systems, such as the nervous, urogenital, endocrine, and digestive systems, and manifest as part of syndromes. Congenital aniridia can be nonsyndromic (75% of cases) and syndromic (20%), including WAGR syndrome (<10%), which, besides aniridia, includes Wilms tumor developing between 1 and 5 years of age, urogenital malformations, developmental delay, and mental retardation. Gillespie syndrome is a genetic disorder characterized by aniridia, cerebellar ataxia, and intellectual disability, which can be suspected in an infant during the first year of life based on the combination of aniridia and pronounced muscular hypotonia. Considering the risk of life-threatening conditions (renal tumors), all patients with aniridia are recommended to undergo genetic testing to rule out WAGR syndrome.

Congenital glaucoma may develop when goniodysgenesis is combined with microphthalmos, microcornea, and microspherophakia.

Axenfeld-Rieger anomalies, Axenfeld-Rieger syndrome (Rieger syndrome) refer to hereditary bilateral pathology of the visual organ with an autosomal dominant inheritance pattern. Pathology of the nervous and skeletal systems, as well as bilateral eye involvement, occur in 50% of cases. Familial cases are not uncommon.

There are 3 degrees of peripheral goniodysgenesis:

Grade 1 – "posterior embryotoxon" – well-noticeable prominence and anterior displacement of Schwalbe's anterior ring (a distinct whitish line is visible on the corneal periphery along the entire circumference or part of the cornea).

Grade 2 – "Axenfeld anomaly" – the posterior embryotoxon is fused with processes or strands of the mesodermal iris leaf extending from the ciliary and sometimes pupillary zone to Schwalbe's ring.

Grade 3 – Axenfeld-Rieger anomaly, in which the symptom complex of Axenfeld anomaly is combined with hypoplasia of the stroma and even iris pigment, up to full-thickness holes in the iris. There are deformations, ectopic pupils, eversion of the pigment epithelium, and possible changes in the cornea (megalocornea or microcornea) and choroid, cataract, and strabismus.

When ocular manifestations of Axenfeld-Rieger anomaly are combined with various systemic changes (midface hypoplasia, telecanthus with a broad, flat nasal bridge, reduced number and size of teeth, umbilical hernia, congenital heart defects, conductive hearing loss, mental retardation, cerebellar hypoplasia), the symptom complex is verified as "Rieger syndrome." Approximately 60% of patients with this syndrome develop glaucoma.

Peters anomaly is a rare genetic disorder with an autosomal dominant or recessive inheritance pattern, though sporadic cases are more common. Mutations have been found in the PAX6, RIEG1, PITX2, and FOXE3 genes. The anomaly represents central corneal dysgenesis – a central corneal opacity with a defect in Descemet's membrane fused with the iris (often with its pupillary margin, involving the stroma of Descemet's membrane and endothelium [Type 1]) and frequent fusion with and opacity of the lens (Type 2). In 80% of cases, eye involvement is bilateral. Peters anomaly is frequently combined with microphthalmos, corneal flattening, sclerocornea, corectopia, iris hypoplasia, and polar cataract. In 30–70% of cases, congenital glaucoma develops due to abnormal structure of the iridocorneal angle. It is more commonly accompanied by an IOP rise after 6–7 years of age (there are cases of early glaucoma manifestation). Peters-plus syndrome (Type 3) is a combination of the ocular manifestations of Peters syndrome with heart defects, CNS pathology, urogenital system pathology, shortening of the trunk and limbs, psychomotor development delay, etc.

Congenital uveal ectropion is a rare, non-progressive anomaly characterized by the presence of a layer of iris pigment epithelium on its anterior surface, anterior insertion of the iris, and dysgenesis of the iridocorneal angle drainage zone. The process is characterized by unilaterality and is rarely inherited.

Frank-Kamenetsky syndrome is a hereditary X-linked recessive pathology characterized by bilateral hypoplasia or aplasia of the iris and the onset of glaucoma. A distinctive feature is the dichromatic appearance of the iris: its pupillary zone is light, while the ciliary zone is dark due to more pronounced stromal atrophy, most often having a chocolate-brown color owing to the exposure of the pigment epithelium. Simultaneously, pupillary anomalies (displacement, irregular shape, absence or hypertrophy of the pupillary ruff), full-thickness iris defects, iridodiastasis, and iridodialysis may be observed. All patients exhibit goniodysgenesis.

Despite the congenital anomaly of the iridocorneal angle, a trend towards increased IOP is more frequently observed in the 2nd–3rd decades of life. Early IOP elevation typically occurs in boys when pronounced goniodysgenesis is combined with megalocornea. At the same time, the process of iris destruction continues into the postoperative period, even upon stabilization of IOP and visual functions.

Marfan syndrome is characterized by lens ectopia (upward and outward), tall stature, joint hypermobility, brachydactyly, scoliosis, severe congenital anomalies, and aortic coarctation. Lens dislocation, as well as the presence of goniodysgenesis, can cause disturbances in ocular hydrodynamics and manifest the glaucomatous process in such patients.

Marchesani syndrome – microspherophakia, anterior lens dislocation, iris sphincter bulging into the anterior chamber, short stature, joint stiffness, mild heart defects. Glaucoma is infrequent. In some cases, IOP elevation is associated with iridocorneal angle dysgenesis, and in certain patients, with pupillary block caused by the spherical lens.

Homocystinuria. The general external manifestations of the disease are similar to those in Marfan syndrome. Unlike the latter, homocystinuria is inherited in an autosomal recessive manner and is often accompanied by intellectual disability. The disturbance of homocysteine metabolism is a consequence of an enzyme defect. Lens dislocation and glaucoma are observed more frequently than in Marfan syndrome. The disease may be complicated by retinal detachment.

Among phakomatoses and angiomatoses accompanied by glaucoma, Sturge-Weber-Krabbe syndrome and von Recklinghausen disease are most commonly encountered.

Sturge-Weber-Krabbe syndrome (encephalotrigeminal angiomatosis, encephalofacial angiomatosis) is a congenital angiomatosis of the nervous system manifested by a facial port-wine stain, seizures, and intracranial calcifications. The prevalence of the disease is 1 case per 100,000 population. It occurs predominantly sporadically. Multiple angiomas (angiomatosis) are observed on the facial skin, usually along the course of the trigeminal or facial nerve. Sometimes the dilated vessels take on the appearance of a red-blue vascular-cavernous tumor. In the brain, angiomatosis affects the pia mater on the same side, predominantly in the occipital and occipitoparietal regions, usually unilaterally. From birth, patients have one large or several confluent blue-red spots on the face ("port-wine stains"). They can also be present on the trunk and limbs. Angiomatous changes sometimes extend to the oral cavity, nose, and pharynx. In some patients, this leads to intestinal bleeding. In the first months of life, patients exhibit seizure attacks. They are most often focal, typically on the side contralateral to the vascular lesion. Patients frequently develop paralysis and paresis, usually of a hemitype. Approximately half of the patients exhibit intellectual disability (usually profound). Changes in the organ of vision are characterized by choroidal hemangioma, colobomas, and iris heterochromia. Congenital heart defects, skull and facial dysplasias are sometimes detected. MRI in children reveals hemispheric atrophy with enlargement of the subarachnoid spaces and lateral ventricles, while computed tomography reveals "railroad track" calcifications. All changes are frequently detected after 4–5 years of age. The incidence of glaucoma in this syndrome reaches 60%. Since cases of bilateral glaucoma have been described in patients with Sturge-Weber syndrome with unilateral facial capillary hemangioma, dynamic monitoring of both eyes in such children is recommended.

von Recklinghausen disease (neurofibromatosis) is classified among phakomatoses. It represents a neuroectodermal dysplasia characterized by the proliferation of peripheral nerve elements with the formation of tumor-like structures. The disease is inherited in an autosomal dominant manner. The main lesions are localized in the skin, peripheral, and central nervous systems. In ophthalmological practice, one has to deal with lesions of the eyelids, conjunctiva, orbit, cornea, uvea, retina, and optic nerve. The upper eyelid is particularly frequently affected, where a plexiform fibroma develops, often extending into the temporal region. The process typically involves one side, with bilateral changes being less common. Neurofibromatotic nodules or diffuse infiltration may occur on the conjunctiva, episclera, cornea, and iris. Significant thickening of the choroid and ciliary body due to tissue proliferation is sometimes noted; meningiomas and gliomas have been described in the optic nerve, and neurofibromas in the orbit. Glaucoma develops rarely, is often combined with upper eyelid lesions, and is usually (though not always) unilateral. The cause of pressure elevation is goniodysgenesis, anomalies of the scleral venous sinus, or pre-trabecular blockade by neurofibromatotic tissue. In some cases, angle-closure glaucoma develops, caused by anterior displacement of the iridolenticular diaphragm due to thickening of the choroid and ciliary body.

Congenital glaucoma is also identified in rarer syndromes:

- Rothmund-Thomson syndrome, characterized by infantile poikiloderma, hypogonadism, and skeletal lesions; Larsen syndrome combined with multiple joint dislocations and short stature;

- Stickler syndrome, manifested by progressive arthropathy, craniofacial and palatal developmental defects, sensorineural hearing loss, progressive myopia, vitreoretinal degeneration, and retinal detachment;

- Rubinstein-Taybi syndrome, the manifestations of which include epicanthus, tear duct pathology, ptosis, strabismus, megalocornea, microphthalmia, iris and optic disc colobomas, and cataract;

- Pierre Robin sequence, characterized by micrognathia (underdevelopment and posterior displacement of the mandible), cleft soft/hard palate, and glossoptosis. A polymorphic pathology of the organ of vision is noted in the form of congenital glaucoma, buphthalmos, megalocornea, microphthalmia, congenital cataract, high myopia, and retinal detachment.

When congenital glaucoma is diagnosed late in children with the listed syndromes, there is a high risk of losing visual functions.

2. Diagnostics, medical indications and contraindications for diagnostic methods

The diagnosis of congenital glaucoma is established based on anamnestic data and clinical examination results, which include a set of standard and highly informative additional research methods (Table 4).

Table 4. Examination methods

In children with early-onset glaucoma and the development of the clinical picture of classic hydrophthalmos, diagnosing glaucoma does not present particular difficulties. With later onset, it may present difficulties due to the absence or weak expression of characteristic symptoms, as well as the protracted development of the pathological process over time.

Early diagnosis aims to detect signs of eye stretching caused by IOP elevation, as well as initial manifestations of atrophic processes in the optic nerve head and the retinal nerve fiber layer. Establishing an early diagnosis of congenital glaucoma should be based on a comprehensive analysis of data, taking into account the asymmetric nature of the clinical and morphofunctional characteristics of fellow eyes.

2.1 Complaints and Anamnesis

• Taking the anamnesis and complaints is recommended for all patients with congenital glaucoma and suspected of having this condition [1-6,17-18,20].

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

Comments: All children should be examined by a pediatrician, and if necessary, by a neurologist, cardiologist, geneticist, and other specialists for the presence of somatic pathology. Eliciting information about the early postnatal period—the frequency and severity of infectious diseases, chronic pathologies, and allergic reactions. Identifying possible causes and predispositions for the onset of the disease (intrauterine infections, nutritional factors, etc.) by reviewing the mothers' health status and obstetric-gynecological history.

An important aspect of interviewing parents is a targeted analysis of the timing of the onset of glaucoma signs, their interdependency, and their severity in fellow eyes.

2.2 Physical Examination

• Physical examination is uninformative. General propaedeutic principles of patient examination must be followed. It is recommended to refer children with congenital glaucoma who have concurrent systemic conditions and risk factors for systemic complications for a preventive appointment (examination, consultation) with a pediatrician prior to surgical treatment in order to identify potential contraindications to this type of treatment or minimize the risk of complications [1-6,17-18,20].

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

2.3 Laboratory Diagnostics

Laboratory diagnostics for glaucoma are currently of little applicability in clinical practice—scientific research is ongoing.

2.4 Instrumental Diagnostics

• Visometry (A02.26.004) and refractometry (A03.26.008) are recommended for all patients with congenital glaucoma and suspected congenital glaucoma during diagnosis, follow-up, and treatment monitoring to determine the severity of visual impairment [1-6,17-18,20].

GRC CLeE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: In children under 3 years of age, visometry is performed using the orienting response to novelty, assessment of reflex motor reactions (pupillary response, following response, etc.), and approximate methods by presenting objects of varying sizes (ball test, etc.); in children aged 3 to 6 years, testing uses pictures, letters, numbers, or other symbols (Orlova, Sivtsev, and Golovin charts, Landolt rings, projector optotypes, etc.). In the absence of form vision, the presence of light perception and light projection is determined. Visual acuity is measured first without correction, and then, if impairments are present, with correction (using a specialized trial frame and lenses).

As is known, in children with congenital glaucoma, myopic refraction develops as the eye stretches, with high myopia occurring in one-third of cases. With further glaucoma progression and significant, often uneven stretching of the eye coats, the degree of astigmatism increases, which substantially reduces visual acuity—already quite low in such children.

Accordingly, clinical refraction testing in children with congenital glaucoma or suspected congenital glaucoma serves two purposes: diagnosing the glaucomatous process and assessing its progression rate on the one hand, and providing timely optical correction of ametropia on the other.

Refraction can be determined using skiagcopy or autorefractometry with a stationary or handheld refractometer. The undeniable advantages of handheld devices include the ability to perform the examination under any conditions, including general anesthesia, as well as the ability to accurately determine the astigmatism axis.

• Ophthalmotonometry (A02.26.015) is recommended for all patients with congenital glaucoma and suspected congenital glaucoma to assess intraocular pressure (IOP) and ocular hemodynamics [1-6,17-18,20,25-27].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

Comments: To monitor IOP, it is recommended to use the Maklakov applanation tonometer (the tonometry standard in Russia), the Goldmann applanation tonometer (the global tonometry standard), or various types of non-contact tonometers, which allow measuring true IOP without local anesthesia, including in infants in various body positions. Non-contact tonometry (pneumotonometry) should be considered as a screening method for determining IOP levels. ICare and PASCAL tonometers, as well as the Ocular Response Analyzer (ORA), are approved for use in the Russian Federation [25-27]. During follow-up, it is recommended to use a single baseline tonometry method for correct comparison of the obtained results.

Many modern methods of "instrumental" tonometry are prone to measurement errors, usually resulting in overestimated IOP readings. These are largely related to the age-specific mechanical properties of the cornea, which undergo even further changes against the background of hydrophthalmos development. Therefore, if contradictory IOP readings are obtained or their reliability is in doubt, it is advisable to perform ophthalmotonometry using a Maklakov tonometer.

IOP values in children may not reflect the true clinical picture of the disease, because stretching of the fibrous tunic of the eye compensates for the pressure elevation. Optimal ophthalmotonus characteristics must be evaluated in conjunction with ocular morphometry.

The main distinctive feature of the pediatric eye is the potential for reverse development of pathological optic nerve changes (cupping) when IOP is compensated in a timely manner [5].

When analyzing tonometric data, absolute IOP levels, daily fluctuations, and the difference in ophthalmotonus between the two eyes are taken into account. Daily IOP fluctuations, as well as asymmetry between fellow eyes in healthy individuals, generally remain within 2–3 mm Hg and only rarely reach 4–6 mm Hg.

P_t refers to tonometry readings obtained using a contact Maklakov tonometer, most frequently with a 10 g weight. P₀ represents true IOP, corresponding to tonometry readings obtained via most modern methods (Goldmann tonometry, pneumotonometry, Icare tonometry, etc.).

The statistical normal range for true IOP (P₀) is 10 to 21 mm Hg, and for tonometric IOP (P_t) is 12 to 25 mm Hg.

Table 5. Optimal upper limit characteristics of the "target" ophthalmotonus in glaucoma patients [20].

Tonometry data are significantly influenced by corneal thickness and diameter, which undergo substantial changes in children during glaucoma development.

• Tonography (A03.26.015) is recommended for certain patients with congenital glaucoma to clarify the characteristics of ocular hemodynamics [2].

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

Comments: Additional information on ocular hemodynamics can be obtained through tonographic studies, where the most important parameters are: IOP level (P0 normal range: 10 to 21 mm Hg), coefficient of outflow facility (C normal range: 0.15–0.6 mm^3/min·mm Hg; for patients over 50 years old: greater than 0.13), minute volume of aqueous humor (F normal range: 2.0–4.5 mm³/min), and Becker coefficient (CB ≤ 100).

• Measurement of corneal thickness (keratopachymetry A03.26.011.001) is recommended for all patients with congenital glaucoma and suspected congenital glaucoma to ensure correct interpretation of tonometry results and to identify a risk factor [2,4,28-35].

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

Comments: The mean corneal thickness in the optical zone (central corneal thickness) in children ranges from 496 to 620 µm; corneal thickness increases with age, measuring 529 ± 0.034 µm at ages 5 to 15.

In children with congenital glaucoma who have uncompensated IOP and corneal edema, corneal thickness increases. With stretching of the ocular tunics and compensated IOP, corneal thickness in children with congenital glaucoma is lower than in healthy children (mean: 540 ± 30 µm). It is advisable to categorize corneas into thin (481–520 µm), medium (521–560 µm), and thick (>561 µm), and to account for this when interpreting IOP values. Tonometry data in eyes with a central corneal thickness greater than 580 µm require downward adjustment (true IOP is lower than the measured values).

• Biomicroscopy of the eye (A03.26.001) is recommended for all patients with congenital glaucoma and suspected congenital glaucoma to assess the structures of the anterior segment and identify signs of glaucoma [1-6,17-18,20].

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

Comments:

Conjunctiva

In suspected congenital glaucoma, as well as in its initial and moderate stages with compensated and subcompensated IOP, the state of the conjunctiva is most often unchanged. In the advanced stage or with persistent elevation of ophthalmotonus, congested or mixed injection of the eyeball may be present.

In glaucoma associated with phacomatoses (Sturge-Weber syndrome), the presence of newly formed vessels organized in a vascular network of varying severity is characteristic.

When filtering blebs are present (following surgical interventions), attention must be paid to their width, height, wall thickness, degree of vascularization, and cystic changes.

Cornea

In the initial stage with minimal corneal stretching, mild edema is observed in the form of opalescence. Notably, it can be easily resolved by instilling hyperosmolar solutions into the conjunctival sac—40% glucose solution, 10% sodium chloride solution, glycerin, and others—which allows it to be differentiated from physiological corneal opalescence frequently observed in newborns, where the opalescence does not disappear.

With further glaucoma progression, the corneal diameter increases, causing the formation of ruptures and cracks on the endothelium and Descemet's membrane in the form of single and subsequently multiple striate opacities. Due to a barrier function failure, aqueous humor penetrates into the corneal stroma, disrupting metabolic processes and causing edema followed by corneal opacification. Enlargement (stretching) of the limbus also occurs, predominantly superiorly, and later, in the advanced stage, in all quadrants (up to 5–6 mm).

When glaucoma develops in children with anterior segment developmental anomalies (Type II—Peters anomaly), corneal opacities of varying severity (most commonly stromal) are present from birth. When glaucoma develops in such children, the rise in IOP can worsen the condition of the cornea, leading to edema or increased opacity density.

Anterior chamber

Normally, the depth of the anterior chamber in the pupillary area is 2.75–3.5 mm. In children with early-stage congenital glaucoma, the anterior chamber is of normal depth or slightly deeper than normal. As the eyeball enlarges in such children, the anterior chamber continues to deepen and may reach 5–6 mm. A comparative assessment of chamber depth in both eyes must also be performed. Asymmetry of this parameter is an important diagnostic sign of the disease.

Iris

In the early stages of glaucoma, pupillary reactions are usually preserved. As the eye enlarges in hydrophthalmos, atrophic changes in the iris increase: the pattern smooths out, atrophy of the pupillary border develops, crypts become less prominent, deep vascular network vessels become visible (must be differentiated from neovascularization), mydriasis appears, and the light reaction decreases. In Axenfeld-Rieger anomaly and Frank-Kamenetsky syndrome, characteristic iris changes are present (discussed above), which usually precede the manifestation of glaucoma and may progress over time: transillumination defects, sectoral atrophy, potential changes in pupil shape, and others appear. Attention should be paid to postoperative changes in the iris, such as a basal coloboma, traces of laser iridectomy, and others.

Lens

Along with transparency, size, and shape, pigment dispersion, phacodonesis, subluxation, or other lens dislocation should be noted.

• Gonioscopy A03.26.002 is recommended for all patients with congenital glaucoma and suspected of this condition if the cornea is clear. This technique allows examination of the iridocorneal angle, including the drainage zone, identification of the level of aqueous humor outflow resistance and the degree of dysgenesis, and determination of pathogenetically oriented treatment tactics [1–6, 17–18, 20].

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

Comments: Congenital glaucoma is characterized by anomalous development or hypoplasia of all structures in the drainage zone of the iridocorneal angle. Characteristic features include:

1. Presence of unabsorbed embryonic mesodermal tissue (most common: according to domestic authors, in 50–60% of cases), which appears as a veil-like tissue in the form of a continuous strip or islands (usually grayish-white or yellowish), covering and thereby blocking the trabecular zone of the iridocorneal angle.

2. High iris insertion, where the iris root is displaced forward and covers the trabecular meshwork (10–15%), most commonly manifested as an unevenly high iris insertion.

3. A group of anomalies leading to trabecular or intrascleral outflow resistance: absence of trabecular differentiation (hypoplasia), inadequate development or absence of Schlemm's canal, which obstruct or block aqueous humor outflow through the iridocorneal angle (15–25%).

4. The discovered anomalies occur in various combinations.

Goniodysgenesis—delayed development and differentiation of the iridocorneal angle—is divided into 3 grades (E.G. Sidorov and M.G. Mirzayants, 1991) [5]. Grade I—broad insertion of ciliary muscle bundles into the hypoplastic trabecular meshwork, relative preservation of the scleral sinus. Grade II—pronounced trabeculodysgenesis with anterior iris insertion, altered sinus topography, and frequent narrowing. Grade III—severe congenital pathology of all elements of the drainage zone: anterior insertion of the iris into the altered trabecular meshwork, sharp narrowing of the scleral sinus.

Using a digital pediatric retinal camera makes it possible to examine the structures of the iridocorneal angle with photographic documentation and dynamic follow-up.

• Ophthalmoscopy A02.26.003 / fundus biomicroscopy A03.26.018 is recommended for all patients with congenital glaucoma and suspected of this condition if the optical media remain clear, in order to detect glaucomatous optic neuropathy and potential retinal changes [1–6, 17–18, 20].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)

Comments: One of the main causes of visual function decline in children with congenital glaucoma is the development of glaucomatous optic neuropathy, which requires a detailed characterization of optic disc changes. The difficulty lies in the frequent inability to visualize fundus structures in children with congenital glaucoma due to corneal opacities.

Glaucoma is characterized by atrophic changes in the optic disc, manifested as decolorization (pallor) of atrophic areas of the disc, along with enlargement and deformation of its cup.

The optimal method for detecting changes in optic disc structure is ophthalmoscopy:

1. indirect slit-lamp ophthalmoscopy using 60, 78, or 90 D lenses;

2. direct slit-lamp ophthalmoscopy through the central part of a Goldmann or Van Beuningen lens.

When examining the optic disc in suspected glaucoma and congenital glaucoma, a quantitative and qualitative assessment of the following parameters must be performed.

1) Quantitative assessment of the optic disc:

• optic disc size;

• cup-to-disc ratio (CDR);

• neuroretinal rim (NRR) to disc ratio.

2) Qualitative assessment of the optic disc:

• shape, height, and color of the NRR, its absence (notched cup) or tendency to thin;

• decolorization of atrophic optic disc areas;

• shift of the vascular trunk.

Optic disc size. Average optic disc sizes range from 1.9 to 2.8 mm². Small optic discs are defined as those with an area less than 1.5 mm², medium discs from 1.51 to 2.5 mm², and large discs >2.51 mm². In congenital glaucoma, larger optic discs are more common due to eye enlargement.

In myopia, it may increase slightly (by 1.2±0.15%) for each diopter of ametropia. The larger the optic disc, the greater the CDR and NRR. Accordingly, a large cup in a large optic disc can be physiological, whereas a small cup in a very small optic disc may indicate glaucomatous optic nerve damage, significantly complicating the ophthalmoscopic diagnosis of this pathology.

Cup-to-disc ratio (CDR). Physiological optic disc cupping typically has a horizontally oval shape: the horizontal diameter is longer than the vertical by approximately 8%. An enlarged physiological cup in a large disc is more frequently round. Normally, cupping is symmetric in both eyes. In 96% of cases, the CDR is within 0.3 disc diameters. In the early stage of glaucoma, clear distinctions between physiological and glaucomatous cupping often do not exist. A shift and kinking of the vascular trunk can be visualized. As congenital glaucoma progresses with high IOP levels, a rather voluminous cup forms even at the moderate stage.

Enlargement of the cup in glaucoma usually occurs in all directions, but most frequently in the vertical direction due to thinning of the NRR in the superior and inferior sectors of the optic disc, which is associated with the structural features of the lamina cribrosa.

Normally, cup depth depends on the cup area and, indirectly, on disc size, while in congenital glaucoma it depends on the IOP level. The deepest cups are observed in eyes with high IOP levels. Exposure of the lamina cribrosa in the upper and lower zones of the cup indicates a glaucomatous nature of the cupping. When examining a patient with elevated IOP, the principle should be followed: the larger the cup, the higher the probability that it is glaucomatous.

Neuroretinal rim (NRR)

As the glaucomatous process develops, the width of the NRR gradually decreases, which can be uniform around the entire circumference, localized to the rim, or combined. Glaucoma is characterized by atrophic changes in the optic disc. Clinically, they manifest as decolorization (pallor) of NRR areas, most commonly in the temporal zone (must be differentiated from non-glaucomatous optic atrophy).

Peripapillary atrophy—thinning/destruction of chorioretinal tissue around the optic disc. In glaucoma, the prevalence of peripapillary atrophy is higher, especially on the nasal side of the peripapillary space.

It should be remembered that each of the listed symptoms individually is insufficient to make a correct diagnosis. Only a comprehensive assessment of the state of the optic disc and peripapillary retina can yield the correct decision. Fundus photography should be used to document the condition of the optic disc.

• Visual field testing (perimetry: static A02.26.005, computer-assisted A03.26.020 ) is recommended for all patients with congenital glaucoma and suspected congenital glaucoma to assess the degree of impairment of the visual system's light sensitivity for comprehensive diagnosis, staging, and monitoring of the glaucoma process [36-38].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

Comments: Peripheral vision testing is extremely important for diagnosing, staging, and monitoring the glaucoma process, but it is feasible only in older children with a sufficient level of psychomotor and intellectual development who possess functional form vision. Furthermore, evaluating the visual field using both moving (kinetic perimetry) and stationary stimuli (static perimetry) is clinically relevant.

Kinetic perimetry is the assessment of the peripheral boundaries of the visual field, the presence of absolute and relative scotomas, and the boundaries of the blind spot.

Static perimetry (computerized or automated) consists of determining the light sensitivity threshold in various areas of the visual field using stationary targets of variable luminance. It can detect even minimal defects in both the central and peripheral visual fields, significantly increasing the monitoring efficiency of early and advanced congenital glaucoma in adolescents, as well as the early diagnosis of glaucoma when it develops in older children.

The parameters to be evaluated include the peripheral boundaries of the visual field, the presence of absolute and relative scotomas, and the boundaries of the blind spot. When evaluating the results of static automated perimetry, indices such as mean defect or mean deviation (MD) and pattern standard deviation (PSD) are also utilized.

Repeat examinations are advisable twice a year; in newly diagnosed glaucoma (or when adjusting therapy, or following surgical treatment), examinations are recommended every 2–3 months during the first two years of follow-up.

Ultrasonic diagnostic methods

• Ocular ultrasound biometry A04.26.004 (A-scan or echobiometry) is recommended for all patients with congenital glaucoma and suspected congenital glaucoma to determine the dimensions and structural changes of the eyeball, as well as the anterior chamber depth, in order to identify a tendency toward glaucoma progression and to assess the stage of the process [1-6,17-18,20].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)

• Ultrasonography of the eyeball A04.26.002 is recommended for all patients with congenital glaucoma and suspected congenital glaucoma; it allows for the assessment of the internal structures of the eye (position and density of membranes, lens, vitreous body, etc.), which is particularly relevant in the presence of opaque refractive media [1-6,17-18,20].

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

• Ultrasound scanning of the anterior segment of the eye A04.26.007 is recommended for children with congenital glaucoma and suspected congenital glaucoma when it is necessary to obtain a clear image of the anterior segment structures (this is especially important in cases of corneal opacity), iridocorneal angle structures, and the drainage zone, particularly the trabecular meshwork (especially in congenital anomalies). It also makes it possible to measure the thickness of the cornea (mm), iris (mm), anterior chamber depth (mm), the size of the iridocorneal angle (deg.), and to determine the presence, structure, and dimensions of pathological formations in the anterior segment of the eye, among other parameters [4,17,20].

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

Comments: In congenital glaucoma, the acoustic pattern of the anterior ocular segment is characterized by flattening and a reduced relief of the iris throughout its extent, hypoplasia of the scleral spur, its abnormal position or absence, a reduced trabecular-iris distance, and other features. Pathological changes can also be detected regarding the structure, size, and position of the ciliary body, its processes, and other structures of the eyeball. Moreover, the specific features of these changes characterize the form and stage of glaucoma to a certain extent, which makes it possible to develop optimal surgical management tactics for such patients, especially when optical media transparency is impaired.

• Optical imaging of the retina using a computer analyzer A03.26.019, optical imaging of the optic nerve head and nerve fiber layer using a computer analyzer A03.26.019.003 (optical coherence tomography (OCT) of the retina and optic disc) is recommended for all patients with congenital glaucoma and suspected congenital glaucoma in the presence of clear media for a detailed, objective, quantitative, and qualitative assessment of the state of the optic nerve, retinal and choroidal changes during diagnosis and disease monitoring [4,39-40].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

Comments: OCT provides a set of objective morphometric data confirming the presence of significant structural and hemodynamic disturbances in the posterior segment of the eye in congenital glaucoma, which progress as the disease advances:

- a significant increase in the main parameters of optic disc cupping: cup volume, maximum cup depth, and cup area;

- a decrease in neuroretinal rim (NRR) parameters: volume, area, and minimum width, starting in the inferonasal quadrant;

- a decrease in the thickness of the retinal nerve fiber layer (RNFL) in the peripapillary zone with predominant changes in the temporal zone;

- a decrease in the thickness of the ganglion cell layer and ganglion cell complex in the macular zone;

- a decrease in choroidal thickness.

Comparative analysis of morphometric parameters in the early and advanced stages of congenital glaucoma, taking into account eye size, in some cases reveals a less pronounced increase in cup depth and area in advanced stages in significantly stretched eyes compared to early stages in eyes with less stretched membranes. This can be explained by the nature of the structural changes in the eye at late stages of congenital glaucoma, when the stretching of the membranes leads to an increase in eye size but reduces the pathological impact on the nerve fibers in the optic disc area.

When intraocular pressure normalizes in children with congenital glaucoma, a regression of certain optic disc changes may be observed: a decrease in cup dimensions and an increase in NRR size, which is explained by the age-related biomechanical characteristics of the pediatric eye.

• Optical imaging of the anterior segment of the eye using a computer analyzer A03.26.019.001 is recommended for patients with congenital glaucoma for a quantitative and qualitative assessment of anterior segment changes [4].

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

Comments. This non-contact imaging method, which surpasses ultrasound in resolving power, makes it possible to evaluate the structure, measure, and record the state of the corneal layers, iris, and iridocorneal angle parameters in children with congenital glaucoma. OCT devices are equipped with computer software that facilitates image acquisition, as well as the creation and maintenance of a database ensuring quantitative image analysis.

At the same time, it should be emphasized that the data obtained using the instrumental methods discussed are not "gold standards" in the diagnosis of the glaucoma process, but merely supplement the results of a comprehensive examination of the child, which should be evaluated in their entirety. However, a confirmed deterioration in the state of the optic disc is an important prognostic sign of glaucoma progression.

• Electrophysiological diagnostic methods (EFP), including full-field electroretinography (A05.26.001), recording of the pattern electroretinogram complex (advanced examination A05.26.001.003), and recording of visual evoked potentials of the cerebral cortex A05.26.002, are recommended for patients to determine the functional state of the eye [1,4,6,20]. All studies are performed in accordance with International Society for Clinical Electrophysiology of Vision (ISCEV) standards.

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

Comments: The electroretinogram (ERG) and its components serve as an objective indicator of the functional state of the retina in children with congenital glaucoma. Progressive stretching of the ocular membranes causes impaired blood supply, metabolic and biochemical processes in the retina, as well as disruption of synaptic connections between retinal cellular elements that form the neuronal network. This leads initially to a compensatory activation of the phototransduction process and hyperpolarization, and subsequently to a decrease in bioelectric activity recorded by ERG.

Visual evoked potentials (VEPs) in congenital glaucoma (CG) show changes in their amplitude-time characteristics already in the initial stage of the disease across the entire spatial frequency range, which reflect the state of the axons of retinal ganglion cells. Modern computer systems are used to record VEPs, allowing low-amplitude potentials to be isolated from noise by employing averaging and filters that neutralize various artifacts. The study is performed both while the child is awake and during medicinal sleep or general anesthesia. The main focus is on latency parameters. When analyzing the obtained data, it is taken into account that the formation of the P1 peak of the VEP is mainly influenced by the integrity of the retinocortical pathway, the maturity of the foveal area of the retina, and the integrity of the striate cortex. In addition, it should be kept in mind that this method does not allow assessing the preservation of associative and cognitive brain functions that ensure "visual recognition".

In CG, a series of sequential electrophysiological investigations (EFIs) before and after intraocular pressure (IOP) normalization makes it possible to assess the state of the retina and optic nerve, the dynamics of changes, and to predict the final functional outcomes. Recording a supernormal ERG simultaneously with high IOP values indicates a short duration of hypertension and a favorable functional outcome. High IOP values with a low ERG amplitude are characteristic of more pronounced pathological changes in the retinal structure and a poorer functional prognosis. Following IOP normalization, the ERG amplitude decreases within 3–6 months to values corresponding to the stage of the disease and the preservation of the retinal neuroepithelium. With sustained IOP normalization, the ERG tends to show a moderate increase in amplitude.

As the disease progresses, visual evoked potentials show a direct correlation between changes in amplitude-frequency characteristics and the stage of CG. Latency increases as the disease progresses and transitions to a later stage, while the amplitude decreases, and by the absolute stage of CG, VEPs are no longer recordable. With sustained IOP compensation, stabilization and subsequent partial restoration of the amplitude-time characteristics of VEPs occur.

EPT data appear particularly important when it is impossible to assess visual acuity due to the child's age and in cases of corneal opacities when the structures of the posterior pole cannot be visualized.

2.5 Other Procedures

Not used in congenital glaucoma in children.

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

3.1 Medical hypotensive treatment

– medical ocular hypotensive therapy (prescription of antiglaucoma drugs and miotics) is recommended during the preparation of the child for surgery, as well as, in a number of cases, after it – in case of an insufficient hypotensive effect of the intervention. Although the main treatment for CG is surgical, in some cases long-term compensation of the glaucomatous process with hypotensive eye drops is also possible [1-6,17-18,20, 41-44].

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

Comments:

When choosing a drug therapy, it is necessary to consider the child's age, and during treatment, carefully monitor the patient's general and local status to rule out potential complications of hypotensive therapy. Drugs with the same pharmacological action must not be used in combination. Choosing drugs for the treatment of CG is quite challenging, since the majority of hypotensive agents developed recently have not undergone clinical trials in children and, accordingly, cannot be recommended for use in pediatric practice. Nevertheless, if there are appropriate indications and, in some cases, with the appropriate informed consent of the parents, it is possible to use ocular hypotensive agents available in the arsenal of "adult" ophthalmologists.

Main principles of hypotensive therapy:

1. treatment should begin with monotherapy;

2. if the first-line drug is insufficiently effective, it is necessary to replace the ineffective drug or add a new or combination drug;

3. using more than 3 drugs is impractical.

4. it is irrational to use drugs with the same pharmacological action in combination.

5. For forms II and III of CG, in most cases of glaucoma, the prescription of combination drugs is indicated.

6. With high IOP, start immediately with combination drugs, and in case of insufficient efficacy, add a drug from another pharmacological group (prostaglandin, alpha-2 adrenergic agonist, or muscarinic receptor agonist).

Efficacy indicators:

1. maintaining IOP within the optimal (tolerable) level with a minimum number of drugs per day;

2. absence of tachyphylaxis (wearing off effect) over a long period;

3. minimal systemic impact;

4. minimum of side effects;

5. good tolerability.

Indications for prescribing modern hypotensive drugs in congenital glaucoma (including preoperative preparation)

The use of these drugs is indicated for children with various forms of CG. They are prescribed:

1. immediately after elevated IOP is detected in a child;

2. included in the preoperative preparation regimen to maximally reduce IOP before surgery or maintain IOP within normal limits and stabilize the glaucomatous process;

3. used to correct the IOP level in the postoperative period, as well as to attempt IOP normalization in operated children while awaiting repeat surgery.

Comments:

Currently, a wide range of modern hypotensive agents is available in Russia. The mechanism of action of the drugs and their efficacy in CG are presented in Table 6.

Table 6. Medicinal agents for glaucoma treatment.

Comments: The main registered medications and their age restrictions are presented in Table 7.

Table 7. Age restrictions for the prescription of the most common hypotensive drugs in the Russian Federation

If treatment with approved drugs is not feasible, and with the informed consent of the patient's parents and the permission of the medical commission, drugs that are not officially approved for use in children may be prescribed.

Comments: For children, preservative-free dorzolamide** or timolol** eye drops are available to lower IOP.

• Medical neurotrophic treatment is recommended to preserve and stimulate visual functions in children with congenital glaucoma. Therapy should be performed regularly (1–2 times a year) [1,2,4-6,14-17,20,48,63].

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

Comments: Optic nerve ischemia, resulting from stretching of the coats and compressive pressure on the retina and choroid in congenital glaucoma, leads to nutrient depletion in cells, accumulation of free radicals and metabolic products, and ultimately to apoptosis of the neuronal elements of the visual system.

The complex of neurotrophic treatment includes drugs that affect peripheral circulation and improve microcirculation: other psychostimulants and nootropics (N06BX), angioprotectors (C05), vitamins, multivitamins in combination with other agents (A11A), and other ophthalmological drugs (S01X). Therapy should be administered regularly twice a year following a consultation with a neurologist (Consultation (examination, consultation) with a neurologist).

If IOP compensation is stable for 6 months, physical therapy methods can be included in the congenital glaucoma treatment complex: optic nerve electrical stimulation A17.26.003, low-frequency magnetotherapy of the eye A17.26.002.

Indications for modern neurotrophic treatment in congenital glaucoma:

Any forms of congenital glaucoma with compensated IOP.

Contraindications for modern neurotrophic treatment in congenital glaucoma:

1. Unstable compensation of the glaucomatous process.

2. Severe concomitant general somatic pathology.

3. Intolerance to the prescribed medications.

4. Inability to regularly monitor IOP.

3.2 Surgical Treatment

Comments:

Indications for urgent surgical treatment (including repeat surgery):

1. presence of hydrophthalmos (form I) or other forms of glaucoma characterized by a high IOP level that cannot be normalized by any other treatment method, including medical therapy, other than surgery;

2. ineffectiveness of other treatment methods in the presence of initially low IOP in children with clinical forms II and III of congenital glaucoma;

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

Repeat surgeries must be performed even in the presence of residual visual functions.

Surgical hypotensive treatment methods

Comment: These techniques are divided into two groups:

1. Operations aimed at eliminating organic obstacles (mainly mesodermal tissue) in the path of aqueous humor to the trabecular meshwork:

1. Goniotomy (including goniopuncture) A16.26.067;

2. Trabeculotomy ab interno A16.26.069;

3. Laser goniotrabeculopuncture A22.26.006;

2. Fistulizing interventions involving the creation of a new channel from the anterior chamber outwards into the intrascleral space:

1. Trabeculotomy ab externo and its modifications A16.26.069;

2. Sinustrabeculectomy (trabeculectomy) and its modifications A16.26.070;

3. Other penetrating antiglaucomatous surgeries A16.26.118 (diathermogoniopuncture; microdiathermogoniopuncture, etc.);

In the 21st century, the scope of "angular" surgeries has expanded: endoscopic goniotomies, illuminated microcatheter trabeculotomies. Abroad, such operations are considered preferable for initial interventions in primary congenital glaucoma. Trabeculectomy is effectively used both as a primary and repeat operation in all forms of childhood glaucomas. The combination of trabeculotomy with trabeculectomy has theoretical and practical advantages and is more commonly used in advanced stages of congenital glaucoma, especially with corneal opacification, when angular surgeries are technically impossible.

Experience shows that sinustrabeculectomy and its modifications currently provide the most stable hypotensive effect; their goal is to create a fistula from the anterior chamber into the intrascleral space (whose volume is expanded by deep sclerectomy).

Most commonly used surgical techniques in children:

Goniotomy. A16.26.067. Stages of surgical treatment include corneal paracentesis and injection of a viscoelastic into the chamber. Then, using a goniotomy knife inserted into the anterior chamber, the tissue covering the trabecular meshwork and the meshwork itself are transected from the opposite side of the chamber for 100⁰–110⁰ (within the visualization range of the gonioscope lens). After a successful manipulation, the aqueous humor drains into Schlemm's canal. In case of failure, the manipulation can be repeated. Possible complications of the surgery include hyphema, cyclodialysis, iridodialysis, peripheral anterior synechiae, and cataract.

Trabeculotomy. A16.26.069 Trabeculotomy can be performed using metal probes (151950) trabeculotomes (reusable 151940 or disposable 341200) as well as using a suture or an illuminated atraumatic microcatheter over a 360-degree circumference.

Standard trabeculotomy. After a conjunctival incision, a scleral flap half the thickness of the sclera is dissected. Schlemm's canal is located, opened radially, and the working probe of the trabeculotome is inserted into the opening as far as the probe's curvature allows, and by rotating it toward the anterior chamber, it is extracted using the "break-and-withdraw" principle.

Trabeculotomy using a 360-degree suture. During the surgery, a polypropylene surgical suture 256860***6/0 with a rounded tip melted using a thermocautery is used. The suture is slowly advanced into the lumen of Schlemm's canal using anatomical forceps, and a goniolens is used to monitor its position. After its passage, the proximal and distal ends are brought out through the scleral incision and pulled in opposite directions with needle holders, thereby performing a 360-degree trabeculotomy. Instead of a polypropylene suture, an illuminated-tip microcatheter can also be inserted into Schlemm's canal for better visualization of the catheter as it advances within the canal.

Possible complications of trabeculotomy include hyphema, serous or hemorrhagic ciliochoroidal detachment, iridodialysis, cyclodialysis, Descemet's membrane detachment, and zonular detachment.

Sinustrabeculectomy (trabeculectomy) A16.26.070 is a fistulizing operation most frequently performed as the primary surgery for glaucoma of various etiologies in children. The goal of the surgery is to create an alternative outflow pathway for aqueous humor by forming a corneoscleral fistula.

Surgical technique. The conjunctival incision is made 6 mm from the limbus, after which the conjunctiva is bluntly dissected as anteriorly as possible. In a primary operation, the incision is located superiorly between 11 and 1 o'clock. A scleral flap is formed, most often U-shaped, measuring 4 mm along the limbus and 3 mm from the limbus, with a thickness of 1/2 to 2/3 of the sclera. Then, radial side cuts are made with a blade in the trabecular zone area up to the entrance of the anterior chamber, and Vannas scissors are used to connect these cuts, excising a rectangular section of trabecular tissue. After the fistula is formed, the iris may prolapse into it, facilitating iridectomy. It is grasped with forceps and excised in the area above the fistula. Iridencleisis may be performed, in which case the root of the iris is not excised, but a flap with its base at the limbus is formed from it and brought out under the scleral flap. Then, the scleral flap is fixed to its bed with interrupted sutures, and a suture is placed on the conjunctiva.

The cause of failures, especially in the long-term period, is postoperative episcleral fibrosis of the filtration site, which is particularly pronounced in children.

The intraoperative use of antimetabolites (fluorouracil**, mitomycin) significantly improves the long-term results of trabeculectomy, but is fraught with serious complications – thinning of the filtering bleb, persistent excessive hypotony, blebitis, and endophthalmitis [3,4,20,45-48]. In Russia, the use of antimetabolites in anti-glaucoma surgeries in children is not yet authorized.

Possible complications of hypotensive surgeries include hypotony, shallow anterior chamber syndrome, hyphema, choroidal detachment, macular edema, formation of anterior and/or posterior synechiae, encapsulation of the filtering bleb, and, extremely rarely, retinal detachment and endophthalmitis.

The advantage of combining trabeculotomy with trabeculectomy is two separate mechanisms for increasing aqueous humor outflow—through the trabecular meshwork and through the trabeculectomy fistula. However, excessive filtration and hypotony are not observed, and IOP can remain normal even if one of the pathways ceases to function.

• Implantation of drainage devices and valves is recommended for patients with refractory congenital glaucoma, more commonly when the aforementioned surgeries fail to normalize intraocular pressure [51,52].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

Comments:

Anti-glaucoma drainage implantation is recommended in the most complex cases with a risk of developing or the presence of excessive scarring in the surgical area, marked conjunctival pathology due to previous surgeries, active neovascularization, aphakia, etc.

The choice of drainage device depends on the technical capabilities and preferences of the surgeon. As a rule, tube shunts serve as secondary interventions in the presence of risk factors for the insufficient efficacy of trabeculectomy with antimetabolites, although recent studies have demonstrated that their implantation is effective and safe as a primary surgical procedure. Depending on the material, anti-glaucoma drains are classified into auto-, allo-, and explant drains. Autologous drains are autologous scleral flaps (or other autologous tissue). Their disadvantages are rapid scarring and gradual blockage of the outflow pathways created by the surgery. Allogeneic drains are biomaterials from donor tissues. The most common domestic drains are collagen drains, as well as spongy allogeneic biomaterial created using the "Alloplant" technology.

The most common domestic drains are collagen drains, as well as spongy allogeneic biomaterial drains. Explant drains are synthetic, made of polymeric and other materials.

In children, the most common and frequently used drains are hydrogel, collagen, and silicone drains: resorbable anti-glaucoma drain, anti-glaucoma filtration device (glaucoma treatment shunt***). The main cause of increased IOP when using drains is the formation of a connective tissue capsule around the distal end of the drain.

• In congenital glaucoma associated with angle-closure by a subluxated lens (Marfan syndrome, spherophakia), it is recommended as a first step to perform removal of the subluxated lens (A16.26.092.002, A16.26.092.004, A16.26.092.005) [24,49,50].

Level of Recommendation CLevel of Evidence 3Level of recommendation C (level of evidence 3)

Comments. In a number of cases, lensectomy makes it possible to achieve IOP compensation. If glaucoma remains uncompensated, one of the anti-glaucoma surgeries should be performed depending on the clinical situation—fistulizing surgery, anti-glaucoma drainage implantation, or cyclodestructive surgery.

• Surgical methods for reducing aqueous humor secretion – cyclodestructive procedures (targeting the ciliary processes, most commonly using lasers, less frequently cryotherapy) are recommended when procedures to restore normal IOP outflow (angular or fistulizing) fail and in children with absolute glaucoma [53-57].

GCR BLoE 3Level of Evidence B (Level of Confidence of Evidence – 3)

Comments. Cyclodestructive procedures are aimed at the destruction and atrophy of the ciliary body. Currently, the most frequently used method is laser cyclophotocoagulation, for which several approaches (transscleral, transpupillary, intraocular) and several types of lasers have been proposed—Nd:YAG laser, diode semiconductor laser. The diode laser (wavelength 809 nm) has a potential advantage over the YAG laser due to greater absorption by the melanin of the pigmented epithelium of the ciliary body while well preserving other structures through which the laser beam passes. Consequently, less energy is required to achieve histological changes in the ciliary body. The most commonly performed procedure is contact diodelaser transscleral cyclophotocoagulation A22.26.018.

The surgery is typically performed for severe refractory glaucoma when angular, fistulizing, and drainage surgery have failed or surgery is unfeasible due to conjunctival scarring, as well as in eyes with a poor functional prognosis.

The treatment energy and the number of burns applied vary depending on the initial IOP level and the degree of iris pigmentation (as an indirect indicator of ciliary process pigmentation). A total of 15–20 applications are made 1.5 mm from the limbus with a perpendicular position of the probe and slight circular indentation, avoiding the superior quadrants. The power and exposure time for the diode laser are 0.5–1.0 W and 0.5–2 s, respectively, starting from minimum values and gradually increasing the radiation dose. If an acoustic snap occurs at the moment of coagulation (pop-corn effect), the power must be reduced to minimize the risk of excessive trauma to the ciliary body.

Possible complications of the surgery include iridocyclitis, hyphema, hemophthalmus, corneal erosion, pupil deformation, and hypotony up to subatrophy of the eyeball. At the same time, careful titration of laser radiation parameters minimizes the number of such complications.

Micropulse diode laser transscleral cyclophotocoagulation is a modern, safer, and minimally invasive method which, unlike continuous-wave cyclocoagulation, has two cycles: an "on" cycle and an "off" cycle. During the "off" cycle, the areas of the ciliary body that have undergone thermal exposure cool down, which protects them from excessive thermal damage. The hypotensive effect is achieved through gentle thermal damage to the ciliary body, reduction of aqueous humor secretion, and enhancement of uveoscleral outflow. The method helps avoid excessive irreversible damage to the ciliary body and, in addition to the indications for standard diode laser cyclocoagulation, can be used not only as a globe-saving method in terminal stages of congenital glaucoma and contraindications to filtering surgeries (like standard diode laser cyclocoagulation), but also as a less invasive primary intervention in the absence of gross angle changes and IOP decompensation in older children, as well as in eyes with high visual functions with early IOP decompensation after trabeculectomy.

• When intra- and postoperative complications develop, conservative medical treatment and, if necessary, surgical treatment are recommended [1-6, 17, 20,45-52].

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

Comments:

Scarring in the surgical area is promoted by: insufficient volume of the excised trabecular portion, closure of the surgical area by goniosynechiae, which are consequences of postoperative iritis and anterior chamber hemorrhages.

Modern methods preventing excessive proliferation and, consequently, closure of surgically created aqueous humor outflow pathways include: reducing surgical trauma, using corticosteroids S01BA, proteolytic enzymes, and antimetabolite cytostatics (antimetabolites widely used in foreign clinical practice are currently not officially registered as ophthalmic drugs in the Russian Federation), needling procedure (transconjunctival revision of the filtration bleb), and laser elimination of internal fistula occlusion after surgery

Comments: In the early postoperative period of congenital glaucoma, recurrence of ocular hypertension may develop due to blockade of the trabeculectomy zone by the root of the iris and the formation of iridocorneal adhesions. Gonioscopic monitoring of the condition of the internal fistula and the anterior chamber angle is necessary after antiglaucoma surgeries for the early detection of internal fistula occlusion and adhesions, and their timely laser elimination. Such non-invasive laser "refistulization" is especially effective in the early periods after trabeculectomy (no later than 1–3 months after surgery)

In addition to excessive scarring, the efficacy of antiglaucoma surgery depends on several other complications: shallow anterior chamber syndrome, ciliochoroidal detachment, hyphema, and macular edema.

Shallow anterior chamber syndrome in the postoperative period may be associated with: increased filtration of aqueous humor through the postoperative fistula, poor adaptation of the conjunctival incision and the presence of external filtration, as well as ciliochoroidal detachment (CCD).

Comments: Causes of CCD:

1. sharp decompression during the opening of the fibrous tunic of the eye, leading to disruption of the anatomical relationships of the eye;

2. tractional displacement of the ciliary body and the iridolenticular diaphragm anteriorly with the formation of negative pressure in the suprachoroidal space and transudation of the liquid part of blood into it;

3. hypotony occurring during surgery due to excessive external filtration of aqueous humor resulting from inadequacy of the antiglaucoma fistula or insufficient sealing of the surgical wound;

4. pathological changes in the hemodynamics of the suprachoroidal fluid.

As a rare complication of trabeculectomy in children, hemorrhagic retinopathy resembling central retinal vein occlusion has been described.

CCD is the most frequent postoperative complication in Sturge-Weber syndrome. The IOP drop that occurs during surgery serves as a trigger for the clinical manifestation of vascular pathology: intraoperative and postoperative hemorrhages, and a high frequency and more severe course of choroidal detachments compared to adults.

In case of bleeding immediately after iridectomy, pressure should be applied to the eyeball with a cotton swab while attempting to wash blood out of the wound. The introduction of sterile air into the anterior chamber is used. If the blood cannot be removed and clots have formed, attempts should not be made to extract them. Over the next few days, further tactics become clear: conservative treatment or additional blood washout.

• For the prevention and treatment of infection and inflammation in children with congenital glaucoma in the postoperative period, the use of anti-inflammatory and antibacterial drugs is recommended [1-6,14-17,20,48,63].

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

Comments: Local therapy is prescribed in the postoperative period –

1. anti-infective agents S01A

2. anti-inflammatory drugs S01B

3. other ophthalmological drugs

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• Medical rehabilitation is recommended for children with compensated congenital glaucoma, which includes drug-based neurotrophic treatment and physiotherapeutic methods aimed at preserving and stimulating visual functions. Therapy should be carried out regularly (1–2 times a year) [1,2,4-6,14-17,20,48,58,59,63].

LeR CLoE 5Level of Recommendation C (Level of Evidence — 5)

Comments: Drugs for drug-based neurotrophic therapy are listed above (Section 3.1). Percutaneous electrical stimulation of the optic nerve (A17.26.002) 6 months after surgery effectively improves residual visual functions in glaucomatous neuropathy. Therapy should be carried out regularly 2 times a year following a consultation with a neurologist (Consultation (examination, consultation) of a neurologist).

The treatment regimens may also include:

1. BRT – bioresonance therapy – treatment with endogenous and exogenous electromagnetic fields.

2. Color pulse therapy according to T.P. Teterina's method

3. Reflexology – Acupuncture.

4. Manual therapy.

Comments:

- Instillations of dorzolamide** S01EC03 often eliminate corneal edema in glaucoma, unlike physiological corneal clouding (opalescence) frequently observed in newborns.

- For corneal edema and initial dystrophic changes of the cornea, trophic gels (other ophthalmological preparations S01XA) and vitamin-enriched solutions (other vitamin preparations A11HA) are also used.

Comments: Functional treatment aimed at combating amblyopia through ametropia correction and pleoptics is important. Children with congenital glaucoma are more frequently diagnosed with myopia, the majority having moderate and high myopia, which strictly requires correction.

5. Prevention and Dispensary Observation

Table 9. Frequency of examinations for children with congenital glaucoma

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

Comments. Regular monitoring of IOP, eye dimensions, and visual acuity is extremely important. All children as part of dispensary monitoring undergo a comprehensive examination, including assessment of the anterior and posterior segments of the eye, IOP measurement, determination of refraction and visual functions: visometry (A02.26.004), refractometry (A03.26.008), ophthalmotonometry (A02.26.015), biomicroscopy of the eye (A03.26.001), ophthalmoscopy (A02.26.003) / fundus biomicroscopy (A03.26.018), gonioscopy (A03.26.002), ocular ultrasound biometry (A04.26.004), ultrasound examination of the eyeball (A04.26.002), computerized perimetry (static A02.26.005, computer-based A03.26.020), if necessary optical examination of the retina using a computer analyzer (A03.26.019), optical examination of the optic nerve head and nerve fiber layer using a computer analyzer (A03.26.019.003), optical coherence tomography, OCT, recording of visually evoked cortical potentials (A05.26.002) and electroretinography (A05.26.001), recording of the pattern electroretinogram complex (expanded study) (A05.26.001.003). It should be noted that contact research methods are not feasible for all children, given their age.

6. Organization of Medical Care

Provision of medical care to patients with congenital glaucoma and suspected of this condition is carried out in accordance with the Procedure for the provision of medical care to children with diseases of the eye, its adnexa and orbit, approved by Order No. 442n of the Russian Ministry of Health dated October 25, 2012.

If a child is suspected of having congenital glaucoma or has a confirmed diagnosis of glaucoma, district pediatricians and general practitioners (family physicians) refer the children for a consultation with an ophthalmologist. The ophthalmologist assesses the condition of the eye and conducts an examination, including instrumental research methods to clarify the diagnosis. If diagnostic procedures require anesthesia, children are referred to the pediatric ophthalmology department.

If there are indications for surgical treatment in a child with an established diagnosis of glaucoma, this treatment is carried out in an inpatient setting – the pediatric ophthalmology department. After the provision of medical care to children in an inpatient setting and in the absence of indications for inpatient medical care, children are referred to the pediatric ophthalmology outpatient clinic. Subsequently, the child is under dispensary observation by the ophthalmologist of the pediatric ophthalmology outpatient clinic.

7. Additional Information

The prognosis of congenital glaucoma in children is determined by the child's age, the time of detection of the disease, the stage and severity of glaucomatous damage to the child's eye at the time of glaucoma detection, and the timeliness of diagnosis and surgical treatment.

Criteria for Evaluating the Quality of Medical Care

Table 10. Quality criteria for medical care

References

Appendix A1. Working Group Composition

1. Lyudmila A. Katargina – Group Leader, Chief freelance pediatric ophthalmologist of the Russian Ministry of Health, Deputy Director for Research at the National Medical Research Center of Eye Diseases named after Helmholtz of the Russian Ministry of Health, Head of the Department of Pediatric Eye Pathology, Professor, MD, Moscow;

2. Arestova Nataliya Nikolaevna – Leading Researcher, Department of Eye Pathology in Children, National Medical Research Center for Eye Diseases named after Helmholtz of the Russian Ministry of Health, Associate Professor, MD, Moscow;

3. Panova Anna Yurievna – Researcher, Department of Eye Pathology in Children, National Medical Research Center for Eye Diseases named after Helmholtz of the Russian Ministry of Health, PhD, Moscow;

4. Denisova Ekaterina Valerievna – Senior Researcher, Department of Eye Pathology in Children, National Medical Research Center for Eye Diseases named after Helmholtz of the Russian Ministry of Health, PhD, Moscow;

5. Brzheskiy Vladimir Vsevolodovich – Head of the Department of Ophthalmology, Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health, Professor, MD, Saint Petersburg;

6. Sadovnikova Nataliya Nikolaevna – Head of the Ophthalmological Department of the Clinic, Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health, PhD, Associate Professor, Saint Petersburg;

Conflict of interest none.

Appendix A2. Methodology for Developing Clinical Guidelines

Methods used for evidence collection/selection: electronic database searches; analysis of current scientific developments on glaucoma in Russia and abroad; synthesis of practical experience of Russian and foreign colleagues.

The preliminary version of these guidelines was reviewed by independent experts who commented on the accessibility and interpretability of the evidence underlying the guidelines for practitioners and patients.

The comments received from experts were carefully systematized and discussed by the chair and members of the working group. Each point was discussed, and appropriate changes were made to the guidelines.

In these clinical guidelines, all data are ranked by level of reliability (evidence) depending on the quantity and quality of studies on the issue.

Target audience for these clinical guidelines:

• Ophthalmologists;

• Pediatricians (Family Physicians)

Table 1. Levels of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Scale for grading levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for assessing the levels of evidence for recommendations (LER) for methods of prevention, diagnosis, treatment, and rehabilitation (preventive, diagnostic, therapeutic, and rehabilitation interventions)

Procedure for updating clinical guidelines.

The clinical guidelines update mechanism provides for their systematic revision—at least once every three years, as well as upon the emergence of new evidence-based data regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

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

1. "Procedure for Providing Medical Care to Children with Diseases of the Eye, Its Adnexa, and Orbit", approved by Order of the Ministry of Health of the Russian Federation No. 442n dated October 25, 2012.

2. International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) (World Health Organization) 1994.

3. Nomenclature of Medical Services (Ministry of Health and Social Development of the Russian Federation), Order of the Russian Ministry of Health No. 804n dated October 13, 2017 (as amended on September 24, 2020, with rev. dated October 26, 2022) "On Approval of the Nomenclature of Medical Services" (Registered with the Ministry of Justice of Russia on November 7, 2017, No. 48808)

4. Federal Law No. 323-FZ of November 21, 2011, "On the Fundamentals of Health Protection of Citizens in the Russian Federation."

5. List of Vital and Essential Drugs for Medical Use for 2020. Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019 (as amended on April 26, 2020), "On Approval of the List of Vital and Essential Drugs for 2020, as well as Lists of Drugs for Medical Use and the Minimum Assortment of Drugs Required for the Provision of Medical Care."

6. Order of the Ministry of Health of the Russian Federation No. 143n dated March 27, 2024, on the approval of the classification of natural therapeutic resources specified in paragraph 2 of Article 2.1 of Federal Law No. 26-FZ dated February 23, 1995, "On Natural Therapeutic Resources, Health Resorts, and Spas", their characteristics, and the list of medical indications and contraindications for sanatorium-resort treatment and medical rehabilitation using such natural therapeutic resources

https://normativ.kontur.ru/document?moduleId=1&documentId=468782#h614

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Congenital glaucoma is a severe congenital disease that is one of the main causes of blindness, low vision, and visual impairment in children from an early age. The success of treatment for children with congenital glaucoma largely depends on early detection of the disease and timely treatment. In late stages of the disease, even after surgical treatment, the chances of a successful outcome are significantly reduced. If treatment is not started in a timely manner, the disease progresses rapidly and leads to irreversible changes in all structures of the eyeball. Children with suspected congenital glaucoma or a confirmed diagnosis are placed on dispensary follow-up at the polyclinic. In case of suspected congenital glaucoma, the child must undergo mandatory examination, and if the diagnosis is not ruled out, examinations are repeated monthly. A child with a confirmed diagnosis and normalized pressure should be examined by an ophthalmologist at least once every three months. Following surgical treatment, the first examination should be performed no later than one week after discharge from the hospital; in case of an unstable course — at least once a month, and in case of a stable course — once every 3–6 months.

An urgent visit to an ophthalmologist is necessary if any of the following symptoms appear: eye redness, photophobia, pain, decreased and/or blurred vision, visual field loss, impaired color perception, changes in iris color, pupil size, and pupil shape.

It is essential to strictly follow all prescriptions and the recommended frequency of examinations by an ophthalmologist.

The patient (the patient's parents) must be informed about potential side effects of therapy and urgently consult an ophthalmologist if they develop.

In cases of irreversible blindness or low vision, the patient (the patient's parents) must have complete information regarding social, psychological, and vocational rehabilitation options.

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

No.