Myopic Macular Degeneration (Myopic Maculopathy): Clinical Guidelines

List of Abbreviations

D – diopter

ILM – internal limiting membrane

ICD — International Classification of Diseases

µm – micrometer

BCVA – best corrected visual acuity

MMD – myopic macular degeneration

MH – macular hole

MRSD – macular hole-related retinal detachment

MR - myopic retinoschisis

MTM – myopic traction maculopathy

mCNV – myopic choroidal neovascularization

NRL – neurosensory retinal layer

OCT – optical coherence tomography

OCT-A – optical coherence tomography angiography

RD – retinal detachment

PVHRD — peripheral vitreochorioretinal dystrophy

AL – axial length of the eye

RPE – retinal pigment epithelium

FA – fluorescein angiography (fundus fluorescein angiography)

PDT ― photodynamic therapy

CNV – choroidal neovascularization

VEGF - vascular endothelial growth factor

Terms and Definitions

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

Posterior staphyloma is a localized outpouching of the eyeball wall, which is considered a hallmark of pathological myopia and is one of the main causes of myopic macular degeneration (MMD).

Intraretinal fluid (neurosensory retinal (NRL) edema) is an intercellular accumulation of fluid within the layers of the NRL, manifesting as retinal thickening.

Fundus autofluorescence imaging is a diagnostic method based on the ability of fluorophores (specifically lipofuscin and its compounds) to autofluoresce upon excitation without the administration of dyes.

Dome-shaped macula is a type of posterior staphyloma, which is often associated with atrophic changes of the retinal pigment epithelium and foveal retinal detachment, leading to decreased visual acuity.

Laquer cracks are linear or stellate breaks in the retinal pigment epithelium (RPE) and/or Bruch's membrane, typically located in the posterior pole of the eye and considered a risk factor for the progression of myopic maculopathy.

Macular hole (MH) is a retinal tissue defect developing due to tractional forces, typically involving the fovea. It can be partial (lamellar) or full-thickness.

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

Optical coherence tomography angiography (OCT-A) is a diagnostic non-invasive, non-contact in vivo visualization method for qualitative and quantitative analysis of microcirculation in fundus structures, taking into account fundus layer segmentation.

Tigroid (mosaic, tessellated) fundus is an ophthalmoscopic pattern characteristic of eyes with RPE thinning: deep pigmentation of the choroid appearing as dark polygonal areas between choroidal vessels; it represents the early stage of fundus changes in myopic maculopathy.

Fuchs spot (Fuchs/Föster-Fuchs spot) is a pigmented scar resulting from myopic choroidal neovascularization, appearing as a rounded lesion, usually dark in color (less commonly gray, yellow, red, or green), caused by the degradation of hemoglobin breakdown products and hyperplasia of retinal pigment epithelium cells. The term is largely of historical significance, though still mentioned in several modern classifications.

Fluorescein angiography (FA, sodium fluorescein angiography**) is a diagnostic method that allows the detection of vascular abnormalities in the fundus and the evaluation of the outer and inner blood-retinal barriers by recording the passage of a dye (intravenously administered sodium fluorescein**) through the ocular vessels using photo- and video-monitoring.

Photodynamic therapy (PDT) is a method of treating certain eye diseases based on the use of photosensitizing agents and light of a specific wavelength to occlude pathological vessels.

Choroidal neovascularization (CNV) is a process of pathological neoangiogenesis induced by the overexpression of pro-angiogenic factors (primarily various isoforms of vascular endothelial growth factor – VEGF) from the choriocapillaris network through defects in Bruch's membrane beneath the RPE and/or NRL.

Chorioretinal atrophy is the result of the loss of choriocapillaris, RPE, and outer layers of the sensory retina due to impaired blood flow in the choriocapillaris or an inflammatory process.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Myopia (myopia, from Greek *myo* – to shut and *ops* – eye) or nearsightedness is a disproportionate type of eye refraction in which parallel rays of light are focused in front of the retina, and a circle of light diffusion is formed on the retina. Myopia is the most frequent cause of deterioration in distance visual acuity. The diagnosis is established if myopic refraction under conditions of cycloplegia is 0.5 diopters or more. With an unfavorable clinical course, myopia causes retinal complications, strabismus, reduced corrected visual acuity, and in severe cases leads to disability at working age [1].

High myopia is myopic refraction with a spherical equivalent refractive error of > 6.0 diopters; it usually manifests in early childhood and progresses. Patients with high axial myopia are at greater risk of developing progressive retinal degeneration and other vision-threatening pathologies. For patients who have undergone refractive surgery and lack documentation of their preoperative status, the main criterion for establishing the diagnosis is an axial length of the eyeball of ≥ 26.0 mm.

Degenerative (pathological) myopia is myopia accompanied by characteristic myopic fundus changes (the presence of myopic maculopathy equal to or more severe than diffuse choroidal atrophy, or the presence of a posterior staphyloma).

Myopic macular degeneration (myopic maculopathy) is a complex of potentially coexisting degenerative changes of the macular region associated with myopia, including atrophic (mosaic changes, focal and diffuse chorioretinal atrophy, mCNV-associated atrophy), tractional (myopic traction maculopathy), and neovascular (mCNV and its sequelae) components. It is considered the most serious, irreversible, vision-threatening complication and the leading cause of bilateral visual impairment and blindness due to myopia.

Myopic choroidal neovascularization (mCNV) is a typical pathological process associated with nearsightedness, characterized by the proliferation of choroidal vessels with the development of fibrovascular cords and membranes beneath the NRL and/or RPE due to increased concentration of vascular endothelial growth factor (VEGF) against the background of choroidal thinning in the peripapillary zone and/or macula, or in the presence of defects in Bruch's membrane.

Myopic traction maculopathy (MTM) or myopic retinoschisis is a combination of macular retinoschisis (schisis-like fluid accumulation in the inner and/or outer retina caused by traction), lamellar or full-thickness macular hole, and/or foveal retinal detachment in eyes with high myopia, caused by tractional forces arising from the interaction of the cortical layers of the vitreous body, epiretinal membrane, internal limiting membrane, retinal vessels, and posterior staphyloma.

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

Myopia is a complex disease with a multifactorial etiology. The concept of the etiology and pathogenesis of nearsightedness in children is reflected in the three-factor theory of myopia origin proposed by Professor E.S. Avetisov (1999). He developed a model of refractogenesis characteristic of nearsightedness. This theory suggests that the main factors in the origin and progression of nearsightedness are weakened accommodation, hereditary (genetic) predisposition, and weakening of the scleral supporting properties. General systemic diseases, connective tissue metabolic disorders, and other factors, which are often assigned a leading role in the origin of myopia, promote the transition of the cause (near work under conditions of weak accommodative ability) into the consequence – myopic refraction [2].

Risk factors for the onset and progression of nearsightedness (according to E.S. Avetisov) [2].

There is evidence of familial inheritance of both pathological non-syndromic high myopia and high myopia associated with certain syndromes. Although non-syndromic high myopia is most commonly inherited in an autosomal dominant manner, multiple chromosomal loci have been identified, suggesting genetic heterogeneity [3]. High myopia is also a symptom of several multisystem complex disorders. Genetic mutations have been identified for these syndromes, and the subsequent structural defects of the eye are most commonly associated with connective tissue and the retina [3]. This type of myopia accounts for only a small fraction of the total myopic population, and to date, there is no known isolated gene associated with physiological myopia.

Syndromic myopia is associated with a number of ocular disorders (congenital glaucoma, retinopathy of prematurity, retinitis pigmentosa, cataract, congenital stationary night blindness, keratoconus, Forsius-Eriksson syndrome, gyrate atrophy, pseudomyopia, albinism), as well as certain multisystem disorders (Stickler syndrome, uncontrolled diabetes mellitus, Marfan syndrome, Weill-Marchesani syndrome, Knobloch syndrome, Ehlers-Danlos syndrome) [3].

In addition to simple, pathological (degenerative), and syndromic myopia, other processes affecting the refractive structures of the eye can also cause myopia. Lens power may be increased by osmotic changes (diabetes, galactosemia, uremia, administration of drugs from the J01E group: sulfonamides and trimethoprim), nuclear sclerotic cataracts, anterior lenticonus, and changes in the position or shape of the lens (miotics, anterior lens dislocation, excessive accommodation). Corneal changes secondary to keratoconus, congenital glaucoma, and contact lens-induced corneal curvature can also cause myopia. Myopia can also result from an increase in axial length due to retinopathy of prematurity, posterior staphyloma, scleral buckling surgery, and congenital glaucoma [4].

The pathogenesis of degenerative myopia is complex and not fully understood. It is known that progressive elongation of the eyeball causes biomechanical stretching of the retina, retinal pigment epithelium, and choroid, accompanied by straightening and thinning of retinal vessels with a decrease in retinal blood flow and a reduction in the density of the retinal capillary network and choriocapillaris [5-8]. The development of degenerative processes in the macular region is associated with circulatory disorders [9-10]. A higher resistivity index in the posterior ciliary arteries of eyes with unilateral myopia complicated by mCNV has been proven compared to the non-myopic fellow eye [11]. Risk factors for the development of mCNV include degenerative changes in Bruch's membrane, thinning of the choriocapillaris, and slowed choroidal blood flow [12, 13]. The presence of a posterior staphyloma is considered a hallmark of pathological myopia and is one of the main causes of maculopathy development [14]. Elevated VEGF levels also play a role in the pathogenesis of mCNV [15]. Predictors of an unfavorable course of pathological myopia and the development of mCNV are lacquer cracks and focal chorioretinal atrophy [16]. Various myopic tractional changes of the retina and fovea are currently considered evolutionary stages of the same disease and are driven by the interaction of various centrifugal and centripetal influences, manifested as foveal (tangential) and retinal (perpendicular) patterns [17].

1.3 Epidemiology of the Disease or Condition

Myopia is the most common ocular pathology, affecting approximately 1.5 billion people worldwide. The highest prevalence rates of myopia are recorded in East and Southeast Asian countries—up to 96% of the population [18-21]. There is evidence of an increasing prevalence in European countries [22] and the USA [23, 24]. It is believed that the increase in myopia prevalence is associated with higher levels of education [22, 25]. It is projected that the number of myopic individuals worldwide will increase from 1.4 billion (22.9% of the world's population) in 2000 to 4.8 billion (49.8%) by 2050, and in Europe this figure will reach 56.2% by 2050 [26], entailing significant clinical and economic consequences [22]. At the same time, a significant increase in the number of people with high myopia worldwide is expected: from 163 million (2.7% of the world's population) in 2000 to 938 million (9.8%) in 2050 [26].

Depending on the clinical course and prognosis, two groups of myopia are distinguished: non-pathological and pathological. In non-pathological (simple, physiological, or school) myopia, ocular structures develop normally, but the refractive power does not correlate with the axial length. The onset of non-pathological myopia typically occurs in childhood or adolescence, with the degree varying from minimal to moderate (up to 6.00 diopters) [4]. Progression of such myopia usually continues throughout the adolescent growth period and slows down or stops during the second decade of life. Less commonly, a second myopic shift may occur at the end of the second or beginning of the third decade [27]. According to estimates by the American Academy of Ophthalmology published in 2010, the majority of myopic patients had non-pathological myopia: approximately 66% of patients had myopia of less than 2 D, and 95% of patients had less than 6 D [28].

Pathological myopia is typically defined as a high-degree myopic refractive error that usually manifests in very early childhood and progresses [4]. Patients with high axial myopia are at a higher risk of developing progressive retinal degeneration and other vision-threatening pathologies. The overall global prevalence of degenerative myopia is estimated at 0.2–3.8% with regional variability, but the varying definitions used in early epidemiological studies limit comparability. The condition ranks 2nd to 5th among causes of blindness in several European and North American studies, with a share ranging from 6.0% to 9.1%, and leads this metric in Japan (22.4%) and China (26.1%) [29]. In Russia in 2016, degenerative myopia ranked third in the structure of visual disability among the adult population (13%) [30]. According to the Russian Ministry of Labor, in 2021 the accumulated disability due to myopia complications amounted to 29,215 individuals (2.00 per 10,000 population), including 28,418 adults (2.45 per 10,000 adult population, 4th place in the nosological structure) and 797 children (0.26 per 10,000 child population, 4th place in the nosological structure).

Conditions for the development of complicated myopia are laid down during the period of active myopia progression, which coincides with schooling. Identification, prevention of the development and progression of myopia and its complications should be carried out precisely during this period [1, 31]. Despite the undoubted successes achieved in recent years in the prevention and treatment of this disease, it frequently leads to the development of irreversible fundus changes and a significant decrease in vision at a young, working age.

1.4 Features of Coding the Disease or Condition

H44.2 - Degenerative myopia.

1.5 Classification of the disease or condition

1.5.1. Clinical classification of myopia (according to E.S. Avetisov, abridged) [2]

1. By degree:

• Low degree (up to 3.0 D inclusively);

• Moderate degree (3.25–6.0 D);

• High degree (more than 6.0 D).

2. By equality or inequality of the refractive value of both eyes:

• Isometropic;

• Anisometropic.

3. By presence or absence of astigmatism:

• Without astigmatism;

• With astigmatism.

4. By age period of onset:

• Congenital;

• Early-acquired (in preschool age);

• School-age acquired;

• Late-acquired (in adulthood).

5. By course:

• Stationary;

• Slowly progressive (less than 1.0 D per year);

• Rapidly progressive (1.0 D or more per year).

6. By presence or absence of complications:

• Uncomplicated;

• Complicated.

7. By stage of functional changes in a complicated course (degree of visual acuity reduction of the better-seeing eye with standard correction):

I. Visual acuity 0.8–0.5;

II. Visual acuity 0.4–0.2;

III. Visual acuity 0.1–0.05;

IV. Visual acuity 0.04 and lower.

1.5.2. Classification of myopia by refractive error (spherical equivalent) (according to Flitcroft et al. [32] with modification [33])

* Mathematical comparison symbols (<, >, ≤, and ≥) are used based on the assumption that the most logically consistent approach is to always treat myopic refractive errors as negative values and use mathematical terms in their strict mathematical sense; therefore, myopia < −6.00 D means refractive errors with values more negative and, consequently, more myopic than −6.00 D.

** Corresponds to Category 2 according to the META-PM classification [34].

There are no fundamental contradictions between the traditional and widely used classification by E.S. Avetisov, which should appropriately continue to be used within the healthcare system of the Russian Federation, and more modern foreign classifications. At the same time, one must take into account discrepancies in the interpretation of refractive error values (the use of inclusive versus exclusive threshold values), mathematical signs ">" and "<", as well as the existence of fundamentally different approaches to defining high myopia (in particular, the WHO approach, which uses a threshold of "-5.00 D" for high myopia to emphasize the significance of visual impairment caused by uncorrected refractive errors in populations with limited access to corrective devices [35]). 

1.5.3. International Photographic Classification and Grading System for Myopic Maculopathy (META-PM) [34]

Three additional features supplementing these categories were defined as "plus" lesions: lacquer cracks, mCNV, and Fuchs spot.

1.5.4. OCT-based Classification of Myopic Maculopathy [36]

1.5.5. Tokyo Medical and Dental University (TMDU) Classification of Posterior Scleral Staphylomas [37], which is a revised classification of B.J. Curtin (1977 [38]):

• Type I – wide, macular

• Type II – narrow, macular

• Type III – peripapillary

• Type IV – nasal

• Type V – inferior

• Other

1.5.6. Tokyo Medical and Dental University (TMDU) Classification of Myopic Traction Maculopathy [39]

1.5.7. The Myopic Traction Maculopathy staging system (MSS) [17] (abridged)

There is no single universally accepted classification of myopic maculopathy, but the following system, which takes into account the atrophic (A), tractional (T), and neovascular (N) components, is of interest.

1.5.8. The ATN myopic maculopathy classification system [14]:

Given that the healthcare system of the Russian Federation is oriented towards formulating diagnoses in accordance with ICD, we consider it appropriate to treat the terms "degenerative (pathological) high myopia", "myopic macular degeneration", and "myopic maculopathy" as synonyms, and to use the ATN system for their classification (as it is sufficiently compact while allowing characterization of all three components of the disease – atrophic, tractional, and neovascular).

1.6 Clinical presentation of the disease or condition

Pathological myopia typically debuts in very early childhood and progresses [4]. The first symptom of myopia is a deterioration of distance visual acuity, while binocular functions remain preserved in the majority of children with myopia. No anterior segment changes are detected. Optical media are clear. Peripapillary changes and characteristic dystrophic changes of the peripheral retina may be found on fundus examination; no macular pathology is observed.

Signs of MMD appear as myopia progresses and manifest in childhood only in congenital myopia (lacquer cracks, coin-shaped hemorrhages, and neovascular membranes); in adolescence (after 14 years of age) in congenital and early-onset myopia; in so-called school myopia, myopic maculopathy occurs only in adults, typically after the age of 30 [1, 40]. It has been established that the probability of visual impairment due to MMD increases sharply in myopes with an axial length ≥ 26 mm, increasing exponentially with age:

Risk of visual impairment according to axial length and spherical equivalent by age category (after J.W.L. Tideman et al., 2016 [41])

It should be borne in mind that individual patients may have specific features that affect the correlation between the axial length of the eye and the degree of myopia [42]. Factors involved in "masking" axial elongation of the eye include the optical power of the lens and cornea, as well as human height (body length) [43 - 45]. This fact emphasizes the importance of biometric examination in the comprehensive assessment of patients with myopia. At the same time, one should take into account the continued axial elongation in adults with high myopia: according to a recent cohort study (1,877 patients, including 1,357 women; mean age 62.1 years; mean AL 29.66 mm), the increase in axial length averaged 0.05 mm/year (with a standard deviation of 0.24 mm/year), and risk factors for a more pronounced increase were female sex, age under 40 years, AL ≥ 28.15 mm, BCVA < 20/400 Snellen (< 0.05 decimal), presence of myopic maculopathy, and prior choroidal neovascularization [46].

In adult patients with myopia, peripapillary fundus changes are widespread, among which it is customary to distinguish light arcuate reflexes, myopic cones (subdivided into a crescentic cone, the cone proper, and a circular cone or false staphyloma). Degenerative myopia is characterized by the formation of a true staphyloma—an outpouching of the posterior segment of the eye, which is a posterior scleral ectasia. The prevalence of true staphylomas increases from 1.4% in eyes with an axial length of 26.5–27.4 mm to 71.4% with an AL of 33.5–36.6 mm [47]. B.J. Curtin's classification (1977 [38]) distinguishes primary staphylomas (types I–V: I – posterior, II – macular, III – peripapillary, IV – nasal, V – inferior staphyloma), as well as combined staphylomas (types VI–X, which, according to modern researchers [48], are variants of type I staphylomas). Currently, "dome-shaped macula" is regarded as a previously unregistered type of posterior staphyloma, which is often accompanied by atrophic changes in the retinal pigment epithelium and foveal retinal detachment leading to decreased visual acuity [49]. It is currently believed that the presence of a posterior staphyloma, along with the elongation of the axial length of the eye, is a key differentiating factor between high and pathologic myopia [14].

Pathological changes in the macular region in degenerative myopia include "tessellated" fundus, "lacquer cracks" (linear or stellate breaks in Bruch's membrane, retinal pigment epithelium, and choriocapillaris), diffuse and patchy chorioretinal atrophy, mCNV and macular atrophy, as well as various variants of tractional changes.

Variants of the progression of pathological changes are clearly demonstrated in the following diagram [50]:

In addition, the following patterns of myopic maculopathy progression have been described.

1. Changes associated with progressive choroidal thinning [50]:

Normal fundusTessellated fundus

Peripapillary diffuse chorioretinal atrophyMacular diffuse atrophy

2. Changes associated with the formation and expansion of breaks in Bruch's membrane [51]:

Lacquer cracksPatchy atrophyMacular atrophy associated with patchy atrophy

Myopic CNVCNV-associated macular atrophy

Morphologically, mCNV is a type 2 ("classic") neovascular membrane, which is most often located subfoveally (in 58–74% of cases it is located under the fovea and has a size less than half of the optic disc), and less commonly within 100–300 µm from the foveola. It may be accompanied by focal retinal detachment and hemorrhages; hard exudate deposits are possible but not characteristic [52 - 54].

The natural history of mCNV is well studied. The activity of mCNV is usually less pronounced than in neovascular age-related macular degeneration. Spontaneous remissions of activity are possible, but the regressive neovascular membrane itself and the surrounding atrophy progress and expand, which can cause progressive function loss. Previously, the term "Fuchs spot" was actively used to describe the outcome of mCNV, but with the introduction of OCT into clinical practice, which allows detailed study of macular morphology, it is gradually losing its relevance. The visual prognosis of mCNV is determined by the age of onset: patients older than 40 years have a worse prognosis. Areas of chorioretinal atrophy are the most significant factors for a poor long-term visual prognosis, and older age and a larger mCNV area are interrelated with the onset of atrophy. In general, the functional prognosis is unfavorable: an increase in the proportion of patients with BCVA <0.1 from 29.6% to 96.3% over 10 years of follow-up has been noted. The probability of developing mCNV in the contralateral eye in patients with bilateral high myopia is 35% over 8 years [52, 55 - 57]. The most frequent causes of vision loss in patients with mCNV receiving anti-VEGF therapy in the long-term period are fibrosis, atrophy, and macular hole formation, the incidence of which within five years after the start of treatment is 34%, 26%, and 8%, respectively [58].

Specific tractional macular changes were first described in 1997: Takano and Kishi first identified and reported that foveal retinal detachment and myopic macular retinoschisis (MMR) were observed in eyes with high myopia prior to the development of retinal detachment (RD) with a macular hole (MH) [59]. In 2004, Pannozzo and Mercanti [60] proposed combining all pathological signs caused by traction in myopia under the name "myopic traction maculopathy" (MTM). Pathogenetic mechanisms and treatment approaches for MTM continue to be actively studied.

The MTM staging system (MSS, see section 1.5.6.) defines the evolution of the disease in two directions: perpendicular to the retina (stages 1–4) and tangential (parallel to the retina and fovea, stages A–C). Outer lamellar holes can occur in stages 2, 3, and 4, whereas epiretinal abnormalities can be present at any stage. MTM can progress from stage 1 to stage 4 and from stage A to C simultaneously or separately. The average time required for transition from one stage to another ranges from weeks to 18 months [17].

In MMR and lamellar MHs, as well as full-thickness MHs uncomplicated by the development of RD, relatively high visual functions are often preserved. At the same time, MHs in eyes with pathologic myopia tend to develop RD, unlike idiopathic MHs in non-myopic eyes. Thus, MH and macular hole-related retinal detachment (MHRD) are severe complications associated with pathologic myopia [61].

Another specific clinical condition characteristic of pathologic myopia is myopia-associated glaucoma-like optic neuropathy, which is characterized by the loss of the neuroretinal rim and an increase in optic disc cupping, occurring in eyes with high myopia with the formation of a secondary macrodisc (an optic disc of large size with increased cupping, normal neuroretinal rim volume, normal visual field, and normal intraocular pressure [62, 63]) or peripapillary delta-zone (defined in the area between the peripapillary ring (which is a continuation of the pia mater of the optic nerve) and the line of fusion of the dura mater of the optic nerve with the posterior part of the sclera [64]) with normal intraocular pressure.

It is also known that as the degree of myopia increases, the probability of developing many pathological conditions also increases [65]:

Questionnaires can be used to assess the quality of life and visual functions of patients with PMD (see Appendix G).

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing a diagnosis of PMD: a combination of specific fundus changes (maculopathy equal to or more severe than diffuse chorioretinal atrophy, or posterior staphyloma) with confirmed myopic refraction (based on a study under conditions of cycloplegia - refraction spherical equivalent values corresponding to myopic refraction of 0.5 D or greater) in patients of any age. In the vast majority of cases, PMD is diagnosed in adults with a refractive spherical equivalent error ≥ 8.00 D or an axial length of the eyeball ≥ 28.0 mm.

Comments: Patients with any degree of myopia (including those who have undergone refractive surgery and lack documentation of their preoperative status) who exhibit a significant increase in eye size (axial length greater than 26 mm) should be considered at risk of developing and progressing MMD [41]. In the event of choroidal neovascularization (CNV) or other complications, the frequency of follow-up may be increased, as determined by the attending physician based on the treatment regimen [69].

Comments: Examinations of patients with high myopia who show no signs of pathological myopia should include a detailed fundus examination, including the far periphery, and optical coherence tomography (OCT), and should be performed every 6–12 months [68].

2.1 Complaints and Anamnesis

Comments: with myopia, patients complain of decreased distance visual acuity (in cases of high, congenital, and complicated myopia, complaints include decreased distance and near visual acuity). With MMD, patients may complain of straight lines appearing distorted (metamorphopsia) or letters missing during reading. In cicatricial or atrophic macular changes, patients report a significant decrease in visual acuity and an inability to read due to organic photoreceptor damage. In the presence of vitreoretinal tractions, the patient may be disturbed by photopsia (flashing "lights", "lightning", "sparks", etc.), numerous floaters, or the appearance of a "curtain" or "cloud" in the visual field. The onset of photopsia is associated with the physical traction exerted by the vitreous body on the retina. Floaters are opaque structures, such as blood, glial cells detached from the optic disc, or collagen fiber clumps that can cast a shadow on the retina.

History of the present illness – time of detection of myopia. When the first glasses were prescribed. When the last glasses were prescribed and which ones. Refraction dynamics (according to previous examinations, previously dispensed glasses, from the patient's words). What treatment was received previously.

Past medical history: family history of myopia. Previous illnesses. Presence of other diseases and allergies. Specifics of visual workload, physical education, sports, and other activities. Characteristics of the residential area. Time spent outdoors [52, 70 - 73].

To assess treatment satisfaction in patients with MMD, the validated MacTSQ (Macular disease Treatment Satisfaction Questionnaire) can be used (Appendix G1) [74].

2.2 Physical Examination

No literature sources were found demonstrating the efficacy of physical examination methods for diagnosing MMD.

Comments: patients with concomitant conditions, including systemic diseases and risk factors for various complications, should be referred to relevant specialists for consultation prior to conservative, laser, or surgical treatment in order to identify potential contraindications to these treatments and minimize the risk of complications. The choice of specialist (general practitioner, otolaryngologist, dentist, endocrinologist, etc.) is determined by the concomitant systemic disease and the risk factor for systemic complications.

2.3 Laboratory Diagnostics

Diagnostic criteria for MMD based on clinical laboratory test data do not exist.

Comments: testing is performed based on voluntary informed consent (Sanitary and Epidemiological Rules SP 3.1.5.2826-10 "Prevention of HIV Infection"). The choice of laboratory test is determined by the patient's concomitant systemic disease and risk factors for systemic complications [76]. Additional laboratory tests are prescribed by the attending physician depending on the presence and clinical features of the patient's concomitant systemic disease and systemic complication risk factors (including to identify potential contraindications to various types of treatment).

2.4 Instrumental Diagnostics

Comments: the standard method is to evaluate visual acuity using charts or a visual acuity projector. It should be noted that in macular disorders, evaluating visual acuity using the decimal or Snellen system is less informative than the ETDRS scale, which has higher sensitivity.

Comments: subjective refraction testing involves determining the lowest minus lens with which the best-corrected visual acuity (BCVA) is achieved [2, 83].

Comments: 0.5-1% tropicamide** induces shallower cycloplegia than 1% cyclopentolate [84, 85].

Comments: the APD is evaluated using an ultrasonic diagnostic device or optical biometer. Determination of APD is recommended as the primary examination method. Determination of the transverse diameter of the eye is recommended as an additional examination method.

An APD length ≥ 26 mm is associated with an increased risk of vision loss and should raise vigilance [41].

Axial elongation in high myopia in adult patients may continue, and risk factors for a more pronounced increase in this parameter include female sex, age under 40 years, APD length ≥ 28.15 mm, best-corrected visual acuity (BCVA) < 0.05, presence of myopic maculopathy, and prior choroidal neovascularization [46].

The necessity and frequency of ocular ultrasound biometry or optical ocular biometry are determined by the ophthalmologist depending on the clinical course of the disease.

Comments: two-dimensional (B-scan) and one-dimensional (A-scan) echography are the main methods [93].

The necessity and frequency of the ultrasound examination of the eyeball are determined by the ophthalmologist depending on the clinical course of the disease.

Comments: the necessity and frequency of fundus biomicrophotography using a fundus camera are determined by the ophthalmologist depending on the clinical course of the disease. It is advisable to perform ultra-widefield fundus photography [34, 66, 67, 95].

Comments: the necessity and frequency of fundus autofluorescence imaging are determined by the ophthalmologist depending on the clinical course of the disease. In patients with myopic choroidal neovascularization (mCNV), fundus autofluorescence imaging should be periodically performed 1 year after its detection to identify mCNV-associated macular atrophy [96].

Comments: the necessity and frequency of FA are determined by the ophthalmologist depending on the clinical course of the disease; in certain cases, FA is recommended 1 month after the initiation of anti-VEGF therapy: the disappearance of dye leakage is an earlier and more accurate marker of decreased mCNV activity than signs detected by OCT or OCT angiography [98].

Comments: the necessity and frequency of ICGA are determined by the ophthalmologist depending on the clinical course of the disease; the method may be more sensitive for detecting mCNV because vascular leakage in pathologic myopia is usually less prominent than in age-related macular degeneration and can be missed on FA.

Comments: when assessing mCNV activity and determining indications for treatment with intravitreal administration of an anti-angiogenic medicinal product, quantitative and qualitative parameters of the tomogram should be evaluated; in patients with a newly established diagnosis initiating anti-VEGF therapy, it is advisable to perform OCT monthly for the first 3 months and then every 2–3 months; in the absence of recurrences during the year, the interval can be further increased: the frequency of monitoring after the first year of treatment is every 6 months. An unscheduled examination is advisable if new complaints appear or symptoms change [97].

OCT is the main method for the diagnosis and monitoring of MTM. The minimum frequency of examinations is once every 12 months for myopic maculoschisis, once every 6 months for lamellar macular hole (MH), and once every 3 months for full-thickness MH with high visual functions. It is determined based on recommendations [17], taking into account that the average time for the development of the next stage of MTM gradually decreases, being respectively 20 months from stage 1 to stage 2, 12 months from stage 2 to stage 3, and 3 months from stage 3 to stage 4. The decision on the optimal monitoring frequency is made by the attending physician, taking into account the specifics of each individual clinical case. The patient must be informed about symptoms requiring emergency medical attention.

Comments: The need for and frequency of OCT-A are determined by the ophthalmologist depending on the clinical course of the disease; it is advisable to perform OCT-A 1 month after initiating anti-VEGF therapy (if FFA cannot be performed) to assess mCNV activity (a reduction in mCNV size on OCT-A is a good marker of treatment efficacy; however, blood flow detected by OCT-A tends to persist after mCNV becomes inactive and even into its atrophic stage) [97].

Comments: Intraocular pressure can be measured using: Maklakov tonometry (under topical anesthesia); non-contact tonometry/pneumotonometry (used for screening); rebound tonometry using Icare-type tonometers; Goldmann applanation tonometry (under topical anesthesia); or digital palpation (if the aforementioned methods are unfeasible).

Comments: In myopia of less than 5.0 D (with astigmatism not exceeding 3.0 D), perimetry is performed without correction; for myopia greater than 5.0 D, it is performed with lower correction than that for distance (taking into account the impact of the spectacle frame on the visual field).

If abnormalities are detected, consultation with a glaucoma specialist may be required, as the risk of primary open-angle glaucoma is elevated and evaluating optic disc parameters is often challenging [68]. Currently, so-called "myopic glaucoma-like optic neuropathy" has been described and continues to be studied, presenting with neuroretinal rim loss and increased cupping in highly myopic eyes despite normal intraocular pressure levels [61].

The necessity and frequency of automated perimetry are determined by the ophthalmologist depending on the clinical course of the disease.

Comments: The necessity and frequency of electroretinography are determined by the ophthalmologist depending on the clinical course of the disease.

2.5 Other Procedures

No other diagnostic investigations are routinely specified.

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

3.1. Optical correction

Comments: When prescribing optical correction, the following factors are considered: the degree of myopia, the status of accommodation, convergence, and binocular vision. Spectacle correction of myopia can be implemented using single-vision lenses, bifocal or progressive lenses, customized corrective lenses with perifocal design for central vision correction and peripheral defocus modification, or alternating anisocorrection [2, 79, 104].

3.2. Functional treatment

3.3 Laser treatment

Comments: When performing laser photocoagulation of neovascular membranes, the high risk of chorioretinal atrophy and mCNV recurrence must be taken into account. Prior to laser photocoagulation, the exact size and location of the mCNV must be determined using multimodal imaging, including FFA, OCT, and potentially OCT-A. Focal fundus laser photocoagulation for mCNV is inferior in efficacy to intravitreal anti-angiogenic therapy.

The feasibility and appropriateness of repeating the procedure are determined by the treating physician based on follow-up findings (repeat ophthalmologist examination/consultation, B01.029.002).

Comments: Photodynamic therapy may be performed as an alternative modality or in combination with intravitreal anti-angiogenic administration. The VIP study demonstrated that PDT was more effective than placebo in reducing the risk of moderate vision loss at 12 months; however, by 24 months, there was no statistically significant difference between the treatment groups [110].

The feasibility and appropriateness of repeating the procedure are determined by the treating physician.

3.4 Surgical treatment

Comments: currently, intravitreal administration of medicinal products inhibiting angiogenesis (anti-angiogenic or anti-VEGF therapy) is the first-line therapy for mCNV.

Ranibizumab** is a fragment of a humanized antibody against vascular endothelial growth factor A (VEGF-A). It selectively binds to VEGF-A (VEGF110, VEGF121, VEGF165), preventing its interaction with receptors on the surface of endothelial cells, which leads to the suppression of neovascularization and endothelial cell proliferation [117].

Aflibercept** is a recombinant fusion protein consisting of fragments of the extracellular domains of human VEGF receptors fused to the Fc portion of human immunoglobulin G. It acts as a soluble decoy receptor that binds VEGF-A and placental growth factor with higher affinity than their natural receptors, and thus can inhibit the binding and activation of VEGFR-1 and VEGFR-2 receptors by multiple growth factors involved in pathological angiogenesis [118].

The prospects of therapy directly depend on its timely initiation and adherence to the optimal injection regimen based on regular dynamic follow-up (subsequent visit (examination, consultation) by an ophthalmologist, B01.029.002).

When treating with ranibizumab**, the following regimen is recommended: treatment is initiated with a single injection (0.5 mg/0.05 ml) per month and continued until maximum stable visual acuity is achieved and/or until signs and symptoms of the disease disappear against the background of ongoing treatment. Many patients may require one or two injections during the first year of treatment. An interval of at least 4 weeks should be observed between injections into the same eye.

When treating with aflibercept**, the recommended dose is a single intravitreal injection (2.0 mg/0.05 ml). If visual acuity and anatomical parameters indicate persistent disease, additional injections may be administered. Recurrences should be treated as a new manifestation of the disease. The interval between two doses must be at least one month.

In each clinical case, the final decision on the indications for treatment with angiogenesis inhibitors and the choice of the intravitreal injection regimen is made by the physician based on the assessment of the clinical presentation and the course of the disease. Prevention of a decrease in visual acuity, even in the absence of its improvement, should be considered a positive outcome compared to the natural course of the disease.

When administering an intravitreal angiogenesis inhibitor, potential risks of complications such as infectious endophthalmitis, non-infectious intraocular inflammation, iatrogenic cataract, hemophthalmos, retinal detachment, and others should be considered. Contraindications to the intravitreal administration of ranibizumab** or aflibercept**:

1. hypersensitivity to the components of the drug;

2. active confirmed or suspected ocular infections or periocular infectious processes;

3. age under 18 years;

4. active intraocular inflammatory process;

5. pregnancy and breastfeeding period.

Comments: Pathogenetic mechanisms and treatment approaches for myopic traction maculopathy (MTM) continue to be actively studied. In myopic foveoschisis (MF) and lamellar MHs, as well as full-thickness MHs not complicated by RD, relatively high visual functions are often preserved. At the same time, MHs in eyes with pathologic myopia tend to develop RD, unlike idiopathic MHs in non-myopic eyes. Thus, MH and MH-associated RD are serious complications associated with pathologic myopia. Pars plana vitrectomy is currently the main treatment method for MTM. However, unresolved issues remain regarding the indications and timing of surgery, as well as its scope and technical features preferable in various situations. It is known that the elimination of retinal traction using vitrectomy with internal limiting membrane (ILM) peeling effectively resolves MTM and prevents the formation of MH and MH-associated RD. At the same time, vitrectomy with ILM peeling is complicated by the development of MH in the postoperative period in 5-20% of cases. To prevent this complication, an ILM peeling technique that spares the fovea has been proposed. Early stages of MTM without foveal detachment proceed relatively stably and asymptomatically and are not an indication for surgical intervention. At the same time, the prognosis of surgery is better when performed before the formation of a macular hole, so the optimal timing of surgery is determined by the dynamics of OCT data and visual functions [60, 134]. There are studies demonstrating the effectiveness of macular buckling in MTM, and the prospects of using this technique alone or in combination (simultaneously or staged) with vitrectomy continue to be studied, although it is not widely used at present [135, 136].

An ophthalmologist referring a patient for vitreal surgery should consider several factors:

- the severity of pathological changes to predict the functional outcome of the surgery [136];

- the degree of lens opacity to plan staged or combined surgery (microincision vitrectomy or vitreolysis combined with phacoemulsification) in case of reduced transparency of optical media [137];

- the severity of the general condition, expected life expectancy of the patient, and anesthesia risk [119].

To perform microinvasive posterior closed 23-27G pars plana vitrectomy or vitreo-schwartrectomy, when indicated, it is necessary to use an ophthalmic surgical system utilizing 23-27G sets (preferably 25G) [122] for posterior vitrectomy, or combined sets. An operating ophthalmic microscope with magnification, focus, translational motion along two axes (X and Y), and rotational movement (general tilt, deviation), contact or non-contact wide-angle visualization systems, and digital visualization systems enabling intraoperative real-time stereoscopic imaging are used [131]. A through scleral puncture is performed 3-4 mm from the limbus (the distance is marked with the opposite end of the trocar having 3 and 4 mm markers) with the placement of 3 or more valved 23-27G ports [122] and an infusion system [132]. Central vitrectomy is performed using a 23-27G vitrectome, along with induction of the posterior hyaloid membrane, membrane peeling [126-128], air or gas-air tamponade, and the use of ophthalmic silicone oil [138].

During microinvasive posterior closed 23-27G pars plana vitrectomy or vitreo-schwartrectomy (preferably 25G), epiretinal membrane removal and internal limiting membrane peeling may be performed [127, 131]. In the presence of a macular hole, various macular hole closure techniques can be used, including internal limiting membrane flap techniques (inverted flap, "floating" flap, "free" flap), and the use of platelet-rich autoplasma (PRP technology, ACP technology) [120, 127]. If optical media transparency is reduced due to lens opacity, phacoemulsification with intraocular lens implantation may be performed [133]. When indicated, procedures may include silicone oil removal from the vitreous cavity, retinal endolaser coagulation [139], temporary perfluorocarbon liquid tamponade, endodiathermocoagulation, endotamponade with ophthalmic gas (e.g., sulfur hexafluoride, perfluoropropane), or perfluorocarbon liquid followed by replacement with silicone oil (using an universal ophthalmic phaco/vitreo surgical system, simultaneous replacement of perfluorocarbon liquid with silicone oil, or sequential replacement of perfluorocarbon liquid with air and then with silicone oil) [132], and other manipulations using an operating ophthalmic microscope (including one coupled with a digital visualization system) [119]. Preoperative preparation of the patient is carried out in conjunction with a general practitioner. If necessary, consultations with a nephrologist (in case of renal dysfunction), cardiologist (in case of cardiovascular complications), or other specialists are scheduled [137, 140].

Prognoses for vitreoretinal surgery in myopic traction maculopathy are generally worse than the results of vitreoretinal surgery in eyes without pathologic myopia. Visual outcomes after vitrectomy for myopic macular hole-associated retinal detachment are typically poor (< 20/200 Snellen). The closure rate of macular holes is approximately 40% after standard internal limiting membrane peeling for these conditions, but the inverted internal limiting membrane flap technique increases the likelihood of hole closure. Removal of residual cortical vitreous layers and epiretinal membranes can reduce the recurrence rate [60, 134]. Given the potential for complications, including those threatening irreversible vision loss, careful postoperative monitoring is required. Standard follow-up intervals are: one day, one week, four weeks, and three months postoperatively; the frequency of examinations is increased if complications develop [141]. Subsequently, dynamic follow-up is advisable (repeat ophthalmologist appointment (examination, consultation), B01.029.002) every 6-12 months, with possible unscheduled examinations if any new visual disturbances occur [142].

Comments: the duration of instillation and injection of medications before and after vitreoretinal surgery is determined by the physician based on a comprehensive assessment of the clinical picture, the course of the surgery, and the postoperative period [125].

Comments: the duration of silicone oil endotamponade of the vitreous cavity is determined by the physician based on the results of repeat ophthalmologist appointments (examination, consultation). The decision to complete silicone oil tamponade is made by the physician based on the evaluation of the following factors:

• absence of signs of proliferative activity;

• absence of tractional forces on the retina;

• normal intraocular pressure;

• degree of silicone oil emulsification [133].

During the removal of silicone oil from the vitreous cavity, a 23-27G pars plana trocar system is used (valved ports are preferred) [122]; procedures may include membrane peeling [127, 128], retinal endolaser coagulation with a 532 nm laser [139], endodiathermocoagulation, endotamponade with ophthalmic gas (e.g., sulfur hexafluoride, perfluoropropane), perfluorocarbon liquid (e.g., perfluorooctane), or silicone oil [143]. If optical media transparency is reduced due to lens opacity, phacoemulsification with intraocular lens implantation and other manipulations using an operating ophthalmic microscope, contact or non-contact wide-angle visualization systems, and a digital visualization system allowing intraoperative real-time stereoscopic imaging may be performed [119, 133].

Comments: the duration of instillation and injection of medications before and after vitreoretinal surgery is determined by the physician based on a comprehensive assessment of the clinical picture, the course of the surgery, and the postoperative period [125].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comments. Contact lenses have an advantage over glasses in correcting high myopia because they have a minimal effect on the size of the retinal image.

Comments. In patients with high myopia with a stable course, the frequency of examinations is 1 time in 6–12 months, and in the case of mCNV or other complications, patients are monitored more frequently, as determined by their treatment regimen [68, 69].

Comments. The treatment strategy for mCNV implies that newly diagnosed patients starting anti-VEGF therapy should be examined monthly for the first 3 months, and then every 2–3 months. In the absence of recurrences during the year, it is possible to further increase the interval: the frequency of monitoring after the first year of treatment is every 6 months. At the same time, patients are advised to seek unscheduled examinations if new complaints appear or symptoms change [102, 145, 146].

Comments. After vitreoretinal surgery, standard follow-up periods are: one day, one week, four weeks, and three months postoperatively; if complications develop, the frequency of examinations is increased [144]. Subsequently, regular dynamic follow-up (repeat ophthalmologist examination and consultation, B01.029.002) every 6–12 months is advisable, with possible unscheduled examinations if any new visual disorders appear [145].

5. Prevention and Dispensary Observation

No compelling data on the efficacy of dietary therapy in patients with myopic maculopathy have been found.

6. Organization of Medical Care

Elective and emergency medical care is provided for myopic maculopathy.

Primary specialized health care for adult patients with myopic maculopathy is provided by an ophthalmologist in the outpatient department of a medical organization.

Treatment (laser intervention, surgical treatment, including intravitreal administration of an anti-angiogenic drug) is carried out by an ophthalmologist in an outpatient setting, day hospital, or inpatient setting.

Indications for scheduled hospitalization in a medical organization:

the need for intravitreal administration of an anti-angiogenic drug and/or laser treatment and/or surgical treatment when outpatient treatment is not feasible;

the need to perform surgical interventions in a day hospital or inpatient setting.

Indications for emergency hospitalization to a medical organization:

endophthalmitis as a complication of intravitreal administration of an anti-angiogenic drug or surgical intervention [149].

Indications for discharging a patient from a medical organization:

1) completion of treatment or one of the stages of specialized, including high-tech, medical care in an inpatient or day hospital setting, provided there are no treatment complications requiring inpatient medical interventions;

2) refusal of the patient or their legal representative from specialized, including high-tech, medical care in an inpatient or day-care setting;

3) need to transfer the patient to another medical organization.

7. Additional Information

Of particular importance is the prevention of the development and progression of myopia, especially in preschool and early school age [1].

It is necessary to inform the patient about the prospects of the natural course of the disease in the absence of treatment, and about the steady progression of anatomical and functional changes in myopic maculopathy up to complete loss of vision. The patient must understand that the effectiveness of myopic maculopathy treatment largely depends on its timeliness [150].

Following laser or surgical treatment, the patient should be instructed on the recommended frequency of follow-up examinations by an ophthalmologist, depending on the clinical features, as well as the necessity of unscheduled examinations if any new visual disturbances occur.

The treatment outlook for patients with mCNV via intravitreal administration of anti-angiogenic drugs depends on timely initiation of treatment and adherence to the optimal injection regimen in accordance with the drug instructions and clinical guidelines based on regular dynamic monitoring data. The most significant manifestations of the disease in the late stage, causing a significant decrease in visual functions, are the development of subretinal fibrosis, macular atrophy involving the fovea, or formation of a macular hole.

In the case of treatment with intravitreal injections of an anti-angiogenic drug, it is necessary to inform the patient about the functional prognosis, recommended treatment regimens and monitoring frequency, existing contraindications to intravitreal injections, and postoperative symptoms requiring emergency care (for patient information, the leaflet "Intravitreal Injections (Patient Information)" has been developed [151]).

In the case of retinal laser photocoagulation or photodynamic therapy, it is necessary to discuss with the patient the need for follow-up examinations and, if necessary, additional laser or surgical treatment.

In the case of vitreoretinal surgery for myopic traction maculopathy, the following points must be discussed with the patient:

• it is important to warn the patient about the specifics of the postoperative course and possible ocular manifestations (irritation, redness of the eye, pronounced eyelid edema combined with abundant discharge, eye pain, foreign body sensation behind the eyelids or discomfort when blinking, etc.), the severity of which depends on the specifics of the surgery performed and individual bodily sensitivity to surgical trauma.

• it is important to explain to the patient that temporary glasses or contact lenses may be required during the rehabilitation period; final spectacle correction should ideally be prescribed no earlier than 2-3 months after surgery (the timing of lens fitting is determined on an individual basis).

• if the patient experiences symptoms and changes in the operated eye characteristic of myopic traction maculopathy (MTM), the need for an unscheduled examination by an ophthalmologist must be explained to them

• it is important to explain that vision will improve gradually in the postoperative period, and that as vision recovers, complaints of distorted lines and objects, as well as double vision, may occur (these symptoms typically resolve gradually over several weeks or months).

• it is important to warn the patient about following the prescribed regimen (specific head positioning, temporary activity restrictions, specific bed rest requirements) after surgery, as this may have a specific therapeutic value. Individual recommendations should be clarified during the doctor's consultation.

• it is important to warn patients of the need to immediately report symptoms that may suggest intraocular inflammation (endophthalmitis): eye pain or increased discomfort in the eye, increased eye redness, blurred or decreased vision, increased photosensitivity, or an increased number of "floaters" in the visual field.

The patient must be informed about the necessity of normalizing blood pressure and other parameters before undergoing surgical treatment for MTM. It is also necessary to encourage the patient to strictly follow all instructions from specialists (ophthalmologist, cardiologist, general practitioner, endocrinologist, etc.).

In the event of irreversible blindness or low vision, the patient must be fully informed about the possibilities of professional, social, and psychological rehabilitation.

Criteria for Evaluating the Quality of Medical Care

Criteria for evaluating the quality of medical care for patients with myopic macular degeneration

References

Appendix A1. Working Group Composition

1. Neroev Vladimir Vladimirovich, Academician of the RAS, Doctor of Medical Sciences, Professor, LLC «Association of Ophthalmologists»;

2. Bobykin Evgeny Valerievich, Doctor of Medical Sciences, LLC «Association of Ophthalmologists»;

3. Zaytseva Olga Vladimirovna, Candidate of Medical Sciences, LLC «Association of Ophthalmologists»;

4. Kovalevskaya Maria Alexandrovna, Doctor of Medical Sciences, Professor, LLC «Association of Ophthalmologists»;

5. Nechiporenko Pavel Andreevich, Candidate of Medical Sciences, LLC «Association of Ophthalmologists»;

6. Fayzrakhmanov Rinat Rustamovich, Doctor of Medical Sciences, LLC «Association of Ophthalmologists».

Conflict of interest: none.

Appendix A2. Methodology for Developing Clinical Guidelines

The protocol for the diagnosis and treatment of myopic macular degeneration in adults was developed taking into account the "Procedure for the Provision of Medical Care to the Adult Population for Diseases of the Eye, Its Adnexa, and Orbit", approved by Order of the Russian Ministry of Health No. 902n dated November 12, 2012 (as amended on February 1, 2022), which outlines the basic provisions for organizing ophthalmologic care. Unlike the "Procedure", which sets out the main stages of ophthalmologic care, "Clinical Practice Guidelines" are methodological guidelines for physicians that detail all stages of ophthalmologic care and differentiated approaches in various situations, adhering to the principles of evidence-based medicine.

Methods used for evidence collection/selection: search in electronic databases; analysis of modern scientific developments on the problem of MMD in Russia and abroad; synthesis of domestic and foreign practical experience.

When selecting publications as potential sources of evidence, the methodology used in each study is examined to ensure its reliability. The result of this examination affects the level of evidence assigned to the publication, which in turn affects the strength of the recommendations derived from it.

A preliminary version of these guidelines was reviewed by independent experts who were asked to comment primarily on whether the interpretation of the evidence underlying the recommendations is reliable and accessible to practicing physicians and patients.

Feedback has been received from ophthalmologists specializing in myopia and primary care physicians regarding the clarity of presentation and the importance of the recommendations as a practical tool for everyday medical practice.

Comments received from experts were carefully systematized and discussed by the chairs and members of the working group. Every item was discussed. Changes and additions recommended as a result of the discussion were incorporated into the text of the guidelines.

Target audience for these clinical guidelines:

Ophthalmologists;

General practitioners (family physicians);

Physiotherapists;

Medical optics optometrists.

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

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

Table 3. Scale for grading grades of recommendation (GR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in 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 regulatory legal documents:

1. Order of the Ministry of Health of the Russian Federation No. 902n dated November 12, 2012 "On Approval of the Procedure for the Provision of Medical Care to the Adult Population for Diseases of the Eye, Its Adnexa, and Orbit" (as amended on February 1, 2022)

2. Order of the Ministry of Health and Social Development of the Russian Federation No. 381 dated May 31, 2007 "On Approval of the Standard of Medical Care for Patients with Myopia (for the Provision of Specialized Care)"

3. Order of the Ministry of Health of the Russian Federation No. 203n dated May 10, 2017 "On Approval of Criteria for Assessing the Quality of Medical Care"

4. Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019 (as amended on June 9, 2023) "On Approval of the List of Vital and Essential Drugs, as well as Lists of Drugs for Medical Use and the Minimum Assortment of Drugs Required for the Provision of Medical Care > State Register of Medicines"

5. Instructions for medical use of the drug "Lucentis" (LSR-004567/08, 2020)

6. Instructions for medical use of the drug "Eylea" (Reg. No.: LP-003544, 2023)

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

8. SanPiN 2.1.3.2630-10 "Sanitary and Epidemiological Requirements for Organizations Performing Medical Activities"; Order of the Ministry of Health and Social Development of the Russian Federation No. 786n dated December 29, 2008 "On the Procedure for the Formation and Approval of the State Assignment for the Provision of High-Tech Medical Care in 2009 to Citizens of the Russian Federation at the Expense of Federal Budget Appropriations" (with amendments and additions).

9. Management of planned hospitalization in a multidisciplinary hospital. Methodological recommendations No. 2001/144: (approved by the Ministry of Health of the Russian Federation on November 9, 2001)

Appendix B. Physician Action Algorithms

Algorithm 1. Examination and treatment scheme for patients with mCNV.

Algorithm 2. Diagnostic and treatment scheme for myopic traction maculopathy (MTM)

Appendix C. Patient Information

Myopia is the most common refractive error. In a myopic eye, light rays refract more strongly than necessary, and as a result, the image is formed not on the retina (the light-sensitive structure of the eye), but in front of it, becoming unclear and blurred. Over the past 20 years, the prevalence of myopia has increased catastrophically worldwide. In young people in the USA and Europe, it reaches 40–45%. In our country, it is observed in 30% of school graduates, and in gymnasiums and lyceums, this figure approaches 50%. It is hard not to notice that in the most computerized and fast-learning region of the world—Southeast Asia (Taiwan, Hong Kong, Singapore)—the prevalence of myopia exceeds 70%. And this "surge" in morbidity cannot be blamed solely on heredity, as this contradicts the laws of genetics. It is obvious that various environmental factors make their damaging contribution. These include early excessive visual strain, various electronic information media, gaming devices, and a sedentary lifestyle among children—where are our noisy and long yard games? A certain role is also played by general health, which is normal in at most 10% of children, as well as poor ecology. As you can see, there are many factors, both external and internal, but in order to lead to the development of myopia, they must be realized through some substrate within the eye itself. And this substrate is weakened accommodation—an adaptive mechanism that allows a healthy person to see clearly at any distance, both far and near. It was precisely the disorder of accommodation that was identified as the "weak link" in the origin of myopia by Professor E.S. Avetisov almost 60 years ago.

Despite successes associated with the development and clinical implementation of modern diagnostic and treatment methods, degenerative myopia remains a serious medical and social problem. The disease currently ranks among the most common causes of low vision and blindness in many developed countries, including Russia. At the same time, according to forecasts, the problem will worsen in the near future, which is associated with a significant increase in the number of people with high myopia worldwide (from 163 million [2.7% of the global population] in 2000 to 938 million [9.8%] in 2050).

Myopic maculopathy (or myopic macular degeneration) is a complex of pathological changes in the macula against the background of high myopia, associated with an increase in the size ("overstretching") of the eye. Atrophic and tractional changes, as well as neovascularization developing in the eye, are distinguished. These are three different mechanisms that, individually or together, damage the retina.

Atrophic changes are caused by impaired nutrition of the retina; they can vary in severity and localization (and, accordingly, affect vision to varying degrees), as well as in the rate of progression. There are currently no effective methods for treating retinal atrophy.

In mCNV, the prospects of treatment with intravitreal injections of an anti-angiogenic drug depend on the timely initiation of treatment and compliance with the optimal injection regimen in accordance with the drug's instructions and clinical guidelines based on regular follow-up data. The most significant manifestations of the disease at a late stage, causing a marked decrease in visual functions, are the development of chorioretinal atrophy involving the fovea or subretinal fibrosis.

Tractional maculopathy is caused by "traction", i.e., various mechanical impacts of altered intraocular structures on the retina, which can lead to retinal tears and breaks. Mechanical damage to the retina (tear, break, detachment) may require laser or surgical treatment.

In addition, high myopia increases the likelihood of developing conditions such as cataract, glaucoma, and retinal detachment. For their prevention and early detection, dispensary observation by an ophthalmologist is necessary. Patients should be informed about the causes of possible complications of peripheral degenerations and the characteristic symptoms that require seeing a doctor: if there are complaints of "sparks" or "flashes" before the eye, physical activity should be restricted and an ophthalmologist should be consulted in the coming days; the appearance of complaints of a "curtain" before the eye and a sharp restriction of the visual field require restriction of physical activity and urgent consultation with an ophthalmologist. Patients with retinal detachment in one eye must be informed of the need for self-monitoring of the vision quality in the fellow eye and immediate visits to a doctor if changes in vision quality occur, especially when characteristic complaints appear.

For patient information support, leaflets have been developed: "Pathological Myopia" [150] and "Intravitreal Injections" [151], presented below and posted on the website of the Association of Ophthalmologists in the "For Patients" section (see Appendices G2 and G3).

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

Appendix G1. MacTSQ (Macular disease Treatment Satisfaction Questionnaire)

Validated MacTSQ (Macular disease Treatment Satisfaction Questionnaire) [74]:

Questions are scored from 0 (lowest satisfaction) to 6 (highest satisfaction) points.

* Questions are excluded from the scoring.

Appendix G2. Leaflet "Pathological Myopia" (patient information) [150]

Appendix G3. Leaflet "Intravitreal Injections" (patient information) [151]