Retinal Vein Occlusions: Clinical Guidelines

List of Abbreviations

BP — blood pressure

WHO — World Health Organization

GCs — glucocorticoids

OD — optic disc

IL — interleukin

LRP — laser retinal photocoagulation

ICD-10 — International Classification of Diseases 10th Revision

ME — macular edema

NSAIDs — nonsteroidal anti-inflammatory drugs

RVO — retinal vein occlusion

OCT — optical coherence tomography

OCT-A — optical coherence tomography angiography

POME — post-occlusion macular edema

PORP — post-occlusion retinopathy

PRP — panretinal laser photocoagulation

ACA — anterior chamber angle

FA — fluorescein angiography

TNF — tumor necrosis factor

CRV — central retinal vein

VEGF — vascular endothelial growth factor

Terms and Definitions

Ocular biomicroscopy — a method of intravital visual examination of the optical media and tissues of the eye based on creating contrast between illuminated and non-illuminated areas, performed using a slit lamp and additional diagnostic lenses (in particular, for fundus biomicroscopy).

Vitreoretinal traction syndrome — disruption of vitreoretinal relationships associated with the contraction of connective tissue within proliferative membranes and vitreous retraction, characterized by fluid accumulation between the neuroepithelium and the retinal pigment epithelium. When secondary retinal breaks and detachment develop, it is classified as tractional-rhegmatogenous.

Hemophthalmus — vitreous hemorrhage, accumulation of blood in the vitreous body or vitreous cavity (in aphakia).

Intravitreal administration (intravitreal injection) — administration of a drug substance into the vitreous body or vitreous cavity (in aphakia).

Macular edema (ME) — retinal thickening associated with fluid accumulation in the intercellular space of the neuroepithelium due to blood-retinal barrier breakdown and a mismatch between fluid transudation and its reabsorption capacity. When intraretinal fluid pockets are large, the edema is termed cystoid.

Microaneurysm — local dilation (outpouching) of the capillary wall.

Cotton-wool spot (soft exudate) — a focus of focal ischemia in the inner retinal layers due to a sharp impairment of retinal perfusion.

Retinal and/or optic disc neovascularization — a variant of the pathological proliferative response to retinal ischemia, manifesting as the growth of new vessels along the posterior surface of the vitreous body, originating from the native retinal vessels.

Neovascular glaucoma — secondary glaucoma resulting from the proliferation of new vessels and fibrous tissue in the anterior chamber angle and on the iris surface.

Optical coherence tomography (OCT) — an optical study of the retina using a computer analyzer—a diagnostic non-invasive, contactless 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) — an optical study of the retina using a computer analyzer in angiography mode—a diagnostic non-invasive, contactless method for in vivo visualization, qualitative and quantitative analysis of microcirculation in fundus structures, taking into account the segmentation of fundus layers.

Opticociliary shunts and shunts between vascular arcades — arteriovenous connecting vessels through which blood passes directly from an artery (retinal or ciliary) into a retinal vein, bypassing the capillary network.

Collaterals — retinal capillaries bypassing adjacent areas of nonperfusion and located within the area drained by the occluded vein. The capillaries connect the distal and proximal parts of the occluded vessel, providing venous drainage.

Preretinal hemorrhage (hemorrhage) — accumulation of blood in the retrohyaloid space.

Rubeosis iridis — the growth of newly formed vessels in the iris, usually accompanied by neovascularization of the structures of the anterior chamber angle and is a consequence of severe retinal ischemia.

"Hard" (lipid) exudate — deposition of proteins and lipids in the layers of the neuroepithelium due to increased vascular permeability and the escape of blood plasma components beyond its limits.

Fluorescein angiography of the eye (FA, sodium fluorescein angiography) — a diagnostic method that allows the detection of vascular bed abnormalities in the fundus, assessing the state of the outer and inner blood-retinal barriers by recording the passage of a dye (intravenously administered sodium fluorescein) through the vessels of the eye in photo and video monitoring modes.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Retinal vein occlusion (RVO) – a pathology of retinal vessels accompanied by impaired blood outflow through the central retinal vein or its branches, characterized by the clinical picture of venous stasis: venous congestion, impaired vascular wall permeability (intraretinal hemorrhages and retinal edema), as well as possible impairment of retinal capillary perfusion.

Post-occlusive (post-thrombotic) retinopathy (PORP) – late manifestations of retinal vein occlusion, which may include: macular edema, and/or epiretinal fibrosis, and/or vitreoretinal traction syndrome, and/or retinal/optic disc neovascularization, and/or recurrent hemophthalmos. At this stage of the disease, secondary neovascular glaucoma may develop.

Post-occlusive macular edema (POME) – retinal thickening associated with fluid accumulation in the intercellular space of the neuroepithelium due to a breakdown of blood-retinal barriers and a mismatch between fluid transudation and its reabsorption capacity.

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

Retinal vein occlusion is a polyetiological disease. One of the most frequent causes of its development is local damage to the integrity of the retinal vein endothelium caused by arterial hypertension (including masked hypertension [1]), dyslipidemia, hyperhomocysteinemia, and hyperglycemia. In some cases, RVO can be caused by vascular wall inflammation (infectious or non-infectious retino- or neuroretinovasculitis). Various hemostatic disorders (hypercoagulation, hypofibrinolysis, increased intravascular platelet activation) associated with congenital or acquired thrombophilic disorders can play a significant role in the pathogenesis of the disease [2, 3, 4, 5, 6].

Schematically, the pathogenesis of retinal vein occlusion can be divided into several components:

1. Mechanical compression of the vein at the level of the lamina cribrosa of the sclera or the arteriovenous crossing on the optic disc or retina, with a change in the laminar flow and velocity of blood movement.

2. Impairment of the functional activity and integrity of the venous wall endothelium with the formation of mural microthrombi.

3. Development of local hypercoagulation and hypofibrinolysis contributing to thrombosis, increased venous pressure, reduced perfusion pressure in retinal capillaries, inflammation, and, consequently, disruption of the inner blood-retinal barrier. The most significant molecular factors involved in the disruption of the inner blood-retinal barrier and increased vascular permeability include angiotensin II, cell adhesion molecules, VEGF factors, prostaglandins, cytokines, interleukins, etc. [3, 4].

4. Blood cells and plasma penetrate through the intercellular spaces into the retinal tissue with preferential fluid accumulation between the retinal layers around the fovea.

At a high concentration of vasoproliferative factors, the neoangiogenesis process is triggered with the development of neovascularization on the optic disc and retina (wherein the new vessels are tightly adhered to the posterior surface of the vitreous body), as well as in the iris and structures of the anterior chamber angle of the eye. This leads to the most severe complications of retinal vein occlusions—recurrent vitreous hemorrhages followed by its fibrosis, with the possible formation of vitreoretinal tractions and traction retinal detachment, as well as the development of secondary neovascular glaucoma.

Currently, it is customary to distinguish non-modifiable and modifiable risk factors for the development of RVO.

Among non-modifiable risk factors, age over 65 years and genetically determined thrombophilia are considered. A causal relationship has been proven between RVO and the presence of coagulation factor V mutation (Leiden factor, protein C resistance) and the G20210A mutation in the prothrombin gene (coagulation factor II) [4, 7].

Among modifiable risk factors, a number of systemic and local risk factors have been identified. The most common systemic risk factors for central retinal vein occlusion and its branches include:

- systemic arterial hypertension;

- hypercholesterolemia;

- hyperlipidemia;

- hyperhomocysteinemia;

- diabetes mellitus;

- smoking;

- acquired blood coagulation pathology (including antiphospholipid syndrome, increased intravascular platelet activity, etc.);

- hematopoietic and immune system disorders (leukemia, lymphoma);

- systemic inflammatory diseases (rheumatic diseases, sarcoidosis, tuberculosis, Goodpasture syndrome, coronavirus infection COVID-19, etc.);

- chronic renal failure and other causes of secondary arterial hypertension and diabetes, such as Cushing's syndrome;

- episodes of nocturnal arterial hypotension;

- sleep apnea syndrome;

- intake of certain medications (oral contraceptives);

- pathological menopause.

Local risk factors include:

- ocular hypertension;

- inflammatory diseases of the eye and orbit;

- impaired venous outflow (retromeliorbellar/retrobulbar compression of the eyeball: tumors, edema, orbital integrity disruption).

Precipitating factors can include excessive physical and emotional stress and hyperthermia [4, 7].

1.3 Epidemiology of the Disease or Condition

RVO is an age-dependent disease. In 2015, the global prevalence of all types of RVO, branch retinal vein occlusion, and central retinal vein occlusion in individuals aged 30–89 years was 0.77%, 0.64%, and 0.13%, respectively, indicating a total number of individuals with this disease of 28.06 million. In the 30–39 age group, the prevalence of RVO is 0.26%, and in the 40–49 age group, it is 0.44%. The disease occurs with equal frequency in men and women [8, 9].

1.4 Features of Coding the Disease or Condition

H34.8 — Other retinal vascular occlusions.

Retinal venous occlusion.

H34.9 — Unspecified retinal vascular occlusion.

H35.6 — Retinal hemorrhage.

1.5 Classification of the disease or condition

Currently, there are classifications of RVO that propose dividing individual forms of the disease according to pathogenesis, location of the occlusion zone, stage, and type of the disease. However, the most widespread and universally accepted classification worldwide is that proposed by S.S. Hayreh (1990) [4, 6, 10, 11, 12].

By anatomical location:

I. Central retinal vein occlusion

II. Hemi-central retinal vein occlusion

III. Branch retinal vein occlusion

By type of occlusion:

1. Non-ischemic (with partially preserved perfusion)

2. Ischemic (with absent perfusion)

To assess the type of RVO, data obtained from FA are most often used. The criterion for assessing the condition is the area of capillary nonperfusion. In the ischemic type of branch retinal vein occlusion, it usually exceeds 5 optic disc areas, and in main trunk occlusion, 10 optic disc areas.

1.6 Clinical presentation of the disease or condition

Non-ischemic branch retinal vein occlusion

Visual acuity depends on the degree of macular involvement. When temporal branches are affected, patients note a sudden drop in vision, a spot in the visual field, and metamorphopsia. With occlusion of nasal and peripheral temporal branches without macular involvement, the onset of the disease is usually asymptomatic. On ophthalmoscopy: veins distal to the occlusion zone are sharply dilated and tortuous, flame-shaped and small spot intraretinal hemorrhages, retinal edema in the macula, isolated "soft" ("cotton-wool") exudates reflecting ischemic edema of ganglion cell axons.

Ischemic branch retinal vein occlusion

A more significant decrease in vision (to 0.01 and worse), a large number of hemorrhages, and "soft" exudates on the fundus suggest an ischemic type of occlusion. Definitive diagnosis of the occlusion type is made based on fundus fluorescein angiography (FFA) immediately after the disease is detected or, if a large number of hemorrhages makes interpretation difficult, 1–1.5 months later.

Non-ischemic central retinal vein occlusion (CRVO)

In all cases, the onset of the disease is accompanied by a sudden, painless decrease in vision in one eye. Sometimes this is preceded by a feeling of heaviness and dull pain in the orbit. Pupillary reactions are preserved. Ophthalmoscopy reveals varying degrees of dilation and tortuosity of all CRVO branches, blurred margins of the optic disc (OD), and intraretinal hemorrhages in the form of multiple spots (most commonly in the periphery) and flame shapes (in all 4 quadrants of the retina). Multiple "cotton-wool" spots may appear, representing zones of retinal infarction in the nerve fiber layer. Symptoms of the acute phase persist for about 1.5–3 months. Late manifestations include microaneurysms, optociliary shunts on the optic disc, shunts and collaterals between the temporal arcades and areas distal and proximal to the occlusion site, epiretinal fibrosis, and macular edema.

Transition from non-ischemic to ischemic RVO is observed in 15% of cases within the first 4 months, and in 34% of cases within a 3-year period after the initial occlusion [6].

Ischemic central retinal vein occlusion (CRVO)

The onset of the disease is accompanied by a sudden, painless decrease in vision in one eye. Visual acuity generally does not exceed 0.1. A characteristic symptom of retinal ischemia is the presence of a relative afferent pupillary defect.

Fundus examination reveals dilation and tortuosity of all CRVO branches, peripapillary retinal edema, and various shapes of intraretinal hemorrhages extending to the fundus periphery and posterior pole. A distinctive feature of ischemic damage is a large number of "cotton-wool" spots. Capillary non-perfusion in the macular region results in its edema and pallor.

A special form of ischemic CRVO is accompanied by the formation of ischemic zones in the periphery. In this case, central vision may change only slightly. The number of hemorrhages and "cotton-wool" spots on the fundus is moderate, but a large number of rounded hemorrhages and vascular attenuation are detected in the periphery. The degree of vision loss depends on the severity of macular edema.

Symptoms of the acute phase disappear within the next 1.5–3 months. Manifestations of post-occlusion retinopathy may include microaneurysms, optociliary shunts and shunts between vascular arcades, neovascularization of the optic disc and/or retina (most commonly at the border with the ischemic zone), epiretinal fibrosis, cystoid macular edema, and subretinal fibrosis, which may be associated with the development of macular degeneration.

Hemiretinal vein occlusion is less common than branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). It is subdivided into hemispheric second-order BRVO (superior or secondary inferior CRVO branch) with the occlusion site located on the surface or at the edge of the optic disc, and hemicentral occlusion affecting one of the second-order branches (superior or inferior CRVO branch) with the occlusion site located in the immediate vicinity of the lamina cribrosa of the sclera (in a "dual-barrel" CRVO).

The disease begins with a sudden altitudinal visual field defect (inferior or superior). Visual acuity ranges from 0.01 to 0.1–0.2. Fundus examination reveals signs of BRVO affecting the upper or lower hemisphere.

One of the leading problems in occlusion of the central retinal vein and its branches is the decrease in central vision, which develops due to three main causes or their combination: macular edema, macular hemorrhage, and macular ischemia.

Post-occlusive macular edema

Macular edema leads to decreased visual acuity. These changes can be reversible (if spontaneous or medication-induced resorption of intraretinal fluid occurs). Chronic macular edema leads to irreversible retinal damage with cystoid degeneration, epiretinal membrane formation (in some cases with a lamellar macular hole), apoptosis and death of retinal cells, and loss of synaptic connections. Timely (early) treatment helps prevent further loss of visual acuity.

Macular edema can be diffuse and cystoid, with fluid accumulation occurring predominantly in the outer plexiform layer of the retina. With adequate macular capillary perfusion after resolution of the underlying process, vision can partially or fully recover after 6 months (in some cases up to 15 months) to 0.5 and higher. However, in 60% of patients, macular edema does not resolve spontaneously. The chronic nature of macular edema is generally associated with macular ischemia and significantly worsens the prognosis for visual function recovery [4, 10, 13, 14].

Neovascular complications of retinal vein occlusion

Mainly as an outcome of ischemic CRVO, and less commonly BRVO, anterior and posterior segment neovascularization may develop. There is a correlation between the incidence of neovascularization and the total area of non-perfused retinal zones.

Neovascular glaucoma most commonly develops in ischemic CRVO (29–34%), and less frequently as an outcome of ischemic hemicentral occlusion (5%), within the first 6 months (at least 2 weeks) from the onset of the disease, and may precede retinal and optic disc neovascularization.

Neovascularization of the optic disc and retina occurs in 6–9% of CRVO cases, 29% of hemicentral occlusions, and 24% of BRVO cases, most frequently at the border of perfused and non-perfused zones, within 3 to 12 months or more [4, 7].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnosis of retinal vein occlusions should focus on detecting early changes, which is especially important given the availability of effective methods in modern ophthalmology to combat complications of this pathology and preserve vision.

The main diagnostic criteria for establishing retinal vein occlusions and post-occlusive retinopathy are presented in Appendix A3, Table 2.

2.1 Complaints and Anamnesis

2.2 Physical Examination

Comments: a physical examination is recommended for all patients with RVO as part of identifying major risk factors (hypertension, diabetes mellitus, dyslipidemia, thrombophilia, etc.) and is performed by a general practitioner or primary care physician [4, 5, 6, 10, 15]. It is also necessary to refer patients with other concomitant systemic diseases and risk factors for systemic complications to appropriate specialists for consultation before laser or surgical treatment (including intravitreal drug administration) to identify potential contraindications to these treatments and minimize the risk of complications [4, 5, 10, 15]. The choice of specialist is determined by the specific clinical course of RVO, planned treatment, and the presence of other concomitant systemic diseases and/or risk factors for systemic complications in the patient.

2.3 Laboratory Diagnostics

Comments: the choice of laboratory testing is determined based on the clinical course of RVO and the presence of a concomitant systemic disease and risk factors for systemic complications in the patient. It is also recommended to prescribe laboratory testing for patients with concomitant systemic diseases and risk factors for systemic complications prior to laser or surgical treatment (including intravitreal drug administration) to identify potential contraindications to these treatment modalities.

Comments: the choice of laboratory tests is determined based on the presence of a concomitant systemic disease and risk factors for systemic complications in the patient.

HIV testing is performed based on informed voluntary consent (Sanitary and Epidemiological Rules SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases") [19, 20].

2.4 Instrumental Diagnostics

Comments: biomicroscopy of the anterior segment of the eyeball must initially be performed without mydriasis, since pupil dilation can make it difficult to detect iris neovascularization. Vitreous biomicroscopy, conversely, should be performed under conditions of pharmacological mydriasis, as this improves diagnostic quality.

Comments: fundus biomicroscopy with aspheric lenses using a slit lamp (or ophthalmoscopy) is the primary diagnostic method for fundus changes in RVO during an ophthalmological examination, regardless of the setting (primary health care, specialized care) or care delivery mode (inpatient, outpatient). In patients with RVO, it must be performed only with a wide pupil (under conditions of pharmacological mydriasis). It is important to remember that the state of the anterior chamber and iris must be assessed prior to pharmacological pupil dilation.

Comments: when evaluating the efficacy of treatment with intravitreal injections of anti-angiogenic agents (angiogenesis inhibitors) or glucocorticoids, both quantitative and qualitative parameters of the tomograms should be assessed. Optical examination of the retina using a computer analyzer is recommended to be performed under conditions of pharmacological mydriasis, as this significantly improves scan quality.

Comments: the necessity and frequency of OCT-A are determined by the ophthalmologist depending on the specifics of the disease course. Optical examination of the retina using a computer analyzer in angiography mode is recommended to be performed under conditions of pharmacological mydriasis, as this significantly improves the quality of the examination.

Comments: the first examination is recommended to be performed immediately or 1-1.5 months after the onset of the disease as intraretinal hemorrhages resolve. The type of retinal vein occlusion is determined after performing FA. In non-ischemic occlusion, retinal capillary perfusion is preserved or impaired in an area less than 5 optic disc areas for a branch RVO and less than 10 for central retinal vein occlusion (CRVO). In ischemic occlusion, capillary perfusion is absent (according to FA) over an area greater than 5 optic disc areas for a branch RVO and greater than 10 for CRVO. Subsequent follow-up FA examinations are performed according to indications, for example, after performed laser retinal photocoagulation to assess its effectiveness.

Comments: in the ischemic type of CRVO, a decrease in the b-wave amplitude, a reduction in the b:a wave amplitude ratio index, and an increase in the b-wave amplification duration on the electroretinogram are determined.

2.5 Other Procedures

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

Comments: a mandatory component is general therapeutic treatment aimed at eliminating modifiable risk factors for RVO: elimination of arterial hypertension, restoration of cardiac rhythm, normalization of blood plasma lipid and homocysteine levels, and, if necessary, pharmacological correction of hypercoagulation and hyperaggregation phenomena. Treatment is prescribed and its effect is monitored by a general practitioner or cardiologist, and if necessary, by an endocrinologist and other specialists. Rapid blood pressure reduction is not recommended, as abrupt hypotension leads to a drop in perfusion pressure and exacerbates capillary dysfunction. In patients with inflammatory CRVO, etiological (antiviral, antibacterial, etc.) and anti-inflammatory therapy consistent with the principles of treatment for retino- or neuroretinovasculitis must be administered.

3.1 Conservative Treatment

3.2 Surgical Treatment

Surgical treatment of RVO is aimed at restoring the function of the blood-retinal barriers and suppressing vascular proliferation, for which anti-angiogenic and/or glucocorticoid therapy and/or laser treatment are used. In the stage of proliferative retinopathy with pronounced vasoproliferative changes, vitrectomy (with or without endolaser photocoagulation of the retina) is recommended.

3.2.1 Intravitreal drug administration

Comments: currently, intravitreal administration of anti-angiogenic agents (angiogenesis inhibitors) is the first-line therapy for macular edema involving the fovea [6]:

- ranibizumab** is a humanized antibody fragment 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 [26, 27, 28, 29];

- aflibercept** is a recombinant fusion protein consisting of extracellular domain fragments 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 these cognate VEGF receptors [30, 31, 32, 33, 34, 35];

- faricimab is a humanized bispecific antibody belonging to the immunoglobulin G1 (IgG1) class that acts by inhibiting two distinct pathways, neutralizing both angiopoietin-2 (Ang-2) and VEGF-A. Ang-2 and VEGF-A act synergistically to increase vascular permeability and stimulate neovascularization. Dual inhibition of Ang-2 and VEGF-A by faricimab decreases vascular permeability and reduces inflammation, suppressing pathological angiogenesis, and may provide greater vascular stability manifested by a more pronounced reduction in vascular permeability compared to anti-VEGF therapy. Due to dual inhibition, it has the potential for a longer duration of action, allowing for maximized intervals between injections [36, 37, 38].

Ranibizumab**. Intravitreal injections of 0.5 mg (0.05 ml) of ranibizumab monthly until the maximum best-corrected visual acuity is achieved and/or until signs and symptoms of disease activity disappear with ongoing treatment. After disease stabilization is achieved with monthly injections, the frequency of follow-up visits and the time interval between injections are determined by the physician based on disease activity assessed by visual acuity and/or anatomical parameters. Disease stabilization is defined as no improvement in vision and/or retinal anatomical parameters for one month after the last monthly injection. Achieving disease stabilization may initially require three or more consecutive monthly injections. If, in the physician's opinion based on the assessment of visual acuity and retinal anatomical parameters, there is no improvement from the treatment, therapy should be discontinued. An interval of at least 28 days should be maintained between two doses of the drug.

When using the treat-and-extend regimen (also known as treat and extend), after achieving maximum visual acuity and/or in the absence of signs of disease activity, a stepwise increase in the intervals between drug administrations is possible, however, currently there are insufficient data to determine the magnitude of the intervals. Upon disease reactivation, shortening of the intervals should be performed with the same step size as the extension.

Therapy can be combined with retinal laser photocoagulation. When performing this combination therapy on the same day, the drug should be administered no earlier than 30 minutes after laser photocoagulation.

The efficacy and safety of ranibizumab** in the treatment of macular edema following retinal vein occlusion have been proven by numerous multicenter randomized trials. An individualized regimen of 0.5 mg ranibizumab**, based on criteria for stabilization of maximum best-corrected visual acuity, provides anatomical and functional improvement in both branch retinal vein occlusion and central retinal vein occlusion [39]. The highest results are obtained with early administration of the drug [6, 40]. Treatment with ranibizumab** involves monthly monitoring in the first year of the disease, followed by extended monitoring and reduced treatment burden as anatomical and visual stabilization of the disease occurs [6].

Aflibercept**. Intravitreal injections of 2 mg (0.05 ml) monthly until the highest possible visual acuity and complete resolution of macular edema are achieved. This requires three or more monthly intravitreal injections. To maintain the achieved effect, therapy can be extended using a treat-and-extend regimen. Therapy can be combined with retinal laser photocoagulation.

Treatment should be discontinued if no improvement in visual acuity and reduction of macular edema is observed during therapy.

The use of aflibercept** treatment regimens involving the extension of intervals between injections already in the first year of treatment has shown high efficacy in the treatment of macular edema in both branch retinal vein occlusion and central retinal vein occlusion [29, 31, 32]. The multicenter CENTERA study, aimed at developing treatment regimens for macular edema following retinal vein occlusion, showed that this treatment option with continuous and prolonged monitoring of the retinal state allows not only stabilizing visual functions, but also reducing the area of retinal non-perfusion zones and lowering the risks of neovascular complications [33, 41].

In each clinical case, the final decision on the indications for treatment with anti-angiogenic agents (angiogenesis inhibitors) and the choice of injection regimen is made by the physician based on the evaluation of the clinical presentation and disease course.

Faricimab. The first 3 intravitreal injections of faricimab 6 mg (0.05 ml solution) are administered at an interval of 4 weeks. Thereafter, the treatment regimen can be individualized according to the treat-and-extend approach in accordance with the evaluation of anatomical parameters of the disease course and visual function characteristics. The interval between drug administrations can vary from 4 to 16 weeks in 4-week steps. If treatment efficacy is insufficient due to an increased interval between injections, the interval can be shortened back to 4 or 8 weeks if necessary. Follow-up time points to assess the patient's condition are determined at the physician's discretion based on the patient's complaints and general condition; monthly examinations are not required.

The multicenter BALATON and COMINO studies demonstrated high efficacy of intravitreal faricimab at a dose of 6 mg in the treatment of post-occlusion macular edema in both central retinal vein occlusion and branch retinal vein occlusion. Following monthly injections administered up to week 24 of the study, the effect persisted up to week 72 even when switching to an injection regimen of once every 12 and 16 weeks (in 82% and 74% of cases, respectively). A significant reduction in retinal venous permeability, confirmed by a decrease in leakage in the macular area on fluorescein angiography performed at week 24 of the study, showed a more pronounced effect compared to the comparator group receiving intravitreal aflibercept (BALATON: 33.6% vs. 21.0%, respectively; p = 0.0023, and COMINO: 44.4% vs. 30.0%, respectively; p = 0.0002) [36, 37, 38].

Contraindications to intravitreal administration of ranibizumab**, aflibercept** or faricimab:

– hypersensitivity to the active substance or any of the excipients,

– active confirmed or suspected ocular infection or periocular infections,

– active intraocular inflammation,

– pregnancy and breastfeeding period.

In each clinical case, the final decision on the indications for treatment with anti-angiogenic agents (angiogenesis inhibitors) and the choice of injection regimen is made by the physician based on the evaluation of the clinical presentation and disease course.

Dexamethasone** - intravitreal implant. A topical glucocorticoid that provides sustained release (up to 6 months) of the active substance in the vitreous body or vitreous cavity. Dexamethasone**, being a potent glucocorticoid, suppresses inflammation by reducing edema, fibrin deposition, capillary permeability, and migration of phagocytes to the site of inflammation. Glucocorticoids suppress the expression of vascular endothelial growth factor and also prevent the release of prostaglandins, some of which are mediators of cystoid macular edema [42, 43, 44].

The use of dexamethasone** as an intravitreal implant requires long-term regular monitoring of intraocular pressure and the prescription of local hypotensive therapy if intraocular pressure increases. Re-administration of the implant is possible approximately in 4-6 months in case of decreased visual acuity and/or increased retinal thickness.

Contraindications to the administration of the dexamethasone intravitreal implant**:

– hypersensitivity to the active substance or any other component of the product;

– active or suspected ocular or periorbital infection, including most viral diseases of the cornea and conjunctiva, including acute herpes simplex, epithelial keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases;

– advanced stage of glaucoma with decompensation of intraocular pressure (IOP) not controlled by medical therapy;

– age under 18 years;

– aphakia with rupture of the posterior lens capsule;

– presence of an anterior chamber intraocular lens, iris-clip intraocular lens, or posterior chamber intraocular lens with transscleral fixation in the simultaneous presence of a posterior lens capsule rupture.

Use with caution: dexamethasone intravitreal implant**:

– history of ocular herpes simplex infection;

– pregnancy and breastfeeding period;

– in patients taking anticoagulants or antiplatelet agents.

Use during pregnancy and breastfeeding: There is no clinical experience with the dexamethasone intravitreal implant during pregnancy, and potential risks are unknown. The dexamethasone intravitreal implant may be used during pregnancy if the expected benefit to the mother outweighs the potential risk to the fetus. Systemic dexamethasone** is excreted in breast milk. Due to low systemic absorption following local administration, no effects of the dexamethasone intravitreal implant on breastfed infants are expected. However, due to the lack of data on drug excretion in breast milk, the risk cannot be completely ruled out; therefore, breastfeeding should be discontinued during treatment when the dexamethasone intravitreal implant is prescribed.

Adverse reactions of the dexamethasone intravitreal implant**:

• Eye disorders:

- Very common: increased IOP, cataract, subconjunctival hemorrhage.

- Common: ocular hypertension, subcapsular cataract, vitreous hemorrhage, visual acuity reduced, visual disturbances (spot, line, or dark area), vitreous detachment, vitreous opacities (including floaters), blepharitis, eye pain, photopsia, conjunctival edema, conjunctival hyperemia.

- Uncommon: necrotizing retinitis, endophthalmitis, glaucoma, retinal detachment, retinal tear, ocular hypotony, anterior chamber cell infiltration/flare, eye discomfort, eyelid pruritus, eye redness.

• General disorders and administration site conditions:

- Uncommon: implant migration sometimes accompanied by corneal edema, administration procedure complication resulting in eye tissue damage (implant misplacement).

Following the first use of the dexamethasone intravitreal implant, the patient's ocular status must be monitored every two weeks to assess individual response to the drug. In other cases, it is advisable to check IOP every 2–8 weeks after the injection. A comprehensive ophthalmologic examination (visual acuity testing, tonometry, biomicroscopy, ophthalmoscopy, and OCT) should be performed 3 months post-injection and repeated if visual function deteriorates while macular edema persists. Re-administration of the dexamethasone intravitreal implant is typically performed after 3–4 months (an average of 2–3 injections per year). Based on generalized data collected to date, the therapeutic effect of the dexamethasone intravitreal implant in macular edema secondary to retinal vein occlusion is approximately 4 months, and intervals using a pro re nata (PRN) treatment scheme do not exceed 6 months [6].

Selection of drugs for the treatment of macular edema secondary to retinal vein occlusion. For initial therapy of macular edema, any anti-VEGF agent (ranibizumab**, aflibercept**, faricimab) [4, 6, 11] or dexamethasone** intravitreal implant [44] may be chosen. The preferred choice of anti-VEGF agents is recommended for patients with a history of ocular hypertension or uncompensated glaucoma, or glaucoma requiring combination hypotensive therapy, as well as younger patients.

The choice of dexamethasone** intravitreal implant as a first-line drug is recommended for patients with cardiovascular diseases accompanied by ischemic events (stroke, myocardial infarction, and transient ischemic attacks), patients unable or unwilling to adhere to a monthly injection schedule, in cases of aphakia or pseudophakia (if used in phakic eyes, the patient must be informed of the high risk of cataract development), and during pregnancy (experience with dexamethasone** intravitreal implant during pregnancy is lacking, potential risks are unknown; dexamethasone** intravitreal implant may be used during pregnancy if the expected benefit to the mother outweighs the potential risk to the fetus).

Its use is possible in the early period for treating post-occlusive macular edema resulting from non-infectious retino- or neuroretinovasculitis (after a full general and ophthalmologic examination ruling out an infectious process; see Clinical Guidelines on Non-infectious Uveitis), as well as in the presence of a pronounced inflammatory component in the acute period of retinal vein occlusion and in cases of resistance to anti-VEGF therapy [6].

There are no large-scale clinical studies investigating combination therapy for post-occlusive macular edema. However, it has been reported that in cases of insufficient efficacy of one anti-VEGF agent (after three consecutive injections), switching to another anti-VEGF agent (most commonly from ranibizumab** and aflibercept** to faricimab) or to the dexamethasone** intravitreal implant is possible [45]. Any of the listed drugs can be used in combination with laser retinal photocoagulation [6]. The use of the dexamethasone** intravitreal implant 1 month after intravitreal ranibizumab** injection leads to a marked enhancement of the therapeutic effect [46]. Furthermore, using the dexamethasone** intravitreal implant 2 weeks after intravitreal ranibizumab** injection increases the interval between injections to an average of 135.5 ± 36.4 days over 6 treatment cycles [47].

When administering intravitreal anti-angiogenic agents or the dexamethasone** intravitreal implant, the potential risk of complications such as infectious and non-infectious endophthalmitis, iatrogenic cataract, vitreous hemorrhage, retinal detachment, and others must be taken into account.

When using anti-angiogenic agents or the dexamethasone** intravitreal implant, preventing a decrease in visual acuity, even in the absence of improvement, should be considered a positive trend compared to the natural course of the disease.

Comments: the duration of antimicrobial instillation (antiseptics and disinfectants) before and after intravitreal administration of any medicinal product is determined by the physician based on a comprehensive assessment of the risk of infectious complications and the condition of the ocular surface.

3.2.2 Vitreoretinal surgery

Comments: vitrectomy helps restore impaired blood flow in the occluded vein, improves metabolic processes between the retina and the vitreous body, increases oxygen transport to ischemic retinal areas, and increases the clearance of VEGF and cytokines in the vitreous cavity, resulting in reduced DME. However, the increased oxygen level may stimulate cataract development, and increased VEGF flow into the anterior chamber can lead to iris neovascularization [6, 49]. Currently, there are no large-scale clinical trials proving the efficacy and safety of vitrectomy in the acute period of RVO. Therefore, this surgery is recommended for complicated courses of PDR [4, 6, 7, 50, 51]. During microinvasive vitrectomy, membrane peeling, retinotomy, retinal endolaser coagulation, endodiathermocoagulation, vitreous cavity tamponade (with perfluorocarbon or another high-molecular-weight compound), endovitreal exchange of perfluorocarbon for silicone, and/or removal of perfluorocarbon or another high-molecular-weight compound from the vitreous cavity, and other procedures can be performed if indicated. Patient preparation for surgery is carried out in conjunction with a general practitioner. If necessary, a cardiologist consultation/examination is scheduled (in the presence of cardiovascular pathology).

The physician referring a patient for vitreous surgery should pay attention to several aspects:

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

- in case of vitreous hemorrhage, the severity of the hemorrhage must be assessed (a minor hemorrhage that does not impede laser treatment and does not lead to disability is not an indication for surgery);

- adequacy of prior retinal laser photocoagulation (hemorrhages may occur due to insufficient coagulation);

- visual acuity of the fellow eye (vitreoretinal surgery may be recommended earlier if the patient is disabled due to low visual acuity in the fellow eye);

- severity of general comorbidities, estimated life expectancy of the patient, and anesthesia risk.

Comments: the duration of silicone oil endotamponade of the vitreous cavity is determined by the physician based on the results of patient monitoring. The decision on the need for repeated endotamponade of the vitreous cavity is made by the physician based on the evaluation of the patient's ocular status, the risk of recurrent hemorrhage, retinal detachment, etc.

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.

3.3 Laser treatment

Comments: standard panretinal laser photocoagulation is typically performed over several sessions. Sessions of panretinal laser photocoagulation can be performed both in inpatient and outpatient settings under maximal drug-induced mydriasis [4].

Comments: panretinal laser photocoagulation of the retina has certain side effects. Therefore, this laser treatment method is generally performed when new vessels are already present or the risk of their appearance is extremely high. The probability of blindness upon the appearance of new vessels is so high that it justifies the use of laser treatment despite the side effects. An indication for immediate panretinal laser photocoagulation is PDR combined with high-risk factors for vision loss:

- retinal neovascularization exceeding 1/2 of the optic disc area;

- neovascularization of the optic disc exceeding 1/3 of the optic disc area;

- presence of vitreous or preretinal hemorrhage.

Panretinal laser photocoagulation of the retina is usually initiated in the lower areas of the mid-periphery, as these zones may become inaccessible in the event of vitreous hemorrhage. Next, laser treatment is continued by applying burns across the entire surface of the mid-periphery of the fundus from the temporal vascular arcades. In the presence of PDR with neovascularization of the iris and/or anterior chamber angle, the extreme peripheral parts of the retina must also be coagulated.

Comments: in the presence of macular edema, the greatest effect from laser treatment (focal or grid laser retinal photocoagulation) is expected when the baseline central retinal thickness does not exceed 350 µm. In other cases, laser treatment of macular edema secondary to retinal vein occlusion is significantly inferior in functional outcome to anti-angiogenic agents (angiogenesis inhibitors). Currently, focal laser photocoagulation should be considered only as second-line therapy compared to pharmacotherapy [6]. Grid laser photocoagulation is most effective in branch retinal vein occlusion (BRVO); however, in individual cases, it can be used for chronic macular edema resistant to intravitreal anti-angiogenic agents or topical glucocorticoids in central retinal vein occlusion (CRVO).

3.4 Dietary Therapy

Comments: nutrition should be part of the therapeutic plan and aimed at the correction and prevention of major risk factors. Dietary recommendations are made by a general physician (general practitioner, primary care physician, or endocrinologist) as part of the management of the underlying disease.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

5. Prevention and Dispensary Observation

Comments: the frequency of ophthalmological examinations for patients with retinal vascular occlusion and non-proliferative retinopathy is presented in Table 2. In the initial absence of macular edema or upon resolution of macular edema due to drug therapy, monthly ophthalmological examinations (consultations) are required for the first 6 months to detect signs of disease progression and complication development. Once the process is stabilized, examinations should be performed at least once every 6 months for two years. If decreased visual acuity is detected, the state of the macular zone should be assessed (macular edema, development of ischemia), followed by resuming treatment with drugs recommended as first-line agents in accordance with the current instructions, or, in the presence of contraindications or resistance, administering the dexamethasone intravitreal implant**. The specified treatment can be combined with focal or panretinal laser photocoagulation depending on indications. If neovascularization is detected, standard panretinal laser photocoagulation is recommended.

Table 1. Frequency of ophthalmological examinations in patients with retinal vascular occlusion and non-proliferative retinopathy [11]

6. Organization of Medical Care

Primary specialized health care is provided by an ophthalmologist in the outpatient department of a medical organization. For any form of retinal vascular occlusion (ischemic or non-ischemic), in any phase of the disease, regardless of complications, primary health care is recommended to be provided on an outpatient basis. Form of medical care: routine (scheduled).

Treatment (laser interventions, intravitreal drug administration, or vitreous surgery) is performed by an ophthalmologist on an outpatient basis, in a day hospital setting, or in an inpatient setting.

Indication for planned hospitalization in a medical organization:

• the need for intravitreal drug administration, laser retinal photocoagulation, or vitreoretinal surgical interventions if treatment cannot be performed on an outpatient basis.

Indication for emergency hospitalization in a medical organization:

• endophthalmitis as a complication of intravitreal drug administration.

Indication for patient discharge from a medical organization:

1) completion of treatment or a stage of specialized, including high-tech, medical care in an inpatient or day-care setting, provided there are no treatment complications requiring drug correction and/or 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

The patient must be informed about the need to normalize blood pressure, glycemia, and lipid metabolism parameters. It is also necessary to encourage the patient to strictly follow all appointments and prescriptions given by specialists (ophthalmologist, cardiologist, general practitioner, primary care physician, endocrinologist, etc.).

It is important to draw the patient's attention to the necessity of being examined by an ophthalmologist at least twice a year, even in the absence of visual complaints, as well as the urgency of seeing an ophthalmologist if they experience decreased vision, spots or distortions, or pain in the eye, orbit, and corresponding half of the head.

It is necessary to inform other specialists treating the patient (cardiologist, general practitioner, primary care physician, endocrinologist, etc.) about the ocular changes detected by the ophthalmologist.

Patients must be informed that the effectiveness of treatment for retinal vascular occlusion and complications associated with non-proliferative retinopathy depends on the timely initiation and comprehensive nature of therapy.

In cases of irreversible blindness or low vision, the patient must be fully informed about the opportunities for vocational, social, and psychological rehabilitation.

When intravitreal drug administration is used, the following points must be discussed with the patient:

The prospects for treatment using intravitreal drug administration in patients with retinal vascular occlusion depend on adherence to the optimal injection regimen in accordance with the drug labeling and clinical guidelines based on regular monitoring data.

It is important to warn patients receiving intravitreal injections about the need to immediately report symptoms indicating the potential development of intraocular inflammation (endophthalmitis): eye pain or increased discomfort in the eye, eye redness, blurred or decreased vision, photophobia, an increase in floaters in the visual field, eyelid and conjunctival edema, or pathological discharge from the palpebral fissure.

If retinal laser photocoagulation is performed, the following points must be discussed with the patient:

• the need for repeated examinations and additional laser treatment;

• panretinal laser photocoagulation reduces the risk of low vision and blindness, but may have side effects;

• laser treatment often impairs peripheral vision and may moderately reduce central vision, but these side effects of laser photocoagulation are outweighed by the long-term reduction in the risk of low vision and blindness;

• in some patients, despite ongoing laser treatment, vitreous hemorrhage may occur as a complication of the underlying disease (in this case, the patient may require additional laser or surgical treatment).

Criteria for Evaluating the Quality of Medical Care

Table 2.

References

Appendix A1. Working Group Composition

1. Astakhov Yu.S., Head of the Research Group, D.Sc. (Medicine), Professor at the Department of Ophthalmology with the Clinic, Pavlov First Saint Petersburg State Medical University, Vice-President of the Association of Ophthalmologists

2. Brovkina A.F., Academician of the Russian Academy of Sciences, Honored Worker of Science of the Russian Federation, D.Sc. (Medicine), Professor at the Department of Ophthalmology, Russian Medical Academy of Continuous Professional Education of the Russian Ministry of Health, member of the Association of Ophthalmologists

3. Gatsu M.V., D.Sc. (Medicine), Professor, Deputy Director for Organizational and Clinical Work, Saint Petersburg Branch of the S.N. Fyodorov National Medical Research Center "Eye Microsurgery" of the Russian Ministry of Health, member of the Association of Ophthalmologists

4. Izmayolov A.S., D.Sc. (Medicine), Professor at the Department of Ophthalmology, North-Western State Medical University named after I.I. Mechnikov of the Russian Ministry of Health, member of the Association of Ophthalmologists

5. Lisochkina A.B., Ph.D. (Medicine), Associate Professor at the Professor Yu.S. Astakhov Department of Ophthalmology with the Clinic, Pavlov First Saint Petersburg State Medical University, member of the Association of Ophthalmologists

6. Tultseva S.N., D.Sc. (Medicine), Professor at the Professor Yu.S. Astakhov Department of Ophthalmology with the Clinic, Pavlov First Saint Petersburg State Medical University, member of the Association of Ophthalmologists

7. Shadrichev F.E., Ph.D. (Medicine), Head of the Ophthalmology Department, Saint Petersburg Territorial Diabetology Center (City Clinical Diagnostic Center No. 1), Assistant at the Professor Yu.S. Astakhov Department of Ophthalmology with the Clinic, Pavlov First Saint Petersburg State Medical University, member of the Association of Ophthalmologists

No conflict of interest is declared.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

• Ophthalmologists

• Internists

• General practitioners (family medicine)

• Hematologist

• Rheumatologists

Methods used for collecting/selecting evidence: electronic database searches; analysis of modern scientific research on retinal vein occlusion and branch retinal vein occlusion in Russia and abroad; synthesis of practical experience from Russian and foreign specialists. Description of methods used for collecting/selecting evidence: the evidence base for these guidelines includes publications from the Cochrane Library, EMBASE, and MEDLINE databases, as well as monographs and articles in leading specialized peer-reviewed domestic medical journals on the subject. Methods used for assessing the quality and strength of evidence: expert consensus, significance assessment according to the grading scheme.

Table 1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing levels of evidence (LE) for prevention, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitative interventions)

Table 3. Grading system for the levels of recommendation conviction (LRC) for methods of prevention, diagnosis, treatment, and medical rehabilitation, including those based on natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitative 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

1. Current instructions for the medicinal products mentioned in these clinical guidelines can be found on the website

http://grls.rosminzdrav.ru 

Table 1. Dose, route of administration, and regimens of medicinal products

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

3. Nomenclature of Medical Services. Order of the Ministry of Health of the Russian Federation 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».

4. Order of the Ministry of Health of the Russian Federation No. 205n dated May 2, 2023 «On Approval of the Nomenclature of Positions of Medical and Pharmaceutical Workers».

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

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

7. Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019 (as amended on January 15, 2025) «On Approval of the List of Vital and Essential Drugs, as Well as Lists of Medicinal Products for Medical Use and the Minimum Assortment of Medicinal Products Required for Medical Care».

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

9. 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».

10. Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 44 dated December 24, 2020 (as amended on March 20, 2024) «On Approval of Sanitary Rules SP 2.1.3678-20 "Sanitary and Epidemiological Requirements for the Operation of Premises, Buildings, Structures, Equipment, and Transport, as Well as the Operating Conditions of Economic Entities Engaged in the Sale of Goods, Performance of Work, or Provision of Services"» // URL: https://docs.cntd.ru/document/573275590?marker=6560IO

11. Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 4 dated January 28, 2021 (as amended on May 25, 2022) «On Approval of Sanitary Rules and Norms SanPiN 3.3686-21 "Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases"» // URL: https://docs.cntd.ru/document/573660140?marker=6560IO

12. «MR 3.1.5.0076/1 – 13. 3.1.5. Epidemiology. Prevention of Infectious Diseases. HIV Infection. Pre- and Post-Test Counseling as Prevention of HIV Transmission. Methodological Guidelines» (approved by Rospotrebnadzor on August 20, 2013).

13. Order of the Ministry of Health of Russia No. 1129n dated October 20, 2020 «On Approval of the Rules for Conducting Mandatory Medical Examination to Detect Human Immunodeficiency Virus (HIV Infection)» (registered with the Ministry of Justice of Russia on November 11, 2020, No. 60847).

14. «Management of Planned Hospitalization in a Multidisciplinary Hospital. Methodological Guidelines No. 2001/144» (approved by the Ministry of Health of the Russian Federation on November 9, 2001).

Table 2. Key diagnostic criteria for establishing RVO and PORP

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

To prevent the development of retinal vascular diseases, it is necessary to regularly undergo clinical health examination (dispensarization), which helps identify the main risk factors for RVO (arterial hypertension, dyslipidemia, hyperglycemia, etc.). It is necessary to follow the recommendations of specialists and the rules for taking prescribed medications.

Routine ophthalmological examinations should be performed at least once a year, especially in the presence of arterial hypertension and diabetes mellitus.

If complaints arise regarding sudden painless vision loss in one eye, the appearance of a «spot» or «distortion» before the eye, it is necessary to consult an ophthalmologist immediately. Vision loss may be preceded by dull pain in the orbital region, short-term episodes of decreased vision, changes in image size, and distortion of lines and objects. Complaints most frequently occur after morning awakening or after abrupt changes in blood pressure levels.

Retinal vein occlusion is a manifestation of general cardiovascular pathology, indicating clear destabilization of the underlying disease. Treatment and examination are generally carried out on an outpatient basis and last for about two years. It should be understood that, despite the acute onset, the disease has a prolonged, chronic character and tends to progress and impair visual functions even with timely and adequate treatment.

Therapeutic success depends on the degree of compensation of concomitant pathology and the timeliness of initiating intravitreal injections. Treatment is administered in courses and is suspended or discontinued only when disease stabilization is achieved. The patient should inform the attending ophthalmologist if it is impossible to follow the recommended examination and treatment regimen. This will help the doctor choose the appropriate management tactics.

The goal of treatment is not to restore the patency of the affected retinal vessel (which is practically impossible), but to eliminate the symptoms of the disease that impair vision.

Patients receiving intravitreal drug injections must strictly follow the recommendations of the attending physician and inform them if new complaints arise (decreased vision after injection, the appearance of pain in the eye or orbital region, or discharge from the palpebral fissure).

Laser treatment for this condition is not aimed at improving visual acuity. The purpose of retinal laser photocoagulation is the prevention and treatment of complications that can lead to the loss of the eye as an organ. The feasibility and timing of retinal laser photocoagulation are determined by the attending physician; sometimes additional examination is required to make a decision.

Laser treatment is typically divided into several sessions, the frequency and extent of which are determined by the physician. Intraocular hemorrhages occurring during or after laser photocoagulation are associated with the underlying course of the retinal disease rather than the laser treatment itself, and may require additional stages of laser therapy and occasionally surgical intervention.

Patients who have suffered retinal vein occlusion must regularly monitor their intraocular pressure (at least once every 2 months during the first year of the disease, and at least twice a year thereafter). The lack of formal vision in the affected eye is not a reason to discontinue follow-up and monitoring of intraocular pressure. If the blind eye becomes red, watery, or painful, or if pain develops in the half of the head on the side of the blind eye, an ophthalmologist must be consulted immediately.

Patients with retinal vein occlusion are advised against smoking, exposure to hyperthermia (saunas, Russian banyas, hot showers or baths), and excessive physical and emotional stress. At the same time, it is important to maintain physical activity appropriate for the patient's age and general condition, and to follow a balanced diet with restricted animal fats and adequate fluid intake. If the patient is taking diuretics or hormonal medications, or has personally experienced (or has blood relatives who experienced) thromboembolic events under the age of 50, this must be reported to the physician, as it will help identify the causes of the eye condition, reduce the risk of involvement of the fellow eye, and prevent other cardiovascular complications.

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

No.