home Audience 2 Exudative (serous) detachment of the retinal pigment epithelium. Detachment of the retinal pigment epithelium Treatment of chorioretinal dystrophy

Exudative (serous) detachment of the retinal pigment epithelium. Detachment of the retinal pigment epithelium Treatment of chorioretinal dystrophy

Detachment of the retinal pigment epithelium in the macula is caused by metabolic disorders, a decrease in the water permeability of Bruch's membrane, which leads to the accumulation of fluid under the pigment epithelium. Clinically manifested by the formation of a dome-shaped elevation in the macula with transparent or turbid contents. Detachment of the retinal pigment epithelium can be complicated by serous detachment of the neuroepithelium and further development of the subretinal neovascular membrane (J. Kanski, 2006). There is a surgical technique that involves performing preretinal vitrectomy over the area of macular detachment, followed by puncture of the detached neuroepithelium with an instrument. Using massage, subretinal fluid is removed into the vitreous cavity, after which the fluid from under the pigment epithelium is drained in a similar way, then air is introduced into the vitreous cavity, and the patient is laid face down for a day, which ultimately ensures adaptation of the detached retina and stabilization of visual functions (G. E. Stolyarenko, 1989). The development of technologies for microinvasive endovitreal and laser surgery creates the prerequisites for finding a solution to this problem with the least amount of surgical intervention. In particular, in situations where the subretinal neovascular membrane has not yet developed, and serous detachment of the retinal pigment epithelium is combined with posterior vitreous detachment. The incidence of posterior vitreous detachment increases with age and is up to 50 years - 10% of cases, and after 70 years - 63% (R. Y. Foos, N. C. Wheeler, 1982).
Target
Development of a combined laser-surgical method for the treatment of serous detachment of the retinal pigment epithelium in the macula, combined with posterior vitreous detachment, with age-related macular degeneration, with a minimal amount of surgical intervention.
Materials and methods
The first stage is transpupillary double-row delimiting laser coagulation of the retina along the border of its detachment. Laser radiation parameters: wavelength – 532 nm, power – 100 mW, exposure – 100 ms, diameter – 100 µm. After 2 weeks, YAG laser retinopuncture is performed at the lower edge of the detachment focus. Laser radiation parameters: wavelength – 1064 nm, energy – 2–4 mJ, number of pulses – 1–2 (until the serous fluid flows out). As a result of the formation of a drainage hole, serous fluid begins to flow into the vitreous body. The next day, the patient is transferred to the operating room, where intravitreal tamponade is performed with perfluoroethane gas (C2F6) with an expansion coefficient of 3.3, microinvasive access through one 25 G port. Using a vitreotome, a channel is formed in the vitreous with dissection of the posterior hyaloid membrane of the vitreous and exit into the retrohyaloid space . Then, through the same access, C2F6 gas is introduced at 100% concentration in a volume corresponding to the removed vitreous body. Gas is introduced into the retrohyaloid space, leaving most of the vitreous intact. After the operation is completed, the patient is placed face down for a day. The gas, which expands for a maximum of 3 days, ensures the displacement of subretinal fluid into the vitreal cavity through the retinopuncture opening and the retina. After the retina has adhered, transpupillary delimiting laser coagulation is performed around the retinopuncture opening.
Using the technology described above, 3 patients with serous detachment of the retinal pigment epithelium in the macula and posterior vitreous detachment with age-related macular degeneration were operated on. The diagnosis was confirmed by optical coherence tomography and ultrasound B-scan data. The initial average value of corrected visual acuity was 0.01.
results
During three days of tamponade, the detached retina in the macula was reattached. On the fourth day, demarcation laser coagulation was performed around the retinopuncture opening. Patients were discharged after laser coagulation with recommendations to limit physical and visual stress for two months. At discharge, the average value of corrected visual acuity was 0.05, the retina in the macula was adjacent. During the observation period of 1 month, 6 months, 1 year, visual functions were stable, the retina in the macula was adjacent, and there was no choroidal neovascularization.
conclusions
The developed laser surgical method for treating patients with serous detachment of the retinal pigment epithelium in the macula with age-related macular degeneration, combined with posterior vitreous detachment, appears to be low-traumatic and reliable. The combination of laser retinopuncture and endovitreal surgery through a 25 G caliber access allows, with a minimal amount of surgical intervention, to ensure the retina fits in the macula and stabilize visual functions.

Central serous chorioretinopathy (CSC) is a serous detachment of the retinal neuroepithelium with or without detachment of the retinal pigment epithelium as a result of increased permeability of Bruch's membrane and leakage of fluid from the choriocapillaris through the retinal pigment epithelium (RPE). To make a diagnosis, pathology such as choroidal neovascularization, the presence of inflammation or tumor of the choroid must be excluded.

For a long time, CSC was considered a disease primarily of young men (25-45 years old). In recent years, reports have appeared in the literature about an increase in the proportion of women and an expansion in the age range of the onset of the disease.

Classic CSC is caused by one or more points of leakage through the RPE, visible on fluorescein angiography (FA) as large areas of hyperfluorescence. However, it is now known that CSC can also be caused by diffuse leakage of fluid through the RPE, which is characterized by detachment of the retinal neuroepithelium overlying the areas of RPE atrophy.

In acute cases Spontaneous absorption of subretinal fluid occurs within 1-6 months with restoration of normal or near-normal visual acuity.
Subacute course In some patients, CSC continues for more than 6 months but resolves spontaneously within 12 months.
A disease lasting more than 12 months is classified as chronic type currents.

In modern ophthalmology, central serous chorioretinopathy is usually divided into two main groups: acute (typical) and chronic (atypical).

Acute form of CSC , as a rule, develops in young patients and has a favorable prognosis, is characterized by idiopathic detachment of the neuroepithelium associated with the appearance of a “filtration hotspot”, which, as a rule, corresponds to a defect in the retinal PE. 3–6 months after the onset of the disease, in 70–90% of cases, spontaneous closure of filtration points, resorption of subretinal fluid and adhesion of the retinal neuroepithelium occurs. A longer period may be required to restore visual acuity and quality.
Chronic form The disease, as a rule, develops in patients over 45 years of age; more often there is a bilateral lesion, which is based on decompensation of PE cells, accompanied by the development of irreversible atrophic changes in the central parts of the retina and impaired visual functions.

Etiopathogenesis

Previous hypotheses associated the development of the disease with disturbances in normal ion transport through the RPE and focal choroidal vasculopathy.

The advent of indocyanine green angiography (ICGA) has highlighted the importance of choroidal circulation status in the pathogenesis of CSC. ICVA demonstrated the presence of multifocal increased choroidal permeability and hypofluorescence over an area suggestive of focal choroidal vascular dysfunction. Some investigators believe that initial choroidal vascular dysfunction subsequently leads to secondary dysfunction of the adjacent RPE.

Clinical studies show the presence of serous detachment of the retina and pigment epithelium and the absence of blood under the retina. With detachment of the pigment epithelium, local loss of pigment and its atrophy, fibrin can be determined, and lipofuscin deposits can sometimes be observed.

Constitution and systemic hypertension may correlate with CSC, apparently due to increased cortisol and adrenaline in the blood, which affect the autoregulation of choroidal hemodynamics. In addition, Tewari et al found that patients with CSC have decreased parasympathetic activity and a significant increase in sympathetic activity of the autonomic nervous system.

Multifocal electroretinography studies demonstrated bilateral diffuse retinal dysfunction, even when CSC was active in only one eye. These studies demonstrate the presence of systemic changes influencing them and support the idea of a diffuse systemic effect on choroidal vascularization.

CSC may be a manifestation of systemic changes that occur with organ transplantation, exogenous steroid administration, endogenous hypercortisolism (Cushing's syndrome), systemic hypertension, systemic lupus erythematosus, pregnancy, gastroesophageal reflux, use of Viagra (sildenafil citrate), and also with the use of psychopharmacological drugs, antibiotics and alcohol.

Diagnostics

Even if central visual acuity remains good, many patients experience discomfort in the form of dyschromatopsia, decreased contrast perception, metamorphopsia and, much less commonly, nyctalopia (“night blindness”).

Suspicion of CSC arises with monocular blurred vision, the appearance of metamorphopsia and diopter syndrome (acquired hypermetropia). Visual acuity after correction with positive glasses is usually 0.6-0.9. Even in the absence of indications of the presence of metamorphopsia, they are easily detected when examined with an Amsler grid.

Careful Questioning usually finds that the patient feels more or less comfortable only at average levels of illumination - bright light causes a feeling of blindness, and in twilight lighting he sees much worse due to a translucent spot appearing in front of the eye. With significantly pronounced micropsia, binocular vision disorders occur, which forces the patient to avoid certain activities (for example, driving a car). It is often revealed that this is not the first case of the disease, and its relapse occurred under similar conditions. However, sometimes a sick person, on the contrary, does not associate the disease with any external circumstances.

On the fundus a bubble of serous detachment of the neurosensory retina is determined, located in the area of the macula, having clear boundaries and usually a round shape. Its diameter is 1-3 times the diameter of the optic disc. In addition to neuroepithelial detachment, defects in the pigment layer, deposits of subretinal fibrin, and lipofuscin are often detected. The subretinal fluid is transparent, the neurosensory retina is not thickened. This detachment is much easier to detect during ophthalmoscopy with a red-free filter, and its boundaries are more clearly visible (sometimes literally “flashing”) during ophthalmoscopy with a maximum aperture light source. This glowing of the boundaries of the detachment is explained by the fact that when the depth of the serous cavity is insignificant, light passes through it, as if through a light guide, entering the vitreous body at the border of the adjacent retina.

The diagnosis of CSC requires angiographic confirmation . Early and delayed images are especially informative. In typical cases, an early appearance of a filtration point is observed. The classic description of the filtration point is the presence of a focus of hyperfluorescence in the zone of serous detachment with a dye current ascending from it in the form of a “column of smoke.” Meanwhile, in practice, dye diffusion in the form of an “ink spot”, spreading concentrically from the filtration point, is much more common.

During the study, fluorescein is distributed throughout the entire volume of the bladder. Delayed images show diffuse hyperfluorescence of the detachment zone. The study may detect alterations in the pigment epithelium in the neighborhood, indicating previous exacerbations of CSC that went unnoticed. The filtration point is most often located in the superonasal square from the center of the macula. Lithographic examination of the fundus with indocyanine in patients with CSC often reveals an area of initial hypofluorescence, slightly larger in diameter than the filtration point. This initial hypofluorescence quickly gives way to hyperfluorescence during the intermediate and late phases of the study (between 1 and 10 minutes). It is explained by the increased permeability of the choriocapillaris. Areas of hyperfluorescence that are not visible on fluorescein angiography are often identified. Thus, indocyanine angiography confirms the diffuse nature of choroidal vascular damage in central serous choriopathy.

Optical coherence tomography (OCT) shows various types of pathophysiological changes in CSC, from the appearance of subretinal fluid and detachment of the pigment epithelium to dystrophic changes in the retina in the chronic form of the disease. OCT is particularly useful in identifying minor and even subclinical retinal detachments in the macular area.

Differential diagnosis

Treatment

In most cases, CSC goes away on its own without any treatment (watchful waiting for 1-2 months), local serous detachment disappears without a trace, and vision is restored to its former limits. However, many patients with fairly good vision still complain of distorted color perception or the sensation of a translucent spot in front of the affected eye. It is possible to objectify these complaints by checking vision using visual contrast tables, according to which, in contrast to standard tables for testing visual acuity, it is still possible to detect differences in perception from the norm, in particular in the area of high frequencies of perception. It is in these individuals that the course of the disease becomes chronic, or is characterized by frequent relapses of serous retinal detachment. Patients with classic CSCR have a risk of recurrence of about 40-50% in the same eye.

The effectiveness of drug treatment is disputed by many researchers, however, taking into account the peculiarities of pathogenesis, namely the presence of a neurogenic factor, it is still advisable to prescribe tranquilizers.

Laser treatment

The decision about laser photocoagulation of the retina should be made in the following cases:

the presence of serous retinal detachment for 4 months or more;
recurrence of CSCR in the eye with an existing decrease in visual acuity after the previous CSCR;
a history of decreased visual function in the fellow eye after CSCR;
professional or other need for the patient requiring rapid restoration of vision.
Laser treatment may also be considered in patients with recurrent episodes of serous detachment with a fluorescein leak point greater than 300 µm from the center of the fovea.

If there are one or more points of dye leakage on fluorescein angiography that are located far from the foveal avascular zone (FAZ), suprathreshold retinal coagulation is an effective and relatively safe method. Moreover, the distance from the avascular zone, according to various authors, varies from 250 to 500 μm. For treatment, laser radiation is used in the visible range at a wavelength of 0.532 microns and near-infrared radiation at a wavelength of 0.810 microns, because It is their spectral characteristics that provide the most gentle effect on the fundus tissues. Radiation parameters are selected individually until the appearance of a type 1 coagulation focus according to the L'Esperance classification. When using radiation at a wavelength of 0.532 μm, the power varies from 0.07 to 0.16 W, exposure duration is 0.07-0.1 s, spot diameter 100-200 µm. When using radiation at a wavelength of 0.810 µm, the power varies from 0.35 to 1.2 W, exposure duration is 0.2 s, spot diameter is 125-200 µm. It should be noted that many researchers believe that the risk of recurrence of the disease less in coagulated eyes than in non-coagulated eyes.

Despite the undoubted effectiveness of suprathreshold coagulation of filtration points, the method has a number of limitations, undesirable effects and complications, such as atrophy of the pigment epithelium, the formation of a subretinal neovascular membrane (SNM) and the appearance of absolute scotomas.

Expansion of possibilities in the treatment of CSC is associated with the widespread use of micropulse laser radiation modes in clinical practice. Moreover, the most promising is the use of diode laser radiation at a wavelength of 0.81 microns, the spectral characteristics of which ensure its selective effect on the microstructures of the chorioretinal complex.

In micropulse mode, lasers generate a series (“packs”) of repeated low-energy pulses of ultra-short duration, the coagulation effect of which, when summed up, causes an increase in temperature only in the target tissue, i.e. in the pigment epithelium. Due to this, the coagulation threshold is not reached in adjacent structures, because they have time to cool down, and this makes it possible to minimize the damaging effect on neurosensory cells to a greater extent.

Thus, in the presence of leakage points located sub- or juxtafoveolar and, especially against the background of atrophic changes in PE, most researchers use subthreshold micropulse laser coagulation of the retina (SMILK) using diode laser radiation at a wavelength of 0.81 μm. After laser interventions, there were no complications characteristic of suprathreshold coagulation.

There are various modifications of SMILC. In recent years, photodynamic therapy (PDT) with the drug visudin has become an alternative treatment method for the chronic form of CSC. This technique, aimed at closing the filtration point due to a PE defect, can accelerate the elimination of exudation due to choriocapillary occlusion and stopping leakage in this area. After PDT, reconstruction of choroidal vessels and a decrease in their permeability occurs. The positive effect of PDT in the treatment of this disease has been obtained by many researchers. According to various authors, approximately 85-90% of patients experience regression of retinal neuroepithelial detachment (NDE), maintaining high visual acuity on average of 0.6-0.7. It is advisable to use the drug at half the standard dose in the treatment of chronic CSC, because this allows you to avoid possible complications (the appearance of patient complaints about an increase in the spot in front of the eye; angiograms in the affected areas revealed new areas of PE atrophy) with the same level of effectiveness that is achieved when using the full dose.

There are isolated reports in the literature on the use of transpupillary therapy in the treatment of chronic forms of CSC. The authors noted statistically significant (p<0,001) уменьшение ОНЭ и стабилизацию зрительных функций.

There is currently no clear opinion regarding the intravitreal administration of vascular endothelial growth factor inhibitors (Lucentis, Avastin) in the treatment of CSC. In clinical practice, angiogenesis inhibitors have proven themselves not only as agents that suppress neovascular growth, but also have demonstrated a pronounced anti-edematous effect. Cases of successful use of Avastin in the treatment of both acute and chronic forms of the disease have been described.

Thus, today, treatment of the acute form of CSC does not cause difficulties. If spontaneous recovery does not occur, traditional or micropulse laser coagulation of the retina is used, depending on the location of the filtration points. There are several directions in the treatment of the chronic form of CSC: micropulse laser coagulation; the prospects for using photodynamic therapy, transpupillary therapy and angiogenesis inhibitors are being studied.

This is an accumulation of fluid between Bruch's membrane and the RPE. Most often it is detected with drusen and other manifestations of age-related macular degeneration (including choroidal neovascularization). The detachment can have different sizes. Unlike serous detachment of the sensory retina, detachment of the pigment epithelium is a rounded dome-shaped local formation with clear contours. Visual acuity may remain quite high, but refraction shifts towards hypermetropia.

Serous detachment of the neuroepithelium is often combined with detachment of the pigment epithelium. In this case, there is a greater prominence of the focus; it has a disc-shaped shape and less clear boundaries.

During the development of the pathological process, flattening of the lesion may occur with the formation of local atrophy of the RPE or rupture of the RPE with the formation of a subretinal neovascular membrane.

Hemorrhagic detachment of the pigment epithelium or neuroepithelium is usually a manifestation of choroidal neovascularization. It can be combined with serous detachment.

Choroidal neovascularization is the ingrowth of newly formed vessels through defects in Bruch’s membrane under the pigment epithelium or under the neuroepithelium. Pathological permeability of newly formed vessels leads to fluid sweating, its accumulation in the subretinal spaces and the formation of retinal edema. Newly formed vessels can lead to the appearance of subretinal hemorrhages, hemorrhages into the retinal tissue, sometimes breaking into the vitreous body. This may result in significant functional impairment (1).

Risk factors for the development of subretinal neovascularization are considered to be confluent soft drusen, foci of hyperpigmentation, and extrafoveal geographic atrophy of the RPE.

Suspicion of subretinal neovascularization during ophthalmoscopy should be caused by retinal edema in the macular area, hard exudates, retinal pigment epithelial detachment, subretinal hemorrhages and/or hemorrhages into the retinal tissue. Hemorrhages may be small. Hard exudates are rare and usually indicate that the subretinal neovascularization is relatively old.

These signs should serve as an indication for fluorescein angiography.

Formation of a disc-shaped scar. The disc-shaped scar lesion represents the final stage of development of subretinal neovascularization. Ophthalmoscopically in such cases, a disc-shaped lesion of gray-white color is determined, often with pigment deposition. The size of the lesion can vary: from small, less than 1 diameter of the optic nerve head (OND), to large, which exceeds the area of the entire macular zone. The size and location of the lesion are of fundamental importance for the preservation of visual functions.

Classification. In practical ophthalmology, the terms “dry” (or non-exudative or atrophic) form and “wet” (or exudative or neovascular) form of age-related macular degeneration are most often used.

The “dry” form is accompanied by slowly progressive atrophy of the retinal pigment epithelium in the macular zone and the underlying choroid, which leads to local secondary atrophy of the photoreceptor layer of the retina. In the “dry” form, drusen are found in this zone.

The “wet” form is usually understood as the germination of newly formed vessels originating in the inner layers of the choroid through Bruch’s membrane into the normally absent space between the pigment epithelium and the retina. Neovascularization is accompanied by exudation into the subretinal space, retinal edema and hemorrhages.

Thus, for a non-exudative form, the following is determined:

Drusen in the macular zone of the retina;

Retinal pigment epithelium defects;

Pigment redistribution;

Atrophy of the RPE and choriocapillaris layer.

The exudative form goes through the following stages:

Exudative detachment of the RPE;

Exudative detachment of the retinal neuroepithelium;

Neovascularization (under the RPE and under the retinal neuroepithelium);

Exudative-hemorrhagic detachment of the RPE and/or retinal neuroepithelium;

Scarring stage.

In clinical studies, to determine prognosis and treatment tactics, choroidal neovascularization is divided into classic, hidden and mixed.

Classic choroidal neovascularization in age-related macular degeneration is the easiest to recognize and occurs in approximately 20% of patients. Classic choroidal neovascularization usually appears clinically as a pigmented or reddish structure beneath the RPE, and subretinal hemorrhages are common. When performing fluorescein angiography (FA), hyperfluorescence is observed in this area (for more details on the signs of FA in this pathology, see below).

Occult choroidal neovascularization can be suspected on ophthalmoscopy if there is focal scattering of pigment with retinal thickening without clear boundaries. Such neovascularization is characterized in FA by sweating in the late phase, the source of which cannot be determined (for more details on the signs of FA in this pathology, see below).

Fluorescein angiography

In many cases, age-related macular degeneration can be diagnosed (apparently diagnosed) based on clinical examination. However, fluorescein angiography makes it possible to more accurately determine structural changes and assess the dynamics of the pathological process. In particular, its results determine treatment tactics. It is advisable to perform it within 3 days after the first examination of a patient with suspected subretinal neovascularization, since many membranes increase quite quickly (sometimes by 5-10 µm per day).

Before the examination, color photographs of the fundus are taken. 5 ml of 10% fluorescein solution is injected intravenously.

If there is evidence of subretinal neovascularization in one eye, mid- and late-phase photographs of the other eye should be taken to identify possible neovascularization (even if it is not clinically suspected).

Hard drusen are usually punctate, give early hyperfluorescence, fill simultaneously, and the fluorescence stops late. There is no sweating from the druzes.

Soft drusen also show early accumulation of fluorescein without sweating, but they can also be hypofluorescent due to the accumulation of lipids and neutral fats.

On FAG, atrophy zones give a defect in the form of a “window”. Choroidal fluorescence is clearly visible already in the early phase due to the lack of pigment in the corresponding areas of the RPE. Since there are no structures that can trap fluorescein, the window defect fades along with background choroidal fluorescence in the late phase. As with drusen, fluorescein does not accumulate during the study and does not extend beyond the edges of the atrophic focus.

When pigment epithelial detachment occurs, fluorescein rapidly and uniformly accumulates in well-defined local rounded dome-shaped formations, usually in the early (arterial) phase. Fluorescein is retained in the lesions in the late phases and in the recirculation phase. There is no leakage of dye into the surrounding retina.

Age-related macular degeneration (AMD, senile macular degeneration, sclerotic macular degeneration, involutional central chorioretinal dystrophy, age-related maculopathy, age-related macular degeneration, senile macular degeneration, AMD - age related macular degeneration) is a chronic degenerative disease of the macular zone of the retina associated with layer damage choriocapillaris, Bruch's membrane, retinal pigment epithelium and photoreceptor layer, causing central vision impairment in patients over 50 years of age.

Its severity is due to the central localization of the process and, as a rule, bilateral damage.

AMD is the leading cause of irreversible vision loss in developed countries and the third leading cause of irreversible vision loss worldwide. It has been proven that the development of AMD is associated with age: if the proportion of people with early manifestations of this pathology at the age of 65-74 years is 15%, then at the age of 75-84 years it is already 25%, and at the age of 85 years and older - 30%. Accordingly, the proportion of people with late manifestations of AMD aged 65-74 years is 1%; at the age of 75-84 years - 5%; aged 85 years and older - 13%. The predominant gender of patients is female, and in women over 75 years of age this pathology is noted 2 times more often. In Russia, the incidence of AMD is more than 15 per 1000 population (8-10 million out of a population of 29 million aged 65 years and older).

In the near future, the increase in the number of people over 60 years of age will inevitably cause an increase in the prevalence of AMD in developed countries. Thus, according to calculations by the World Health Organization, taking into account the increase in the average age of the population, by 2020, 80 million people worldwide will suffer from AMD. The share of the population of the older age group in economically developed countries is currently about 20%, and by 2050 it will probably increase to 33%. Accordingly, a significant increase in patients with AMD is expected. All this makes us consider AMD as a significant medical and social problem that requires active solutions.

Risk factors

Pathogenesis

With age, focal deposits of lipofuscin (glycolipoprotein matrix), called drusen, appear between the retinal pigment epithelium (RPE) layer and Bruch's membrane (the border between the RPE and the choroid). Drusen accumulate due to a violation of the permeability of these structures, a deterioration in their supply of nutrients and a slowdown in the removal of metabolic products from them. It has now been proven that the development of AMD (and primarily drusen) is based on local inflammation, the pathophysiological mechanisms of which are similar to the process of formation of atherosclerotic plaques. Excessive drusen deposition damages the RPE, and the accompanying chronic inflammatory response leads to tissue ischemia and either large areas of retinal atrophy or expression of VEGF proteins leading to neovascularization. Ultimately, an area of geographic atrophy or an extensive subretinal fibrous scar is formed. These processes are accompanied by severe dysfunction of the macula with a sharp decrease in central vision.

Thus, AMD is a chronic degenerative (dystrophic) process in the RPE, Bruch’s membrane and choriocapillaris layer. As is known, the RPE is a multifunctional cellular system that performs a number of important functions. In particular, the RPE is involved in the formation of the external hematoretinal barrier, the absorption of excess light quanta, phagocytosis of waste photoreceptor disks (each pigmentocyte phagocytizes 2000-4000 waste disks daily) with subsequent restoration of the photoreceptor membrane, as well as the synthesis and accumulation of vitamin A (retinol), antioxidant protection tissues from free radicals and other toxins. Impaired evacuation of breakdown products, which normally pass through Bruch's membrane and are removed by the choriocapillaris, leads to the formation of large molecular chains that are not recognized by the enzymes of pigment epithelial cells, do not disintegrate and accumulate with age, forming drusen (containing lipofuscin). Lipofuscin (“age pigment”) is a round, yellowish granule with a brown tint, surrounded by lipid membranes and exhibiting autofluorescence. In turn, lipofuscin granules and the associated retinyl-retinylidene ethanolamine are phototoxic, as they are capable of generating reactive oxygen species under the influence of light, provoking lipid peroxidation. The retina is very sensitive to damage associated with oxidative processes, which is due to its constant high oxygen consumption with almost continuous exposure to light.

Pigments contained in the macula (in the inner layers of the retina), and related to carotenoids, play the role of natural sunglasses: they absorb the short-wave part of blue light, thus participating in the antioxidant protection of the macula. This pigment, composed of lutein and zeaxanthin, serves as a highly effective free radical inhibitor. Zeaxanthin is present only in the macula, lutein is distributed throughout the retina. Currently, there is work that shows that low levels of carotenoids in the fovea may be a risk factor for AMD.

With age, the thickness of Bruch's membrane also increases, its permeability to serum proteins and lipids (phospholipids and neutral fats) decreases. Increased lipid deposits reduce the concentration of growth factors required to maintain normal choriocapillaris structure. The density of the choriocapillaris network decreases, and the supply of oxygen to RPE cells deteriorates. Such changes lead to increased production of growth factors and matrix metalloproteinases. Growth factors (VEGF-A and PIGF) promote pathological growth of newly formed vessels, and metalloproteinases cause defects in Bruch's membrane. Thus, AMD begins with the dry form, that is, with changes in the RPE and the appearance of hard drusen. At a later stage, soft drusen appear, then they turn into confluent drusen. Progressive damage to the RPE leads to atrophic changes in the retinal neuroepithelium and choriocapillaris. When defects appear in Bruch's membrane, neovascularization spreads beneath the pigment epithelium and neurosensory retina. As a rule, this is accompanied by retinal edema, fluid accumulation in the subretinal space, subretinal hemorrhages and hemorrhages into the retinal tissue (sometimes into the vitreous body).

In the future, with the onset of a late phase, the development of AMD can proceed in two ways.

The first path is geographic atrophy, a relatively slowly progressing process. With an increase in the number and size of drusen and expansion of the dispigmentation zone, the death of photoreceptors and disruption of choroidal circulation occurs, which leads to thinning of the choroid and complete atrophy of the choriocapillaris layer, thus closing a vicious circle.
The second path is the formation of choroidal neovascularization (CHN), which leads to rapid and irreversible loss of central vision. Choroidal neovascularization results from an imbalance between vascular growth factor (VEGF) and vascular growth inhibitory factor (PEDF), which occurs due to oxidative stress. Violation of the permeability of the choriocapillaris layer, which occurs at the drusen stage, leads to a deterioration in the supply of retinal layers with nutrients and insufficient removal of metabolic products. As a result, tissue ischemia develops, causing the production of VEGF factor and the growth of newly formed vessels. At the first stage, vessels form at the border of the RPE and the choriocapillaris layer, then they can perforate the RPE, penetrating into the subretinal space. Exudation of fluid through the vascular wall, hemorrhages from newly formed vessels lead to exudative and hemorrhagic detachment of the RPE and neuroepithelium, causing the death of photoreceptors.

Although the pathogenesis of the formation of the dry form of AMD is not fully understood, modern advances in molecular genetics, angiographic, and histological studies help to understand the mechanism of development of the process. Atrophic foci can develop after exudative-hemorrhagic detachment of the neuroepithelium or without it. In the latter case, it is assumed that the growing drusen of the vitreous plate put pressure on the pigment epithelium, as a result of which it thins, the pigment disappears, and its hyperplasia occurs between the drusen.

At the same time, in the area of the drusen, thinning of Bruch's membrane is detected, in some cases with calcification of its elastic and collagen portions. In the choriocapillaris layer, thickening and hyalinization of stromal tissue occurs. Large choriodal vessels remain intact. Thus, foci of atrophy of the pigment epithelium and choriocapillaris layer are formed.

Classification

Different views on the pathogenesis of the disease and the emergence of new diagnostic methods determine the presence of several variants of AMD classifications (D. Gass (1965), L.A. Katsnelson (1973), Yu.A. Ivanishko (2006), Balashevich L.I. (2011) and etc). In practical ophthalmology, it is customary to divide AMD into dry and wet forms. The dry form includes such manifestations as drusen, dyspigmentation, atrophy of the RPE, choriocapillaris layer, and geographic atrophy. The wet form implies the presence of choroidal neovascularization and associated exudative and hemorrhagic complications, such as detachment of the RPE and/or neuroepithelium.

In 1995, the international classification of AMD was adopted, according to which AMD is divided into early (age-related maculopathy) and late forms (age-related macular degeneration). Early forms involve the presence of drusen, hyper- or hypopigmentation. Late forms are divided into geographic atrophy and choroidal neovascularization in its various manifestations.

The most convenient for practical use at the moment is the classification of AMD proposed by prof. L. I. Balashevich et al. in 2011. This classification takes into account both the traditional division of AMD into dry and wet forms, as well as the stages and various variants of each form in accordance with modern ideas about the pathogenesis of AMD.

Dry (or non-exudative, predisciform) form of AMD - it is characterized by the appearance of drusen in the macular zone of the retina, RPE defects, pigment redistribution, atrophy of the RPE and choriocapillaris layer.
Dyspigmentation (hypo- and hyperpigmentation) of the macula looks like areas of rarefied pigment, combined with interspersed small dark brown particles, and usually does not lead to a clear decrease in visual function. It is associated with changes occurring in the RPE: proliferation of cells in this layer, accumulation of melanin in them or migration of melanin-containing cells into the subretinal space. Focal hyperpigmentation is regarded as a significant risk factor for the development of choroidal (subretinal) neovascularization (CHN). Localized hypopigmentation often corresponds to the location of the drusen, as the RPE layer overlying them becomes thinner. However, local hypopigmentation can also be determined by atrophy of RPE cells, independent of drusen, or a decrease in the content of melanin in cells. As the pathological process progresses, dyspigmentation may develop into geographic atrophy of the RPE. This is a late form of dry AMD, manifested by the presence of clearly defined areas of depigmentation with clearly visible large choroidal vessels (resembling a continent in the ocean). With geographic atrophy, in addition to the RPE, the outer layers of the retina and the choriocapillaris layer in this area are affected. With FA, atrophy zones form a “window” type defect, and already in the early phase, choroidal fluorescence is clearly visible due to the absence of pigment in the corresponding zones of the RPE without accumulation and sweating. Geographic atrophy can be not only an independent manifestation of AMD, but also a consequence of the disappearance of soft drusen, flattening of the focus of RPE detachment, and may even occur as a result of regression of the SUI focus.
Wet (or exudative, disciform) form of AMD :
- predominantly classic choroidal neovascularization- clinically manifests itself as a pigmented or reddish structure under the RPE, often accompanied by subretinal hemorrhages. With FA, the newly formed subretinal vessels fill earlier than the retinal vessels (in the prearterial phase) with sweating under the detached neurosensory retina. Retinal hemorrhages can partially shield SUI.
- minimally classic choroidal neovascularization;
- occult choroidal neovascularization without classical component- suspected due to focal dispersion of pigment with simultaneous thickening of the retina, which does not have clear boundaries. With FA, gradually (2-5 minutes after injection), “speckled” fluorescence becomes visible, the degree of which increases with the addition of sweating (without its obvious source). An accumulation of dye in the subretinal space, which does not have clear boundaries, is also noted.
- suspected choroidal neovascularization;
- retinal angiomatous proliferation-has 3 stages: intraretinal neovascularization, subretinal neovascularization and fibrovascular detachment of the RPE, retino-choroidal anastomosis. It is characterized by a demographic profile (older age, Caucasian race), always extrafoveolar localization of the primary lesion ("non-capillary" zone), frequent intra- and preretinal hemorrhages with subsequent formation of SUI (without characteristic hyperpigmentation) and serous detachment of the RPE. With RAP, a retino-choroidal anastomosis is formed, that is, the retinal vessel expands, follows deep into the retina and ends in the subretinal space with newly formed vessels.
- idiopathic polypoid choroidovasculopathy- these are recurrent bilateral serous-hemorrhagic detachments of the RPE (the “lasso” sign on OCT - the atypical nature of the RPE with a wavy profile). Characteristic is the appearance in the inner layers of the choroid of a network of dilated choroidal vessels with multiple aneurysmal-ending processes, which gives the changes a polypoid appearance (more common in women of the Negroid race). It most often manifests itself in the peripapillary zone, but macular localization of the process is not uncommon. On ophthalmoscopy, it manifests itself as drusen-like protruding foci, often with areas of RPE detachment, hemorrhages and hard exudates.

Serous (exudative) detachment of the RPE is an accumulation of fluid between Bruch's membrane and the RPE and is most often detected in the presence of drusen and other manifestations of AMD (including SUI). Its dimensions may vary. Unlike serous neuroepithelial detachment, RPE detachment has, according to optical coherence tomography (OCT), the appearance of a dome with gentle slopes. Visual acuity may remain quite high, but often there is a shift in refraction towards hypermetropia. According to FA data, RPE detachment is characterized by a rapid, uniform and persistent accumulation of fluorescein from the early (arterial) phase until the recirculation phase without sweating. Detachment of the neuroepithelium often accompanies detachment of the RPE. As the pathological process progresses, flattening of the lesion with the formation of geographic atrophy or rupture of the RPE with the formation of SUI may occur.

Choroidal (subretinal) neovascularization (CHN) is characterized by the growth of newly formed vessels through defects in Bruch's membrane under the RPE or under the neuroepithelium. In this case, the pathological permeability of newly formed vessels leads to fluid sweating, its accumulation in the subretinal spaces and the formation of retinal edema. Neovascularization can lead to the appearance of subretinal and intraretinal hemorrhages. In this case, significant impairment of visual functions occurs. In case of SUI, serous detachment of the RPE can be combined with its hemorrhagic detachment.

By localization, choroidal neovascularization is classified depending on its location relative to the foveal avascular zone

Subfoveal - 0 µm - located under the center of the foveola in the avascular zone
Juxtafoveal - SNM or area of hemorrhage is within 1-199 µm from the center of the foveal avascular zone
Extrafoveal - the edge of the SNM, the area of fluorescence blockade by pigment and/or hemorrhage are at a distance of ≥200 µm from the center of the foveal avascular zone

Clinical picture

Patients with initial manifestations of the dry form of AMD may complain of blurring, gradual deterioration of central vision, difficulty reading, especially in low light conditions, decreased contrast sensitivity, and moderate metamorphopsia. At the same time, in some cases, the initial forms of AMD may not cause any complaints and may be random findings during examination of the fundus.

The main ophthalmoscopic sign of the dry form of AMD is drusen. Drusen appear as isolated yellow inclusions under the retinal pigment epithelium. Hard drusen are small, isolated from each other, round-shaped inclusions with clear boundaries. Soft drusen appear as larger yellow inclusions with poorly visible boundaries and a tendency to merge. The presence of single small hard drusen with a diameter of less than 63 microns in the macular zone is usually asymptomatic and occurs in many people. This circumstance is not considered a sufficient basis for making a diagnosis of AMD, but should serve as a reason for caution and dynamic monitoring in order to timely detect the progression of the process.

Dry form of AMD occurs in 80-90% of all cases of AMD. Visual impairment usually begins to appear in the early stage of AMD, which is ophthalmoscopically characterized by the presence of multiple small drusen, as well as a small number of medium-sized drusen (diameter 63-125 μm) in combination with changes in the retinal pigment epithelium in the form of hyper- and hypopigmentation. The appearance of metamorphopsia is associated with an increase in the size of drusen, the appearance of soft and confluent drusen, which corresponds to the intermediate stage of AMD (many medium-sized drusen and at least one large drusen with a diameter of 125 μm). Central and paracentral scotomas are noted in the field of view, which sometimes precede the appearance of visible atrophy. Fluorescein angiography reveals the disappearance of the choriocapillaris layer, zones of hyperfluorescence corresponding to areas of pigment epithelium atrophy, and hypofluorescence in areas of hyperplasia.

Differential diagnosis carried out with central areolar choroidosis of Sorsby. These diseases have a similar ophthalmoscopic picture of the fundus and a hereditary nature with an autosomal dominant type of transmission, however, Sorsby's choroidal sclerosis develops at an earlier age (20-30 years), and there are no dominant drusen in its clinical picture.

A similar picture of the fundus can be observed in multifocal chorioretinitis, in particular toxoplasmosis etiology, the hallmarks of which are unilateral lesions, different localization of foci in the fundus, and an inflammatory cellular reaction in the vitreous.

Intermediate stage AMD The development of geographic atrophy that does not affect the fovea also corresponds. Risk factors for the progression of the dry form of AMD are the number of drusen more than 5, the size of more than 63 microns, the confluent nature of the drusen and the presence of hyperpigmentation. Areas of geographic atrophy appear as well-defined, rounded areas of RPE atrophy with loss of choriocapillaris and thinning of the choroid, through which, over time, large choroidal vessels become visible.

With the involvement of the foveal zone in the atrophic process, a significant and irreversible decrease in visual acuity occurs. These manifestations correspond to the late stage of the dry form of AMD.

The first symptoms wet form of AMD resulting from the formation of SUI, there may be metamorphopsia, positive scotoma and “fogging” of central vision. Without treatment, choroidal neovascularization progresses rapidly, with a very poor visual prognosis.

Exudative detachment of the pigment epithelium occurs as a result of its disconnection from Bruch’s membrane and is a slightly protruding focus of a round, oval or horseshoe shape. It is better determined by ophthalmoscopy in reflected light. The most common localization is in the macular and paramacular zone. On a fluorescein angiogram, the serous fluid in the area of exudative detachment of the pigment epithelium is early stained with fluorescein, causing a focus of hyperfluorescence with clear boundaries. Detachment of the pigment epithelium can exist for a long time without dynamics and spontaneously disappear or increase. The most common complaints of patients are the appearance of a grayish spot in front of the eye, metamorphopsia, micropsia, and sometimes photopsia. Visual functions are slightly impaired; relative scotomas may be detected in the visual field. In some cases, detachment of the pigment epithelium is asymptomatic. Its complication is rupture of the pigment epithelium, which occurs spontaneously or as a result of laser coagulation. In this case, visual acuity is significantly reduced.

Exudative detachment of the neuroepithelium does not have clear boundaries and occurs due to a violation of the barrier function of the pigment epithelium. Patients complain of blurred central vision, distortion and changes in the shape of objects. Visual acuity decreases more significantly than with pigment epithelial detachment and may fluctuate throughout the day. Relative and absolute scotomas appear in the field of view. On a fluorescein angiogram with neuroepithelial detachment, in contrast to pigment epithelial detachment, slow staining of the transudate and the absence of clear boundaries are observed.

The development of a subretinal neovascular membrane hidden under the exudate cannot always be diagnosed, however, there are a number of ophthalmoscopic symptoms on the basis of which neovascularization can be assumed, in particular a change in the color of the exfoliated neuroepithelium (dirty gray or slightly greenish tint), the appearance of perifocal hemorrhages and the deposition of hard exudate . Fluorescein angiography plays an important role in the diagnosis of subretinal neovascularization, which allows one to observe the evolution of choroidal neovascularization. For its early diagnosis, angiography with indocyanine green is important, which makes it possible to remove the shielding effect of the pigment epithelium and observe choroidal changes. The subretinal neovascular membrane is identified in the early phases in the form of a lace or bicycle wheel. The fluorescein angiogram shows the classic lacy background of choroidal newly formed vessels. In the later phases, prolonged bright extravasal hyperfluorescence is observed in the area of neovascularization.

Based on localization, they distinguish between type I SNM, located under the pigment epithelium, and type II, extending into the subretinal space. Type I SUI is defined as a grayish-green or purplish-yellow, slightly raised lesion. Type II SUI may appear as a subretinal halo or pigmented lesion. SUI is also characterized by the appearance of signs associated with fluid exudation: serous retinal detachment, macular edema, and deposits of hard exudates. In the future, SUI may be complicated by hemorrhagic detachment of the pigment and neuroepithelium, subretinal hemorrhages, which are ultimately organized into a subretinal (disc-shaped) scar, which is accompanied by an irreversible severe loss of central vision. This is the final stage of development of SNM, ophthalmoscopically manifested in the form of a disc-shaped lesion of gray-white color, often with pigment deposition. The preservation of visual functions depends on the size and location of the lesion.

Rupture of newly formed vessels leads to subpigmental, sub- and preretinal hemorrhages. In rare cases, a breakthrough of hemorrhage into the vitreous body with the development of hemophthalmos is possible. Subsequently, the organization of blood and exudate is observed with the proliferation of fibrous tissue and the formation of a scar.

Ophthalmoscopically, a disc-shaped protruding yellowish lesion is visible, the retina above it is cyst-shaped. Often, a secondary exudative-hemorrhagic detachment of the neuroepithelium is formed along the edge of the scar and the process spreads over the area.

Differential diagnosis

Exudative detachment of the pigment epithelium can be a symptom not only of age-related macular degeneration, but also of central serous choriopathy (CSC), and can also be observed in central inflammatory processes. The difference is that CSC is characterized by a younger age of patients (men are more often affected), a favorable outcome with restoration of visual function and a recurrent course of the disease, while age-related macular degeneration is characterized by a steadily progressive course and the presence of dominant drusen or other dystrophic age-related changes in the fellow eye.

Differential diagnosis with a central inflammatory process is based on the younger age of patients, the presence of an inflammatory cellular reaction in the vitreous and the absence of changes in the fellow eye.

Extensive dystrophic changes, accompanied by exudative detachment of the neuroepithelium, massive exudative deposits and hemorrhages with prominence into the vitreous body, may represent a picture of pseudotumor. In these cases, echography, fluorescein angiography and the absence of changes in the fellow eye allow us to establish the correct diagnosis.

Diagnostics

The diagnostic algorithm for AMD includes determining visual acuity, biomicroscopy (to identify other possible causes of symptoms, such as age-related cataracts), ophthalmoscopy (including at the slit lamp using aspheric lenses, as well as Goldmann, Meinster and other lenses after pupil dilation for a short time acting mydriatics), perimetry. We can also recommend a study of color perception (monocularly), the Amsler test. Important tests for AMD include optical coherence tomography of the retina, fluorescein angiography (FAG), or indocyanine green angiography. Electrophysiological studies (ganzfeld electroretinography, rhythmic electroretinography, pattern electroretinography, multifocal electroretinography) are also indicated in AMD to assess the functional state of the affected retina.

When collecting an anamnesis, it is necessary to take into account the patient’s complaints about decreased visual acuity, the presence of a “spot” in front of the eye, difficulties in reading, especially in low light conditions (sometimes patients notice the loss of individual letters when reading fluently), metamorphopsia. SNM is characterized by complaints of a sharp decrease in vision and metamorphopsia. It is important to pay attention to the duration of symptoms, the unilateral or bilateral nature of the lesion, the presence of concomitant cardiovascular pathology and metabolic disorders, smoking, and heredity.

According to fluorescein angiography, choroidal neovascularization can be:

Classical - characterized by openwork clear outlines, manifested in the earliest phases of the passage of the dye; in the later phases, gradual leakage of fluorescein into the subretinal space around the SNM is noted
Hidden (or occult) - has less clear outlines, in the early phases of angiography the boundaries are not clearly visible, in the later phases there is diffuse or multifocal leakage.

In their pure form, these types of SUI are rare; in most cases, predominantly classical or predominantly hidden SUI occurs.

Optical coherence tomography of the retina is a new non-invasive method that allows one to obtain images of optical sections of the retina using a scanning laser beam. The method is used for diagnosis, dynamic monitoring and evaluation of the effectiveness of treatment of various forms of AMD. OCT allows you to: assess the condition of all layers of the retina, determine the severity of damage to the RPE, the height and area of macular edema; note the structural characteristics of edema (cystic changes, neuroepithelial detachment); detect the presence of a neovascular membrane; identify the presence of epiretinal fibrosis; determine the position of the posterior hyaloid membrane of the vitreous body; monitor the effectiveness of treatment for SUI and macular edema; carry out differential diagnosis with other retinal diseases. OCT is recommended to be performed at the first visit, and subsequently: to assess the dynamics - with an interval of 6 months for dry macular degeneration, every month - for SUI for the first six months of the disease; then - depending on changes in the retina.

New opportunities in visualizing the choroid have become available with the development of “in-depth” scanning technology (EDI - Enhanced Depth Imaging) using spectral optical tomographs. The ability to penetrate beyond the retinal pigment epithelium (RPE) and visualize the choroid opens new frontiers in understanding the pathogenesis of diseases of the posterior segment of the eye. In the presence of a submacular neovascular membrane, the thickness of the choroid is on average 234.2±47.7 µm with emmetropic refraction and 184.3±56.5 µm with myopic refraction. Considering these indicators, special attention should be paid to reducing the thickness of the choroid of the fellow eye, as the risk of developing SUI increases. The paired eyes of these patients should be observed at least once every 1-3 months, which will make it possible to identify SUI in the early stages of its formation and allow timely therapy to be prescribed, as well as to maintain high visual functions.

OCT characteristics of pathognomonic signs of AMD

Hard drusen are small, clearly differentiated, hyper-reflective, homogeneous formations, without a decrease in reflectivity in the center; cause slight elevation of the RPE, outer segments of photoreceptors and the IS/OS layer; may cast a slight vertical shadow on underlying layers.
Soft drusen are larger formations with clear boundaries and a rounded upper contour; in the center, as a rule, they have somewhat less reflectivity than at the borders; Bruch's membrane is visualized; elevation of the RPE, outer segments of photoreceptors and the IS/OS layer is more pronounced, deformation of the outer nuclear and reticular layers is possible.
Confluent drusen - even larger conglomerates formed by the fusion of soft drusen, have a flatter, uneven, wavy upper contour. They can reach large sizes both in area and in height.
In some cases, the fusion of a large number of drusen forms drusenoid detachment of the RPE.

Atrophy of the pigment epithelium - thinning of the pigment epithelium in combination with destruction of the outer layers of the retina, up to their complete loss; sharp thinning of the neuroepithelium in the atrophy zone. Signs of RPE atrophy on OCT are:

thinning or complete loss of the RPE. A thin line of Bruch's membrane is visualized at the site of the RPE;
thinning or complete absence of the outer nuclear layer (in the most severe cases);
direct contact of the outer plexiform layer with Bruch's membrane;
a relative increase in the reflectivity of the choriocapillaris layer behind the area of atrophy due to a violation of the light-absorbing function of the RPE.

OCT angiography serves as a modern non-invasive method for visualizing the microvascular bed in ophthalmology, expanding the capabilities of OCT due to the ability to differentiate blood vessels from surrounding tissues throughout the scanning depth without the use of a contrast agent. Visualization of the vascular bed of the retina and choroid is based on recording the movement of blood in the lumen of the vessel and is presented in the form of maps of vascular structures in the layer of the retina, pigment epithelium or choroid that is being examined. The use of OCT angiography in AMD makes it possible to identify changes not only in the area of the neovascular complex, but also in the density, thickness of newly formed vessels and the nature of their branching, differentiate classic and latent types of SUI, and assess the dynamics of the area of the neovascular complex during anti-VEGF therapy. However, angioOCT plays the role of an auxiliary study in the diagnosis of AMD and does not replace FA.

Intraretinal deposits - visualized as hyperreflective formations, usually not associated with the RPE. Deposits can be located anterior to the RPE, next to the RPE, or directly within the RPE. Unlike drusen, intraretinal deposits are not associated with Bruch's membrane and most often consist of lipofuscin granules of various sizes. Deposits can also spread into the inner layers of the neuroepithelium, causing their destruction.

Exudative detachment of the pigment epithelium - a dome-shaped formation with a clear, smooth hyperreflective contour that corresponds to the RPE. The content is usually hypo- or are-reflective. Bruch's membrane is visualized as a thin, weakly reflective line. A characteristic feature: attachment of the RPE to Bruch’s membrane at the border of the detachment zone occurs at an angle of more than 45°.

Exudative detachment of the neuroepithelium - accumulation of hypo- or arereflective content, which is a serous fluid sweating from defective newly formed vessels under the neuroepithelium. The outline of the outer layers of the neuroepithelium above the fluid may be uneven and unclear. A characteristic feature: attachment of the neuroepithelium to the RPE at the border of the detachment zone occurs at an angle of less than 30°.

Choroidal neovascular membrane - visualized on OCT if SUI belongs to type II, i.e. is predominantly classical. Classic subretinal SUI has the appearance of a mid-reflective formation with unclear boundaries, located between the RPE and the neuroepithelium. As a rule, it is surrounded by are-reflective or hypo-reflective contents of an exudative nature. Characteristic OCT signs of classic choroidal neovascularization are:

increase in retinal thickness in the foveal region, deformation or disappearance of the foveal recess;
intraretinal fluid in the form of cystic cavities and/or hemorrhagic inclusions;
the presence of a heterogeneous mid-reflective formation with unclear boundaries located between the neuroepithelium and the RPE;
exudative detachment of the neuroepithelium.

Occult choroidal neovascularization (type I SUI, subpigment epithelial, occult, hidden) is not directly visible on OCT, but its presence in 98% of cases is accompanied by more or less pronounced detachment of the RPE, under which in some cases moderately moderately reflective content is visualized. For a more reliable delineation of classical and hidden SUI, it is recommended to use FA and OCTA, which makes it possible to accurately determine at which layer the SNM is located.

Electroretinography

To study the nature of functional changes in the retina at various stages of age-related macular degeneration and monitor the progression of the process, the results of electroretinography and (with early diagnosis) electrooculography are of greatest importance.

Changes in the electrooculogram (EOG) are explained by the involvement in the pathological process of a larger part of the retinal pigment epithelium than is determined ophthalmoscopically. However, G.A. Fishman (1976) observed a normal EOG in a large number of patients with age-related macular degeneration, which allowed him to suggest the locality of changes in this type of pathology.

Early changes in visual functions in patients with AMD can be detected using psychophysical methods for studying dark adaptation, light, color and contrast sensitivity of the retina.
Early changes in the visual field are determined using the Amsler grating by testing spatial contrast sensitivity.
Changes in the visual field may be the first symptom of subretinal fluid accumulation in the macular area. Distortion of objects, blurred vision, and difficulty reading are the most common signs of the disease.
Color vision is usually not affected as long as the fovea is intact. Red-green dichromasia is observed already in the early stages of the disease, and changes in sensitivity in the green-blue part of the spectrum are observed in the advanced stage of the process. However, these changes in color vision are not specific to age-related macular degeneration.
Changes in the topography of contrast sensitivity and a decrease in the on/off activity of the cone system to stimuli lighter than the background are detected already at an early stage of the disease.

Electroretinographic research methods include analysis of the general, macular and rhythmic electroretinogram (ERG, MERG and RERG) and ERG for reverse chess patterns (pattern ERG). It has also been shown that, along with EOG, registration of the ERG c-wave is informative for early diagnosis of changes in the retinal pigment epithelium.

Pathological EOG is detected in most patients already in the early stages of the disease, while general ERG for a long period of time remains at the lower limit of the age norm or is recorded slightly subnormal. A more pronounced decrease in ERG waves is found in older people who have had the disease for many years.

As a rule, ERG is normal in the stage of dominant drusen. Previously A.E. Kril and V.A. Klein (1965) revealed the subnormal nature of a- and b-waves of the ERG in patients with dominant drusen, but they established the restoration of the amplitude of ERG waves in the process of dark adaptation, which indicates the preservation of the function of the scotopic system in the initial stages of AMD.

According to the ERG results, functional disorders in the outer and inner layers of the retina are more pronounced in developed and advanced stages of macular degeneration associated with age, in disciform forms of dystrophy of the Kunt-Junius type, detachment of the pigment epithelium, when the ERG b-wave is subnormal in nature . At the same time, in the fundus of patients, atrophic changes are noted in the chorocapillary layer and pigment epithelium, pronounced sclerotic changes in the vessels of the retina, which, although not a pathognomonic sign of AMD, can also be the cause of the subnormal nature of the ERG caused by metabolic disorders in the retina. The literature also describes cases where sharply pathological ERG and EOG were recorded, which is explained by old occlusive lesions of the venous bed, disciform detachment of the pigment epithelium, diabetic retinopathy, generalized hypopigmentation and “geographical” atrophy of the pigment epithelium noted in AMD.

It should also be borne in mind that the degree of changes in the amplitude of the general ERG depends on the stimulus intensity used and significant deviations of biopotentials from the norm are detected with flashes of light of lower brightness. The increased sensitivity of electroretinography in detecting subtle functional abnormalities in the retina at moderate intensity of light stimulation has been used to obtain electroretinographic characterization of various stages of age-related macular degeneration. Significant differences in the amplitude of the b-wave of the general ERG from the lower limit of normal values were established only in developed and advanced stages of the disease. However, in 43% of patients with the initial stage of AMD (non-exudative form), suppression of the ERG a-wave was detected, the value of which did not exceed 80% of the lower norm, and in 70% - suppression of high-frequency RERG to stimulation with a frequency of 40 Hz.

Macular ERG (MERG) has the greatest diagnostic value when examining patients with age-related macular degeneration, since this functional test reflects the activity of neurons of the cone system of the macular region, and therefore the degree of MERG changes depends on the nature of structural and metabolic disorders in the central region retina. It practically does not change with drusen and the initial form of chorioretinal changes, however, as the disease develops, MERG progressively decreases, which reflects more complex destructive processes in the macular region of the retina.

High-frequency rhythmic ERG (RERG) is the total activity of the entire cone system of the retina, not directly reflecting the electrogenesis of its central part, however, with moderate intensity of stimulating light (15-20 cd/m2), the contribution of the activity of the macular region increases significantly (up to 25% of the amplitude of the total rhythmic answer), increasing the diagnostic capabilities of RERG. The degree of suppression of RERG in non-exudative forms of AMD is less than that of MERG, but it increases sharply in disciform and exudative-hemorrhagic forms of the disease. Moreover, in the early stages of AMD, macular edema is often accompanied by normal or supernormal MERG. At the same time, the amplitude of high-frequency RERG is reduced by more than 2 times compared to the lower limit of normal values.

Pattern reverse ERG is a less common method for diagnosing AMD. It is used for objective assessment of retinal visual acuity (ROA), in particular to monitor the effectiveness of laser coagulation of subfoveal neovascular membranes and the progression of age-related macular degeneration. The assessment of ROZ is carried out by calculating the ratio of the logarithm of the spatial frequency of the stimulus (the size of the checkerboard cell) to the amplitude of the ERG pattern.

Treatment

Goals of therapy:

achieving stabilization of the pathological process, and not improvement of vision - in the presence of SUI;
prevention of complications (in the dry form - the appearance of SUI, in the wet form - the occurrence of hemorrhages of various locations, increased retinal edema, etc.);
prevention of severe vision loss leading to disability;
maintaining visual acuity, allowing the patient to care for himself independently - in case of advanced pathology.

In the dry form of AMD, drugs are used to improve regional blood circulation (vinpocetine 5 mg 3 times a day orally in courses of 2 months, pentoxifylline 100 mg 3 times a day orally in courses of 1-2 months, ginkgo biloba leaf extract 1 tablet 3 times per day orally in courses of 2 months). However, today their use fades into the background, since many authors question the theory of circulatory failure as the main etiopathogenetic factor in the development of AMD. In this form of AMD, stimulant therapy is also used. It is possible to use drugs with a different mechanism of action - for example, peptide bioregulators and, in particular, polypeptides of the retina of livestock eyes (retinalamine).

As mentioned above, exposure to sunlight promotes the appearance of free radicals, polyunsaturated fatty acids in the outer layers of the retina, in the RPE and Bruch's membrane. In this regard, attempts have been made to reduce the impact of oxidative stress by introducing dietary supplements containing antioxidants into the diet of patients: carotenoids, vitamins, lutein, zinc, copper. The most well-studied antioxidants include vitamins C and E, betacarotene, carotenoids (lutein and zeaxanthin), and polyphenols. The attention of specialists was also drawn to zinc, which is part of the structure of the key enzyme of the first line of antioxidant defense - zinc, copper-dependent superoxide dismutase (Cu,Zn-SOD). Superoxide dismutase catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide, inhibiting the formation of peroxynitrite, which is dangerous for eye tissue (including in the RPE). Plant carotenoids (lutein and zeaxanthin) accumulate in the macula and block the harmful effects of ultraviolet light. They act as strong antioxidants, blocking the action of free radicals that damage eye tissue and contribute to vision loss. Vitamins C and E are considered the most common antioxidants, which enhance and complement each other’s action, protecting eye tissue from damage, helping to restore visual pigments (rhodopsin, etc.) of rods and cones, which are responsible for normal light and color perception. They also strengthen the walls and increase the elasticity of blood vessels, including the vessels of the fundus. Participate in tissue respiration and other processes of cellular metabolism. They have a neuroprotective effect. Zinc, copper, selenium are essential microelements for maintaining vision function; they also have an antioxidant effect and compensate for the adverse effects of the environment. They help improve the nutrition of the fundus of the eye and maintain the functional state of the optic nerves.

Thus, the results of the AREDS randomized study on the use of various nutritional supplements show positive effects on the rate of progression of AMD - a 25% slowdown - from the use of high doses of antioxidants (vitamins C, E, β-carotene and zinc), a decrease in the likelihood of vision loss (3 lines) by 19%.

An example of such a dietary supplement is Retinorm containing 10 mg of lutein, 2 mg of zeaxanthin, 500 mg of vitamin C, 150 mg of vitamin E, 100 mcg of selenium, 25 mg of zinc and 2 mg of copper (copper and zinc are in the form of aspartates, which provides high bioavailability of microelements). The composition of Retinormar was developed based on the AREDS2 formula - the largest clinical multicenter study conducted under the auspices of the US National Eye Institute (6 years - 4203 patients with AMD, 82 medical centers), which confirmed the positive effect of lutein (10 mg) and zeaxanthin (2 mg) in combination with high doses of vitamins C (500 mg) and E (268 mg), microelements (zinc 25 mg and copper 2 mg) to reduce the progression of AMD. Lutein/zeaxanthin supplementation was associated with a 11% reduction in the risk of neovascularization and a 10% reduction in the risk of advanced AMD. When replacing β-carotene in the AREDS formula with lutein + zeaxanthin, an additional reduction in the risk of developing late stages of AMD was observed from 34 to 30%, and the issue of cancer alertness in smokers was also eliminated (β-carotene is a carcinogen and is not recommended for use by smokers) in comparison with AREDS results.

Currently for laser retinal stimulation the most commonly used are helium-neon lasers with a radiation wavelength of 632 nm, helium-cadmium lasers (441 nm) and infrared laser radiation (1.3 µm). It is believed that laser stimulation of the retina is indicated for all manifestations of non-exudative forms of AMD, with the exception of retinal drusen. Laser coagulation of soft confluent drusen located bilaterally is especially indicated, in which choroidal neovascularization most often develops. However, despite the fact that after laser coagulation the number of drusen decreases and they become flattened, according to the literature, choroidal neovascularization develops in 3% of cases 5-11 months after laser coagulation.

Laser coagulation of the retina is more effective in the treatment of exudative and exudative-hemorrhagic stages of AMD. It is used to reduce swelling of the macular area, destroy the subretinal neovascular membrane, and delimit or “close” exudative detachments of the pigment epithelium.

The basic principle of laser coagulation for these pathological conditions is the inviolability of the fovea; Laser coagulation can be carried out in this area only in cases where extrafoveal vision is preserved and irradiation of the macula will allow the degenerative process to be stopped. To carry out coagulation of the central zone, argon, krypton and diode lasers are used. According to L.A. Katsnelson et al. (1990), it is more expedient to carry out laser coagulation in this zone using a krypton red source with a radiation wavelength of 647 nm, since it is absorbed in the pigment epithelium layer with minimal damage to the retina.

The timing of laser exposure is determined by the state of visual functions and the nature of changes in the macula. In case of exudation and visual impairment, it is advisable to perform fluorescein angiography and, if indicated, laser coagulation. In case of exudative detachment of the retinal pigment epithelium (RPE) in the macular zone, barrier laser coagulation is performed in the form of a “horseshoe”, open towards the papillomacular bundle. Exudative detachment of the pigment epithelium outside the macular area is completely “closed” with coagulates. With widespread exudative detachment of the neuroepithelium, “lattice” laser coagulation is required in the central zone of the retina. In the presence of a choroidal or subretinal neovascular membrane, complete closure of the pathological focus with grade III laser coaculates is recommended. In this case, it is necessary to take into account the localization of the neovascular membrane and its distance from the avascular zone.

The prognosis for the effectiveness of laser surgery worsens when RPE detachment is combined with local choroidal neovascularization, especially when it is localized directly under the area of detached RPE. At the same time, with a parapapillary location of choroidal neovascularization, the best anatomical and clinical results are often achieved.

In recent years, encouraging results have also been obtained using diode lasers and photodynamic therapy to coagulate choroidal neovascular membranes, as well as low-dose radiotherapy to treat subfoveal neovascularization.

Drug treatment of choroidal (subretinal) neovascularization

An effective method of treating neovascular AMD is the use of neovascular growth factor inhibitors - anti-VEGF drugs. In Russia, two drugs are currently approved for the treatment of SUI: aflibercept and ranibizumab. Considering the fact that VEGF is the main factor stimulating subretinal neovascularization in wet AMD, antiangiogenic therapy has become an essential element of its treatment, as it is considered pathogenetically oriented and safe. VEGF inhibitors demonstrate superior visual acuity outcomes compared with other treatments and have become the first choice drugs for the treatment of neovascular AMD. As shown by the results of a number of clinical studies, the prospects of therapy directly depend on both its timely initiation (the earlier treatment is started, the better the result; the therapeutic window for starting treatment is up to 12 months from the onset of the disease), and on mandatory monitoring. To assess the effectiveness and timely identify the need for re-therapy, monthly monitoring is required (the instructions recommend 3 consecutive monthly injections followed by administration of the drug “as needed”), necessarily including visometry and OCT of the macula.

In the wet form of AMD, to reduce swelling, you can use subconjunctival and retrobulbar injections of glucocorticoids (dexamethasone 0.5 ml, triamcinolone 1.0 ml 10 injections) and in the form of subconjunctival injections, acetazolamide orally (250 mg 1 time per day in the morning for half an hour 3 days before meals, then after a 3-day break the course can be repeated), as well as intravitreal injection of an implant with prolonged dexamethasone.

Laser treatment of subretinal neovascularization

In some situations, laser techniques are the method of choice, the purpose of which is to reduce the risk of further decline in the patient’s visual acuity. To do this, the subretinal neovascular membrane is completely destroyed within healthy tissues, applying intense confluent coagulates. Argon laser photocoagulation can be used to destroy “classic” extrafoveal SLMs, reducing the likelihood of their spreading to the foveola and causing serious vision loss. For juxtafoveal subretinal membranes, it is recommended to use a krypton red laser. For subfoveal membranes, photodynamic therapy is used. The intervention should be carried out according to the results of FA. The use of the technique is limited by the insignificant prevalence of these localizations of SUI (13-26%), significant damaging effect and high risk of membrane recurrence.

Transpupillary thermotherapy is a low-energy laser effect (wave energy of the infrared part of the spectrum with a length of 810 nm), proposed for a biostimulating effect on hidden SNM (with a minimal classical component) of central localization. However, widespread implementation of the method turned out to be impossible due to the short duration of the therapeutic effect, the risk of complications (hemorrhages, rupture of the RPE, occlusion of retinal vessels, progression of fibrosis, etc.) and a significant number of contraindications (classical component of SNM, previous laser coagulation, RPE detachment, etc.). Transpupillary thermotherapy can be used in cases in which there is virtually no positive effect from photodynamic therapy (PDT). However, when using transpupillary thermotherapy, frequent complications are noted, primarily associated with an overdose of laser energy (normally, the effect should be subthreshold): infarctions in the macular zone, occlusion of retinal vessels, ruptures of the RPE, subretinal hemorrhages and atrophic foci in the choroid are described. The development of cataracts and the formation of posterior synechiae were also noted.

Low-energy argon laser coagulation of drusen to prevent disease progression and development of SUI was studied in the 1990s (Choroidal Neovascularization Prevention Trial). The method is relatively safe and gives good immediate results, but in the long term there is a high probability of the development of subretinal neovascular membranes in the areas of laser exposure. Currently, the method is not actively used.

Photodynamic therapy

This is a method of selectively influencing the SNM with diode laser radiation with a wavelength of 689 nm (duration 83 s). The photosensitivity substance verteporfin is preliminarily administered intravenously - 6 mg/kg body weight for 5 minutes, which selectively accumulates in the endothelium of newly formed vessels, causing their thrombosis and obliteration. Thus, laser radiation selectively damages the target tissue without affecting surrounding structures, which leads to vascular occlusion and slower progression of SUI. Since recanalization can occur after vascular occlusion, patients require an average of 5-6 PDT sessions (more than half of them are performed within 1 year after the start of treatment).

The effectiveness of PDT has been proven for classical and predominantly classical SUI (including subfoveal localization) with an area of up to 5400 µm. If SNM activity persists, the procedures are repeated every 3 months. Prospects for the use of PDT with membrane sizes of 5400 µm and initial visual acuity<0,1, cкрытых и минимально классических СНМ сомнительны. На сегодняшний день ФДТ чаще рассматривается не как самостоятельный способ лечения, а как дополнение к более эффективной терапии ингибиторами ангиогенеза. В России данный вид терапии практически не используется. В последнее время ФДТ реже применяют в тех странах, где разрешено интравитреальное введение ингибитора ангиогенеза.

Surgical treatment of choroidal (subretinal) neovascularization

Submacular surgery, macular translocation, choroidal transplantation, RPE cell transplantation and other techniques are also not widely used. This is due to their significant technical complexity, the risk of serious complications and low functional outcomes (long-term visual acuity after even successful intervention rarely exceeds 0.1).

When removing subretinal neovascular membranes, vitrectomy is first performed according to the standard technique, then retinotomy is performed paramacularly, from the temporal side. A balanced saline solution is injected through the retinotomy hole to detach the retina. After this, using a horizontally curved peak, the membrane is mobilized and the membrane is removed by inserting horizontally curved tweezers through the retinotomy. The resulting bleeding is stopped by lifting the bottle with infusion solution and thereby increasing intraocular pressure (IOP). The liquid is partially replaced with air. In the postoperative period, the patient must maintain a forced position face down until the air bubble is completely resolved. Such interventions can reduce metamorphopsia and provide more constant eccentric fixation, which is often regarded by patients as a subjective improvement in vision. The main disadvantage is the lack of improvement in visual acuity as a result of the intervention (in most cases after surgery it does not exceed 0.1).

Methods have been developed for the removal of massive subretinal hemorrhages through their evacuation through retinotomy holes.

Surgical interventions for translocation of the macula are also performed. The main idea of such an intervention is to displace the neuroepithelium of the foveal retina, located above the SNM, so that the unchanged RPE and choriocapillaris layer are located under it in a new position. To do this, first perform a subtotal vitrectomy, and then completely or partially detach the retina. The operation can be performed by performing a retinotomy around the entire circumference (360°), followed by rotation or displacement of the retina, as well as by folding (i.e. shortening) the sclera. The retina is then “fixed” in its new position using an endolaser, and the neovascular membrane is destroyed using laser coagulation. Pneumoretinopexy is performed, after which the patient must remain in a forced position (face down) for 24 hours. During interventions for macular translocation, a number of complications are possible: proliferative vitreoretinopathy (19% of cases), retinal detachment (12-23%), formation of a macular hole (9%), as well as complications encountered during vitrectomy for other indications. In this case, loss of not only central, but also peripheral vision may occur. Currently, this technique has not found wide application.

About the prospects of treatment

Retinal pigment epithelium transplantation

In recent years, attempts have been made to implement RPE transplantation in experimental settings as an alternative or complementary treatment for age-related macular degeneration. If 15 years ago retinal tissue transplantation seemed impossible, today it is successfully performed on animals in several experimental laboratories in different countries.

There is also experience with RPE cell transplantation in more than 20 patients with AMD. In addition, the same number of patients with retinitis pigmentosa underwent transplantation of neuronal retinal cells.

In the exudative form of AMD, after removal of subretinal neovascular membranes, local grafts (so-called patches) are used, and in the “dry” form, small grafts (or Wok plaques) and a suspension of RPE cells are used.

It has been shown that the survival time of fetal human allografts in the subretinal space depends on the size and characteristics of the graft itself, its retinal localization, and local conditions (degree of exudation) under which the operation is performed. Small extrafoveal grafts in non-exudative forms of AMD survive for a long time (years). However, most other grafts, especially those at the disciform stage, do not survive, which is believed to be a consequence of their rejection by the body.

Thus, a major direction for future research in this area is the development of methods to prevent flap rejection and immunological incompatibility of the grafted tissue. According to P. Gouras and a group of American researchers from Columbia University (1998), two main conditions are necessary for successful transplantation.

The first is the improvement of surgical technique to prevent or minimize any inflammatory reaction at the graft site, since inflammation provokes immune reactions, and the widespread use of electronically controlled "microinjection" techniques to create the conditions necessary for detachment of the neuronal retinal vesicle within which the graft is to be placed . The quality of the graft is also of great importance. N.S. Bhatt et al. (1996) believe that the most subtle, precision approach to transplantation is the introduction into the subretinal space of fetal human RPE cells cultured on a collagen substrate. According to D. BenEzra (1996), to minimize the inflammatory reaction, it is preferable to use not a suspension of RPE cells, but a local layer of embryonic RPE. In addition, he suggests that the clinical use of epidermal growth factor has great potential due to its significant and specific activity as a stimulator of RPE cell proliferation. In this regard, L.V. Del Priore et al. (1996) focus on cytokines that may be responsible for the autoregulation of pigment epithelial cell proliferation.

The second condition that determines the success of transplant surgery, according to P. Gouras (1998), is the development of methods that suppress the rejection of transplanted tissue. Attempts are already being made to systematize the methods of immunosuppression used in the treatment of AMD, which are currently standard in organ transplantation: the use of cyclosporine, azathioprine and steroids. Under these conditions, the resistance of the RPE flap to rejection increases by more than 1 week. The authors concluded that it is necessary to develop in animal experiments the minimum doses necessary to achieve adequate immunosuppression in order to prevent rejection of the RPE allograft.

Given the novelty of the method, all surgical procedures performed in humans should be considered experimental, and the possibility of more moderate immunosuppression in older patients with AMD should be evaluated. Currently, an experimental model (rabbit) is being used to study the effectiveness of slow release of cyclosporine-A capsules, which, when placed in the vitreal chamber, should create local rather than generalized immunosuppression. The challenge is to ensure a truly slow release of cyclosporine-A, since the accelerated release of the capsules causes some damage to the photoreceptors, which is not conducive to the success of the transplant.

Despite increasing clinical experience with RPE transplants, the question of whether pigment epithelial allografts can actually influence the course of age-related macular degeneration remains unclear. It is assumed that the possibility of surgical treatment of this disease will become obvious if successful reconstruction of a monolayer of healthy RPE (at least in the allograft region) through all layers in the macula is achieved, which in turn requires improvement of subfoveal surgical technique.

There is also no doubt that to maintain the integrity of the cells, testing and modification of their “delivery” technology will be required. It is still unknown whether a healthy monolayer placed on the surface of the atrophic layer of the host RPE will function well: as an integral bilayer or as a multilayer of pigment epithelium. As shown in studies in monkeys, the multilayer of transplanted human fetal RPE, i.e. xenograft, can support some outer segments of rods and cones for at least 6 months.

Today, one of the promising methods for treating severe forms of age-related macular degeneration (AMD) is transplantation of retinal pigment epithelium (RPE) in the form of a cell suspension or choroid-pigment complex (CPC). A more modern approach is the creation of 3D RPE spheroids for subsequent subretinal transplantation. A spheroid is a conglomerate of cells that gather under the force of their own gravity and are interconnected by intercellular connections. 3D spheroids have a diameter of several hundred micrometers (200-700), which could allow them to be injected under the retina using modern microinvasive instruments; they quickly settle in liquid, and also, when attached to a flat surface, exhibit the effect of spreading a layer of cells around myself. However, transplantation of RPE in the form of 3D spheroids requires preclinical studies. The traditional model for ophthalmological research is rabbits.

The standard composition of the nutrient medium (DMEM/F12, FBS, L-glutamine and antibiotic solution) is acceptable for the cultivation of rabbit RPE. 3D RPE spheroids delivered subretinal using the proposed technology exhibit pronounced adhesive properties to the choroid.

Genetic Engineering

Recently, studies have been carried out on the transduction of cultured human fetal RPE using a retrovirus (antivirus), which introduces two genes into these cells: a gene producing green fluorescent protein (GFP) and a gene producing endostatin or angiostatin (potential anti-neovascular factors).

ZFB is useful in experiments because it allows one to view grafts in the living retina in a non-invasive manner using a scanning laser ophthalmoscope (488 nm argon laser through a fluorescent barrier filter). In a similar manner, it is possible to monitor the rejection of xenotransylantate in the retina in vivo and compare the effects of slow-release cyclosporine-A capsules with placebo.

The endostatin gene is useful in preventing neovascularization, but due to existing rejection reactions it cannot yet be actively used for either allografts or xenografts. However, there is hope for a solution to this problem in the near future.

Another strategy for using genetic engineering of cells to combat neovascularization, being developed at Columbia University (USA), is to attempt to transduce the virus into the patient's iris pigment epithelium obtained by simple iridectomy. Iris pigment epithelium can be cultured, transduced with subsequent gene expression in vitro, and then transplanted into the submacular space in close proximity to the area of neovascularization. Such allografts should, according to P. Gouras, survive indefinitely and locally release endostatin to suppress neovascularization. There are also controller genes, the addition of which to the viral construct will allow the expression of endostatin to be “switched on” and “switched off” using an antibiotic.

It is believed that such a strategy for treating neovascularization is promising and promising. One of its disadvantages is the relative duration of the procedure for growing and transducing a sufficient amount of iris pigment epithelium in vitro (2-3 weeks), while in most cases the process of neovascularization requires rapid intervention. However, to temporarily suppress neovascularization during this period of time, the use of other methods of therapy, such as photodynamic therapy, is proposed.

Central chorioretinal is degenerative changes in the retina in the area of best vision. In the area of the macula, the cells do not receive blood, so they gradually die and are replaced by connective tissue. Without treatment, a person completely loses central vision. The disease in the first stages is asymptomatic, so it is difficult to diagnose at an early stage of development. To slow down the pathological process, complex treatment is carried out with drugs, physiotherapy, and surgery.

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What is central chorioretinal dystrophy?

Central chorioretinal dystrophy or CCRD is a disorder of retinal nutrition in the macula or area of best vision. An alternative name for the pathology is senile macular degeneration. The disease is considered age-related because it occurs most often in older people over 60 years of age, mainly in women.

During the aging process, retinal tissue degenerates, which leads to irreversible changes in the macula area. As a result, the person loses much of his central vision. Tissues distant from the vessels die and subsequently become scarred - replaced by fibrous connective tissue. The pathological process in most cases affects both eyes, but in rare cases it can progress faster in one of the retinas.

At the same time, in the absence of timely treatment, CCRD does not lead to complete loss of vision. does not extend to the peripheral zone of the retina, so the person continues to see objects at the boundaries of the visual field. But in this case, he becomes unable to work, since he loses the basic abilities that require clear vision: writing, reading, driving.

With age, the risk of pathology increases:

from 51 to 64 years, the probability of developing CCRD is 1.6%;
from 65 to 74 years - 11%;
in people over 75 years of age, the risk reaches 28%.

The disease is chronic and progresses slowly. CCRD does not lead to retinal detachment. Dystrophic changes affect the choriocapillaris layer, the pigment layer of the retina and Bruch's membrane, or vitreous plate, located between them.

Causes

Chorioretinal dystrophy does not occur for one specific reason. The development of pathology is provoked by several factors:

hereditary predisposition if the disease manifested itself in one of the parents or close relatives;
the presence of high myopia;
circulatory disorder in the eye vessels, microcirculation disorder in the choreocapillaries;
exposure to free radicals and ultraviolet rays on the retina;
injury to the eyeball, severe poisoning or infection;
bad habits;
weakened immunity;
diseases of the endocrine system: diabetes mellitus, damage to the thyroid gland;
pathologies of the cardiovascular system: high blood pressure, atherosclerosis, increased blood clotting and a tendency to form blood clots;
unbalanced diet, obesity.

CCRD can occur as a congenital disease, inherited in an autosomal dominant manner, or as an acquired pathology. In the latter case, retinal dystrophy is provoked by intoxication, severe infectious-inflammatory disease or eye injury.

REFERENCE. Not only women, but also people with light irises and skin are at risk. The likelihood of pathology occurring increases in patients who have recently undergone cataract surgery.

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What is retinal dystrophy?

Signs of the disease

The dry form of CCRD begins asymptomatically and is characterized by a slow course, so at first the patient does not complain of discomfort or pain. The person maintains normal visual acuity. In some cases, patients note:

distortion of the shape and size of visible objects;
distortion of straight lines;
splitting of objects;
the appearance of blind spots;
Over time, the image blurs, as if a person is looking through a glass of water;
visual acuity slowly decreases.

The pathology may stop at some stage and no longer appear or continue to progress until the person completely loses central vision. In this case, the disease first affects one eye. Changes in others become noticeable only after 5-6 years.

Possible complications

Degenerative changes in the retina lead to a sharp deterioration in vision, which does not recover after undergoing drug therapy or surgery. In some cases, CCRD leads to complete loss of central vision. As a result, a person sees only 2-3% of the outside world on the periphery of the retina. If the pathological process continues to progress and the retina begins to peel off in peripheral areas, complete blindness may develop.

The following complications are possible with CCRD:

increased intraocular pressure, which increases the risk of developing angle-closure glaucoma;
hemorrhages into the vitreous cavity;
clouding of the transparent media of the eyeball.

Retinal detachment in CCRD leads to the formation of chorioretinal scars at the junction of the macular zone with the choroid of the fundus. With timely treatment, vision is not restored, because the area of best vision is partially overgrown with connective tissue. A person sees dark spots before his eyes.

Prevention

To prevent the development of pathology, several principles should be followed:

take multivitamin complexes containing vitamins A, B, E, biological supplements with zinc;
perform exercises from the eye gymnastics complex daily;
balance the diet by supplementing it with fresh fruits and berries high in minerals and vitamins;
protect eyes from ultraviolet radiation and sunlight;
do not overstrain your vision, give your eyes a rest;
If possible, get rid of bad habits.

In the early stages, the disease is asymptomatic, so you should undergo a preventive examination by an ophthalmologist at least 2 times a year every 6 months.

Conclusion

Central chorioretinal dystrophy affects the retina in the macula area. In this case, as the disease progresses, the patient is able to distinguish only objects in the periphery of vision. He will not be able to see in front of him, so he loses his reading or writing skills.

To slow down the development of the pathological process, complex treatment is prescribed. A person takes medications and undergoes physical procedures. If the effectiveness of conservative treatment is low, laser coagulation of the retina is prescribed or surgery is performed.

Anastasia Zharova

Internet journalist, copywriter.

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