RU2541834C1 - Method of treating age-related wet macular degeneration - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: with the drug-induced mydriasis, a transcleral cryopexy of chorioretinal structures is performed on the extreme periphery of an eye ground in a projection of a dentate line. The performed cryopexy is ophthalmoscopically controlled by means of a head-mounted binocular ophthalmoscope and lens 20.0D or 29.0D. A cryocoagulate size makes no more than 1 diameter of an optic disk; cryocoagulate gaps are no more than 1 diameter of the optic disk. The cryoexposure continues until the retina whitens within the exposure. That is followed by the intravitreal insertion of Lucentis 0.5mg.

EFFECT: well-timed resolution of an inflammation on the on the extreme periphery of the eye ground in a combination with administering an angiogenesis inhibitor in the given group of patients provides the complex, pathogenetically ground exposure, promoting stabilising the pathologic process in the macular region that in turn ensures the prolonged stable clinical-functional effect.

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Description

The invention relates to the field of clinical medicine, in particular ophthalmology, specifically to methods for treating the “wet” form of age-related macular degeneration (AMD).

Age-related macular degeneration (AMD) is one of the first causes of blindness in people over 60 years of age and is the leading cause of central vision loss in developed countries [1, 3, 13, 14, 15]. In recent years, this disease is diagnosed not only in the elderly, but also in a relatively young age in people of the working population, which leads to primary disability in 11% of cases in people of working age and in 28% of cases in the elderly.

The severity of damage to the central parts of the retina during the development of AMD can vary: from redistribution of pigment and the appearance of drusen-like deposits to exudative-hemorrhagic detachment of the pigment epithelium and neuroepithelium with the subsequent development of a subretinal fibrovascular membrane.

Since the clinical picture and the course of the disease are very diverse, the etiology and pathogenesis of AMD for many years have been the subject of discussion by domestic and foreign researchers [1, 7, 8, 13, 14, 15].

Four fundamental theories of the pathogenesis of AMD are examined in scientific research: primary aging of the retinal pigment epithelium and Bruch’s membrane, their damage by lipid peroxidation products and other metabolic products formed during “oxidative stress”, primary genetic defects, as well as pathological changes in the hemodynamics of the eyeball, caused by circulatory disorders, in particular with atherosclerosis.

However, in recent years, increasing attention has been paid to studying the role of chronic inflammation in the mechanisms of development and progression of AMD. According to clinical observations [6, 10, 16], in patients with a “wet” form of this pathology, along with damage to the macular region, signs of chronic inflammation of varying severity at the extreme periphery of the fundus are revealed: gross disigmentation, atrophic chorioretinal foci, edema and whitening of the retina , preretinal exudation in the form of small-cell suspension or parietal exudates of the vitreous. It is assumed that phlogogenic factors developed in the zone of chronic inflammation near the dentate line, together with the flow of intraocular fluid from the ciliary body to the posterior pole, reach the retinal vessels and block myogenic autoregulation at the level of the microvasculature [5, 6, 10, 16]. The consequence of this is a violation of the movement of interstitial fluid from the choroid to the vessels of the retina and the development of exudative detachment of the retina, which exacerbates the damage to the chorioretinal structures of the macular region that occur during AMD.

Closest to the proposed is a method of treating a “wet” form of age-related macular degeneration, which consists in the intravitreal administration of the drug Lucentis from the group of angiogenesis inhibitors, which is performed in the operating room after epibulbar anesthesia with an insulin syringe by injection of 0.05 ml (0.5 mg) drug into the vitreous body through a puncture of the sclera and underlying structures 3-4 mm from the limb [12].

A prerequisite for the effectiveness and stability of the clinical and functional results of the application of this method is the sequential three-time introduction of Lucentis with a frequency of 1 time per month. Subsequently, regularly, at least 1 time per month, visual functions are checked and, with a decrease in visual acuity, treatment with the drug is resumed.

However, the widespread use of this method in clinical practice is significantly limited due to the short clinical effect and the need for repeated intravitreal injections of an angiogenesis inhibitor, which, in turn, increases the risk of complications in the postoperative period (endophthalmitis, partial hemophthalmus, transient ophthalmic hypertension), and also significantly increases the economic cost of treating patients with a "wet" form of AMD.

A new technical challenge is to obtain a long and stable clinical effect.

To solve the problem in a method of treating a “wet” form of age-related macular degeneration (AMD), by intravitreal administration of Lucentis at a dose of 0.5 mg, before administering the drug under conditions of drug mydriasis under ophthalmoscopic control, it is additionally performed under conditions of drug mydriasis under ophthalmoscopic control with using the forehead binocular ophthalmoscope and 20.0D or 29.0D lens, transcleral cryopexy of chorioretinal structures at the extreme periphery of the fundus in the projection and the dentate line, cryoapplications with a size of not more than 1 diameter of the optic disc and intervals between cryocoagulates of not more than 1 diameter of the optic disc, while the exposure is carried out until the retina is whitened at the site of exposure.

The method is carried out in the following way: after processing the surgical field in accordance with aseptic and antiseptic rules, an eyelid expander is applied to the eyeball under local instillation anesthesia, epibulbar anesthesia is performed with 2% lidocaine solution and the sclera conjunctiva is opened at 3 and 9 hours 5 mm from the limbus. Further, under conditions of drug mydriasis under ophthalmoscopic control, using a forehead binocular ophthalmoscope and a 20.0D or 29.0D lens, cryocoagulator performs transcleral cryopexy of chorioretinal structures at the extreme periphery of the fundus in the projection of the dentate line: cryoapplication of no more than 1 diameter and the gaps between the cryocoagulates are also not more than 1 diameter of the optic nerve head, while cryotherapy continues until the retina is whitened at the site of exposure. Then, using an insulin syringe through a puncture of the sclera and underlying structures, at an angle of 35-40 ° 3-4 mm from the limbus in one of the oblique meridians, 0.05 ml (0.5 mg) of Lutsentis angiogenesis inhibitor is injected into the vitreous body. A subconjunctival injection of the antibiotic solution in a standard dosage is performed. In the postoperative period, an antibiotic solution is instilled into the conjunctival cavity.

The proposed method is based on the analysis of the results of clinical observations.

Clinical studies were performed on the basis of the ophthalmological clinic SBEI HPE SibGMU (Tomsk). Patients with a "wet" form of AMD, depending on the treatment method, were divided into 2 groups: the main and comparisons.

The main group included 37 patients (37 eyes). Patients of this group during surgical treatment underwent treatment according to the proposed method, including transscleral cryocycle of the peripheral parts of the retina and intravitreal administration of Lucentis.

The comparison group included 38 patients (38 eyes). Patients in this group underwent intravitreal administration of Lucentis according to the standard procedure at a dose of 0.05 ml (0.5 mg).

Clinical examination of patients in both groups included the collection of complaints and medical history, medical history. Ophthalmological examination included the following research methods: visometry, perimetry, campimetry, tonometry, echobiometry, optical coherence tomography (OCT), fluorescence angiography (FAG), biomicroscopy of the anterior eye segment and ophthalmoscopy of the posterior segment of the eye.

Patients of both groups are comparable in sex, age and severity of damage to the peripheral parts of the retina.

Research results

Clinical studies are based on the analysis of the treatment of 75 patients (75 eyes) with a "wet" form of AMD. Depending on the type of treatment, patients were divided into 2 groups - the main and comparisons.

Among 37 patients (37 eyes) of the main group there were 16 men (43.2%) and 21 women (56.8%) aged 58-77 years. The average age of the patients was 65 ± 2.5 L.

Among 38 patients (38 eyes) of the comparison group, there were 15 men (39.5%) and 22 women (60.5%) aged 57-78 years. The average age of the patients was 66 ± 2.7 l.

The clinical picture of the disease in all examined patients at the time of hospitalization in the hospital had similar features. Patients revealed metamorphopsia, micropsy, and decreased visual acuity. Ophthalmoscopically in the central parts of the fundus were found soft drainage drusen, pronounced retinal edema, intra- and subretinal hemorrhages, serous detachment of the neuroepithelium in the form of a grayish-yellow color focal area with not quite clear borders (Figure 1, B-naya S., 75 l Diagnosis: “wet” form of age-related macular degeneration OS. State of the central parts of the fundus at the time of hospitalization). When FAG was detected dye perspiration in the late venous phase of the study (Figure 2, B-naya S., 75 L. Diagnosis: "wet" form of age-related macular degeneration OS. Late phase of fluorescence angiography before treatment).

According to OCT (Figure 3, B-naya S., 75 L. Diagnosis: “wet” form of age-related macular degeneration OS. Optical coherence tomography of the central parts of the fundus before treatment) detachment of pigment epithelium and neuroepithelium of various heights and lengths was detected damage to the pigment epithelium, a decrease in the transparency of the photoreceptor layer and the presence of racemose cavities in it, dystrophic changes in all layers of the retina.

On binocular ophthalmoscopy with sclerocompression at the extreme periphery of the fundus of the eye of both groups, signs of chronic inflammation of various severity were diagnosed: gross dispigmentation, atrophic chorioretinal foci, edema and whitening of the retina (Figure 4, B. S., 75 L. Diagnosis : "Wet" form of age-related macular degeneration OS. State of the extreme periphery of the fundus at the time of hospitalization), as well as preretinal exudation in the form of small-cell suspension, and in the form of parietal exudates with eklovidnogo body.

The main clinical and morphological forms of chronic peripheral uveitis detected in patients of both groups are presented in Table 1. (Clinical and morphological forms of chronic peripheral uveitis in the examined patients)

A comparative analysis of the treatment results revealed a significant effectiveness of the new combined method of surgical treatment of “wet” AMD.

The positive dynamics of the ophthalmoscopic picture in the form of a gradual resorption of retinal edema and hemorrhage in the central parts of the fundus, as well as a decrease in the area and height of the serous detachment of the neuroepithelium in patients of the main group was observed already during the first 6-7 days after surgical treatment. The restoration of the normal anatomical and topographic position of the retina of the macular region was observed on the 14-16th day (Figure 5, B-naya S., 75 L. Diagnosis: “wet” form of age-related macular degeneration OS. The state of the central parts of the fundus on the 14th day after surgical treatment in a combined way. 6, B-naya S., 75 L. Diagnosis: "wet" form of age-related macular degeneration OS. Late phase of fluorescence angiography on the 14th day after surgical treatment in a combined way), which is consistent with the results research ritelnyh functions (visometry, campimetry) (Table 3, 4) and OCT data (Table 2).

Patients of the comparison group showed a gradual - within 14-17 days - reduction of retinal edema and resorption of hemorrhages in the central parts of the fundus, the fit of the macular retina was observed only on 21-23 days after surgical manipulation.

According to the results of OCT (Table 2, which presents data on the dynamics of the thickness of the retina in the central parts of the fundus of patients with a “wet” AMD form depending on the type of treatment, (M ± m), Note: ∗ is the significance level of the differences compared to the initial ones data p <0.01, ∗∗ is the level of significance of differences compared with the initial data p <0.05, M is a sample mean value, m is the error of the mean), restoration of the thickness of the retina in the central parts of the fundus during treatment was observed in patients of both groups occurring dnako a faster rate in the study group. So, for example, 7 days after combined surgical treatment, the thickness of the retina in the central parts of the fundus of the eye in patients of the main group decreased by 12%, while in patients of the comparison group - only 8.4%. 14 days after surgery, the thickness of the retina in patients of the main group decreased by 24.5% from the initial level, in patients of the comparison group - by 11.4%, after 21 days - by 35.2% and 28.9%, respectively (table .2). 30 days after the surgery, the thickness of the retina in patients of the main group decreased by 38% compared with the initial data, amounting to 243 ± 28.6 μm, in patients of the comparison group - by 32.9%, reaching 264 ± 31.3 μm.

According to the results of a clinical study, the application of the proposed method for treating a “wet” form of AMD has a positive effect on the state of visual functions (Table 3, which presents the data on the visual acuity dynamics of the examined patients depending on the type of treatment, (M ± m), Note: ∗ - the significance level of differences compared to the initial data p <0.01, ∗∗ is the significance level of differences compared to the initial data p <0.05, M is the sample mean value, m is the error of the mean) in patients of the main group.

At the time of hospitalization, visual acuity in patients of both groups was 0.04-0.05. However, after 7 days from the start of treatment, this indicator in patients of the main group increased by 50%, while in patients of the comparison group - only by 28.5% (Table 3).

Further improvement in visual acuity was observed in patients of both groups, which, however, occurred more rapidly in the main group. So, for example, after 14 days from the start of treatment, this indicator in patients of the main group increased by 60% compared with the achieved level, in patients of the comparison group - by 22.3%, after 21 days - by 50% and 10%, respectively. By the 30th day after the surgical treatment, visual acuity in patients of the main group was 0.4 ± 0.02, while in patients of the comparison group - 0.1 ± 0.02.

During the entire observation period, an improvement in the state of the central departments of the field of view in patients of both groups was also noted. Before treatment, the patients with both groups showed a central relative scotoma measuring 56.45-57.43 ° (Table 4, which presents the dynamics of the central relative scotoma depending on the type of treatment (M ± m). Note: ∗ - level the significance of differences compared to the initial data p <0.01, ∗∗ is the level of significance of differences compared to the initial data p <0.05, M is a sample mean value, m is the error of the mean).

However, already 14 days after surgical treatment with the new combined method, in the patients of the main group, the scotoma area decreased by 38.7%, in patients of the comparison group - only 23.1%, after 21 days - by 59.4% and 33.6 % respectively. 30 days after the treatment, this indicator decreased by 66.1% in patients of the main group and by 53.1% in patients of the comparison group.

Clinical example

Patient S., 75 years old, complained of a “dark spot” in front of her left eye and decreased visual acuity.

Medical history: complaints have been troubling for several years. Periodically, the patient underwent conservative treatment for the "wet" form of AMD.

Objective inspection:

Visus OD = 1.0

OS = 0.05 paracentrally outside n / a

When OS ophthalmoscopy in the central parts of the fundus was found, soft drainage drusen, pronounced retinal edema, intra- and subretinal hemorrhages, serous detachment of the neuroepithelium in the form of a grayish-yellow color focal area with not quite clear boundaries (Figure 1).

On the extreme periphery of the fundus of the patient during binocular ophthalmoscopy with sclerocompression revealed: gross dispigmentation, atrophic chorioretinal foci, edema and whitening of the retina (Figure 4).

According to OCT (Figure 3), in the patient in the macular region of the left eye, detachment of the pigment epithelium and neuroepithelium, gross damage to the pigment epithelium, a decrease in the transparency of the photoreceptor layer, degenerative changes in all layers of the retina were detected.

According to the results of the examination, the diagnosis was made: "wet" form of AMD OS.

On the day of treatment, the patient underwent transscleral cryocycle of the peripheral parts of the retina OS and intravitreal administration of Lucentis.

The dynamics of the disease

7 days after the surgical treatment, a positive dynamics of the clinical picture was noted. Subjectively, the patient noted a decrease in the “spot” in front of the left eye and an improvement in visual acuity.

Objectively:

Visus OS = 0.07 paracentrally outside n / a

With OS ophthalmoscopy, retinal edema in the macular region was significantly reduced, serous detachment of the pigment epithelium significantly decreased in area and height, and intra- and subretinal hemorrhages partially resolved.

During binocular ophthalmoscopy with sclerocompression OS - whitish foci after cryopexy were revealed along the dentate line.

On the 14th day from the start of treatment:

Visus OS = 0.1 paracentral n / a

With OS ophthalmoscopy, the restoration of the normal anatomical and topographic position of the chorioretinal structures, resorption of edema and hemorrhages was noted in the macular region (Fig. 5, 6).

During binocular ophthalmoscopy with OS sclerocompression at the extreme periphery, a significant decrease in retinal edema and the formation of cryocoagulates were also revealed.

According to OCT, in the central parts of the fundus of the OS, the patient noted a fit of the pigment epithelium and neuroepithelium, as well as a gradual restoration of the thickness of the retina by reducing its edema (Fig. 7, B. S., 75 L. Diagnosis: “wet” form age-related macular degeneration OS. Data of optical coherence tomography of the central parts of the fundus 14 days after surgical treatment of the proposed method).

On the 21st day from the start of treatment:

Visus OS = 0.2 paracentrally n / a

With OS ophthalmoscopy, the normal anatomical and topographic position of the pigment epithelium and neuroepithelium is preserved in the macular region, there is no retinal edema and fresh hemorrhages.

During binocular ophthalmoscopy with sclerocompression OS at the extreme periphery, chorioretinal atrophic foci were detected after cryopexy, the retina is calm.

According to OCT, in the central parts of the fundus of the OS, the thickness of the retina corresponded to normal values.

During the dynamic observation within 3 months after the surgical treatment of the proposed method, the preservation of the achieved clinical and functional effect was noted.

Timely relief of inflammation on the extreme periphery of the fundus using transscleral cryopexy in combination with the intravitreal administration of an angiogenesis inhibitor in patients with a “wet” AMD form provides a complex, pathogenetically substantiated effect, helping to stabilize the pathological process in the macular region.

As a result of clinical studies, the need for the proposed cryotherapy regime was proved. Insufficient effects in the form of single cryoapplications or effects only in oblique meridians do not give a pronounced anti-inflammatory effect, since the remaining parts of the chorioretinal structures continue to produce activators and products of inflammation to the central parts of the retina. With a more extensive and powerful effect, destruction and death of all layers of the chorioretinal tissue develops, which in turn causes an uncontrolled inflammatory reaction, which even more triggers the fibrovascular process in the cavity of the eyeball.

Thus, the proposed method for the treatment of “wet” AMD, including cryocirculation of the peripheral parts of the retina and intravitreal administration of Lucentis, provides stable, lasting for 3 months, clinical and functional results.

Literature

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Table 1 Group of patients Forms of chronic peripheral uveitis Creeping dystrophy of the pigment epithelium White retina with / without sclerocompression Parietal vitreous exudates the main 9 (24.3%) 20 (54%) 8 (21.7%) comparisons 10 (26.3%) 20 (52.6%) 8 (21.1%)

table 2 Group of patients Duration of observation Before treatment In 7 days In 14 days In 21 days After 30 days the main 392 ± 64.5 345 ± 51.8 ∗∗ ∗ 296 ± 32.4 ∗ 254 ± 29.4 ∗ 243 ± 28.6 ∗ comparisons 394 ± 63.4 361 ± 53.1 ∗∗ 349 ± 51.4 ∗∗ 280 ± 40.2 ∗ 264 ± 31.3 ∗

Table 3 Group of patients Duration of observation Before treatment In 7 days In 14 days In 21 days After 30 days the main 0.04 ± 0.01 0.08 ± 0.01 ∗∗ ∗ 0.2 ± 0.02 ∗ 0.4 ± 0.02 ∗ 0.4 ± 0.02 ∗ comparisons 0.05 ± 0.01 0.07 ± 0.01 ∗∗ 0.09 ± 0.01 ∗∗ 0.1 ± 0.02 ∗ 0.1 ± 0.02 ∗

Table 4 Group of patients Duration of observation Before treatment In 14 days In 21 days After 30 days the main 57.43 ° ± 3.15 35.17 ° ± 2.94 ∗∗ 23.28 ± 1.86 ∗ 19.46 ± 1.67 ∗ comparisons 56.45 ° ± 2.97 43.36 ° ± 2.88 ∗∗ 37.49 ° ± 2.75 ∗∗ 26.44 ° ± 1.94 ∗

application

Figure 1. B-naya S., 75 l. Diagnosis: “wet” form of age-related macular degeneration of OS. The state of the central parts of the fundus at the time of hospitalization.

Figure 2. B-naya S., 75 l. Diagnosis: “wet” form of age-related macular degeneration of OS. Late phase of fluorescence angiography before treatment.

Figure 3. B-naya S., 75 l. Diagnosis: “wet” form of age-related macular degeneration of OS. Data of optical coherence tomography of the central fundus before treatment

Figure 4. B-naya S., 75 l. Diagnosis: “wet” form of age-related macular degeneration of OS. The state of the extreme periphery of the fundus at the time of hospitalization.

Figure 5. B-naya S., 75 l. Diagnosis: “wet” form of age-related macular degeneration of OS. The condition of the central parts of the fundus on the 14th day after surgical treatment in a combined way

6. B-naya S., 75 l. Diagnosis: “wet” form of age-related macular degeneration of OS. Late phase of fluorescence angiography on the 14th day after surgical treatment in a combined way.

Table 1. Clinical and morphological forms of chronic peripheral uveitis in the examined patients.

Table 2. Dynamics of the thickness of the retina in the central parts of the fundus in patients with a “wet” form of AMD, depending on the type of treatment (M ± m).

Table 3. The visual acuity dynamics of the examined patients depending on the type of treatment (M ± m).

Note: ∗ is the significance level of differences compared to the original data p <0.01, ∗∗ is the significance level of differences compared to the original data p <0.05, M is a sample mean value, m is the error of the mean.

Table 4. Dynamics of the magnitude of the central relative scotoma depending on the type of treatment (M ± m).

Note: ∗ is the significance level of differences compared to the original data p <0.01, ∗∗ is the significance level of differences compared to the original data p <0.05, M is a sample mean value, m is the error of the mean.

Claims (1)

A method of treating a “wet” form of age-related macular degeneration (AMD) by intravitreal administration of a 0.5 mg dose of Lucentis, characterized in that before administration of the drug under medical mydriasis under ophthalmoscopic control using a forehead binocular ophthalmoscope and a 20.0 D lens or 29,0 D perform transscleral cryopexy of chorioretinal structures on the extreme periphery of the fundus in the projection of the dentate line, while the size of the cryocoagulum is not more than 1 diameter of the optic disc the moat, the gaps between the cryocoagulates are not more than 1 diameter of the optic disc, while cryotherapy is performed until the retina is whitened at the site of exposure.

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