RU2718847C1 - Complex method of macular oedema treatment in retinal vein occlusions - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, specifically to ophthalmology. For complex treatment of macular retinal oedema accompanying retinal vein occlusions, laser exposure of macular retina is performed. First, laser radiation power is selected during applicator testing to achieve sub-threshold level of laser exposure. That is followed by a two-component therapeutic exposure comprising a sub-threshold micropulse laser exposure of high density in the perimacular area by 180° in the upper or lower half of the eye bottom and in the panmacular area, not reaching 500 mcm to central avascular zone, wherein circular rows of draining applications are applied without intervals, and after 50–60 minutes, intravitreal introduction of VEGF inhibitor. Complex treatment may be re-used if necessary.

EFFECT: method provides higher clinical effectiveness in the post-thrombotic macular oedema at an early stage before the onset of irreversible changes with vision loss, provides earlier anatomical and functional macular repair with improved visual functions without causing complications.

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Description

The invention relates to medicine, namely to ophthalmology, and is intended for effective and more “sparing”, atraumatic treatment of macular edema (MO) of the retina with retinal vein occlusions. Macular edema - a serious complication of retinal vein occlusion, causing a decrease in central vision; with the natural course and treatment inefficiency leads to pathological changes in the macula, decreased vision and disability. A long-standing MO irreversibly changes the structure of the retina, so it is more advisable to start its treatment as soon as possible.

The applied panretinal laser coagulation (PRLK) is not always effective, it is recommended to start laser exposure in the eyes with MO phenomena with treatment of the macular region (Early Treatment Diabetic Retinopathy Study).

Analogs

For the treatment of MO with retinal vein occlusions, intravitreal administration of vascular endothelial growth factor inhibitors (VEGF) or corticosteroids in combination with retinal laser coagulation (LK) is used: PRLK for thrombosis of the central retinal vein and LK according to the “lattice” type - for occlusion of the CVC branch. LC as a “lattice” in the form of monotherapy with post-thrombotic MO does not significantly increase visual acuity, does not stop a further decrease in visual functions (Central Vein Occlusion Study, 1997; Algorithm for the management of patients with retinal venous occlusions. Message 2. Macular edema. M.V. Budzinskaya, NK Mazurina, Bulletin of Ophthalmology, No. 6, 11.2015.2015; Federal clinical guidelines on ophthalmology of the Ministry of Health of the Russian Federation 2013-2015).

Intravitreal administration of prolonged-acting corticosteroids (triamcinolone acetonide, slow-release dexamethasone) reduces vascular permeability, prevents the hematoretinal barrier, reduces inflammation and edema, contributing to increased visual acuity, but prolonged corticosteroid therapy leads to negative side effects and development, such as cataracts and development , up to the operable stage in some patients, which is a significant drawback.

In retinal LCs of the “lattice” type, coagulates of 100 μm are applied to the macula area in several rows, staggered, departing 1,500 μm or more from the foveola, in the peripheral rows with a diameter of up to 200 μm, at a distance of 1 coagulum diameter, with small edema - in 2 diameters. Threshold LC leads to damage to the neuroepithelium that performs visual functions; its side effects: decreased visual acuity, central photosensitivity (CSC) of the retina; atrophy of the pigment epithelium (PE), choroid; retinal scars that cause defects in the central field of vision; epiretinal fibrosis, growth of neovascular membranes at the border of laser coagulates (C.A. Kiire, S. Sivaprasad, V. Chong. 2011), increased production of pro-inflammatory cytokines (Khodzhaev N.S. et al. 2011).

The subthreshold laser exposure in the micropulse mode is selective at the level of PE-choriocapillaris, is absorbed to the maximum by melanin, is not absorbed by the internal environments of the eye, neuroepithelium, and does not injure the sensory layer of the retina. SMILV-810 nm of the infrared spectrum in the micropulse mode is pathogenetically substantiated; its therapeutic effect in the resorption of MOs is comparable to threshold LC without its inherent complications (Volodin P.L., Doga A.V. Appendix No. 2 to the order of the Ministry of Health of the Russian Federation No. 433n 2015 ; Izmailov A.S., Kotsur T.V. Use of a 0.81 micron diode laser in the high-density microphotocoagulation mode for the treatment of macular edema. Ophthalmology, 2016). The safety of these parameters was proved in an experimental clinical study, recommended for clinical use (Doga A.V., Zhuravleva E.S. Infrared micro-pulse diode laser radiation in the treatment of macular pathology, 2011). As a result of stimulation of PE cells, they increase the production of anti-inflammatory factors, pigment epithelium factor (PEDF), an endogenous angiogenesis inhibitor, comparable in strength to artificially administered anti-VEGF, which also has neuroprotective and neurotrophic properties (Takhchidi H.P., Gavrilova N.A. ., Lanevskaya N.I.,. Comparative characteristics of the effects of PEDF and avastin. Ophthalmic surgery. 2009).

Prototype

As a prototype of the selected "Method of modified subthreshold panmacular microphotocoagulation of the retina in diabetic macular edema" (RF patent No. 2308920). The essence of the prototype method consists in laser exposure: test retinal coagulation in the areas farthest from the center of the macula: using pulse packets of 0.2 s duration, they select energy until barely noticeable burns occur, then the exposure is reduced to 0.1 s. Subthreshold microphotocoagulation near the source of local transudation, coagulates are placed with an interval equal to the diameter of the coagulate, in two or more rows concentrically around the source of leakage, within the zone of local retinal edema; then the entire macula is treated, the coagulates are placed in the form of radial rows with an interval equal to the diameter of the coagulate, with the capture of the edge of the avascular zone.

The prototype disadvantages

According to the prototype method, only a partial pathogenetic effect on the retina occurs, since the production of VEGF, which is important in the genesis of MO, occurs not only in the macular region of the retina and near the source of local transudation, where the effect of the laser exposure of the prototype is realized, but also in the entire perimacular zone retina corresponding to the thrombosed branch of CVC. The application of lasercoagulants only to the MO region is not effective enough for long-term stable treatment results; pathological changes leading to the development of edema of the macula also occur in the perimacular zone, from where the fluid seeps and again accumulates in the macula.

The technique is somewhat laborious in practical use, since not all microaneurysms and transudation zones can be seen ophthalmoscopically for their targeted barrage, which requires preliminary fluorescence angiography followed by mapping on the fundus.

purpose

The aim of the proposed method is to increase the effectiveness of the treatment of post-thrombotic MO with occlusion of the CVS branch due to the integrated use of subthreshold micropulse laser exposure and anti-VEGF in the early stages, to irreversible vision loss; providing an earlier, stable anatomical and functional restoration of the macula, using a more “sparing”, atraumatic treatment technique; reduction in the rate of intravitreal injection of anti-VEGF.

The essence of the proposed method

The method is intended for the treatment of MO, resulting from thrombosis of the CVC branch, and is a two-component integrated technique consisting of sequential steps, with a time interval between the first and second stage of 30-60 minutes

Stage 1 - SMILW on an infrared diode laser IRIS Medical IQ 810 (IRIDEX) with a wavelength of 810 nm in micropulse mode (the Russian analogue is the diode ophthalmic coagulator ALOD-01 810 nm, ALKOM-Medica, St. Petersburg). Maximum pupil dilatation with midriacyl 1%, local anesthesia with alkaine 0.5%, Reichel-Mainster 1x (0.95x) contact laser lens on the anterior segment of the eye: testing with a pulse packet in the most pigmented area near the superior temporal vascular arcade by gradually selecting power to a barely noticeable tissue trace, with its subsequent reduction and repeated testing, a subthreshold level of laser exposure is achieved; expanded perimacular SMILV: on the perimacular zone, not reaching 500 microns to the vascular arcade and optic nerve head, circular rows of laser applicates - 180 ° in the upper or lower half of the fundus, depending on the location of the thrombus - in the upper or lower branches of the CVS; panmacular SMILV: circular rows of laser applicates for the entire macula region, not reaching 500 μm to the central avascular zone, and one row outward from the outer borders of the MO; parameters: the diameter of the applicate is 100 μm, the application of applicators is of a draining nature, the duration of the microimpulse is 25-50 μs, the duty cycle is 2-9%, the duration of the pulse packet is 0.2 s, the power is 1-2 W, were selected individually, depending on the transparency of the eye media, the height of the edema, the degree of pigmentation of the fundus. After removing the contact laser lens, locally an antiseptic for the prevention of infectious and inflammatory complications.

Stage 2 - intravitreal administration of anti-VEGF ranibizumab (lucentis 0.5 mg-0.05 ml) or aflibercept (eilea 2 mg-0.05 ml) in the operating room, under aseptic conditions, local anesthesia with alkain 0.5%, aseptic treatment operating field with betadine, chlorhexidine 0.05%, blepharostat overlay, 4 mm from the limbus in the upper outer quadrant, in the pars plana projection, followed by local administration of the antibiotic, antiseptic dressing, antibiotics and antihypertensives locally for 2 weeks.

Features of the invention, distinctive from the prototype

Signs of the prototype

In the prototype method, the pan-macular subthreshold microphotocoagulation is carried out in radial rows and the distances between the coagulates can be different. It is necessary to barrage around each microaneurysm - a source of extravasation.

Features of the invention

1. According to the proposed method, a subthreshold micropulse laser exposure is performed in circular rows, by drain (without intervals) applying laser applicates (since with such an effect, the traces of the applicates are invisible on the retina, their drain application is possible, but this does not cause tissue damage), which increases the area therapeutic effect. High-density SMILV increases absorption at the level of PE-choriocapillaris, helps to reduce the production of VEGF, increase the production of the anti-angiogenic factor PEDF, a number of anti-inflammatory factors, and it appears on the entire area of the retina involved in the pathological process.

2. The proposed method of treatment, in contrast to the prototype, provides for complex simultaneous high-density SMVL and intravitreal administration of anti-VEGF in post-thrombotic MO, which allows you to summarize both selective therapeutic actions and get a faster, more stable and long-term restoration of the anatomy of the macula with achieving higher visual functions.

Case Studies

Patient M., 67 years old, was admitted to hospital with a diagnosis of thrombosis of the upper temporal branch of the central eye of the right eye, initial cataract of both eyes; related diagnosis: hypertension II tbsp., arterial hypertension 3 tbsp., risk 3. Passed a 10-day course of conservative pathogenetic therapy, antihypertensives.

Upon receipt, Visus OD = 0.2; OS = 0.8 n / k. Biomicroscopy OD: crystalline lens, slight opacification in the cortical layers. Stereoscopic Ophthalmoscopy OD: edema and hemorrhage in the superior temporal segment. Optical coherence tomography (OCT) of the retina OD: rarefaction of the layers of the retina in the region of the macula with a portion of the serous detachment of the neuroepithelium, the height of the macula - 386 microns, swelling of the macula. A comprehensive method for treating the right eye was performed: SMILV according to the described technique; after 50-60 minutes in the operating room, under aseptic conditions, and / or injection of anti-VEGF lucentis (ranibizumab) 0.5 mg-0.05 ml, topically antibiotic, aseptic. bandage; within 2 weeks: phloxal 1 to 3 r, betoptic 0.5% 1 k at night.

After 1 month after treatment, Visus OD = 0.4; OS = 0.8 n / k. OCT of the retina OD: the profile of the macula is normal, traces of rarefaction of the layers of the retina in the macular region, the height of the macula is 269 microns. Computer Static Perimetry OD: An increase in the retinal DSC from 15.2 dB to 16.9 dB. No cattle detected. With ophthalmoscopy: resorption of hemorrhages.

Patient K., 65 years old, was admitted to hospital with a diagnosis of thrombosis of the inferior temporal branch of the central eye of the left eye; related diagnosis: hypertension II tbsp., arterial hypertension 3 tbsp., risk 3. 10 days passed. course of conservative therapy, hypotensive. Upon receipt of Visus OD = 0.7 n / a; OS = 0.3. Ophthalmoscopy: edema and hemorrhage in the inferior temporal segment of the fundus of the left eye; OCT of the retina OS: rarefaction of the layers of the retina in the macula with a portion of the serous detachment of the neuroepithelium, macula height - 378 microns, macular edema. A complex method of treatment was performed on the left eye: SMILV, after 50-60 minutes - and / in the injection of ailea (aflibercept) 2 mg-0.05 ml. After 1 month: Visus OS = 0.5. On OCT retina OS: the profile of the macula is normal, the height of the macula is 263 microns. Computer-assisted static perimetry OS: an increase in the retinal DSC from 16.1 dB to 17.4 dB. No cattle detected. Ophthalmoscopy: resorption of hemorrhages.

The advantages of the method

1. Subthreshold micropulse diode laser exposure is safe for the neurosensory layer of the retina, in contrast to the threshold LC, in which the death of photoreceptors inevitably occurs due to burn thermal action on the retina. The use of the indicated subthreshold parameters excludes the possibility of damage to the retina both in the laser irradiation zone and in the adjacent areas; it does not cause complications characteristic of LC - atrophy of the PE, choroid, decrease in photosensitivity of the retina, etc. High-density SMVI over the entire affected area of the retina, improves chorioretinal metabolism, absorption of intra- and subretinal fluid, reduces retinal ischemia, VEGF production, increases the production of PE's own anti-angiogenic and anti-inflammatory cells x factors, which confirms an earlier feasibility of onset of laser action.

2. The proposed method of treatment provides for complex simultaneous high-density SMVI and intravitreal administration of anti-VEGF in post-thrombotic MO, which allows summarizing both selective therapeutic effects. Anti-VEGF help in a short time to achieve a decrease in MO and increase visual acuity, but their effect is temporary, limited by the duration of their therapeutic effect, repeated administration is necessary. The use of high-density SMILV simultaneously with anti-VEGF allows for a more complete and stable anatomical and functional restoration of the macula in the early stages, to provide a more lasting result, and to reduce the number of intravitreal injections. In turn, anti-VEGFs reduce secondary retinal edema after laser exposure.

3. The early use of high-density SMILV in combination with anti-VEGF promotes faster resorption of post-thrombotic MO, restoration of photoreceptor integrity, visual acuity, prolonged, stable treatment effect; can be reused if necessary without causing complications.

Information taken into account:

“A method of modified subthreshold pan-macular macrophotocoagulation of the retina in diabetic macular edema” (RF patent No. 2308920, Balashevich LI, Chizh LV, Gatsu MV, 2007). - prototype.

Claims (2)

1. A method for the complex treatment of macular edema of the retina with occlusions of the retinal veins by laser irradiation of the macular zone of the retina, characterized in that the laser radiation power is preliminarily selected during preliminary testing of applicates to achieve a subthreshold level of laser irradiation, then a two-component therapeutic effect is performed, including subthreshold micropulse laser exposure of high density in the perimacular zone at 180 ° in the upper or lower half of the eyes bottom and in the panmacular zone, not reaching 500 μm to the central avascular zone, while applying circular rows of drain applicates without intervals, and after 50-60 minutes intravitreal administration of a VEGF inhibitor. 2. A method for the complex treatment of macular edema of the retina with occlusions of the retinal veins according to claim 1, characterized in that the complex treatment can be reused if necessary.