RU2562022C2 - Method of treating macular oedema accompanying retinovasculitis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: ranimizumab is injected through a two-stage self-sealing scleral puncture with a 30G injection needle into a vitreous body at 3.5-4.0mm from the limb. A control optical coherent tomography and a fluorescent angiography of the retina are performed 2-3 weeks later. The persistent ischemia and extravasation regions require a paravasal transpupillar laser retinal coagulation to be performed. The exposure parameters: wave length 659nm, power 0.13-0.15mWt, 100-250 coagulates, exposure 0.1-0.15 s, spot diameter 200mcm. The retina is exposed along the temporal arcades.

EFFECT: method enables providing the stable therapeutic effect ensured by relieving or eliminating a macular oeodema with improving the visual functions by suppressing the extravasation and blocking of the ischemic regions in a combination with reducing the anti-inflammatory and haemorrhagic reaction.

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Description

The alleged invention relates to medicine, namely to ophthalmology, and relates to methods for treating macular edema with retinovasculitis of non-infectious etiology.

Macular edema is the most common complication of inflammatory lesions of the posterior segment of the eye of non-infectious etiology and the main cause of decreased vision and blindness in these patients [Okhravi N, Lightman S. Cystoid macular edema in uveitis. // Ocul Immunol Inflamm. - 2003. - Vol.11 - P. 29-38]. Macular edema develops as a result of an increase in the permeability of the vascular wall as a result of a violation of the blood-retinal barrier against a background of prolonged severe intraocular inflammation and ischemia. Clinical signs of macular edema with retinovasculitis are fluid accumulation in the outer plexiform layer of the retina of the macular region with the formation of multiple thin-walled cysts and pseudo-tears against the background of inflammatory changes in the retina (hemorrhage, paravasal couplings and lining, soft exudates, altered caliber and the course of the vessels of the retina and paravasal). Edema of retinal tissue very quickly causes the death of the neurosensory epithelium of the retina, especially in the macular region, resulting in a sharp significant progressive decrease in visual acuity up to complete functional death of the eye. There are various methods of treating macular edema with retinovasculitis. Currently, the generally accepted method of treating macular edema with retinovasculitis of non-infectious etiology is the systemic and topical use of anti-inflammatory drugs steroid (glucocorticoids) and non-steroidal series (Rothova A. Medical treatment of cystoid macular edema. // Ocul Immunol Inflamm. - 2002. - Vol. 10 - P. 239-246). However, although this treatment allows you to stop the phenomena of inflammation, but it causes a large number of systemic side effects, with little effect on the size of macular edema. A known method of treatment is the intravitreal administration of triamcinolone acetonide (Kok H., Maycock N., et al. Outcome of intravitreal triamcinolone in uveitis // Ophthalmology. - 2005. - Vol. 112 - 1916.e 1-1921.e7). The disadvantages of this method are a low functional result (only half of the treated patients have increased visual acuity) and a high level of local side effects, including the development of cataracts and secondary steroid glaucoma. Also known is a method for laser coagulation of the retina in the central zone in the form of a so-called “grating” (“Greed lazer photocoagulation))), in which 20-40 coagulates were applied to the retina in the areas of macular edema using a yellow laser (wavelength 577 nm) with the following parameters: spot diameter 100-200 μm, exposure from 0.07 to 0.15 s, coagulation power was selected starting from low, gradually increasing until visible coagulates appeared (Lardenoye CW, van Schooneveld MJ, Treffers WF, et al. Greed lazer photocoagulation for Macular Edema in uveitis or the Irvine-Gass syndrome // Br.J. Ophthalmol. - 1998. - Vol. 82. - P. 1013-1016). However, with pronounced edema of the retinal tissue (significantly increased retinal thickness), laser retinal coagulation in the central zone either cannot be performed at all, or may be performed in insufficient volume, which can lead to a relapse of the disease. To achieve the maximum result of laser coagulation, an increase in its power is required, which inevitably leads to damage to the sensorineural epithelium with the subsequent development of retinal atrophy and a decrease in functions.

Closest to the proposed one is a method of intravitreal administration of a VEGF inhibitor ranibizumab, in which 0.5 mg of ranibizumab is administered transsclerally in the projection of the flat part of the ciliary body sequentially, with an interval of 1 month. In this case, the initial number of injections is 3, then, if necessary, in case of increased edema, additional injections are carried out (Acharya NR., Hong K., Lee SM. Ranibizumab for Refractory Uveitis-related Macular Edema // Am.J. Ophthalmol. - 2009. - Vol.148. - No. 2. - P. 303-309). However, the main disadvantage of this method is the short period of action of the VEGF inhibitor ranibizumab - 1-1.5 months, which requires a repeated repeated injection (from 3 to 6 or more) to achieve a lasting effect. This increases the risk of local and systemic side effects and leads to a significant increase in the cost of treatment.

The technical result of the proposed method is to achieve a lasting effect due to the clinical reduction or complete disappearance of macular edema with an increase in visual functions and the final suppression of extravasation and blocking of ischemic zones while reducing the inflammatory and hemorrhagic reaction in the postoperative period, as well as reducing the duration of treatment of the disease.

New in achieving the set technical result is that ranibizumab is injected through a two-stage self-sealing puncture of the sclera into the vitreous body 3.5-4.0 mm from the limbus using a 30G injection needle.

Also new is that after 2–3 weeks control optical coherence tomography and fluorescence angiography of the retina are performed and paravasal laser retinal coagulation is performed in areas of persistent ischemia and extravasation.

Also new is the fact that 100–250 coagulates with an exposure of 0.1–0.15 s and a spot diameter of 200 μm are applied to the retina along the vessels of the temporal arcades transpillary using a diode laser with a wavelength of 659 nm and a power of 0.13–0.15 mW. .

Performing laser coagulation of the retina and intravitreal administration of VEGF inhibitors is pathogenetically justified, because VEGF inhibitors temporarily reduce the permeability of the vascular wall and reduce edema of the retinal tissue, as well as the inflammatory and hemorrhagic reaction, and laser coagulation of the retina prolongs these effects due to the final and targeted blocking of extravasation and ischemia zones. In addition, a decrease in retinal edema during therapy with ranibizumab promotes laser retinal coagulation in the required volume, but with the most sparing parameters.

Comparative analysis with the prototype shows that the claimed method differs from the prototype in that ranibizumab is injected through a two-stage self-sealing puncture of the sclera into the vitreous body 3.5-4.0 mm from the limbus using a 30 G injection needle, then after 2-3 weeks control optical coherence tomography of the retina and fluorescence angiography of the retina, and paravasal laser coagulation of the retina is performed in areas of persistent ischemia and extravasation, for this, transpillary using a diode laser with a length of wavelength 659 nm and a power of 0.13-0.15 mW on the retina along the temporal vascular arcades applied from 100 to 250 with the exposure 0.1-0.15 coagulates with a diameter of 200 micron spots, which corresponds to the criterion "novelty".

The combination of the proposed features allows to reduce the number of surgical interventions and to achieve a permanent decrease or complete disappearance of macular edema with an increase in visual functions and stabilization of the inflammatory process without complications, which meets the criterion of "industrial applicability".

The method is as follows.

Against the background of systemic treatment of retinovasculitis with drugs of the glucocorticoid series, intravitreal administration of a VEGF inhibitor (Ranibizumab) is carried out in the operating room according to the following procedure. After treating the surgical field under local installation anesthesia with an injection needle 30 G in the projection of the flat part of the ciliary body 3.5-4.0 mm from the limbus, 0.5 mg (0.05 ml) of ranibizumab is injected into the vitreous body through a two-stage self-sealing puncture of the sclera. After 2-3 weeks, the patient undergoes control optical coherence tomography of the retina (OCT) and fluorescence angiography of the retina (FAG) to determine the presence and localization of zones of ischemia and extravasation. Then, retinal paravasal laser coagulation is performed after 2-3 weeks. For this, under local installation anesthesia through a contact panfundus, the lens is transpupillary using a diode laser with a wavelength of 659 nm, a power of 0.13-0.15 mW on the retina along the vessels of the temporal arcades in the areas of persistent ischemia and extravasation, from 100 to 250 coagulates with exposure are applied 0.1-0.15 s and a spot diameter of 200 microns.

In the postoperative period, systemic anti-inflammatory treatment is continued and local anti-inflammatory treatment is prescribed with non-steroid and steroid drugs. To evaluate the effectiveness of the proposed method, the severity of edema in the macular region of the retina according to optical coherence tomography and the dynamics of extravasation (leakage) of the dye from the vessels of the retina and zones of retinal ischemia according to fluorescence angiography are taken into account, visual functions are evaluated before and after treatment. According to the proposed method, 5 people (5 eyes) were treated. In all cases, a persistent clinical effect was achieved, complete disappearance or a significant reduction in macular retinal edema during the observation period of more than 6 months. There were no complications both during treatment and in the postoperative period.

The proposed method is illustrated by the following clinical examples.

Example 1. Patient L., 35 years old, came to the IF FSBI MNTK “Eye Microsurgery” with a diagnosis of Retinovasculitis against a background of a systemic disease of the connective tissue of both eyes, complicated by macular edema of the left eye. Incomplete complicated (steroid) cataract of both eyes. When handling a complaint: a sharp decrease in vision of the left eye. From the anamnesis: vision decreased from 10.2010, was treated at the place of residence with a diagnosis of CVT thrombosis, macular edema of the left eye, diclofenac drops 5 times a day and dorzolamide 2 times a day were prescribed. It was also found from the anamnesis that within a year before treatment, the patient suffers from idiopathic dermatomyositis, polymyositis, in confirmed seropositive form, is constantly being treated by a rheumatologist. She took a long-term regimen of glucocorticosteroid drugs (prednisone) and periodically conducted lymphosorption courses. At the time of treatment was at a maintenance dose of 30 mg of prednisone per day.

During the examination: Visual acuity of the left eye of 0.03 s -1.5D = 0.1.

Biomicroscopy revealed posterior subcapsular opacification of the lenses of both eyes. Ophthalmoscopic picture of the fundus of the left eye: the optic nerve disk (optic nerve disc) is sharply hyperemic, the borders are fuzzy on the nasal side, the size of the excavation of the optic nerve disc is not determined due to edema, in the macular zone there is pronounced cystic edema. In the vascular arcades - paravasal couplings and hemorrhages. The veins are sharply dilated, convoluted. On the middle periphery of the fundus - preretinal hemorrhage.

According to OST, on the left eye in the macular zone of the retina revealed intraretinal accumulation of fluid in the form of cysts, pronounced edema. The thickness of the retina in the center of the left eye is 929 microns. To clarify the diagnosis, a phage was performed. On the angiogram of the left eye along the vascular arcades, a convoluted vascular pattern, local areas of reduced retinal perfusion (ischemia), marked pathological leakage (extravasation) of the dye from the veins, accumulation of the dye in the vessel wall, and shunts were not detected. There was no association of the changed sites with arteriovenous crosses. In the late phase, parafoveolar accumulation of the dye was detected (which corresponds to the angiographic signs of macular edema). After examination, the patient received an intravitreal injection of ranibizumab in an amount of 0.5 mg in the left eye. 1 month after surgery, the visual acuity of the left eye increased to 0.35 with correction, the thickness of the retina in the center decreased to 266 microns. After 2 months, the patient experienced a relapse of retinal edema with an increase in the thickness of the retina in the center to 900 μm and with a decrease in vision to 0.15 with correction.

Given the short-term effect of monotherapy with ranibizumab, after consultation, the patient was treated according to the proposed method.

Stage 1: - intravitreal administration of VEGF ranibizumab initiator according to the method described above against the background of ongoing systemic and local treatment of retinovasculitis (prednisone 30 mg per day per os, drops of indocollyr 0.1% 5 r / day in the left eye).

Stage 2: after 18 days, control OST and FAG were performed, then the patient underwent retinal paravasal laser coagulation in the areas of persistent ischemia and extravasation according to the FAG. Localization of the application of coagulates: in the superior temporal vascular arcade. Exposure parameters: wavelength 659 nm, the number of coagulates - 239, energy - 0.13 mW, exposure - 0.1 s, spot diameter - 200 microns.

When viewed after 8 months, the dynamics are positive: Visual acuity of the left eye of 0.3 s -1.5D = 0.55. Ophthalmoscopic picture of the fundus of the left eye: optic nerve disc disease - no hyperemia, physiological excavation, e / d 0.3, clear boundaries, in the macular zone - no retinal edema. Paravasal couplings and hemorrhages in the vascular arcades and in the retina are not visualized. The tortuosity of the venous bed decreased significantly. No signs of retinal inflammation were found. According to OST, the thickness of the retina in the center (TSC) of the left eye is 210 μm, there is no macular edema. According to the FAG, there is a positive trend: there is no extravasation of the dye from the vessels, there are no zones of non-perfusion (ischemia), pathological para-bovolar accumulation of the dye corresponding to macular edema was not detected.

Example 2. Patient A., 24 years old, came to the IF FSBI MNTK “Eye Microsurgery” with a diagnosis of Retinovasculitis on the background of a systemic disease of the connective tissue of both eyes (Behcet's disease), complicated by macular edema of the left eye. Incomplete complicated cataract of both eyes. When handling a complaint: a sharp decrease in vision of the left eye. From the anamnesis: vision decreased from 01.2011, the place of residence was diagnosed with CVC thrombosis, left eye retinovasculitis, which was treated conservatively in a hospital. It was also revealed from the anamnesis that since 2006, the patient was diagnosed with Behcet's disease, about which he is constantly observed by a rheumatologist. Metipred tablets are taken - 8 mg per day, as well as cyclosporin - 200 mg per day.

During the examination: visual acuity of the left eye 0.02 s - 5.0 D = 0.04.

Biomicroscopically revealed posterior subcapsular opacities of the lenses of both eyes. During ophthalmoscopy of the fundus of the left eye: the optic nerve disc is hyperemic, the borders are fused, the retina around the optic nerve disc is edematous, the size of the excavation is e / d = 0.3, and in the macular zone there is pronounced cystic edema. On the retina - multiple hemorrhages and paravasal couplings. The vessels are sharply convoluted, dilated.

According to OST, on the left eye in the macular region of the retina is pronounced cystic edema. The thickness of the retina in the center (TSC) of the left eye is 848 microns. According to the FAG data, local areas of reduced retinal perfusion (ischemia) of the retina, pronounced extravasation of the dye from the veins, accumulation of the dye in the vessel wall, and shunts were not detected on the angiogram of the left eye. The relationship of the changed sites with arteriovenous cross-sections was not traced. In the late phase, paraveveolar accumulation of the dye was detected.

The patient was treated according to the proposed method.

Stage 1: - intravitreal administration of ranibizumab VEGF inhibitor according to the method described above against the background of ongoing systemic and local treatment of retinovasculitis (metipred - 8 mg per day, cyclosporine - 200 mg per day per os, drops of indocollyr 0.1% 5 r / day in the left eye )

Stage 2: after 2 weeks, the patient underwent retinal paravasal laser coagulation in areas of persistent ischemia and extravasation according to the phage. Coagulates are inflicted on the inferior temporal vascular arcade. Exposure parameters: Wavelength 659 nm, the number of coagulates - 200, energy - 0.14 mW, exposure - OD s, spot diameter - 200 microns.

When viewed after 6 months, the dynamics are positive: Visual acuity of the left eye of 0.06 s -5.5 D = 0.3. Low visual acuity due to pronounced progressive opacities of the lens.

Ophthalmoscopic picture of the fundus of the left eye: there is no optic nerve congestion - there is no hyperemia, slight nasal congestion with a tendency to decrease remains, excavation e / d 0.3, in the macular zone there is no retinal edema.

Paravasal couplings are not visualized, along the vascular arcades and on the retina - single old hemorrhages with a tendency to resorption.

The tortuosity of the venous bed decreased significantly. No signs of retinal inflammation were found. According to OST, the thickness of the retina in the center (TSC) of the left eye is 235 μm, there is no macular edema. According to the FAG, positive dynamics are noted: pathological para-bovolar accumulation of the dye, corresponding to macular edema, was not detected, the dye was not extravasated from the vessels, nor were there non-perfusion (ischemia) zones. In the future, in order to improve visual functions, the patient is planned to undergo surgical treatment of cataracts with lens replacement.

Claims (1)

A method for treating macular edema with retinovasculitis, comprising administering a ranibizumab VEGF inhibitor, characterized in that ranibizumab is injected through a two-stage self-sealing sclera puncture into the vitreous body 3.5-4.0 mm from the limbus using a 30 G injection needle, then after 2-3 weeks, control optical coherence tomography of the retina and fluorescence angiography of the retina are performed and paravasal laser coagulation of the retina is performed in areas of persistent ischemia and extravasation, for this, transpupillary using dio of a single laser with a wavelength of 659 nm and a power of 0.13-0.15 mW, from 100 to 250 coagulates with an exposure of 0.1-0.15 s and a spot diameter of 200 μm are applied to the retina along the vessels of the temporal arcades.