RU2468775C1 - Method of transpupillary thermotherapy of amelanotic melanoma of choroid - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to ophthalmology, and is intended for transpupillary thermotherapy of amelanotic melanoma of choroid of medium size. Transpupillary thermotherapy by infrared diode laser 810 nm is performed to tumour tissue temperature 50-60°C, irradiation power being selected depending on degree of tumour pigmentation and on its size in central zone. At the first stage of treatment laser with wavelength 561 nm is used to perform laser barrage around neoplasm with power parameters - 200 mW, exposure - 0.05 msec, coagulant diameter 300 mcm, coagulants being laid in tiled way with formation of coagulant strip of III degree, up to 1 mm wide. After that, coagulation of intra-tumour vessels is performed with parameters of radiation power 1200 mW, exposure 0.5 sec, spot diameter 1000 mcm, in tiled way for coagulant of II degree. The second stage is carried out after 2 weeks by laser 810 nm, power of radiation is selected depending on rate of manifestation of calorimetric signs of laser impact. Coagulants are applied by method of "daisy", starting with the edge of tumour, allowing their small overlay on each other, central the highest part of tumour being processed last.

EFFECT: method makes it possible to reduce the number of intra- and post-operative complications.

Description

The invention relates to medicine, namely to ophthalmology, and is intended for transpupillary thermotherapy of amelonatic melanoma of the choroid of the eye of medium size.

One of the most important problems of ophthalmic oncology today is the choice of the method of organ-preserving treatment of eye tumors, especially with choroid melanomas up to 5 mm high. When referring to a patient's ophthalmologist with such a pathology, the question of further treatment tactics often puts the doctor in a problematic situation. On the one hand, choroid melanoma is an early metastatic malignant tumor (approximately 80% mortality at five-year follow-up), and this circumstance inclines the doctor towards radical surgical tactics. At the same time, high indicators of visual functions in such patients with off-center localization of the neoplasm make enucleation a difficult psychological problem. Indeed, timely adequate organ-preserving treatment at this stage gives good results (Panova I.E., Bukhtiyarova N.V., Efimenko I.N. Transpupillary thermotherapy in organ-preserving treatment of uveal melanoma // Ophthalmosurgery and therapy. - T.4 - No. 3 .- S. 32-36). All this dictates the need to develop new not only organ-preserving, but also functionally-saving methods of treating tumors.

For more than 15 years, laser ophthalmic surgeons have been using the method of transpupillary thermotherapy (TTT) (Aaberg T.M., Bergstrom CS, Hickner ZJ, Lynn MJ Long-term results of primary transpupillary thermal therapy for the treatment of choroidal malignant melanoma // Br. J Ophthalmol. - 2008 - Vol. 92. - No. 6 - P.741-746 /).

Transpupillary thermotherapy (TTT) is a laser infrared subthreshold photocoagulation method.

TTT was first used by Oosterhuis in 1995 during and after local radiation therapy of choroidal melanoma with insufficient tumor regression. Subsequently, Shields in 1996 studied the effectiveness of only TTT alone, without radiotherapy in the treatment of small melanomas of the choroid. In our country, the first steps to use the TTT method were taken in 1999 on the basis of GU MNTK "MG" them. S.N. Fedorova in the field of treatment of small choroidal melanomas (Linnik L.F., Magaramov DA., Yarovoy A.A., Semikova T.S., 2002). The hyperthermic (45-55 ° С) effect of TTT induces, according to foreign authors, local tumor necrosis up to 3.9 mm deep (Journee-de Korver J.G., Oosterhuis J.A., De Wolff-Rouendaal D., Kemme H., 1997). According to our data, a single exposure to infrared radiation from a diode laser causes necrosis of choroid melanoma up to 2.2 mm (Linnik L.F., Magaramov D.A., Yarovoy A.A., 2003), does not damage structures located along the laser path beam, and enables accurate dosing.

Necrosis of uveal melanomas after TTT consists of exposure to the tumor cell itself and its immunogenetics. The effect on the melanoma cell is, first of all, a “blow” to its energy base, to mitochondria, as a result of which they swell and decay. The fact of the effect of TTT on tumor cell immunogenetics is also proven. As a result of laser exposure, the penetration of macrophages into the tumor and the removal of irradiated tumor cells through phagocytosis are stimulated. Free radical oxygen released during and after TTT initiates oxidative stress and thrombosis of the tumor’s own vessels. In some cases, 3-6 months after laser irradiation, either a calcified or a focus of subretinal fibrosis with residual dark jelly-like substance surrounded by a zone of atrophy of the choroid is formed at the tumor site. It does not progress and does not respond to additional laser effects of various wavelengths.

For the prototype of the proposed method, a well-known method of transpupillary thermotherapy of amelonatic melanoma of the choroid of the eye is selected, including TTT using an infrared diode laser with a power of 810 nm, to a tumor tissue temperature of 59-60 ° C (see Yarovoy A.A., Linnik L.F., Magaramov D.A. et al. Transpupillary diode-laser thermotherapy: possibilities in the treatment of small choroid melanomas // Clinical Ophthalmology. - 2004. - M. - T.5. - No. 2. - P.77-82).

The known method is as follows.

For TTT use infrared laser radiation with a wavelength of 810 nm. Laser exposure is carried out using a three-mirror Goldman lens. The diameter of the light spot is from 1.5 to 3 mm, depending on the area of the tumor and its location: the proximity of the macular zone and the papillomacular beam dictated the need to use a smaller spot diameter to avoid damage to these structures. The number of applications 4-26, depending on the area of the neoplasm, is applied to the entire surface of the tumor with the capture of healthy tissues by 1-2 mm (taking into account the phage data). The radiation power is selected during the session by gradually increasing until a barely noticeable whitening of the tumor appears. The power density during the procedure ranged from 3.9 to 24.15 W / cm ² . The prototype authors developed a method for determining the initial power density during TTT, depending on the calorimetric parameters of the tumor surface. In accordance with it, TTT of darkly pigmented MX begins with 4.2 W / cm ² , medium-pigmented with 7.8 W / cm ² , pigmentless with 11.4 W / cm ² . The diameter of the spot is dynamically changed during one session, it depends on the area of the neoplasm, the proximity of functionally significant structures (macula and papillo-macular bundle) and the position of the vessels on the surface of the tumor. The exposure time is 60 s in continuous mode. Repeated TTT sessions are conditionally divided into planned and unplanned. After 2-3 months or more after the first session, scheduled TTT sessions are performed with signs of partial tumor regression. Unscheduled are carried out with signs of continued growth of choroid melanoma (MX). Their number depends on the degree of tumor regression and is 1-6 sessions with an interval of 1-9 months.

The results obtained by the authors of the known method indicate the high efficiency of the TTT method of small MX both medicinally and functionally.

However, the known method has the following disadvantages.

When using TTT for treatment of melanoma with TTT by infrared (810 nm) diode laser, various complications may occur, the most common of which are:

- the formation of a retinal rupture of regmatogenous retinal detachment;

- release of pigment into the vitreous body after an overdose of energy during the procedure;

- the occurrence of subretinal choroidal neovascularization;

- subretinal central and peripheral pigment dispersion;

- the formation of macular folds of the retina, the occurrence of exudative detachment of the retina with peripheral localization of the neoplasm and thrombosis of the branches of the central retinal vein with the development of macular edema with paracentral localization of the tumor.

The task of the invention is to reduce intra- and postoperative complications.

The problem is solved in that in the known method of transpupillary thermotherapy of amelonatic melanoma of the choroid, including conducting transpupillary thermotherapy with an 810 nm infrared diode laser, to a tumor tissue temperature of 50-60 ° C, radiation power of 400 mW, a solid-state laser is used at the first stage of treatment 561 nm wavelength, which is used for laser barrage around the neoplasm with power parameters of 200 mW, exposure 0.05 ms, and coagulum diameter 300 μm, while the coagulates are applied to the tile figuratively with the formation of a coagulum strip of the III degree, up to 1 mm wide, after the restrictive coagulation with the same laser is completed, the intratumoral vessels are coagulated with radiation power parameters of 1200 mW, exposure time 0.5 s, spot diameter 1000 μm, tiled to the second degree coagulum, second stage transpupillary thermotherapy is carried out after 2 weeks and performed with an infrared diode laser of 810 nm, the radiation power is selected depending on the rate of occurrence of calorimetric signs of laser exposure, such as pale the tumor disappears for 30–40 s and acquires a milky white color for 55–60 s with a radiation power of 400 mW, in the absence of the indicated calorimetric signs, the power is increased to 1000 mW and the effect is increased by 60 s, the coagulates are applied according to the “chamomile” method, starting from the edge of the tumor, allowing their slight overlap, the central, highest part of the tumor is treated with the latter.

The present invention meets the criteria of the invention of "novelty", since the conducted patent information research did not reveal the sources of scientific, technical and patent literature discrediting the novelty of the invention.

The present invention meets the criterion of "inventive step", since the conducted FDI did not reveal treatment methods with essential features of the proposed technical solution.

Currently, in the treatment of various pathologies in ophthalmology, laser radiation is used, the biological effect of which largely depends on the wavelength. Different wavelengths have their own level of retinal macular phototoxicity. So, its maximum peak occurs at 440 nm, that is, the blue spectrum. With blue argon radiation (488 nm), phototoxicity is 30%, argon green (514 nm) - 5%, solid green (532 nm) - 2.35%, krypton yellow (568 nm) - 2.28%, and with diode infrared (810 nm) - less than 0.1% of the maximum. Thus, the radiation of a diode infrared laser with sufficient therapeutic efficiency has less damaging effect compared to other types of laser radiation. However, when using a diode infrared laser (810), postoperative complications nevertheless arise, a list of which is presented in the criticism section of the prototype.

When implementing the proposed method, a solid-state laser with a wavelength of 561 nm is used. Yellow 561 nm laser radiation penetrates deeper into the retina than 532 nm green and has maximum absorption by hemoglobin and oxyhemoglobin. With coagulation of the retina, it passes more easily through opaque light-conducting media (initial cataract, opacification of the vitreous body). The desired degree of intensity of the coagulum on the retina when using the yellow spectrum is obtained when using about a third of the lower radiation power than at the green wavelength. When a yellow laser spectrum is exposed to a tumor, its own vascular network is first selectively coagulated. Exposure to heat-resistant tumor vessels leads to thrombosis, desolation, and ultimately to ischemic necrosis of the tumor. This, in turn, deprives the tumor of blood supply, destroys its "skeleton", reducing or completely preventing the intensive transudation of fluid from melanoma after TTT, preventing possible exudative retinal detachment.

The proposed method of transpupillary thermotherapy with melanoma of the choroid is a functionally-saving method of laser treatment and allows to obtain the following technical effect.

It has high efficiency, safety and the ability to accurately dose radiation energy. The treatment process combines two different laser effects, and this is not just a total combination. The method allows to obtain a completely different and significantly higher and less traumatic effect. An analogy with the artillery preparation by the “yellow” 561 nm laser, followed by a blow to the preserved tumor tissue with an infrared (810 nm) laser, is obvious. The first stage is a laser barrage with a “yellow” 561 nm laser around the neoplasm, that is, its complete limitation. Further, the destruction of intratumoral vessels with their coagulation and thrombosis, which ultimately leads to ischemic necrosis of the tumor. This deprives the tumor of blood supply, destroys its frame. Reduces or completely prevents the intense transudation of fluid from melanoma after TTT and prevents exudative detachment. Subsequently, under the influence of thermotherapy, melanous cells are finally necrotic.

Healthy tissues not involved in the pathological process are not exposed to destructive and necrotic effects. Two-stage laser coagulation of medium-sized choroid melanomas (T2-T4 according to TNM) and weak pigmentation localized in the paracentral and middle peripheral areas of the fundus allows minimizing the risk of intra- and postoperative complications and can be performed in cases previously considered unpromising for laser treatment. Positive results were also observed in 7 patients with choroid melanoma treated with the proposed method.

The proposed method is as follows.

In the preoperative period, a thorough examination of the patient is carried out to determine whether the process is primary or secondary, as well as the exclusion of metastases. Ophthalmic status includes the determination of visual acuity with maximum correction, non-contact and contact ophthalmoscopy, color photographing of the neoplasm and fluorescence fundus angiography (FAGD). Somatic examination includes radiography of the lungs, ultrasound, examination of the liver and mammary glands, consultations of a pulmonologist, gynecologist and mammologist.

At the first stage of treatment, a solid-state laser with a wavelength of 561 nm “Trion Combi” Carl Zeiss (Germany) is used, which performs laser barrage around the neoplasm with parameters of 200 mW power, 0.05 ms exposure, 300 μm coagulate diameter. Coagulates are applied tile-like with the formation of a strip of coagulate III degree, up to 1 mm wide. Immediately after completion of restrictive coagulation with the same laser, coagulation of intratumoral vessels is carried out with parameters of radiation power of 1200 mW, exposure time 0.5 s, spot diameter 1000 μm, to coagulate II degree (gray-white). The technique of applying tile-like. The second stage of the TTT method is carried out after 2 weeks with an infrared (810 nm) diode laser using an IQ 810 IRIDEX near-infrared ophthalmic coagulator (USA), using an adapter for a wide spot. Use a REICHEL-MEINSTER 1X laser contact lens. Tumor tissues are heated to a temperature of 59-60 ° C, the radiation power is selected depending on the rate of occurrence of calorimetric signs (traces) of laser exposure, the radiation power is set to 400 mW, while the tumor turns pale for 30-40 s and becomes milky white for 55 -60 s exposure. In the absence of these calorimetric features, the power is increased to 1000 mW and the effect is increased by 60 s. Coagulates are applied according to the “chamomile” technique, starting from the edge of the tumor, allowing them to be slightly superimposed on each other, the central, highest part of the tumor is treated with the latter.

Specific example 1

Patient S., 68 years old. Dz: minimally pigmented choroid melanoma with a TK size of TNM. Visual acuity before surgery - 1.0 with correction. All necessary preoperative examinations were performed.

The first step was a laser barrage around the neoplasm with a “yellow” 561 nm laser using a Carl Zeiss ophthalmic coagulator “Trion Combi”. Parameters: power 200 mW, exposure 0.05 ms, diameter 300 μm. The coagulates were applied tile-like with the formation of a white band (coagulate III degree), a width of 1 mm. Immediately after the completion of restrictive coagulation, a 561 nm yellow laser coagulation of intratumoral vessels was performed with the following radiation parameters: power 1200 mW, exposure 0.5 s, spot diameter 1000 μm, application procedure - tiled to coagulate II degree (gray-white) .

Second stage: TTT was carried out after 2 weeks. During thermotherapy with an infrared (810 nm) diode laser, the tumor tissue was heated to a temperature of 59-60 ° C. This patient used a moderate energy level of 400 mW and a large irradiation spot size of 3 mm. The procedure was performed on a near infrared ophthalmocoagulator “IQ 810” IRIDEX (USA) using an adapter for a wide spot. A REICHEL-MEINSTER 1X laser contact lens was used. Coagulates were applied according to the “chamomile” technique, starting from the edge. Allowed their slight overlap. The last treated central highest part of the tumor.

7 months after the treatment, pronounced positive dynamics was determined, a decrease in the size of the tumor in area and height, sclerotherapy of the vessels of the tumor, leakage and accumulation of contrast, the formation of subretinal fibrosis. Visual acuity with correction remained the same = 1.0 with correction.

Case Study 2

Patient A., 67 years old. Dz: minimally pigmented choroid melanoma with a TK size of TNM. Visual acuity before surgery - 1.0 with correction. All necessary preoperative examinations were performed.

The first step was a laser barrage around the neoplasm with a “yellow” 561 nm laser using a Carl Zeiss ophthalmic coagulator “Trion Combi”. Parameters: power 200 mW, exposure 0.05 ms, diameter 300 μm. The coagulates were applied tile-like with the formation of a white band (coagulate III degree), a width of 1 mm. Immediately after completion of restrictive coagulation, a 561-nm yellow laser coagulation of intratumoral vessels was performed with the following radiation parameters: power 1200 mW, exposure 0.5 s, spot diameter 1000 μm, application procedure - tiled to coagulate II degree (gray-white) .

Second stage: TTT was carried out after 2 weeks. During thermotherapy with an infrared (810 nm) diode laser, the tumor tissue was heated to a temperature of 59-60 ° C. A moderate energy level of 400 mW and a large irradiation spot size of 3 mm were used. The procedure was performed on a near infrared ophthalmic coagulator “IQ 810” IRIDEX (USA) using an adapter for a wide spot. A REICHEL-MEINSTER 1X laser contact lens was used. Coagulates were applied according to the “chamomile” technique, starting from the edge. Allowed their slight overlap. However, the expected calorimetric signs are not registered. Power was gradually increased to 1000 mW and increased impact by 60 s. The last treated central highest part of the tumor.

7 months after the treatment, pronounced positive dynamics was determined, a decrease in the size of the tumor in area and height, sclerotherapy of the vessels of the tumor, leakage and accumulation of contrast, the formation of subretinal fibrosis. Visual acuity with correction remained the same = 1.0 with correction.

Claims (1)

A method of transpupillary thermotherapy of amelonatic melanoma of the choroid of the eye, including conducting transpupillary thermotherapy with an infrared diode laser of 810 nm to a tumor tissue temperature of 50-60 ° C, a radiation power of 400 mW, characterized in that a solid-state laser with a wavelength of 561 nm is used in the first stage of treatment, which carry out laser barrage around the neoplasm with parameters of power 200 mW, exposure 0.05 ms, coagulate diameter 300 μm, while the coagulates are imposed tiled with the formation of bands coagulate III degree, up to 1 mm wide, after restrictive coagulation with the same laser is completed, coagulation of intratumoral vessels is carried out with radiation power parameters of 1200 mW, exposure time 0.5 s, spot diameter 1000 μm, tiled to coagulate II degree, the second stage of transpupillary thermotherapy is carried out after 2 weeks and performed with an 810 nm infrared diode laser, the radiation power is selected depending on the rate of appearance of calorimetric signs of laser exposure, such as blanching of the tumor for 30-40 s and acquired milky white color for 55-60 s with a radiation power of 400 mW, in the absence of the indicated calorimetric signs, the power is increased to 1000 mW and the effect is increased by 60 s, the coagulates are applied according to the “chamomile” method, starting from the edge of the tumor, allowing a slight overlap one on top of the other, the central, highest part of the tumor is treated last.