RU2445944C1 - Method of photodynamic therapy of posterior aggressive retinopathy in premature newborns - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely ophthalmology and may be used for photodynamic therapy of early posterior aggressive retinopathy of premature newborns with no demarcation line and demarcation bar observed. A photosensitiser (PS) 2.0 mg/kg in the form of a herbal porphyrin derivative is introduced orally with baby food in the amount sufficient for single feeding. Thereafter 2 hours later, an avascular retinal area at an extreme periphery is exposed to transconjunctival contact laser light at 3.0 mm from a limb with using a light guide tip at wave length matched to maximum PS adsorption of optical emission. Power density makes 120 J/cm². The exposure covers one line of 15% overlapping spots of the diameter 4 mm in a circle.

EFFECT: invention provides stable regression of posterior aggressive retinopathy in premature newborns with decreased total power of laser exposure covering the retina, reduced length of a laser coagulation session and hence a general anaesthesia care in a premature newborn.

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Description

The invention relates to medicine, namely to ophthalmology, and can be used for photodynamic therapy of posterior aggressive retinopathy of premature infants in the stage of its early manifestations, when there is no line of demarcation or a shaft of demarcation.

According to the existing unified International Classification of Premature Retinopathy (RN), the most unfavorable prognosis regarding the severity and speed of the course of active RN is observed in cases of the development of posterior aggressive RN - the most dangerous, rapidly progressive and difficult to treat form of the disease.

As a rule, posterior aggressive pH is detected in a group of deeply premature infants with low body weight at birth, as well as a severe somatic condition. The frequency of development of the posterior aggressive pH, according to domestic experts, ranges from 7 to 24%, and the effectiveness of its treatment is 60-80% (Katargina L.A., Kogoleva L.V., Khvatova A.V. et al. Factors, affecting the effectiveness of prophylactic coagulation of the retina with active retinopathy of premature babies. // Russian Pediatric Ophthalmology. - 2007. - No. 1. - P.25-27; Kulakova MV Laser coagulation of the retina in the treatment of retinopathy of premature babies with different course options: Abstract. ... Candidate of Medical Sciences. - Chelyabinsk, 2007. - 24 p.). According to foreign authors, the frequency of favorable outcomes after laser coagulation does not exceed 45% (Azuma N., Ishikawa K., Hama Y. et al. Early vitreous surgery for aggressive posterior retinopathy of prematurity // Am. J. Ophthalmol. - 2006. - Vol.142. - N4. - P.636-43).

There is a method of treating posterior aggressive retinopathy of premature infants (Kulakova M.V. Laser retinal coagulation in the treatment of retinopathy of premature infants with various flow options: Abstract of diss. ... Ph.D. medical sciences. Chelyabinsk, 2007. - 24 p.), Including laser exposure to avascular retina. The disadvantages of this method are: late treatment, a large energy of laser exposure to the retina, which provokes proliferative activity, a long duration of a laser treatment session.

The objective of the invention is to develop an effective and safe method for photodynamic therapy of posterior aggressive retinopathy of premature infants in the stage of its early manifestations, when there is no line of demarcation or a shaft of demarcation.

The technical result of the proposed method is to reduce the total energy of laser exposure to the retina, reducing the duration of the laser coagulation session of the retina and, accordingly, anesthetic benefits to the premature baby; persistent regression of posterior aggressive retinopathy of prematurity, lack of clinical signs of disease activity.

The technical result is achieved due to the fact that:

1. The chlorine-type photosensitizers (PSs) used are characterized by a high degree of purity, low toxicity, and the ability to exhibit high photochemical activity in low doses under laser irradiation.

2. FS is taken orally, which ensures the absence of allergic reactions, as well as the risk of infection with viral diseases, which occurs with intravenous administration of drugs.

3. Oral administration of FS followed by transconjunctival irradiation (photodynamic therapy (PDT)) of the avascular zone of the retina at the extreme periphery for given parameters of laser exposure leads to photoinduced thrombosis of the choriocapillaries with subsequent formation of foci of chorioretinal atrophy, corresponding to the zone of laser exposure, which inhibits the production of factors leads to persistent regression of posterior aggressive retinopathy of premature infants.

4. Parameters of PDT: the dose of orally administered FS is 2.0 mg / kg, the wavelength of laser radiation is 662 nm, the energy density is 120 J / cm ² , the spot diameter is 4 mm with the overlapping of adjacent spots by 15% of the area and can significantly reduce dose of the total laser radiation energy on the retina and accelerate the treatment session (due to the use of low-intensity laser radiation in the spot ⌀ 4 mm, in contrast to high-intensity laser radiation in the spot ⌀ 300-500 μm with standard laser coagulation).

5. Photodynamic therapy is carried out: a) at the stage of early manifestations of posterior aggressive retinopathy prematurely before the formation of the demarcation line or demarcation shaft; b) in the avascular zone of the retina at the extreme periphery, laser spots are applied in a circle in a row.

The claimed technical result can be obtained only by using the totality of the techniques proposed by us method.

The method is as follows.

PDT is carried out at the stage of early manifestations of posterior aggressive retinopathy prematurely before the formation of the line of demarcation or the shaft of demarcation.

Preoperative preparation of the patient includes examination by an anesthetist, instillation and injection of mydriatics, connection of monitoring devices for vital functions (heart rate, blood oxygen saturation).

PDT is performed under mask anesthesia (a mixture of sevoflurane, nitrous oxide and oxygen). Initially, the patient is given orally with baby food in an amount sufficient for a single feeding, a derivative of a porphyrin of plant origin, for example, pheophytin, or pheoforbide, or methylpheophorbide, at a dose of 2.0 mg / kg is given. After 2 hours, transconjunctively, departing from 3.0 mm from the limbus, irradiating the avascular zone of the retina at the extreme periphery with laser radiation with a wavelength corresponding to the maximum absorption of PS of light radiation, for example, with a wavelength of 662 nm when using FS chlorin row, with an energy density of 120 J / cm ² , spots with a diameter of 4 mm in a circle in a row with overlapping neighboring spots on 15% of the area.

The fiber nozzle comprises a transparent cylindrical stop body, a retaining ring and a lock nut. The stop body consists of an upper part with a neck, on which an external thread is applied, and a lower hollow part. A through channel for introducing a fiber is made in the upper part of the stop body along the axis of rotation, the lower part of the stop body is intended for contact with the irradiated surface and ends with a circular edge marker at the end. The fiber is tightly fixed in the channel of the upper part of the stop body by means of a locking ring and a lock nut, which is screwed onto the neck thread of the upper part of the stop body, while the end of the fiber goes into the cavity of the stop body.

The dimensions of the body-stop: length - 40 mm, of which 24 mm - the length of the upper part, of which 6 mm - the length of the neck; diameter, with the exception of the neck, is 8 mm; the diameter of the body in the neck of the upper part is 5 mm. The inner diameter of the base of the lower part of the device casing is selected according to the required diameter of the laser spot and is 4 mm. The thickness of the circular edge of the marker is 0.3 mm. The diameter of the through channel of the upper part of the casing should be sufficient for the introduction of a fiber into it.

The stop body can be made, for example, of polymethyl methacrylate, photoplastic-4, the fixing ring is made of silicone, and the lock nut is made of stainless steel.

Contact transconjunctival irradiation of the avascular zone of the retina at the extreme periphery during photodynamic therapy according to the proposed method is as follows.

The required therapeutic dose of laser irradiation is verified by measuring the power at the output of the nozzle using a power meter. If necessary, adjust the laser parameters.

After the patient has consumed FS and its exposure, a coloring agent is applied to the marker edge, for example, a 1% aqueous-alcoholic solution of brilliant green. Retreating 3.0 mm from the limb, set the nozzle with the butt end of the lower part with the marker edge onto the conjunctiva and carry out contact transconjunctival irradiation of the avascular zone of the retina at the extreme periphery with fields, overlapping adjacent fields by 15% of the area, by sequentially moving the nozzle in a circle within the target zones. In this case, the boundaries of each field are visualized by means of a coloring matter.

All actions with the photosensitizer are carried out in a dark environment, ensuring the inability to penetrate into the room in direct sunlight. During the day after PDT, the patient should also be kept in a darkened room. This condition is well known and standard for PDT sessions.

The invention is illustrated by the following data.

Under observation were 14 premature infants (28 eyes) with early manifestations of posterior aggressive pH. Gestational age - 25-33 weeks, body weight at birth - 820-1530 grams.

All patients showed pronounced vascular activity: the diameter of the arteries (D arteries) - 99.50 ± 2.25 μm, veins (D veins) - 138.00 ± 3.25 μm, the coefficient of tortuosity of the arteries (CI) - 1.43 ± 0.05 - in the absence of vascular growth dynamics in the avascular zone (retinal vascularization coefficient (KB) - 0.18 ± 0.05). In most cases, a demarcation shaft was revealed, extending to 4-6 hour meridians along the border of the vascularized retina, an increase in tortuosity and progressive expansion of the terminal vessels at the border with the avascular retina, the formation of multiple arteriovenous shunts and the appearance of petechial hemorrhages from capillaries in this region were detected. The retina thickness in fovea centralis was 208 ± 0.06 μm.

In 14 eyes (7 patients) (group 1), PDT was performed in the avascular area of the retina according to the proposed method. PDT parameters: the dose of orally taken FS is 2.0 mg / kg, the wavelength of the laser radiation is 662 nm, the laser energy density is 120 J / cm ² , the diameter of the laser spot is 4 mm with overlapping neighboring spots on 15% of the area. Transconjunctival laser irradiation was performed 2 hours after oral administration of FS. Pheophytin, or pheophorbide, or methylpheophorbide, was used as a PS.

The remaining 7 patients (14 eyes) (group 2) underwent standard laser coagulation of the entire avascular area of the retina. Laser coagulation parameters: wavelength - 532 nm, radiation power - 120-180 mW, exposure time - 0.1 sec, spot diameter - 300-500 microns, distance between adjacent coagulates - 1 / 2d coagulate. The total number of coagulates ranged from 1750 to 2500.

In group 1, the duration of a PDT session according to the proposed method was 17 ± 8 minutes, in group 2, the duration of the laser coagulation session was 42 ± 7 minutes. Accordingly, the duration of anesthesia allowance in group 1 was 2.5 times less than in group 2.

As a result of treatment by the proposed method (in group 1), a stable regression of the posterior aggressive pH was noted in 10 eyes (71.4%). After 1 month, foci of chorioretinal atrophy were observed ophthalmoscopically at the extreme periphery, corresponding to the laser exposure zone in the absence of clinical signs of disease activity. After 2 months, the positive dynamics of the process was confirmed by the fixed normalization of morphometric and tomographic indices (Table 1). 6 months after treatment, registration of morphometric parameters of the retina did not reveal their pronounced changes (Table 1).

Table 1 Dynamics of morphometric parameters of the retina and retinal vessels before and after photodynamic therapy in group 1 Morphometric indicator To LKS Dates after PDT 1 week 1 month 2 month 6 months D veins, microns 138.00 ± 3.25 * 124.50 ± 3.50 112.50 ± 3.00 93.75 ± 3.25 * 92.50 ± 2.75 * D arteries, microns 99.50 ± 2.25 * 91.75 ± 2.50 83.25 ± 1.75 74.50 ± 2.25 * 71.25 ± 3.25 * KI 1.43 ± 0.05 1.42 ± 0.05 1.36 ± 0.05 1.31 ± 0.04 1.26 ± 0.05 KB 0.18 ± 0.05 * 0.19 ± 0.05 0.26 ± 0.04 0.77 ± 0.06 * 0.80 ± 0.05 * Retinal thickness in fovea centralis, microns 208 ± 6 * 187 ± 6 156 ± 5 137 ± 7 * 125 ± 6 * * - criterion for pairwise comparisons of Duncan, p <0.05

There were no cases of allergic and phototoxic reactions in group 1.

In group 2, after standard laser retinal coagulation, sustained regression of the posterior aggressive pH was observed in 9 eyes (64.3%). The dynamics of morphometric and tomographic indices did not significantly differ from that in group 1 (Table 2).

table 2 Dynamics of morphometric parameters of the retina and retinal vessels before and after standard laser coagulation in the 2nd group Morphometric indicator To LKS Terms after standard laser coagulation 1 week 1 month 2 month 6 months D veins, microns 137.75 ± 1.75 * 127.00 ± 2.25 111.25 ± 3.75 98.25 ± 3.75 * 92.75 ± 1.50 * D arteries, microns 98.25 ± 2.50 * 95.25 ± 1.75 84.75 ± 2.25 76.50 ± 1.50 * 70.75 ± 3.00 * KI 1.45 ± 0.05 1.42 ± 0.05 1.39 ± 0.04 1.30 ± 0.05 1.28 ± 0.04; KB 0.20 ± 0.04 * 0.20 ± 0.05 0.24 ± 0.06 0.71 ± 0.06 * 0.76 ± 0.08 * Retinal thickness in fovea centralis, microns 217 ± 9 * 184 ± 3 153 ± 6 134 ± 9 * 123 ± 7 * * - criterion for pairwise comparisons of Duncan, p <0.05

Thus, the inventive method provides a decrease in the total energy of laser exposure to the retina, a decrease in the duration of the laser coagulation session of the retina and, accordingly, anesthetic benefits to the premature baby; persistent regression of posterior aggressive retinopathy of prematurity, lack of clinical signs of disease activity.

Claims (1)

A method for the photodynamic therapy of posterior aggressive retinopathy of premature infants, including laser exposure to the avascular retina, characterized in that the patient is given orally with baby food in an amount sufficient for single feeding, a photosensitizer (PS) is a derivative of plant-derived porphyrin in a dose of 2.0 mg / kg , after 2 h, transconjunctival, departing 3.0 mm from the limbus, irradiating the avascular zone of the retina at the extreme periphery with laser radiation with a wavelength of contact using a nozzle on a fiber, the maximum absorption of PS of light radiation, with an energy density of 120 J / cm ² , spots with a diameter of 4 mm in a circle in a row with overlapping neighboring spots on 15% of the area.