RU2281073C2 - Method for surgical treatment of glaucoma - Google Patents

Abstract

FIELD: medicine, ophthalmology.

SUBSTANCE: one should carry out nonpenetrating deep sclerectomy. Then one should lance suprachoroid space to introduce a viscoelastic in it. Then it is necessary to implant a drainage out of amniotic membrane into the space developed between the sclera, a ciliary body and a vascular membrane. The innovation provides the opportunities for functioning shunted uveoscleral outflow way and prevents cicatrisation of outflow ways in post-operational period.

EFFECT: higher efficiency of therapy.

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Description

The invention relates to medicine, namely to ophthalmology.

Activation of uveoscleral outflow is an important area in the treatment of glaucoma. This is due to the fact that the uveoscleral path, which plays an auxiliary role in the outflow of intraocular fluid, is normally the only real way for the outflow of aqueous humor in glaucoma, when the main one - the outflow through corneoscleral trabeculae (the so-called anterior outflow pathway) - basically does not function (Nesterov A .P., 1985). The activation of the uveoscleral pathway is based on the action of the modern most effective antiglaucomatous drugs (prostaglandins, eicosanoids). However, in conditions when drug treatment ceases to be effective, the question arises of surgery, and in this case, increased filtration of intraocular fluid into the suprachoroidal space is of particular importance, in other words, the creation of a new outflow pathway directed along the uvescleral path. It should be emphasized that most classical antiglaucomatous interventions are aimed at activating the anterior pathway - through the scleral sinus or under the conjunctiva. At the same time, many surgeons recognize the need to create conditions to strengthen the posterior outflow tract - uveoscleral. For this purpose, for example, during the operation, the choroid is partially exposed (N.V. Kosykh. The use of multiple posterior sclerectomy in the treatment of "unpromising" glaucoma // Ophthalmic surgery. - 1989. - No. 1-2. - P.40-41; S. Yu. Astakhov, Patent for the invention No. 2189208; A. Mermoid, T. Sharaawy. Surgery for glaucoma in the 21-th century // Br.Ophthalmol. - 2003. - Vol.87. - P.250).

The aim of the proposed tool is to create the maximum possible prerequisites for enhancing the uveoscleral path of the outflow of intraocular fluid.

An important aspect in modern glaucoma surgery is the use of viscoelastics, which are given increasing importance in recent years, especially with non-penetrating antiglaucomatous operations. It is believed that injection of high-density viscoelastic into the lumen of the Schlemm canal (the method proposed by R. Stegmann in 1998) leads to microcracks of its internal endothelial wall, which expands the trabecular network and spaces in its juxtancanicular part. Of interest, apparently, is the introduction of viscoelastic into the suprachoroidal space as well.

Another aspect of the developed method for the surgical treatment of glaucoma was the prevention of excessive scarring of the outflow pathways created during the operation, which involves the use of physiological regulators of reparative processes. The use of physiological repair regulators of reparation, in particular those with immunomodulatory activity, seems to be the most promising at the present time (P. Khaw, 2000, 2003), since this direction of therapy is devoid of complications typical for antimetabolites traditionally used in glaucoma surgery (Mitomycin C and 5 -fluorouracil) (WuDunn D., Cantor L. A prospective randomized trial comparing intraoperative 5-fluorouracil vs mitomycin C in primary trabeculectomy // American J. of Ophthalmology. - 2002. - Vol.134. - P.52-528, Nuyts R., Van Diemen H., Greve E. Occlusion of the retinal vasculature after trabeculectomy with mitomicin C // Int. Ophthalmol. - 1994. - Vol. 18. - P.167-170, Daugeliene L., Yamamoto T., Kitazawa Y. Cataract development after trabeculectomy with mitomycin C: a one-year study // Jap. J. Ophthalmol. - 2000. - Vol. 44. - P.52-57).

In recent years, cryopreservation of the amniotic membrane has been successfully applied in various fields of medicine, in particular in ophthalmology (Tseng SCG, Prabhasawat P., Barton K. Amniotic membrane transplantation with or without limbal autografts for comeal surface reconstruction in patients with limbal sterm cell deficiency // Arch. Oththalmol. - 1998. - Vol. 116. - P.431-441). One of the advantages of amnion is its immune activity. Other important properties of amnion include its ability to accelerate epithelization, reduce inflammation, suppress excessive scarring, reduce tissue adhesion and vascularization (Trelford JD, Sander M. The amnion in surgery, past and present // Am J Obstet and Gynecol. - 1979 . - Vol.134. - P.833-845). The listed biological effects of amnion are associated with the fact that it contains a number of cytokines, including IL-4, 6 and 10, growth factors (EGF, FGF, TGF, HGF), as well as protease inhibitors. An important feature of the amnion is its ability to suppress the activity of systems responsible for the production of growth factors in conjunctiva and sclera fibroblasts (TGF-signaling system), which significantly reduces their mitogenic activity. From this point of view, the possibility of using amnion to prevent excessive scarring of eye tissues after antiglaucomatous surgery (AGO) is essential, since this complication of glaucoma surgery is associated with overproduction of a number of cytokines, in particular, TGF-β1 growth factor. This cytokine has the strongest proliferative effect [Cordeiro M., Reichel M., Gay J. et al. Transforming growth factor beta-1 in cultured human Tenon's capsule fibroblasts // Eur. J. Ophthalmol. - 2000. - Vol. 10. - P.110-115], which even suppresses the effect of MMS in vivo [Khaw P., Doyle J., Sherwood M. et al. Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C // Arch. Ophthalmol. - 1993 .-- Vol. 111. - P.263-267]. There is evidence in the literature on the ability of amnion to inhibit fibroblast proliferation (Lee S., Li D., Tan D., Tseng S. Suppression of TGF-β signaling in both normal conjunctival fibroblasts and pterygial body fibroblasts by amniotic membrane // Curr. Eye Res . - 2000. - Vol.20. - P.325-334) by modulating the production of TGF-β1.

However, until now, the amniotic membrane has been used most often as a conjunctival coating for external filtration after antiglaucomatous operations (Mucuno H., Kanamori A. Revision of filtrering bleb with late-on-set leakage by transplantation of amniotic membrane // Japanese Journal of Clinical Ophthalmology. - 2003. - Vol. 57. - P.1699-1704, Barton K., Budenz D., Khaw P., Tseng S. Glaucoma filtration surgery using amniotic membrane transplantation // Invest. Ophthalmol. Vis. Sci. - 2001. - Vol. 42, N 8. - P. 1762-1768). Single studies describe the use of amnion as an intrascleral implant (A.A. Kasparov, 2003; Zhong P., Dong Y., Li R. The combination of non-perforating trabeculecular surgery and amniotic membrane implantation in the treatment of secondary open-angle glaucoma // Chinese Ophthalmic Research. - 2003. - Vol.21. - P.524-526; Demir T., Turgut B., Akyol N., Ozercan I., Via F., Celiker U. Effects of amniotic membrane transplantation and mitomycin C on wound healing in experimental glaucoma surgery // Ophthalmologica - 2002. - Vol.216. - P.438-442).

The theoretical assumptions discussed above formed the basis of the proposed method for the surgical treatment of glaucoma. The technical result of the proposed method is aimed at increasing the effectiveness of antiglaucomatous operations by enhancing the uveoscleral pathway of the outflow of intraocular fluid, as well as the immunoregulatory properties of amnion, which inhibits the production of endogenous TGF-β1.

The study included the experimental part and a comprehensive examination of glaucoma patients operated on by our method (see below for a description of the operation).

Operation description.

The operation began with a conjunctival section at 12 hours, then a quadrangular superficial scleral flap 5 × 5 mm in size was cut out. From the deep layers of the sclera, a flap 3 × 4 mm in size was formed, exposing the Schlemm canal, then the surface layers of the cornea 1-1.5 mm above the Schlemm canal were removed, achieving filtration through the peripheral sections of the endothelial layer. Then, a 2 mm sclera was linearly cut 2 mm from the limbus, into which 0.05 ml of Healon (Pharmacia), which is a hyaluronic acid based viscoelastic, was injected. Thanks to this manipulation, a space was formed between the sclera, ciliary body and choroid, filled with a solution of sodium hyaluronate. Then, drainage from a human amniotic membrane 2 × 5 mm in size was introduced into the formed space. The amniotic membrane was preliminarily made from human placenta and was subjected to cryopreservation according to the S.Tseng method. Drainage was placed so that one end was above the descemet membrane, and the other end was submerged beneath the sclera above the ciliary body and choroid. This method of fixing the drainage, forming a local exudative detachment of the choroid, activates uveoscleral outflow in the area of drainage implantation. The scleral wound was sealed with two interrupted sutures. The operation was completed by injection of a corticosteroid and antibiotic under the conjunctiva.

Experimental studies were performed on 20 eyes of chinchilla rabbits. In the first group of animals, a sclerectomy was performed with subscleral implantation of the amniotic membrane (10 eyes); in the second - sclerectomy with the application of an antimetabolite - mitomycin C (0.2 mg / ml) for two minutes (5 eyes); in the third (control), a sclerectomy without amnion implantation and the use of antimetabolites (5 eyes).

In terms of one, three, six and twelve weeks after surgery, the animals were removed from the experiment by air embolism. Eyeballs were preserved in a 10% formalin solution. The preparations were subjected to histological examination, which was performed on paraffin sections with a thickness of 4-6 microns. Sections stained with hematoxylin-eosin were examined using a Photomicroscope III light microscope (Opton, Germany).

Clinical studies were conducted on 42 patients (42 eyes) with primary open-angle glaucoma in advanced (20 eyes) and advanced stages (22 eyes) with uncompensated ophthalmotonus, which were performed by AGO according to the method described above. The comparison group consisted of 15 patients (15 eyes) who underwent normal HSE (without amnion implantation, opening of the suprachoroidal space and the introduction of viscoelastic), and in order to prevent excessive scarring of the eye tissue, subconjunctival injections of 5-fluorouracil every other day were used (per course: 5 injections) . The groups were comparable by gender and age (patients were between the ages of 40 and 80; the average age was 64 years) and the stages of glaucoma.

Observation in the dynamics was carried out for 6 months. The state of the intraocular fluid outflow paths created during the operation was judged by biomicroscopy data (paying attention to the state of the filtering pad), ultrasound biomicroscopy data (paying attention to the sizes of intrascleral and suprachoroidal cavities) and gonioscopy results, as well as the level of ophthalmotonus.

The content of transforming growth factor TGF-β1 in the lacrimal fluid was determined for all patients both before and in dynamics after the operation. The study was carried out by enzyme immunoassay using commercial test systems (BIOSOURCE, Belgium). The sensitivity of the method is 15 pkg / ml. For comparison, tear fluid of 10 healthy donors of the same age was examined.

Statistical processing was carried out using Student's criterion and χ ² .

Morphological studies showed that subscleral implantation of the amnion leads to the expansion of the underlying choroid vessels (Fig. 1), as a result of which a significant part of the intraocular fluid enters the suprachoroid space and is then drained by the intra- and episcleral vessels. In other words, the conditions for a shunted uveoscleral outflow path are created: posterior chamber → spongy filtering structure of the implant → suprachoroidal space → episcleral veins. Comparative morphological studies performed on the eyes of rabbits receiving mitomycin C applications during surgery revealed reduced tissue regeneration (FIG. 2).

The results of clinical studies have shown the high efficiency of the proposed surgical method of treatment.

So, in cases of implantation into the suprachoroidal space of the amniotic membrane, the ophthalmotonus remained within the normal range in 40 eyes (97%). At the same time, the filtration pad was visualized and could be characterized as a low spilled one. With gonioscopy, a fairly pronounced intrascleral gap was traced. The results of ultrasound biomicroscopy revealed the formation of a pronounced suprachoroidal space, which remained at all stages of the examination (figure 3).

In the comparison group, stable normalization of ophthalmotonus was observed in 13 eyes (87%), which also indicates the high effectiveness of the use of 5-fluorouracil antimetabolite to prevent excessive scarring after AGO. However, in this group of patients, complications were more often observed in the early postoperative period: if detachment of the choroid developed in two patients of the main group (amnion), then in the comparison group (5-fluorouracil) it was observed twice as often. Against the background of treatment with 5-fluorouracil, in three cases there was a divergence of the conjunctival wound, and in one patient the divergence of the edges of the wound was repeated twice, about which the conjunctival plastic was performed with an amniotic membrane.

The results of ultrasound biomicroscopy indicated the formation of an intrascleral gap, but the suprachoroidal space was less pronounced or was not at all traced (Fig. 4).

Comparing the course of the postoperative period and its outcomes in patients of the main group and those who received 5-fluorouracil, we noted the clear advantages of the method of surgical treatment we proposed in comparison with the traditional method of combating excessive scarring. Indeed, the use of 5-fluorouracil after surgery, although it helped to maintain normal ophthalmotonus (its average values at the end of the sixth month was 16.3 ± 5.1 mm Hg), but was accompanied by a large number of complications, the main of which was the discrepancy between the edges of the operating room wounds.

Clinical and immunological analysis showed a steady decrease in the level of TGF-β1 in the lacrimal fluid of patients of the main group from initially high values on the eve of the operation to normal by the end of the first month after the operation (Fig. 5).

During treatment with 5-fluorouracil, there was no such a significant decrease in the level of TGF-β1 in the lacrimal fluid (Fig. 6), which is apparently associated with other mechanisms of the effect of this antimetabolite on fibroblast proliferation, possibly by blocking DNA synthesis (Michalikova L., Ferkova S., Stremen P. Antimatabolites in glaucoma surgery: long term study // Ceska a Slovenska Oftalmologie. - 2002. - Vol. 58. - P.180-186).

The immunomodulatory effect of the amniotic implant in combination with its suprachoroidal introduction after preliminary expansion of the suprachoroidal space with viscoelastic allows us to explain the effectiveness of the proposed method.

An important advantage of the proposed method for the treatment of glaucoma is the maintenance of the uveoscleral space, ensuring the outflow of intraocular fluid in the posterior way.

The effectiveness of the proposed treatment is confirmed by a clinical example.

Example. Patient K., 59 years old. Diagnosis: open-angle developed glaucoma with high ophthalmotonus of the right eye. Hydrodynamic indicators: P ₀ = 35.5 mm Hg; C = 0.02. A deep non-penetrating sclerectomy was performed, during which implantation into the suprachoroidal space of drainage from the amniotic membrane was performed. The course of the operation without complications. In the postoperative period, the patient received a solution of maxitrol and naklof in instillations. The postoperative period proceeded calmly: an inflammatory reaction in the form of a minor mixed injection was observed only in the first two days after the operation. Biomicroscopy results showed that the filter pad was low, moderately pronounced, the anterior chamber moisture was clear, the pupil reaction was preserved, and the fundus reflex was pink. A week after the operation, the hydrodynamic indicators: P ₀ = 11.0 mm Hg; C = 0.31. Dynamic observation showed the preservation of the filter pad at all stages of the examination. A well-defined intrascleral gap was determined gonioscopically. The results of ultrasound biomicroscopy showed the formation of a pronounced intrascleral gap and suprachoroidal space.

Six months after surgery, P ₀ = 16.0 mm Hg; C = 0.23. A study of TGF-β1 lacrimal fluid showed a decrease in its level from 780.0 pcg / ml on the eve of surgery to 386.0 pcg / ml at the end of the first week after surgery and to 294.5 pcg / ml in a month. The results of ultrasound biomicroscopy showed the preservation of the intrascleral gap and suprachoroidal space.

Thus, the claimed tool has a targeted therapeutic effect, preventing scarring of the outflow paths after antiglaucomatous surgery, which allows to achieve a stable normalization of intraocular pressure in patients with primary glaucoma.

Claims (1)

A method for the surgical treatment of glaucoma, including non-penetrating deep sclerectomy, characterized in that the suprachoroidal space is additionally opened and viscoelastic is inserted into it, after which drainage from the amniotic membrane is implanted into the space formed between the sclera, ciliary body and choroid.

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