V.N. GERMANOVA

Samara State Medical University, 158 Novo-Sadovaya Str., Samara, Russian Federation, 443068

  Germanova V.N. – resident of Ophthalmology Department, e-mail: [email protected]

Mechanism of Cyclosporine A (CsA) action supposes that it can safely and efficiently substitute cytostatic agents in glaucoma surgery to counteract postoperative scarring. The largest effect can be used when prolonging the CsA action in the operative zone during at least 6 days, when the concentration of T-lymphocytes is the highest, which are the target for the drug.

Objective. To elaborate a simple technique for saturation of anticoagulation glaucoma drainage (GD) with CsA solution for prolonged release of the drug in therapeutic concentrations in vitro during 7-10 days.

Methods. We analyzed the ability of a porous drainage of poly(lactic-co-glycolic) acid (PLCGA) and biodestruction-resistant xenocollagen to absorb CsA from solutions with various drug concentrations (50 – 1 mg/ml). To assess the dynamic  of CsA absorption under close to real conditions, we determined the drug concentration in solutions after the drainages were kept in them for 12 hours, 24 hours, 2, 4, 6 and 10 days. Quantity assessment was made by enxyme immunoassay.

Results. Both PLCGA and collagen drainages can absorb CsA from solutions. The optimal and safe conditions of drainage saturation were found: during 15 minutes in solution with CsA concentration of 1.6 mg/ml. The complete desorption of the drug from the collagen drainage takes place during 4 days, which is insufficient for anti-proliferation effect. When PLOGA drainage is saturated, the therapeutic CsA concentration was maintained for 8 days.

Conclusions. PLCGA drainage is an optimal platform for CsA saturation ex tempore to maintain the therapeutic CsA concentration in vitro for a period of time essential in terms of intense inflammation and scarring process triggering.

Key words: cyclosporine A, glaucoma, scarring, anti-glaucoma drainage.

(For citation: Germanova V.N. Saturation of glaucoma drainages with cyclosporine to prolong their effect of postoperative scarring prevention. Practical Medicine. 2018)

REFERENCES

1. Peng T. Khaw, Jones E., Mireskandari K., Dahlmann A., Cambrey A. Modulating wound healing after glaucoma surgery. Glaucoma today, 2004, pp. 12-19
2. Russkov K.N., Zolotarev A.V., Milyudin E.S. Pharmaceutical composition for the prevention of the proliferative cellular reaction «Mitomycin-O». Prakticheskaya meditsina, 2012, no. 4 (59), pp. 260-262 (in Russ.).
3. Khaw P.T. Advances in glaucoma surgery: evolution of antimetabolite adjunctive therapy. J Glaucoma, 2001, vol. 10, pp. 81–4.
4. Ghasem Fakhraie, Joao F. Lopes, George L. Spaeth, Juliana Almodin, Parul Ichhpujani, Marlene R. Moster, Wills Eye Institute, Philadelphia, USA. Effects of postoperative cyclosporine ophthalmic emulsion 0.05% (Restasis) following glaucoma surgery. Clinical and Experimental Ophthalmology, 2009, vol. 37, no. 9, pp. 842-8
5. Faulds D, Goa KL, Benfield P. Cyclosporin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in immunoregulatory disorders. Drugs, 1993, vol. 45, no. 6, pp. 953-1040
6. Lattanzio, Frank A Jr. PhD; Crouch, Earl R Jr. MD; Mitrev, Peter V MD; Williams, Patricia B PhD; Allen, Robert C MD. Cyclosporin as an Adjunct to Glaucoma Filtration Surgery. J Glaucoma, 2005, vol. 14, no. 6.
7. Cvenkel B., Kopitar A.N.a., Ihan A. Inflammatory molecules in aqueous humour and on ocular surface and glaucoma surgery outcome. Mediators of Inflammation, 2010, article ID 939602. P. 7.
8. Yamanaka O., Kitano-Izutani A., Tomoyose K., Reinach P. Pathobiology of wound healing after glaucoma filtration surgery. BMC Ophthalmology, 2015, no. 15 (suppl. 1), pp. 19-27
9. Dai Z., Yu X., Hong J., Liu X., Sun J., Sun X. Development of a novel CsA-PLGA drug delivery system based on a glaucoma drainage device for the prevention of postoperative fibrosis. Mater Sci Eng C Mater Biol Appl., 2016, vol. 66, pp. 206-214. doi: 10.1016/j.msec.2016.04.077
10. Slonimskiy A.Yu., Alekseev I.B., Dolgiy S.S. New possibilities of preventing excessive scarring in glaucoma surgery. Oftal’mologiya, 2012, vol. 9, no. 3, pp. 36-40 (in Russ.).
11. Anisimova S.Yu., Anisimov S.I., Rogacheva I.V. Long-term results of surgical treatment of refractory glaucoma using biodegradable collagen drainage. Glaukoma, 2011, vol. 10, no. 2, pp. 28-33 (in Russ.).
12. Karlova E.V., Pavlov D.V., Lebedev O.I. et al. Surgical treatment of primary open-angle glaucoma by activation of uveoscleral outflow with the use of collagen drainage. Prakticheskaya meditsina, 2012, vol. 4-1, no. 59, pp. 201-203 (in Russ.).
13. Garweg J.G, Wegmann-Burns M., Goldblum D. Effects of daunorubicin, mitomycin C, azathioprine and cyclosporine A on human retinal pigmented epithelial, corneal endothelial and conjunctival cell lines. Graefe’s Archive for Clinical and Experimental Ophthalmology, 2006, vol. 244, no. 3, pp. 382-9.