Φωτοδυναμική θεραπεία ακτινωτού σώματος με verteporfin: πειραματική και κλινική μελέτη

Abstract

Glaucoma is one of the leading causes of blindness worldwide, due to progressive irreversible loss of optic nerve fibers (23,24). The main risk factor of glaucoma is the intraocular pressure (IOP) and all current anti-glaucoma treatments aim to its reduction (19). Topical anti-glaucoma medications and current surgical treatments, cannot always control the IOP (25,27,28,29,51). Current cyclodestructive procedures have a high rate of serious complications (33,34,30,31,52). The purpose of this study is to investigate the potential of transcleral ciliary body photodynamic treatment with verteporfin (CBPDT) for use in refractory glaucoma cases. Four experiments with rabbits were first performed, to test safety and efficacy of CBPDT. Since all IOP measurements in rabbits were performed with TonoPen-XL under general anesthesia, the first experiment studied its accuracy and concluded it is reliable for IOPs between 10 and 70mmHg and that it slightly underestimates IOP in rabbits (Real_IOP = 1.3472*TONO-PEN-7.0333 mmHg). The second experiment studied the treatment settings necessary for CBPDT in pigmented rabbits, without thermal damage (controlled with histology), and resulted in verteporfin dose 1mg/Kg, laser power 25-35mW and irradiation time 3 min (100μm core optic fiber). These settings produced significant IOP reduction for 4-6 days. In an effort to increase efficacy, a 600μm core optic fiber was used in the third experiment and treatment parameters were readjusted to laser power 40mW and treatment time 1,5min per spot. These settings produced significant IOP reduction again for 6 days. Four consecutive CBPDT every 4 days (same settings) was then performed, which concluded that both IOP reduction and photodymic ciliary body histological alterations (vascular thrombosis, edema and separation of the 2 epithelial layers) are reversible a week after. No serious adverse events were observed in experiments 2 and 3. In the fourth experiment cyclocryotherapy was performed in rabbits, which resulted in IOP reduction for more than a month, permanent ciliary processes' destruction and significant side effect during the first week after treatment. All 4 experiments concluded that CBPDT is a cyclosuppressive procedure safe for human use. In the first, pilot, clinical study CBPDT settings were readjusted for human use, in verteporfin dose and continuous infusion as for macular PDT, laser power 80mW (thicker human sclera) and irradiation time 3 min per spot, for 12 spots. CBPDT with these settings in cases of refractory glaucoma and blind eyes, under retrobulbar anesthesia, produced IOP reduction that lasted from some hours to few days. In the second clinical study, a new triple optic fiber was used, to irradiate 3 spots contemporarily, and verteporfin (dose same as for macular PDT) was infused in bolus. These settings reduced whole treatment time to 15min. Irradiation was performed again under retrobulbar anesthesia and total number of spots was 12 (360o of ciliary body). The metallic tip of the optic fiber was in contact with conjunctiva-sclera, with mild pressure, 1 mm behind the sclerocorneal limbus. Five cases of refractory glaucoma and legally blind eyes were so treated. IOP reduction of about 30% of the initial value was observed in all cases during the first week after CBPDT. In 2 cases the IOP returned to pretreatment values 1-2 months after treatment, while in the rest 3 cases the IOP reduction lasted for more than 3 months. No serious adverse events were observed in any case. This study concluded that CBPDT is a cyclosuppressive procedure safe for human use, which has a short term efficacy. Further study is required in order to increase efficacy and best determine its possible role in the treatment of glaucoma.