Aim. To justify the application of the transscleral approach to hybrid photodynamic therapy for uveal melanoma based on experimental morphological research. Materials and Methods. In the first phase of the study, the penetration of laser photodynamic radiation through the sclerotic coat of a human cadaver eye was evaluated experimentally, followed by a morphological examination of the dissected scleral flap. In the second phase, a patient with stage T4aN0M0 IIIA ciliochoroidal melanoma of the left eye underwent hybrid photodynamic therapy two days prior to enucleation of the eyeball as a preventive measure against hematogenous metastases. Results. Dosimetric control showed that optical light passes through the cadaveric sclerotic coat of the eye but suffers power loss, necessitating adjustments to the initial parameters to achieve an adequate therapeutic dose. Histological examination of the dissected scleral flaps (both lasered and intact) after transscleral photodynamic therapy showed no differences in the morphological structure of the two specimens. After hybrid photodynamic therapy in the patient with uveal melanoma, signs of partial thrombosis in the episcleral vessels at the base of the tumor and a decrease in the number of feeding intra-tumoral vessels were observed. Pathomorphological examination confirmed ciliochoroidal melanoma (spindle cell variant, type B, basal diameter — 1.7 cm, height — 1.7 cm) with minimal and maximal distances from the sclera to the necrotic zone of 0.3 mm and 0.5 mm, respectively, together with focal necroses and fibrin-erythrocytic thrombi in the lumens of some vessels, with a distance of 6.0 mm from the sclera to the vessel containing a fibrin-erythrocytic thrombus. Conclusion. The prospects of using transscleral approaches in hybrid photodynamic therapy are supported by experimental morphological studies that have demonstrated the safe passage of laser photodynamic radiation through the sclerotic coat of the eye, as well as the development of necrotic changes and blood clots in the intra-tumoral vessels of ciliochoroidal melanoma after hybrid photodynamic therapy with chlorinbased photosensitizers. The findings provide justification for employing transscleral and hybrid approaches in photodynamic therapy as independent methods for organ-sparing treatment of uveal melanoma. © 2025 Autonomous non-profit scientific and medical organization. All rights reserved.