Photodynamic therapy for ciliary body melanoma: experience with an isolated transscleral approach

Ciliary body melanoma (CBM) accounts for up to 20% of uveal melanoma cases and presents challenges for organ-preserving treatment due to its peripheral location and proximity to critical ocular structures. This study presents the first clinical results evaluating the efficacy and safety of isolated transscleral photodynamic therapy (TSPDT) with a chlorin e6 photosensitizer in 7 patients with CBM. The procedure was performed using an «ALOD-01» laser system (λ=662 nm) and standardized irradiation parameters (energy density 519.5 J/cm², accounting for power loss during scleral transmission). The mean follow-up period was 19.0±5.9 months and demonstrated high local tumor control: complete regression was achieved in 4 patients, and partial regression in 3 patients. A statistically significant reduction in tumor height (from 4.69±2.58 mm to 1.36±1.14 mm; p=0.0062) and basal diameter (from 8.54±3.56 mm to 6.65±3.70 mm; p=0.016) was accompanied by a pronounced vasculo-occlusive effect, manifested as complete tumor avascularity in the majority of patients according to ultrasound with color Doppler Imaging (CDI). Echodenstitometry recorded a statistically significant decrease in mean acoustic density from 35.53±1.26 dB to 28.97±0.83 dB (p=0.0002), which may indicate tumor tissue destruction. No intra– or postoperative complications were recorded throughout the observation period, and a trend towards stable visual acuity was noted. The obtained data suggest that TSPDT is a promising minimally invasive organ-preserving method for treating CBM, requiring further investigation to define its role as either a standalone or combined therapy.

1. Klinicheskie rekomendacii «Uveal'naja melanoma», 2020; Accessed January 07, 2022. https://oncology-association.ru/wp-content/uploads/2020/09/uvealnaja_melanoma.pdf

2. Brovkina A.F. Local treatment of choroidal melanoma: possibilities and limitations. Russian Annals of Ophthalmology, 2018, vol. 134, №4, рр. 52-60. (In Russ.) doi: 10.17116/oftalma201813404152.

3. Saakyan S.V., Tsygankov A.Y., Amiryan A.G. Vital prognosis in patients with ciliochorioidal melanoma. Head and Neck, 2016, vol. 1-2, pp. 20-23 (In Russ).

4. Grishina E.E., Kim I.D., Izotova E.N. Episcleral spread of ciliochoroidal melanoma following surgeries: a case report. Russian Journal of Clinical Ophthalmology, 2023, vol. 23, №2, pp. 107-110 (In Russ). doi: 10.32364/2311-7729-2023-23-2-107-110.

5. Panova I.E., Vorob'ov N.A., Samkovich E. V., Bykhovskii A.A., Martynova N.I., Svistunova E.M. Proton therapy for uveal melanoma (preliminary results). Fyodorov Journal of Ophthalmic Surgery, 2023, vol. 3S, pp. 90–101 (In Russ). doi: 10.25276/0235-4160-2023-3S-90-101.

6. Saakyan S.V., Chentsova E.V., Andreyeva T.A. Functional outcomes in patients with tumors of the iridociliary zone after block excision combined with simultaneous and postponed cataract extraction. Russian Ophthalmological Journal, 2010, vol. 3, № 1, pp. 23-28 (In Russ).

7. Lee S.M., Kim M. Surgical treatment of uveal melanoma: Exoresection versus endoresection. Taiwan J. Ophthalmol., 2025, vol. 6,15, №1, pp. 34-44. doi: 10.4103/tjo.TJO-D-24-00131.

8. Romano M.R., Ferrara M., Feo A., Merico A., Angi M. Optimizing Surgical Performance and Safety in Endoresection of Uveal Melanoma. Retina, 2025 Jun, vol. 1, 45, №6, pp. 1230-1235. doi: 10.1097/IAE.0000000000004273.

9. Banou L., Tsani Z., Arvanitogiannis K., Pavlaki M., Dastiridou A., Androudi S. Radiotherapy in Uveal Melanoma: A Review of Ocular Complications // Curr. Oncol., 2023 Jul, vol. 3, 30, №7, pp. 6374-6396. doi: 10.3390/curroncol30070470.

10. Fleury E., Pignol J.P., Kiliç E., Milder M., van Rij C., Naus N., Yavuzyigitoglu S., den Toom W., Zolnay A., Spruijt K., van Vulpen M., Trnková P., Hoogeman M. Comparison of stereotactic radiotherapy and protons for uveal melanoma patients. Phys. Imaging Radiat. Oncol., 2024 Jun, vol. 26, 31, p. 100605. doi: 10.1016/j.phro.2024.100605.

11. Panova I.E., Bikhovsky A.A., Samkovich E.V., Svistunova E.M. Glucocorticosteroids and Postradiation Macular Edema: Rationale for Choice of Therapy and Efficacy of Use. Ophthalmology in Russia, 2024, vol. 21, №3, pp. 533-539 (In Russ.) doi: 10.18008/1816-5095-2024-3-533-539.

12. Panova I.E., Svictunova E.M., Vorobyov N.A., Samkovich E.V., Martynova N.I., Bykhovsky A.A. Neovascular glaucoma as a complication of proton therapy for uveal melanoma. Russian Journal of Clinical Ophthalmology, 2024, vol. 21, № 4, pp. 185- 192 (In Russ). doi: 10.32364/2311-7729-2024-24-4-4.

13. Saakian S.V., Amirian A.G., Valsky V.V., Mironova I.S. Plaque radiotherapy for anterior uveal melanomas. Russian Annals of Ophthalmology, 2015, vol. 131, №2, pp. 5-12 (In Russ). doi: 10.17116/oftalma201513125-11.

14. Boiko E.V., Samkovich E.V., Panova I.E., Svistunova E.M., Ivanov A.A., Bikhovsky A.A. Hybrid photodynamic therapy as part of combined treatment for uveal melanoma (preliminary results). Ophthalmology in Russia, 2024, vol. 21, №4, pp. 755–763 (In Russ). doi: 10.18008/1816-5095-2024-4-755-763.

15. Belyj J.A., Tereshhenko A.V., Volodin P.L., Kaplan M.A. Fotodinamicheskaja terapija s fotosensibilizatorom Fotoditazin v oftal'mologii. Kaluga: MNTK "Mikrohirurgija glaza", 2008 (In Russ).

16. Zhyliayeva K.P., Demeshko P.D., Navumenka L.V., Krasny S.A., Tzerkovsky D.A., Zherko I.Yu. Photodynamic therapy of primary and recurrent forms of weakly pigment choroidal melanoma. Biomedical Photonics, 2022, vol. 11, №3, рр. 17-23 (In Russ). doi: 10.24931/2413-9432-2022-11-3-17-23.

17. Samkovich E.V., Panova I.E., Boiko E.V., Svistunova E.M., Bykhovskii A.A. Photodynamic therapy in the combined treatment of choroidal melanoma. Fyodorov Journal of Ophthalmic Surgery, 2024, vol. 139, №2, pp. 99–108 (In Russ). doi: 10.25276/0235-4160-2024-2-99-108.

18. Yordi S., Soto H., Bowen R.C., Singh A.D. Photodynamic therapy for choroidal melanoma: What is the response rate? Surv Ophthalmol, 2021 Jul-Aug, vol. 66, №4, pp. 552-559. doi: 10.1016/j.survophthal.2020.09.006.

19. Navumenka L.V., Zhyliayeva E.P. Transpupillary Photodynamic Therapy of the Uveal Melanoma. Ophthalmology. Eastern Europe, 2020, vol. 10, №4, pp. 489–500. doi: 10.34883/PI.2020.10.4.021.

20. Bely Yu.A., Tereshchenko A.V., Volodin P.L. Transpupillary photodynamic therapy of medium-sized choroidal melanoma with the drug «Photoditazine» (clinical case). Refractive surgery and ophthalmology, 2008, vol. 8, №1, pp. 22–26 (In Russ).

21. Panova I.E., Boiko E.V., Samkovich E.V., Gvazava V.G. Isolated Transpupillary Photodynamic Therapy in Local Treatment of Choroidal Melanoma. Ophthalmology in Russia, 2025, vol.22, №1, pp. 159-168 (In Russ). doi: 10.18008/1816-5095-2025-1-159-168.

22. Boiko E.V., Samkovich E.V., Panova I.E., Shevchenko S.B., Vorobyev S.L., Kalashnikova E.S., Masian E.A., Gvazava V.G. Transscleral Photodynamic Therapy with a Chlorin e6 Photosensitizer in a Rabbit Experimental Model of an Intraocular Mass Lesion: TSPDT in experimental ocular mass lesion model. Journal of Lasers in Medical Sciences, 2025, vol. 16, p. e26. Retrieved from https://journals.sbmu.ac.ir/jlms/article/view/47901.

23. Samkovich E.V., Boiko E.V., Panova I.E., Vorobiev S.L., Bikhovsky A.A., Masian E.A. Experimental and morphological justification of approaches to hybrid photodynamic therapy of uveal melanoma. Voprosy Onkologii = Problems in Oncology, 2025, vol. 71, № 2, pp. 325-333 (In Russ). doi: 10.37469/0507-3758-2025-71-2-325-333.

24. Li X., Lovell J.F., Yoon J., Chen X. Clinical development and potential of photothermal and photodynamic therapies for cancer. Nat Rev Clin Oncol, 2020, vol. 17, №11, pp.657-674. doi: 10.1038/s41571-020-0410-2.

25. Grin M., Suvorov N., Ostroverkhov P., Pogorilyy V., Kirin N., Popov A., Sazonova A., Filonenko A. Advantages of combined photodynamic therapy in the treatment of oncological diseases. Biophysical Reviews, 2022, vol. 14, № 4, pp. 941-963. doi: 10.1007/s12551-022-00962-6.

26. Lim H.S. Reduction of thermal damage in photodynamic therapy by laser irradiation techniques. J. Biomed. Opt., 2012, vol. 17, №12, p. 128001. doi: 10.1117/1.JBO.17.12.128001.

27. Blasi M.A., Pagliara M.M., Lanza A., Sammarco M.G., Caputo C.G., Grimaldi G., Scupola A. Photodynamic Therapy in Ocular Oncology. Biomedicines, 2018, vol. 6, №1, p. 17. doi: 10.3390/biomedicines6010017.

28. Zhou Z., Song J., Nie L., Chen X. Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy. Chem Soc Rev, 2016, vol. 21, 45, №23, pp. 6597- 6626. doi: 10.1039/c6cs00271d.

29. Stranadko E.F., Baranov A.V., Duvansky V.A., Lobakov A.I., Morokhotov V.A., Riabov M.V. Photodynamic therapy of cancer of large duodenal papilla and extrahepatic bile ducts. Biomedical Photonics, 2020, vol. 9, №2, pp. 18-28. doi: 10.24931/2413-9432-2020-9-2-18-28.

30. Panova I.E., Samkovich E.V., Nechiporenko P.A. Doppler ultrasound in the assessment of blood supply to choroidal melanoma: parallels with contrast angiography and histography. Russian Annals of Ophthalmology, 2023, vol. 139, №1, pp. 27-34 (In Russ). doi: 10.17116/oftalma202313901127.

31. Patent 2745691 C1 Russian Federation, IPC A61B 8/10, A61F 9/00. Method for assessing the vascularization of choroidal melanoma based on its acoustic density: no. 2020125755: filed 03.08.2020: publ. 30.03.2021 / E. V. Boiko, I. E. Panova, E. V. Samkovich; applicant Federal State Autonomous Institution "National Medical Research Center "Interbranch Scientific and Technical Complex "Eye Microsurgery" named after Academician S.N. Fedorov" of the Ministry of Health of the Russian Federation.

32. Quirk B.J., Brandal G., Donlon S., Vera J.C., Mang T.S., Foy A.B., Lew S.M., Girotti A.V., Jogal S., LaViolette P.S., Connely J.M., Whelan H.T. Photodynamic therapy (PDT) for malignant brain tumors--where do we stand? Photodiagnosis Photodyn. Ther., 2015, vol. 12, №3, pp. 530-44. doi: 10.1016/j.pdpdt.2015.04.009.

33. Ferreira J., Menezes P.F.C., Sibata C.H., Allison R.R., Zucoloto S., Castro e Silva J.R.O. et al. Can efficiency of the photosensitizer be predicted by its photostability in solution? Laser Phys, 2009, p. 1-7. doi: 10.1590/S1516-80342009000100003.

34. Kwiatkowski S., Knap B., Przystupski D., Saczko J., Kędzierska E., Knap-Czop K. et al. Photodynamic therapy – mechanisms, photosensitizers and combinations. Biomed. Pharmacother., 2018, vol. 106, pp. 1098-1107. doi: 10.1016/j.biopha.2018.07.049.

35. Filonenko E.V. Clinical implementation and scientific development of photodynamic therapy in Russia in 2010-2020. Biomedical Photonics, 2021, vol.10, №4, pp.4-22 (In Russ). doi: 10.24931/2413-9432-2021-9-4-4-22.

36. Dereski M.O., Chopp M., Garcia J.H., Hetzel F.W. Depth measurements and histopathological characterization of photodynamic therapy generated normal brain necrosis as a function of incident optical energy dose. Photochem. Photobiol., 1991 Jul, vol. 54, №1, pp. 109-12. doi: 10.1111/j.1751-1097.1991.tb01992.x.

37. Muller P.J., Wilson B.C. An update on the penetration depth of 630 nm light in normal and malignant human brain tissue in vivo. Phys. Med. Biol., 1986 Nov, vol. 31, №11, pp. 1295-7. doi: 10.1088/0031-9155/31/11/012.