Abstract
AIMS/BACKGROUND--Neovascularisation occurs in many major ocular diseases such as diabetes, age-related macular degeneration, and sickle cell disease. Laser photocoagulation is typically used to obliterate the vessels but it also causes severe damage to adjacent normal tissues. This is a very significant limitation especially in the treatment of choroidal neovascularisation which often covers large areas of the posterior pole and the fovea. A method, laser targeted delivery, has been developed capable of releasing drugs locally and non-invasively in the choroidal or retinal vasculature. This method could be used to target a photo-sensitiser to neovascular membranes and cause their selective occlusion by irradiating them. The targeting properties of the method promise to yield a treatment for neovascularisation that does not damage adjacent tissues and thus preserves vision. The purpose of the present study was to test the feasibility of occluding ocular vessels with this method. METHOD--The iris vessels of the albino rat were chosen because the treatment could be assessed unequivocally and followed with time. Aluminium phthalocyanine tetrasulphonate was encapsulated in heat sensitive liposomes and administered systemically. The iris vessels were irradiated with a yellow laser to raise their temperature to 41 degrees C, cause a phase transition in the liposomes and thereby locally release the photosensitiser. The laser was also used to excite the released photosensitiser and cause occlusion. The effect was monitored immediately and for 8 months thereafter. Controls for the effect of the laser and the unencapsulated drug were conducted. RESULTS--The results demonstrated that occlusion can be achieved and sustained for the period of follow up. The controls showed that the effect was not due to heat or to the activation of the low dose of free drug. CONCLUSION--These preliminary findings indicate that laser targeted photo-occlusion is a promising new method for the treatment of neovascularisation.
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- Bebie H., Fankhauser F., Lotmar W., Roulier A. Theoretical estimate of the temperature within irradiated retinal vessels. Acta Ophthalmol (Copenh) 1974;52(1):13–36. doi: 10.1111/j.1755-3768.1974.tb00351.x. [DOI] [PubMed] [Google Scholar]
- Ferris F. L., 3rd Senile macular degeneration: review of epidemiologic features. Am J Epidemiol. 1983 Aug;118(2):132–151. doi: 10.1093/oxfordjournals.aje.a113624. [DOI] [PubMed] [Google Scholar]
- Gabizon A., Peretz T., Sulkes A., Amselem S., Ben-Yosef R., Ben-Baruch N., Catane R., Biran S., Barenholz Y. Systemic administration of doxorubicin-containing liposomes in cancer patients: a phase I study. Eur J Cancer Clin Oncol. 1989 Dec;25(12):1795–1803. doi: 10.1016/0277-5379(89)90350-7. [DOI] [PubMed] [Google Scholar]
- Guran T., Zeimer R. C., Shahidi M., Mori M. T. Quantitative analysis of retinal hemodynamics using targeted dye delivery. Invest Ophthalmol Vis Sci. 1990 Nov;31(11):2300–2306. [PubMed] [Google Scholar]
- Kiryu J., Shahidi M., Mori M. T., Ogura Y., Asrani S., Zeimer R. Noninvasive visualization of the choriocapillaris and its dynamic filling. Invest Ophthalmol Vis Sci. 1994 Sep;35(10):3724–3731. [PubMed] [Google Scholar]
- Kliman G. H., Puliafito C. A., Grossman G. A., Gregory W. A. Retinal and choroidal vessel closure using phthalocyanine photodynamic therapy. Lasers Surg Med. 1994;15(1):11–18. doi: 10.1002/lsm.1900150104. [DOI] [PubMed] [Google Scholar]
- Kliman G. H., Puliafito C. A., Stern D., Borirakchanyavat S., Gregory W. A. Phthalocyanine photodynamic therapy: new strategy for closure of choroidal neovascularization. Lasers Surg Med. 1994;15(1):2–10. doi: 10.1002/lsm.1900150103. [DOI] [PubMed] [Google Scholar]
- Kreimer-Birnbaum M. Modified porphyrins, chlorins, phthalocyanines, and purpurins: second-generation photosensitizers for photodynamic therapy. Semin Hematol. 1989 Apr;26(2):157–173. [PubMed] [Google Scholar]
- Leibowitz H. M., Krueger D. E., Maunder L. R., Milton R. C., Kini M. M., Kahn H. A., Nickerson R. J., Pool J., Colton T. L., Ganley J. P. The Framingham Eye Study monograph: An ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and visual acuity in a general population of 2631 adults, 1973-1975. Surv Ophthalmol. 1980 May-Jun;24(Suppl):335–610. [PubMed] [Google Scholar]
- Mayhew E., Ito M., Lazo R. Toxicity of non-drug-containing liposomes for cultured human cells. Exp Cell Res. 1987 Jul;171(1):195–202. doi: 10.1016/0014-4827(87)90262-x. [DOI] [PubMed] [Google Scholar]
- Miller H., Miller B. Photodynamic therapy of subretinal neovascularization in the monkey eye. Arch Ophthalmol. 1993 Jun;111(6):855–860. doi: 10.1001/archopht.1993.01090060145039. [DOI] [PubMed] [Google Scholar]
- Ogura Y., Guran T., Shahidi M., Mori M. T., Zeimer R. C. Feasibility of targeted drug delivery to selective areas of the retina. Invest Ophthalmol Vis Sci. 1991 Jul;32(8):2351–2356. [PubMed] [Google Scholar]
- Pallikaris I. G., Tslimbaris M. K., Iliaki O. E., Naoumidi I. I., Georgiades A., Panagopoulos I. A. Effectiveness of corneal neovascularization photothrombosis using phthalocyanine and a diode laser (675 nm). Lasers Surg Med. 1993;13(2):197–203. doi: 10.1002/lsm.1900130207. [DOI] [PubMed] [Google Scholar]
- Panagopoulos J. A., Svitra P. P., Puliafito C. A., Gragoudas E. S. Photodynamic therapy for experimental intraocular melanoma using chloroaluminum sulfonated phthalocyanine. Arch Ophthalmol. 1989 Jun;107(6):886–890. doi: 10.1001/archopht.1989.01070010908039. [DOI] [PubMed] [Google Scholar]
- Perez-Soler R., Lopez-Berestein G., Lautersztain J., al-Baker S., Francis K., Macias-Kiger D., Raber M. N., Khokhar A. R. Phase I clinical and pharmacological study of liposome-entrapped cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II). Cancer Res. 1990 Jul 15;50(14):4254–4259. [PubMed] [Google Scholar]
- Rahman A., Treat J., Roh J. K., Potkul L. A., Alvord W. G., Forst D., Woolley P. V. A phase I clinical trial and pharmacokinetic evaluation of liposome-encapsulated doxorubicin. J Clin Oncol. 1990 Jun;8(6):1093–1100. doi: 10.1200/JCO.1990.8.6.1093. [DOI] [PubMed] [Google Scholar]
- Reed M. W., Miller F. N., Wieman T. J., Tseng M. T., Pietsch C. G. The effect of photodynamic therapy on the microcirculation. J Surg Res. 1988 Nov;45(5):452–459. doi: 10.1016/0022-4804(88)90195-3. [DOI] [PubMed] [Google Scholar]
- Roberts W. G., Smith K. M., McCullough J. L., Berns M. W. Skin photosensitivity and photodestruction of several potential photodynamic sensitizers. Photochem Photobiol. 1989 Apr;49(4):431–438. doi: 10.1111/j.1751-1097.1989.tb09191.x. [DOI] [PubMed] [Google Scholar]
- Rosenthal I. Phthalocyanines as photodynamic sensitizers. Photochem Photobiol. 1991 Jun;53(6):859–870. doi: 10.1111/j.1751-1097.1991.tb09900.x. [DOI] [PubMed] [Google Scholar]
- Schmidt S., Wagner U., Oehr P., Krebs D. Klinischer Einsatz der photodynamischen Therapie bei gynäkologischen Tumorpatienten--Antikörper-vermittelte photodynamische Lasertherapie als neues onkologisches Behandlungsverfahren. Zentralbl Gynakol. 1992;114(6):307–311. [PubMed] [Google Scholar]
- Subfoveal neovascular lesions in age-related macular degeneration. Guidelines for evaluation and treatment in the macular photocoagulation study. Macular Photocoagulation Study Group. Arch Ophthalmol. 1991 Sep;109(9):1242–1257. [PubMed] [Google Scholar]
- Vosika G. J., Cornelius D. A., Gilbert C. W., Sadlik J. R., Bennek J. A., Doyle A., Hertsgaard D. Phase I trial of ImmTher, a new liposome-incorporated lipophilic disaccharide tripeptide. J Immunother (1991) 1991 Aug;10(4):256–266. doi: 10.1097/00002371-199108000-00004. [DOI] [PubMed] [Google Scholar]
- Zeimer R. C., Guran T., Shahidi M., Mori M. T. Visualization of the retinal microvasculature by targeted dye delivery. Invest Ophthalmol Vis Sci. 1990 Aug;31(8):1459–1465. [PubMed] [Google Scholar]
- Zeimer R. C., Khoobehi B., Niesman M. R., Magin R. L. A potential method for local drug and dye delivery in the ocular vasculature. Invest Ophthalmol Vis Sci. 1988 Jul;29(7):1179–1183. [PubMed] [Google Scholar]
- Zeimer R. C., Khoobehi B., Peyman G., Niesman M. R., Magin R. L. Feasibility of blood flow measurement by externally controlled dye delivery. Invest Ophthalmol Vis Sci. 1989 Apr;30(4):660–667. [PubMed] [Google Scholar]


