treating a range of lesion types, including predominantly classic lesions and occult with no classic subfoveal lesions. A combined analysis of the two main VPDT studies showed that VPDT can be used to treat lesions of £4 DA. Finally, subfoveal minimally classic lesions that meet additional criteria may, in some cases, be managed successfully with VPDT.

13.5Safety and Adverse Events

13.5.1 Laser Photocoagulation

Despite the promise that laser photocoagulation offered for some patients, the benefits were inconsistent. Photocoagulation of the fovea was rare, but did not destroy a large central retinal area. The pain level depended on the wavelength (absorption), the duration of application (pulse length) and the level of energy applied. The occurrence of deep bleeding is due to the perforation of the wall of a newly formed capillary and immediate closure of the vessel can be obtained by proceeding with thermal photocoagulation.

Retinal function is directly damaged by thermal energy, with immediate and irreversible scotoma at the site of laser light application. An increased risk of foveal impact exists, inducing an immediate visual loss. The precise location of the xanthophyll pigment on a blue light frame can avoid accidental burns as well as inadequate location. Recurrences were frequent (Figs. 13.5 and 13.6). In 1990, the MPS group also showed that when patients were treated with krypton red laser photocoagulation, one third would have persistent neovascularization within 6 weeks of the initial treatment, and 47% would have recurrent neovascularization within 5 years. Thus, despite the complete destruction of the neovascular membrane, a successful course of treatment may be followed by recurrences, which represent the main complication of coagulation therapy. Both persistent and recurrent disease was associated with severe vision loss.

Laser photocoagulation was applicable only for lesions that can be clearly defined in the early phase of fluorescein angiography. One should bear in mind that these results were obtained before the recognition of subepithelial occult CNV and are based only on FA. It is probable that the results would be better with the use of the actual diagnostic technologies and based on improved knowledge.

Fig. 13.9 Indocyanine green angiography. (a) Before PDT with large central vessels visible within a hypofluorescent area. (b) After PDT (1 h) profuse leakage of dye demonstrating the alterations of the endothelial cells of the new vessels

13.5.2 Photodynamic Therapy

The presence of porphyria or hypersensitivity to the porphyrin or severe hepatic insufficiency is an absolute con- tra-indication for the realization of PDT with verteporfin.

Some drugs could influence the results of the treatment. Calcium channel blockers and polymyxin B can increase the concentration of verteporfin in the vascular endothelium. Alternatively, some frequently used photosensitizing drugs, such as tetracycline, sulfonylurea, and diuretics can increase the possibilities of an undesirable skin photoreaction. Other agents can reduce the activity of verteporfin: antioxidants neutralize the free

radicals reactions and the inhibitors of the thromboxane A2 inhibit platelet aggregation.

Adverse events were reported more frequently with verteporfin therapy than with placebo and occurred in 1–10% of patients. Most were transient and spontaneously resolutive as infusion-related back pain, photosensitivity reactions or visual alterations.

The early and transient leakage of ICG and accumulation of fluid on OCT could be related to the inflammatory response to its relative selectivity (Fig. 13.9). The morphological findings of choroidal closure correlate well with characteristic indocyanine green angiography features documented after standard verteporfin therapy. The choroidal hypofluorescence maximum at 1 week after treatment, comparable in

size with the treatment spot used, is regularly documented by indocyanine green angiography. At least partial reperfusion of the choriocapillaris is seen at 3 months’ follow-up however, repeated verteporfin therapy in patients treated in the TAP trial with PDT led to persistent choriocapillary non-perfusion in most eyes. Associated with choriocapillary occlusion, an angiogenic response with upregulation of vascular endothelial growth factor (VEGF) was documented in human eyes that could account for the CNV regrowth or repermeabilization.

A severe adverse event was a visual decrease of more than three lines with or without subretinal, retinal or vitreous hemorrhage, due to either subretinal bleeding (Fig. 13.10) or retinal pigment epithelial tear. The