Current Role of Photodynamic Therapy in Ophthalmic Practice

Introduction Photodynamic therapy (PDT) is a form of lighttherapy using light-sensitive compounds that when exposed to light selectively become toxic to targeted cells (phototoxicity). Most PDT applications involve three components: a photosensitizer, a light source and tissue oxygen. The combination of these three components leads to chemical destruction of tissues which have taken-up the photosensitizer and have been locally exposed to light of appropriate wavelength to produce reactive oxygen species (ROS). These ROS are free radicals (Type I PDT) generated through electron abstraction or transfer from a substrate molecule and highly reactive state of oxygen known as singlet oxygen (Type II PDT). It is important to distinguish PDT from other light-based and laser therapies such as laser wound healing and rejuvenation, or intense pulsed light hair removal, which do not require a photosensitizer. PDT is used clinically to treat a wide range of medical conditions. The era of PDT in Ophthalmology was initiated by results of the TAP study. The first indication for which PDT was approved in ophthalmology was choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). The technique of administering PDT requires the combination of laser and photosensitizer Visudyne®. PDT utilizes photosensitizer Visudyne® [liposomal benzoporphyrin derivative monoacid ring A (BPDMA)] given via intravenous infusion at a dose of 6 mg/m of body surface area. Fifteen minutes after the infusion, the ‘standard’ protocol of focal light (light dose of 50 J/cm, irradiance of 600 mW/cm of 689 nm light over 83 seconds) is delivered. This treatment is ‘selective’ in that the photosensitizer is selectively taken up by the proliferating endothelial cells of the neovascular tissue thus leading to occlusion and reducing collateral damage. PDT was first recommended for cases of subfoveal classic or occult CNV in AMD. The approval of intravitreal Ranibizumab for treatment of CNV in AMD has led to decline in the use of PDT. The main advantage of anti-VEGF when compared with PDT is more improvement in BCVA (77% vs 28%) and less reduction in BCVA (21% vs 60%) at 2-year follow-up. PDT is currently recommended for CNV in AMD either refractory to anti-VEGF therapy or as monotherapy in patients with contraindications for anti-VEGF therapy. The PDT use in myopic CNV was established by the results of the VIP reports 1 and 2 where reduction in BCVA was less with PDT as compared to placebo (36% patients lost at least eight EDTRS letters as compared to 51% with placebo) while more number of patients had improvement in BCVA (improvement in BCVA of at least five ETDRS letters was seen in 40% with PDT as compared to 13% with placebo) at 24-month follow-up. Currently, PDT is recommended for use in myopic CNV in cases where anti-VEGF has been ineffective or is contraindicated. In patients with CNV due to angioid streaks, stability in BCVA is achieved with the use of PDT. However, the success rate achieved with anti-VEGF in angioid streaks by Browning et al. tilted the balance towards anti-VEGF as the preferred modality of treatment. PDT has also been used with some success in cases of inflammatory CNV due to multifocal choroiditis, punctate inner choroidopathy (PIC) and toxoplasmosis. Polypoidal choroidal vasculopathy (PCV) is a disorder characterized by subretinal polypoidal vascular lesions. PDT was found to be successful in improving BCVA in 56% cases and maintaining vision in 31% cases of PCV. Currently, PDT is recommended for treatment of juxtafoveal and subfoveal PCV, alone or in combination with intravitreal Ranibizumab (0.5 mg/0.1 ml). Central serous chorioretinopathy (CSCR) is a disorder characterized by pigmentary epithelial detachment with subretinal fluid. The use of PDT is based on the rationale that primary choroidal hyperpermeability is the basic cause of CSCR. Treatment with PDT leads to visual improvement of ≥2 lines in 43% cases while loss of ≥2 lines of BCVA occurs in about 7.5%. cases. RPE atrophy seen in about 4% cases. Apart from retinal lesions, various ocular tumors have been treated with PDT with variable success rates. PDT is the one of the treatment alternatives in recurrent choroidal melanoma. PDT is also a good option for treatment of symptomatic choroidal nevi, especially in cases with subretinal fluid. However, despite resolution of subretinal fluid, it does not provide good local tumor control. The use of PDT in patients with retinal capillary hemangioblastomas achieves regression of the tumor, resolution of macular edema. However, improvement in BCVA is not always seen (around 50% cases). On the contrary, the use of PDT Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, 18 College Road, Chennai 600006, India