Photodynamic Therapy (PDT), introduced to ophthalmology in 2000, is a therapeutic procedure which utilizes the photosensitive intravenous drug, verteporfin (Visudyne, Bausch & Lomb) in combination with a low power, long duration infrared laser. In the eye, it is used to treat vascular issues in the retina and choroid. It was first indicated for neovascular age related macular degeneration (AMD), with large randomized clinical trials showed an improvement in visual acuity versus placebo. Photodynamic therapy’s role in ophthalmology was spurred by the success of the treatment of AMD with PDT (TAP) and Verteporfin in PDT (VIP) studies. The studies proved PDT’s efficacy in treating AMD patients with classical subfoveal choroidal neovascularization. As new therapies have evolved, it is now typically used as a second-line treatment for neovascular AMD. PDT is now most often used to effectively treat cases of Central Serous Retinopathy (CSR) and have been shown to be efficacious by several published studies.
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PDT first requires the intravenous administration of a photosensitizer, followed by the administration of nonthermal red light into the affected eye. After light is absorbed by the photosensitizer, it is transformed to its excited state. Oxygen, highly reactive, short-lived singlet oxygen, and reactive oxygen radicals are generated, causing local photo-oxidative damage because of its short life time. This damage is induced by an effect on nucleic acid, enzymes, and cellular membranes, and is caused by both cellular and vascular, and immunological mechanisms. For the effect to be induced, the three most important parameters to be taken into account are the characteristics of the photosensitizer, the involved tissue, and treatment parameters. Aside from preference of verteporfin to accumulate in areas of abnormal neovascularization, verteporfin also appears to accumulate in the choroidal vasculature. For CSC, PDT is thought to lead to short-term hypoperfusion of the choriocapillaris and to longterm remodeling of choroidal vasculature, resulting in a reduction of leakage of fluid to under the retina. The latter mechanism is of special interest in the treatment of CSC, because the disease primarily affects the choroidal circulation, resulting in areas of choroidal vascular hyperpermeability that might finally result in the accumulation of subretinal fluid (SRF).
Before performing PDT, the pupil of the treated eye requires dilation, for instance with 1.0% tropicamide and 2.5% phenylephrine. Subsequently, an intravenous infusion of verteporfin is administered over a period of 10 minutes.
For half-dose PDT, 3mg/m2 verteporfin is used, while 6mg/m2 is given for PDT with using half the standard fluence (half-fluence PDT), half the standard treatment time (half-time), or nonreduced standard (full) settings. Fifteen minutes after the start of the infusion, an anesthetic eye drop is given (oxybuprocaine 0.4% or equivalent), a contact lens (a Volk PDT lens) is positioned on the eye that requires treatment, and the aiming beam of the laser is focused on the treatment area. The magnification factor should be considered in the settings of the PDT machine. For indocyanine green angiography (ICGA)-guided PDT, the area of treatment is chosen based on the hyperfluorescent areas on mid-phase ICGA(approximately 10–15minutes) that often roughly corresponds to the areas with SRF on optical coherence tomography (OCT), as well as the areas of leakage on the midphase fluorescein angiogram (FA; approximately 3minutes). The area of the aiming beam corresponds to the area of the subsequent laser spot area. The spot size can be defined based on the diameter of the hyperfluorescent area on ICGA. In cases with separated multifocal areas of active SRF leakage, multiple treatment spots can be applied to the additional areas immediately after the first treatment, taking care that the macular area should be treated first after verteporfin infusion.
Although most studies have performed ICGA-guided PDT, aiming to treat the underlying—supposedly primarily abnormal—choroid/choriocapillaris, some authors also have described good results with PDT guided by hyperfluorescent leaking (hot spot) areas on FA. As choroidal abnormalities on ICGA often are more extensive than areas of leakage on FA, a potential risk in FA-guided PDT is under-treatment because smaller treatment spots tend to be used. It has been advocated to keep the edge of a treatment spot at least 200μm away from the optic disc rim, to prevent potential damaging effects of PDT to the optic disc, but evidence suggests that this is not necessary. In half-dose PDT, the treatment is performed with standard fluency (50 J/cm2 ; can be reduced to 25 J/cm2 in a half-fluence treatment protocol), a PDT laser wavelength of 689 nm, and a standard treatment duration of 83 seconds (can be reduced to 42seconds in a half-time treatment protocol). Treatment must be performed at 15 minutes after the start of the verteporfin infusion to maximize the localization of the effect of treatment to the choroid and minimize possible damage to the adjacent retinal structures.
No studies regarding the recommended minimum time period between ICGA and PDT treatment have been conducted yet.
Although the exact number is not known, it is suggested that 15%–50% of patients with acute CSC might experience one or more recurrences or persistent SRF within the first year after onset of symptoms. Because PDT has been shown to be effective in acute CSC, it is now often used in cases with persistent SRF for more than 3 months. A recent study by Mohabati et al. showed that acute CSC cases that received early PDT treatment had a significantly lower number of SRF recurrences during long-term follow-up (4% recurrences in PDT-treated patients versus 24% recurrences in untreated patients), and similar findings previously were reported by Ozkaya et al. (Mohabati et al., under review).
In summary, there is strong evidence that PDT with reduced settings in acute CSC is effective in resolving SRF and improving vision, and early PDT also could reduce the number of recurrences. Long-term follow-up studies in chronic CSC (cCSC) cases that underwent PDT treatment have proven that PDT is a safe intervention. It might be expected that this is also true for PDT in acute CSC.
In 2018, the results of the PLACE trial—the first large prospective multicenter randomized controlled treatment trial for cCSC—were published. In this European investigator initiated study by Van Dijk et al., ICGA-guided half-dose PDT was compared to ICGA-guided high-density subthreshold micropulse laser treatment. The results clearly showed superiority of half-dose PDT over micropulse laser treatment. With regard to the primary end point of complete resolution of SRF, 67% of cases achieved complete resolution after half-dose PDT at final follow-up as compared to 29% of patients who received micropulse laser in the PLACE trial.
Editors: Jay Chhablani
eBook ISBN: 9780128173015
Paperback ISBN: 9780128168004
Imprint: Academic Press
Published Date: 19th March 2019
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