Photodynamic Therapy for Focal RPE Leaks

Abstract

I read Ober et al’s article on photodynamic therapy for focal retinal pigment epithelial (RPE) leaks secondary to central serous chorioretinopathy (CSC)1Ober M.D. Yannuzzi L.A. Do D.V. et al.Photodynamic therapy for focal retinal pigment epithelial leaks secondary to central serous chorioretinopathy.Ophthalmology. 2005; 112: 2088-2094Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar with interest.My personal experience using photodynamic therapy with verteporfin to treat subfoveal focal RPE leaks has been encouraging. We conducted a small, prospective, uncontrolled interventional trial involving 19 patients, each of whom presented with acute CSC. None of the cases presented with subretinal hemorrhage. All cases underwent indocyanine green angiography to exclude underlying polypoidal choroidal vasculopathy. Baseline readings of visual acuity (VA), optical coherence tomography, and fluorescein angiography were performed. All patients had photodynamic therapy with verteporfin (6 mg/m2 body surface area) but with reduced fluence (300 mW/cm2 over 83 seconds). All other parameters were in accordance with standard protocols used in the treatment of choroidal neovascularization.2Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study GroupPhotodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials—TAP report.Arch Ophthalmol. 1999; 117: 1329-1345Crossref PubMed Scopus (1734) Google Scholar The minimum follow-up period was 6 months.To summarize our early results, we treated 16 male and 3 female patients with a mean age of 32.4 years (range, 23–45). All patients had neurosensory detachment at the macula, resulting from focal leakage at the level of the RPE beneath the fovea. Most patients demonstrated unifocal leaks, with the exception of 2 cases. None of the patients showed subretinal hemorrhage at baseline. Indocyanine green angiography excluded underlying polypoidal choroidal vasculopathy. Other relevant baseline data included mean initial VA of 20/50 and mean foveal thickness of 357 μm. At 6 months after photodynamic therapy, mean VA was 20/25 and mean foveal thickness was 198 μm. Both end points statistically differed from baseline values. There was complete resolution of macular fluid in all but 2 cases with a single treatment. One of the latter cases required a second treatment before resolution; the other developed secondary choroidal neovascularization, which subsequently responded to PDT with full fluence (2 treatment sessions) (Fig 1 [available at http://aaojournal.org]).Figure 1A, Pretreatment fundus photograph and fluorescein angiography showing subfoveal smokestack pattern acute central serous chorioretinopathy (CSC). B, Pretreatment indocyanine green angiogram excluding underlying polypoidal choroidal vasculopathy. Later diffuse choroidal hyperpermeability supports a diagnosis of CSC. C, Three months after low-fluence photodynamic therapy for acute CSC, a subfoveal hemorrhage from secondary choroidal neovascularization was observed.View Large Image Figure ViewerDownload (PPT)The rationale for using photodynamic therapy to close focal RPE leakage points in CSC is still unclear. However, the current understanding of the pathogenesis of CSC is not centered on the RPE leak, but rather on the concept of choroidal hyperpermeability. Chan et al described choroidal vascular remodeling in patients with chronic CSC, in which photodynamic therapy effected a reduction in vascular caliber and resolution of late leakage on indocyanine green angiography.3Chan W.M. Lam D.S. Lai T.Y. et al.Choroidal vascular remodelling in central serous chorioretinopathy after indocyanine green guided photodynamic therapy with verteporfin: a novel treatment at the primary disease level.Br J Ophthalmol. 2003; 87: 1453-1458Crossref PubMed Scopus (316) Google Scholar We propose that the reason for photodynamic therapy’s effectiveness in acute CSC is based on the ability to reduce choroidal congestion and hyperpermeability, to the point that there is no longer focal RPE decompensation. The use of low fluence energy in PDT has been described in the treatment of occult choroidal neovascularization.4Visudyne in Minimally Classic Choroidal Neovascularization Study GroupVerteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial.Arch Ophthalmol. 2005; 123: 448-457Crossref PubMed Scopus (193) Google Scholar There is histological evidence that lower fluences result in reduced recruitment of inflammatory cells and release of cytokines, as well as less extensive and prolonged choriocapillaris closure.5Xu T. Li Y. Wu X. Application of lower fluence rate for less microvasculature damage and greater cell-killing during photodynamic therapy.Lasers Med Sci. 2004; 19: 150-154Crossref PubMed Scopus (7) Google Scholar There is also suggestion that vascular endothelial growth factor upregulation and release after PDT may be minimized by using low fluence.6Schmidt-Erfurth U. Schlotzer-Schrehard U. Cursiefen C. et al.Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor.Invest Ophthalmol Vis Sci. 2003; 44: 4473-4480Crossref PubMed Scopus (317) Google Scholar Because there is little if any neovascular drive in CSC, a minor alteration to choroidal hemodynamics may be all that is required for resolution.It would be interesting to observe the effects of intravitreal anti–vascular endothelial growth factor agents such as pegaptanib on choroidal hyperpermeability in CSC. I read Ober et al’s article on photodynamic therapy for focal retinal pigment epithelial (RPE) leaks secondary to central serous chorioretinopathy (CSC)1Ober M.D. Yannuzzi L.A. Do D.V. et al.Photodynamic therapy for focal retinal pigment epithelial leaks secondary to central serous chorioretinopathy.Ophthalmology. 2005; 112: 2088-2094Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar with interest. My personal experience using photodynamic therapy with verteporfin to treat subfoveal focal RPE leaks has been encouraging. We conducted a small, prospective, uncontrolled interventional trial involving 19 patients, each of whom presented with acute CSC. None of the cases presented with subretinal hemorrhage. All cases underwent indocyanine green angiography to exclude underlying polypoidal choroidal vasculopathy. Baseline readings of visual acuity (VA), optical coherence tomography, and fluorescein angiography were performed. All patients had photodynamic therapy with verteporfin (6 mg/m2 body surface area) but with reduced fluence (300 mW/cm2 over 83 seconds). All other parameters were in accordance with standard protocols used in the treatment of choroidal neovascularization.2Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study GroupPhotodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials—TAP report.Arch Ophthalmol. 1999; 117: 1329-1345Crossref PubMed Scopus (1734) Google Scholar The minimum follow-up period was 6 months. To summarize our early results, we treated 16 male and 3 female patients with a mean age of 32.4 years (range, 23–45). All patients had neurosensory detachment at the macula, resulting from focal leakage at the level of the RPE beneath the fovea. Most patients demonstrated unifocal leaks, with the exception of 2 cases. None of the patients showed subretinal hemorrhage at baseline. Indocyanine green angiography excluded underlying polypoidal choroidal vasculopathy. Other relevant baseline data included mean initial VA of 20/50 and mean foveal thickness of 357 μm. At 6 months after photodynamic therapy, mean VA was 20/25 and mean foveal thickness was 198 μm. Both end points statistically differed from baseline values. There was complete resolution of macular fluid in all but 2 cases with a single treatment. One of the latter cases required a second treatment before resolution; the other developed secondary choroidal neovascularization, which subsequently responded to PDT with full fluence (2 treatment sessions) (Fig 1 [available at http://aaojournal.org]). The rationale for using photodynamic therapy to close focal RPE leakage points in CSC is still unclear. However, the current understanding of the pathogenesis of CSC is not centered on the RPE leak, but rather on the concept of choroidal hyperpermeability. Chan et al described choroidal vascular remodeling in patients with chronic CSC, in which photodynamic therapy effected a reduction in vascular caliber and resolution of late leakage on indocyanine green angiography.3Chan W.M. Lam D.S. Lai T.Y. et al.Choroidal vascular remodelling in central serous chorioretinopathy after indocyanine green guided photodynamic therapy with verteporfin: a novel treatment at the primary disease level.Br J Ophthalmol. 2003; 87: 1453-1458Crossref PubMed Scopus (316) Google Scholar We propose that the reason for photodynamic therapy’s effectiveness in acute CSC is based on the ability to reduce choroidal congestion and hyperpermeability, to the point that there is no longer focal RPE decompensation. The use of low fluence energy in PDT has been described in the treatment of occult choroidal neovascularization.4Visudyne in Minimally Classic Choroidal Neovascularization Study GroupVerteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial.Arch Ophthalmol. 2005; 123: 448-457Crossref PubMed Scopus (193) Google Scholar There is histological evidence that lower fluences result in reduced recruitment of inflammatory cells and release of cytokines, as well as less extensive and prolonged choriocapillaris closure.5Xu T. Li Y. Wu X. Application of lower fluence rate for less microvasculature damage and greater cell-killing during photodynamic therapy.Lasers Med Sci. 2004; 19: 150-154Crossref PubMed Scopus (7) Google Scholar There is also suggestion that vascular endothelial growth factor upregulation and release after PDT may be minimized by using low fluence.6Schmidt-Erfurth U. Schlotzer-Schrehard U. Cursiefen C. et al.Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor.Invest Ophthalmol Vis Sci. 2003; 44: 4473-4480Crossref PubMed Scopus (317) Google Scholar Because there is little if any neovascular drive in CSC, a minor alteration to choroidal hemodynamics may be all that is required for resolution. It would be interesting to observe the effects of intravitreal anti–vascular endothelial growth factor agents such as pegaptanib on choroidal hyperpermeability in CSC. Author replyOphthalmologyVol. 113Issue 11PreviewWe thank Dr Koh for his thoughtful response and knowledgeable analysis of the proposed mechanisms. We do not dispute that photodynamic therapy acts at the level of the choroid in normal eyes and those with choroidal neovascularization; however, the mechanism of action in central serous chorioretinopathy (CSC) remains unknown. Lower fluence levels for CSC treatment have not been well studied, but have been reported in uncontrolled patients with anecdotal success. It is possible that this type of treatment is adequate and may reduce the risk of photodynamic therapy–associated complications. Full-Text PDF