Author: Peyman, Gholam A
Date published: July 1, 2011
Photodynamic therapy (PDT) has been used successfully to treat choroidal neovascularization (CNV) secondary to high myopia, age-related macular degeneration (AMD), and ocular histoplasmosis syndrome (OHS).1-3 It entails the intravenous administration of verteporfin (Visudyne; Novartis AG, Basel, Switzerland). CNV membranes can be treated with a red diode laser (689 nm wavelength), administered to the CNV, locally activating the verteporfin in the area covered by the laser. The use of a nonthermal laser in photodynamic therapy (PDT) may avoid the risk of permanent destruction of the adjacent neurosensory retina as seen with conventional photocoagulation therapy.
The retinal pigment epithelium (RPE) and choriocapillaris, which together constitute the blood-retinal barrier (BRB),4 play a pivotal role in the viability and functionality of the neurosensory retina.5 RPE changes may adversely affect photoreceptor function and survival due to disruption of the BRB and leakage of fluid into the subretinal space. PDT has been shown to induce structural changes in the RPE both experimentally6-10 and clinically11-13. Observed changes in the RPE and choriocapillaris depend on light intensity, duration of exposure, concentration of the photosensitizer, and interval between dye administration and laser therapy.8
Mennel et al7 reported that the combination of a therapeutic concentration of verteporfin and application of non-thermal laser led to a morphologically and functionally detectable breakdown of the outer BRB function of the RPE without damage to RPE cells in vitro. However, they stated that increasing the concentration of verteporfin (2 mg/ml) resulted in RPE cell damage. Several factors were reported to influence verteporfin concentration adjacent to RPE cells including blood flow, low density lipoprotein (LDL) uptake, concentration of LDL receptors, size, location and type of CNV, and leakage. Persistent RPE cell destruction is more severe in younger subjects,11,12 which can be due to better perfusion (higher dosage of verteporfin at the RPE) as well as clearer media (greater activation of verteporfin by the laser)14. Animal models have revealed other factors which may influence the effectiveness of PDT including media opacity,14 intraocular pressure, location of treatment within the fundus, equivalent fluence (lower energy and longer duration), and retreatment as well as fundus pigmentation.15
The non-thermal laser used in PDT, like thermal lasers, can induce alterations in the RPE and breakdown of the BRB, resulting in dysfunction of the neurosensory retina. Such PDT-induced RPE damage might be reduced by individualized treatment that takes into account parameters such as media transparency, age and gender, and optimized laser energy dosage. For example, reduced-fluence PDT has been reported to be effective16-18 in terms of visual outcomes and safer than standard PDT regarding choroidal alterations17,19 as well as RPE changes.18 Sacu et al19 reported that reducedfluence PDT is more effective than standard photodynamic therapy. Additionally, Azab et al20 reported a 3-line loss of visual acuity in 14% of eyes assigned to reduced-fluence PDT as compared to 28% of eyes undergoing standard PDT.
PDT is now infrequently used as monotherapy for AMD; it is most often used in combination with other treatment modalities.21-25 Reduced laser dose and verteporfin concentration may be achieved by the simultaneous use of intravitreal triamcinolone26,27 or anti- vascular endothelial growth factor (VEGF) agents. The latter counteract the effect of VEGF,28,29 which is known to be increased in PDT-treated area.30,31 On the other hand, the addition of reduced laser dose PDT (12 or 25 J/cm2) to bevacizumab therapy has been shown to decrease the number of bevacizumab treatments.32
Peyman et al33 used indocyanine green (ICG) assisted oscillatory thermotherapy (OTT) at individualized subthreshold energy levels to elicit primarily a photodynamic effect from the laser while reducing the thermal effect. This was achieved by applying the predetermined subthreshold thermal energy level in an oscillatory mode instead of the standard stationary mode. OTT prevents accumulation of thermal energy in the tissues, permitting choriocapillary blood flow and convection to cool down heated tissues, thus avoiding potential photocoagulative damage. This approach allows treating the retina for an extended period of time, thereby providing more ICG-induced photodynamic effect.
In this pilot study, we studied the primary outcomes of oscillatory photodynamic therapy (OPDT) using verteporfin. We believe that the oscillatory mode allows more precise and customized treatment of the lesion. It provides flexibility in treating areas of pathology without extending treatment into unaffected tissues; at the same time it allows prolonged treatment over the neovascular membrane.
Consent for off-label treatment was obtained after consultation with the Ophthalmic Medical Insurance Company (OMIC). This prospective study was approved by the Tulane University Institutional Review Board. Seven eyes of 6 female patients underwent OPDT between September 2008 and December 2009. Underlying abnormalities included central serous retinopathy (CSR, 2 eyes), idiopathic CNV (2 eyes), CNV due to AMD (2 eyes), and peripapillary CNV from presumed OHS (1 eye). Two eyes (cases #3 and 6) had history of treatment with anti-VEGF agents and one eye (case #4) had frequent recurrences, initially treated with thermal laser as well as anti-VEGF therapy. Complete ophthalmologic examination at baseline, 2 weeks post-treatment, and monthly thereafter included assessment of visual acuity, fundus examination (non-contact 90-diopter lens), color fundus photographs, and optical coherence tomography (OCT). Fluorescein angiography (IMAGEnet System, Topcon, Tokyo, Japan) was performed at baseline and repeated based on clinical findings. Visual acuity was measured with a Snellen chart (CP-690, Nidek, Gamagori, Japan) calibrated for 20 feet (6 meters) by the line assignment method and converted to logMAR notations by the Standard Conversion Table for statistical analyses.
Intravenous verteporfin (6 mg/m2 body surface area) was infused over 10-minutes. The Zeiss Visulas 690s laser system (689-nm wavelength, Carl Zeiss Meditec Inc., Dublin, California, USA) was used to treat the lesion for 83 seconds (except case #5 who received 166 seconds of treatment). In all cases, an Area Centralis lens was applied and laser was delivered at a standard fluence of 600 mW/cm2 and dose of 50 mJ/cm2. During the procedure, the operator kept the fundus contact lens steady while oscillating the laser beam at 2-3 Hertz using a spot size equal to half the size of the lesion to cover the entire lesion. Precautions for exposure to light were reviewed with the patient, who was instructed to stay out of sunlight and excessive light exposure for 5 days. The treatment was well tolerated and no complications were observed.
Intravitreal injections of bevacizumab (1.25 mg) and dexamethasone (1 mg) were performed at the same session in 4 eyes with CNV. In one eye with recalcitrant idiopathic CNV and a possible episode of post-anti-VEGF stroke (case #4), intravitreal dexamethasone (360 mcg) and triamcinolone acetate (400 mcg) were injected.
Baseline variables are summarized in Table 1. Mean follow-up was 7.1 ± 5.1 months. Mean visual acuity improved from 0.87 ± 0.69 logMAR (20/160) to 0.58 ± 0.65 logMAR (20/80) after the procedure (Wilcoxon signed-rank test, P = 0.027, Table 1). Central subfoveal thickness on OCT decreased from 322.3 ± 62.1 µm at baseline to 240.1 ± 34.8 µm after the procedure (Wilcoxon signed-rank test, P = 0.018). Volumetric measurements in case #5 showed that pigment epithelial detachment/scar and subretinal fluid were significantly reduced.
There were no instances of infusion-related back pain, photosensitivity reactions, or injection site adverse events. Two representative cases are described below in detail.
The first patient was a 70-year-old lady with longstanding CSR in her left eye and no history of treatment. Pigment mottling was evident on color fundus photography with angiographic activity in the inferotemporal macula. Subretinal fluid was present on OCT with serous neurosensory detachment in the macula (Figures 1a-c). At baseline, visual acuity was 20/100 and OCT demonstrated central subfoveal thickness of 310 µm with loss of photoreceptor inner and outer segments. She was treated with OPDT and verteporfin (2400-µm spot size, 600 mW/cm2 fluence rate, and 50 mJ/cm2 dose for 83 seconds). After treatment, the serous detachment resolved and the patient remained clinically stable as determined by angiography and OCT (Figures 1d-e). Visual acuity improved to 20/40 without metamorphopsia and central subfoveal thickness was decreased to 180 µm. Due to disruption of the photoreceptor layer and RPE attenuation due to longstanding neurosensory detachment, recovery of visual acuity was incomplete. The patient remained stable up to 11 months.
This 34-year-old lady had mild myopia and reduced visual acuity in her left eye. She presented with a grayish subretinal lesion in the nasal fovea associated with subretinal hemorrhage, exudation and retinal thickening extending into the center of the fovea. Leakage and retinal thickening in the nasal fovea were confirmed with fluorescein angiography and OCT (Figures 2a-c). She was diagnosed with idiopathic choroidal neovascular membrane, which did not respond to an injection of intravitreal bevacizumab. At baseline, visual acuity was 20/40 and central subfoveal thickness was 263 µm. She was treated with OPDT and verteporfin (800-µm spot size for 83 seconds) as well as adjunctive intravitreal bevacizumab/ dexamethasone. After treatment the patient had a consolidated subretinal scar in the nasal fovea without persistent leakage on angiography, or fluid on OCT which demonstrated central subfoveal thickness of 250 µm (Figures 2d-f). The treated perifoveal retina showed relatively preserved photoreceptor structure on OCT. Visual acuity improved to 20/25 without metamorphopsia. There was no recurrence up to 5 months after treatment.
Herein, we report the preliminary outcomes of OPDT with a strong photosensitizer, verteporfin in 7 eyes with CNV or CSR. This report describes a novel application of PDT in an oscillatory fashion. The current realistic goal of PDT is to retard progression of CNV due to AMD and other causes, and possibly restore normal vision without causing significant scarring. We believe that oscillatory PDT reduces the risk of retinal pigment epithelial damage since it decreases total fluence which itself depends on the speed of the oscillation. By using small spot size and moving it over the treatment area, one can avoid treatment of healthy retina; this advantage is especially marked for irregularly shaped lesions.
The primary outcome measure in PDT studies is to assess the proportion of eyes that avoid moderate visual loss (loss of fewer than 3 lines or 15 letters).1 Our clinical outcomes with mean follow-up of 7 months showed that OPDT with verteporfin was successful in improving central vision in all eyes except one (case #7), in which the 1-line reduction in visual acuity could be attributed to progression of the disease or increased cataract. The remaining cases showed 37.4% improvement in visual acuity equivalent to 3 Snellen lines. Additionally, post-treatment findings on funduscopy, fluorescein angiography, and OCT were suggestive of cessation of vascular leakage as well as resolution of hemorrhage and subretinal fluid in all cases.
Cardinal features of PDT include the coexistence of a sensitizer, light, and oxygen. The main mechanism of action of PDT is vascular occlusion due to damage to endothelial cells and subsequent thrombosis of both neovascular and normal choriocapillaris.34,35 The response to PDT appears to be caused by a combination of direct cytotoxicity to vascular endothelial cells, subsequent platelet adhesion and degranulation, thrombosis, and vasoconstriction, leading to blood flow stasis and vaso-occlusion of the choriocapillaris. PDT exerts its cytotoxic effect by generation of reactive oxygen species, which can induce cell death either by apoptosis or necrosis; it can even initiate a remodeling response.34,35 This vascular reaction has been associated with variable damage to the RPE and photoreceptors.6-13
Application of the laser in an oscillatory fashion can potentially reduce damage to the RPE by reducing overall fluence. A laser beam with spot size of approximately one half the size of the lesion is moved 2-3 times per second in continuous fashion over the entire treatment area. The term fluence takes into account the energy level used for treatment, with laser spot and application time for coverage of the entire lesion in stationary fashion. It can be estimated that if the laser is in any particular spot for about 0.5 second during the 2 Hz oscillatory mode, total fluence is approximately reduced to half the standard method of application. The power setting in our series (600 mW/cm2) and application time (83 seconds) were equal to a standard protocol. No visible whitening or subsequent fibrotic reaction was observed from OPDT application. We used bevacizumab and dexamethasone in combination with OPDT for most of our patients.36 Dexamethasone, and in one case, triamcinolone acetate, was added to control the inflammatory response to laser therapy.29
Peyman et al15 showed that PDT retreatment resulted in progressive thinning of the neurosensory retina with loss of photoreceptor outer segments and nuclei in the rabbit eye. In the current study, no patient required retreatment and no significant loss of photoreceptors was observed on OCT. This outcome can be due to both the oscillatory mode of PDT application and triple therapy. Triple therapy significantly reduces the number of treatments.22,37-39 It is noteworthy that three treated eyes had been recalcitrant to previous anti-VEGF therapy (Table 1).
OPDT is an improved mode of applying standard treatment allowing greater activation of the photosensitizer and less cytotoxic damage to the neuroretina due to reduced fluence. This is evidenced by the lack of a "burn spot" or loss of photoreceptors on post-treatment color images, fluorescein angiography, and OCT. It is impossible to completely prevent the recurrence of CNV in choroidal disease, especially in AMD. Thus, there will likely be subjects who require retreatments. Standard PDT retreatments can cause scarring and fibrosis,40,41 but we expect this to be less likely with oscillatory PDT.
PDT with verteporfin has been effective for chronic CSR by improving visual acuity and reducing subretinal fluid.42-47 PDT treatment for CSR causes short-term choriocapillaris hypoperfusion and long-term choroidal vascular remodeling, leading to reduction in choroidal congestion, vascular hyperpermeability, and extravascular leakage.42,48,49 However, complications such as secondary CNV, persistent choriocapillaris hypoperfusion, and pigmentary RPE changes in the treated zone have been reported.42,46,50,51 Modified PDT protocols in terms of verteporfin dosage, fluence rate, time course of delivery, or a combination thereof have been suggested.52 Reibaldi et al53 showed that low-fluence PDT is effective in long-standing chronic CSR with foveal and gravitational atrophy of the retina and reported functional improvement without significant retinal or choroidal damage. In a comparative study17 they reported that both standard- and lowfluence PDT resulted in complete subretinal fluid reabsorption and visual improvement. PDT-related choroidal hypoperfusion could be reduced by low-fluence PDT.
OPDT offers the choice of early treatment for CSR; this may prevent atrophy of photoreceptors caused by long-standing subretinal fluid leading to compromised retinal function. Two subjects in this study had chronic CSR (cases #1 and #2). They both showed significant improvement in visual acuity as well as resolution of subretinal fluid with a single OPDT treatment, without PDT-related side effects and need for retreatment. The chronic nature of subretinal fluid was the reason for incomplete recovery of visual acuity. There was no significant disruption of the neuroretina on post-treatment OCT.
This pilot study reports on the outcomes of therapy with a novel method of oscillatory PDT with verteporfin. Standard PDT has fallen out of favor due to the success of anti-VEGF therapy. However, drawbacks to repeated intraocular injections include the risk of endophthalmitis and retinal detachment, as well as an overwhelming cost to healthcare systems. OPDT may be applied for all CNV lesions and reduce the need for repeat injections. Even though there are reports of CSR responding to anti-VEGF therapy, there are recalcitrant cases that will still require laser treatment.54,55 OPDT appears to be an improved method of administering PDT and is effective in treating CNV lesions and CSR. It may be superior to standard PDT because of reduced total fluence and enhanced photodynamic effect. Furthermore, it allows the operator to customize treatment over the lesion, potentially spending more time over more aggressive components of the choroidal neovascular membrane. Smaller spot size also reduces inadvertent treatment of normal retina which may occur with irregular shaped lesions.
Conflicts of Interest
1. Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year result of 2 randomized clinical trials- TAP report. Arch Ophthalmol 1999;117:1329-1345.
2. Bressler NM, Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials- TAP report 2. Arch Ophthalmol 2001;119:198-207.
3. United States Food and Drug Administration Center for Drug Evaluation and Research. Approval letter, Application 21-119. http://www.accessdata.fda. gov/drugsatfda_docs/nda/2002/21-119%20S-004_ Visudyne_Approv.PDF. Accessed May 30, 2011.
4. Raviola G. The structural basis of the blood-ocular barriers. Exp Eye Res 1977;25:27-63.
5. Marmor MF. Control of subretinal fluid: experimental and clinical studies. Eye (Lond) 1990;4:340-344.
6. Miller JW, Walsh AW, Kramer M, Hasan T, Michaud N, Flotte TJ, et al. Photodynamic therapy of experimental choroidal neovascularization using lipoprotein-delivered benzoporphyrin. Arch Ophthalmol 1995;113:810-818.
7. Mennel S, Peter S, Meyer CH, Thumann G. Effect of photodynamic therapy on the function of the outer blood-retinal barrier in an in vitro model. Graefes Arch Clin Exp Ophthalmol 2006;244:1015-1021.
8. Schmidt-Erfurth U, Hasan T, Gragoudas E, Michaud N, Flotte TJ, Birngruber R. Vascular targeting in photodynamic occlusion of subretinal vessels. Ophthalmology 1994;101:1953-1961.
9. Husain D, Miller JW, Michaud N, Connolly E, Flotte TJ, Gragoudas ES. Intravenous infusion of liposomal benzoporphyrin derivative for photodynamic therapy of experimental choroidal neovascularization. Arch Ophthalmol 1996;114:978- 985.
10. Schnurrbusch UEK, Welt K, Horn LC, Wiedemann P, Wolf S. Histological findings of surgically excised choroidal neovascular membranes after photodynamic therapy. Br J Ophthalmol 2001;85:1086-1091.
11. Postelmans L, Pasteels B, Coquelet P, El Ouardighi H, Verougstraete C, Schmidt-Erfurth U. Severe pigment epithelial alterations in the treatment area following photodynamic therapy for classic choroidal neovascularization in young females. Am J Ophthalmol 2004;138:803-808.
12. Wachtlin J, Behme T, Heimann H, Kellner U, Foerster MH. Concentric retinal pigment epithelium atrophy after a single photodynamic therapy. Graefes Arch Clin Exp Ophthalmol 2003;241:518-521.
13. Mennel S, Meyer CH, Eggarter F, Peter S. Transient serous retinal detachment in classic and occult choroidal neovascularization after photodynamic therapy. Am J Ophthalmol 2005;140:758-760.
14. Höh H, Marzelin S, Methlin D. Individualisierung der Behandlungsparameter der PDT. Klin Monatsbl Augenheilkund 2004;221:10.
15. Peyman GA, Kazi AA, Unal M, Khoobehi B, Yoneya S, Mori K, et al. Problems with and pitfalls of photodynamic therapy. Ophthalmology 2000;107:29- 35.
16. Yamashita A, Shiraga F, Shiragami C, Ono A, Tenkumo K. One-year results of reduced-fluence photodynamic therapy for polypoidal choroidal vasculopathy. Am J Ophthalmol 2010;149:465-471.
17. Reibaldi M, Cardascia N, Longo A, Furino C, Avitabile T, Faro S, et al. Standard-fluence versus low-fluence photodynamic therapy in chronic central serous chorioretinopathy: a nonrandomized clinical trial. Am J Ophthalmol 2010;149:307-315.
18. Besozzi G, Sborgia L, Furino C, Cardascia N, Dammacco R, Sborgia G, et al. Low-fluence-rate photodynamic therapy to treat subfoveal choroidal neovascularization in pathological myopia. A study of efficacy and safety. Graefes Arch Clin Exp Ophthalmol 2010;248:497-502.
19. Sacu S, Varga A, Michels S, Weigert G, Polak K, Vécsei-Marlovits PV, et al. Reduced fluence versus standard photodynamic therapy in combination with intravitreal triamcinolone: short-term results of a randomised study. Br J Ophthalmol 2008;92:1347- 1351.
20. Azab M, Boyer DS, Bressler NM, Bressler SB, Cihelkova I, Hao Y, et al. Verteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial. Arch Ophthalmol 2005;123:448-457.
21. Augustin AJ, Puls S, Offermann I. Triple therapy for choroidal neovascularization due to agerelated macular degeneration: verteporfin PDT, bevacizumab, and dexamethasone. Retina 2007;27:133-140.
22. Maberley D, Canadian Retinal Trials Group. Photodynamic therapy and intravitreal triamcinolone for neovascular age-related macular degeneration: a randomized clinical trial. Ophthalmology 2009;116:2149-2157.
23. Ahn JK, Moon HJ. Changes in aqueous vascular endothelial growth factor and pigment epitheliumderived factor after ranibizumab alone or combined with verteporfin for exudative age-related macular degeneration. Am J Ophthalmol 2009;148:718-724.
24. Kiss CG, Simader C, Michels S, Schmidt-Erfurth U. Combination of verteporfin photodynamic therapy and ranibizumab: effects on retinal anatomy, choroidal perfusion and visual function in the protect study. Br J Ophthalmol 2008;92:1620-1627.
25. Chaudhary V, Mao A, Hooper PL, Sheidow TG. Triamcinolone acetonide as adjunctive treatment to verteporfin in neovascular age-related macular degeneration: a prospective randomized trial. Ophthalmology 2007;114:2183-2189.
26. Chan WM, Lai TY, Wong AL, Tong JP, Liu DT, Lam DS. Combined photodynamic therapy and intravitreal triamcinolone injection for the treatment of subfoveal choroidal neovascularisation in age related macular degeneration: a comparative study. Br J Ophthalmol 2006;90:337-341.
27. Nicolò M, Ghiglione D, Lai S, Nasciuti F, Cicinelli S, Calabria G. Occult with no classic choroidal neovascularization secondary to age-related macular degeneration treated by intravitreal triamcinolone and photodynamic therapy with verteporfin. Retina 2006;26:58-64.
28. Hatta Y, Ishikawa K, Nishihara H, Ozawa S, Ito Y, Terasaki H. Effect of photodynamic therapy alone or combined with posterior subtenon triamcinolone acetonide or intravitreal bevacizumab on choroidal hypofluorescence by indocyanine green angiography. Retina 2010;30:495-502.
29. Saito M, Shiragami C, Shiraga F, Kano M, Iida T. Comparison of intravitreal triamcinolone acetonide with photodynamic therapy and intravitreal bevacizumab with photodynamic therapy for retinal angiomatous proliferation. Am J Ophthalmol 2010;149:472-481.
30. Tatar O, Adam A, Shinoda K, Stalmans P, Eckardt C, Lüke M, et al. Expression of VEGF and PEDF in choroidal neovascular membranes following verteporfin photodynamic therapy. Am J Ophthalmol 2006;142:95-104.
31. Schmidt-Erfurth UM, Pruente C. Management of neovascular age-related macular degeneration. Prog Retin Eye Res 2007;26:437-451.
32. Potter MJ, Claudio CC, Szabo SM. A randomised trial of bevacizumab and reduced light dose photodynamic therapy in age-related macular degeneration: The VIA study. Br J Ophthalmol 2010;94:174-179.
33. Peyman G, Tsipursky M, Gohel P, Conway M. Regression of peripapillary choroidal neovascularization after oscillatory transpupillary thermotherapy and anti-VEGF pharmacotherapy. Eur J Ophthalmol 2011;21:162-172.
34. Woodburn KW, Engelman CJ, Blumenkranz MS. Photodynamic therapy for choroidal neovascularization: a review. Retina 2002;22:391-405.
35. Dhubhghaill SS, Cahill MT, Campbell M, Cassidy L, Humphries MM, Humphries P. The pathophysiology of cigarette smoking and agerelated macular degeneration. Adv Exp Med Biol 2010;664:437-446.
36. Augustin A. Triple therapy for age-related macular degeneration. Retina 2009;29:S8-S11.
37. Katome T, Naito T, Nagasawa T, Shiota H. Efficacy of combined photodynamic therapy and sub- Tenon's capsule injection of triamcinolone acetonide for age-related macular degeneration. J Med Invest 2009;56:116-119.
38. Yip PP, Woo CF, Tang HH, Ho CK. Triple therapy for neovascular age-related macular degeneration using single-session photodynamic therapy combined with intravitreal bevacizumab and triamcinolone. Br J Ophthalmol 2009;93:754-758.
39. Bakri SJ, Couch SM, McCannel CA, Edwards AO. Same-day triple therapy with photodynamic therapy, intravitreal dexamethasone, and bevacizumab in wet age-related macular degeneration. Retina 2009;29:573-578.
40. Tzekov R, Lin T, Zhang KM, Jackson B, Oyejide A, Orilla W, et al. Ocular changes after photodynamic therapy. Invest Ophthalmol Vis Sci 2006;47:377-385.
41. Rogers AH, Martidis A, Greenberg PB, Puliafito CA. Optical coherence tomography findings following photodynamic therapy of choroidal neovascularization. Am J Ophthalmol 2002;134:566- 576.
42. Chan WM, Lam DS, Lai TY, Tam BS, Liu DT, Chan CK. 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;87:1453-1458.
43. Yannuzzi LA, Slakter JS, Gross NE, Spaide RF, Costa DL, Huang SJ, et al. Indocyanine green angiography-guided photodynamic therapy for treatment of chronic central serous chorioretinopathy: a pilot study. Retina 2003;23:288- 298.
44. Battaglia Parodi M, Da Pozzo S, Ravalico G. Photodynamic therapy in chronic central serous chorioretinopathy. Retina 2003;23:235-237.
45. Canakis C, Livir-Rallatos C, Panayiotis Z, Livir- Rallatos G, Persidis E, Conway MD, et al. Ocular photodynamic therapy for serous macular detachment in the diffuse retinal pigment epitheliopathy variant of idiopathic central serous chorioretinopathy. Am J Ophthalmol 2003;136:750- 752.
46. Cardillo Piccolino F, Eandi CM, Ventre L, Rigault de la Longrais RC, Grignolo FM. Photodynamic therapy for chronic central serous chorioretinopathy. Retina 2003;23:752-763.
47. Taban M, Boyer DS, Thomas EL, Taban M. Chronic central serous chorioretinopathy: photodynamic therapy. Am J Ophthalmol 2004;137:1073-1080.
48. Schlotzer-Schrehardt U, Viestenz A, Naumann GO, Laqua H, Michels S, Schmidt-Erfurth U. Doserelated structural effects of photodynamic therapy on choroidal and retinal structures of human eyes. Graefes Arch Clin Exp Ophthalmol 2002;240:748-757.
49. Schmidt-Erfurth U, Laqua H, Schlotzer-Schrehard U, Viestenz A, Naumann GO. Histopathological changes following photodynamic therapy in human eyes. Arch Ophthalmol 2002;120:835-844.
50. Colucciello M. Choroidal neovascularization complicating photodynamic therapy for central serous retinopathy. Retina 2006;26:239-242.
51. Yaman A, Arikan G, Saatci AO, Cingil G. Choroidal neovascularization following photodynamic therapy in a patient with chronic central serous chorioretinopathy. Bull Soc Belge Ophtalmol 2007;303:69-73.
52. Stewart JM. Half dose verteporfin PDT for central serous chorioretinopathy. Br J Ophthalmol 2006;90:805-806.
53. Reibaldi M, Boscia F, Avitabile T, Russo A, Cannemi V, Uva MG, et al. Low-fluence photodynamic therapy in longstanding chronic central serous chorioretinopathy with foveal and gravitational atrophy. Eur J Ophthalmol 2009;19:154-158.
54. Artunay O, Yuzbasioglu E, Rasier R, Sengul A, Bahcecioglu H. Intravitreal bevacizumab in treatment of idiopathic persistent central serous chorioretinopathy: a prospective, controlled clinical study. Curr Eye Res 2010;35:91-98.
55. Lim SJ, Roh MI, Kwon OW. Intravitrreal bevacizumab injection for central serous chorioretinopathy. Retina 2010;30:100-106.
Gholam A Peyman1,2, MD; Michael Tsipursky2, MD; Nariman Nassiri3, MD; Mandi Conway1,2, MD
1Department of Ophthalmology, Tulane University, New Orleans, Louisiana, USA
2University of Arizona Biomedical Sciences, Phoenix, Arizona, USA
3Department of Ophthalmology, Northwestern University, Chicago, Illinois, USA
Correspondence to: Gholam A Peyman, MD. Professor of Basic Medical Sciences, University of Arizona. 10650 W. Tropicana Circle, Sun City, Arizona 85351, USA; Tel: +1 602 242 4928, Fax: +1 602 249 4813; e-mail: firstname.lastname@example.org
Received: February 22, 2011 Accepted: May 3, 2011