Verteporfin and Intravitreal Triamcinolone Acetonide Combination Therapy for Occult Choroidal Neovascularization in Age-Related Macular Degeneration
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Verteporfin and Intravitreal Triamcinolone Acetonide Combination Therapy for Occult Choroidal Neovascularization in Age-Related Macular Degeneration ALBERT J. AUGUSTIN, MD, AND URSULA SCHMIDT-ERFURTH, MD ● PURPOSE: To evaluate the efficacy and safety of pho- ● CONCLUSIONS: Verteporfin PDT combined with intra- todynamic therapy (PDT) with verteporfin combined vitreal triamcinolone may improve the outcome of standard with intravitreal triamcinolone (IVTA) in occult choroi- verteporfin PDT in the treatment of occult CNV secondary dal neovascularization (CNV) secondary to age-related to AMD. An improvement in visual acuity was observed in macular degeneration (AMD). most of the treated patients and was maintained during a ● DESIGN: Single center, nonrandomized interventional two-year follow-up period. Retreatment numbers were case series. lower than expected from monotherapy trials. (Am J ● METHODS: A prospective, noncomparative, interven- Ophthalmol 2006;141:638 – 645. © 2006 by Elsevier Inc. tional case series of 41 eyes of 41 patients with a All rights reserved.) two-year follow-up period. Verteporfin PDT was per- formed using the recommended standard procedure for P HOTODYNAMIC THERAPY (PDT) WITH VERTEPORFIN IS approved forms of AMD. A solution containing 25 mg of an established therapy in patients with predominantly crystalline triamcinolone acetonide was injected intravit- classic subfoveal choroidal neovascularization (CNV) really 16 hours post PDT. The procedure was repeated secondary to age-related macular degeneration (AMD).1–3 after three months in case of persistent CNV leakage. PDT with verteporfin is also useful in the treatment of ● RESULTS: The mean number of treatments needed was predominantly occult CNV secondary to AMD. The patients 1.8. Thirty-four eyes (82.9%) required one retreatment who benefited from photodynamic therapy in the Verteporfin at three months. No additional retreatments were neces- in Photodynamic Therapy (VIP) Trial were occult with no sary. Visual acuity improved gradually in most of the classic CNV measuring less than four Macular Photocoagu- patients with mean values of 20/133 and 20/115 at lation Study (MPS) disk areas or with visual acuity worse baseline and three months; 20/101 and 20/84 at six and than 20/50 at baseline.4 The treatment is well tolerated and twelve months; and 20/83 and 20/81 at eighteen and visual loss can often be prevented.4 However, reactivation twenty-four months. Eleven of 41 treated study eyes and persistence of CNV is not uncommon and frequent (26.8%) underwent cataract surgery between six and retreatments may be required.2 Particularly in the subpopu- fifteen months after the first treatment. Nine patients required local or systemic glaucoma therapy because of a lation of purely occult lesions, outcomes may vary. In the transient steroid induced intraocular pressure increase. overall population of occult lesions in the VIP trial, a mean loss of five lines was observed in PDT-treated eyes compared with a loss of 4 lines in untreated eyes.4,5 Lesions larger than Accepted for publication Nov 26, 2005. four MPS disk areas had an even worse outcome; severe From the Department of Ophthalmology, Klinikum Karlsruhe, Karlsruhe, adverse events with massive vision loss were seen more Germany (A.J.A.); and Department of Ophthalmology, University of frequently in this subgroup.4,5 Vienna, Vienna, Austria (U.S-E.). Ursula Schmidt-Erfurth, MD, is an inventor on the patent on the use The persistence and recurrence of CNV, requiring frequent of verteporfin therapy in ocular neovascular disease under the guidelines retreatments, can compromise the success of therapy. The of the Wellman Laboratories of Photomedicine, Harvard Medical School, Boston, Institutional Patent Policy and Procedures. pathogenesis of CNV is thought to involve not only The authors gratefully acknowledge Piotr Sczecsny for his scientific photodynamic processes, but also oxidative and inflamma- expertise and assistance with the statistical analysis. tory mechanisms.6,7 Such mechanisms include cell mediated Inquiries to Ursula Schmidt-Erfurth, MD, Department of Ophthalmol- ogy, Medical University of Vienna, Waehringer Guertel 18-20, 1090 inflammation, leukocyte adhesion, leukocyte extravasation, Vienna, Austria; e-mail: ursula.schmidt-erfurth@meduniwien.ac.at and angiogenesis, features that are similar to but not 638 © 2006 BY ELSEVIER INC. ALL RIGHTS RESERVED. 0002-9394/06/$32.00 doi:10.1016/j.ajo.2005.11.058
necessarily identical to those of wound healing.7 Evidence is also increasing that upregulation of vascular endothelial growth factor (VEGF) can be responsible for vascular leakage and neovascularization.6 While demonstrating therapeutic benefit in controlled clinical trials, PDT itself, by triggering the generation of free radicals and lipid perox- ides, may contribute to the oxidation-induced VEGF- expression that has been observed in PDT treated-areas.6 PDT-induced release of VEGF enhances the decrease in choroidal perfusion and resultant hypoxia associated with the promotion of CNV.6 Multiple PDT applications, with renewed choroidal alteration and angiogenic stimulation, may trigger more persistent and accelerated regrowth and lesion activity.6 Intravitreal administration of a corticosteroid, such as triamcinolone acetonide (TA), has been used for a variety of eye diseases, for example, diabetic macular edema,8,9 retinal vein occlusion,10,11 uveitis,12,13 and AMD.14 –18 Treat- ment with intravitreal TA (IVTA) alone was shown to improve visual acuity in patients with exudative AMD FIGURE 1. Occult choroidal neovascularization attributable to with optimal outcomes observed one to three months after age-related macular degeneration. Mean change in visual acuity treatment.14,15 IVTA was also combined with photocoag- (VA) from baseline to month 24 in patients suffering from ulation in the treatment of subfoveal recurrence of CNV.16 occult choroidal neovascularization attributable to age-related macular degeneration and treated with a combination of pho- More recently, verteporfin PDT with adjunct IVTA was todynamic therapy and triamcinolone. The mean visual acuity suggested in pilot studies.17,18 These studies evaluated the at baseline significantly (P < .0001) improved from 20/133 to effects of 4 mg intravitreal TA as an adjunct to PDT with 20/84 at the twelve-month follow-up visit. This improvement verteporfin in the treatment of patients with subfoveal or was maintained at the twenty-four-month visit (VA: 20/81). juxtafoveal CNV. All studies showed beneficial effects regarding visual acuity outcomes. The treatment was well tolerated and no patients experienced severe visual loss. measurement using Snellen charts, slit-lamp, and fundus However, patient numbers were small, follow-up was limited, examination, as well as intraocular pressure (IOP) mea- and lesion types were ill defined. surement. Fluorescein angiography (FA) was performed to The aim of the present study was to evaluate whether identify the lesion type and to assess CNV leakage, using verteporfin PDT combined with IVTA can reduce the the criteria described previously1,4 that included evidence number of retreatments needed and improve visual out- of CNV caused by AMD that extended under the geomet- comes in patients with purely occult CNV secondary to ric center of the foveal avascular zone. All patients were AMD. reevaluated with fluorescein angiography every three months. Following an oral informed consent, each participant METHODS signed a written informed form detailing the experimental character of the triamcinolone procedure. The protocol of PATIENTS SUFFERING FROM OCCULT ONLY CNV SECOND- the study adhered to the European Good Clinical Practice ary to AMD were included in this prospective interven- Guidelines and the Declaration of Helsinki. tional case series. Recruitment was consecutive for all PDT with verteporfin (Visudyne, Novartis Ophthal- patients presenting in a tertiary referral center. Inclusion mics, Basel, Switzerland) was performed according to the criteria adhered to the recommendation of the VIP trial recommended standard procedure for approved forms of regarding angiographic criteria and symptoms of recent AMD.1,2,4 Within a mean of 17 hours (16 to 18 hours) after disease progression. The complete VIP criteria are: (1) PDT, the patients received retrobulbar anesthesia and the patients with macular degeneration, with subfoveal cho- ocular surface was disinfected using polyvidone iodine roidal neovascularization lesions measuring no greater than solution. Retrobulbar anesthesia was performed to avoid 5400 m in greatest linear dimension with occult with no lens or retinal damage attributable to fixation problems of classic choroidal neovascular, (2) best-corrected visual score the patients. According to pathophysiological findings, the of at least 50 (Snellen equivalent of 20/100), and (3) induction of oxidative and inflammatory reactions follow- evidence of hemorrhage or recent disease progression. At ing PDT is necessary for vessel closure. However, this baseline all patients underwent a standardized ophthalmo- finally leads to enhanced VEGF expression. When starting logic examination including best-corrected visual acuity this case series, the rationale for designing the therapy was VOL. 141, NO. 4 VERTEPORFIN PDT AND TRIAMCINOLONE IN OCCULT CNV 639
FIGURE 2. Purely occult choroidal neovascularization. (Top panel) Fluorescein angiography (FA) of a patient presenting with a purely occult choroidal neovascularization. Late FA frames demonstrated intensive leakage originating from the subfoveal lesion (Right image). The diagnosis was consistent with a fibrovascular pigment epithelium detachment. Visual acuity at baseline was 20/63. One single course of photodynamic therapy and intravitreal triamcinolone acetonide was performed at the baseline visit. (Bottom panel) Fluorescein angiography (FA) documentation three months after combination treatment. The lesion appeared hypofluorescent in the early phase FA (Left image); leakage was absent during late phase FA (Right image) and had not recurred by the 24th month. to antagonize PDT side effects after the initiation of was administered intravitreally through pars plana in- biochemical reactions necessary for vessel closure. jection using a 27 gauge needle. Preservative-cleared Subsequently, 25 mg of preservative-cleared crystal- TA was prepared by the institutional pharmacy using line triamcinolone acetonide (TA), prepared from Vo- the method previously described by Jonas and cowork- lon A, (Triamcinolon-Acetonide, Dermapharm AG, ers.14 To prevent a potentially toxic effect of a vehicle Grünwald, Germany), in a volume of 0.2 ml solution, to intraocular tissues, the pharmacy prepared the solu- 640 AMERICAN JOURNAL OF OPHTHALMOLOGY APRIL 2006
FIGURE 3. Occult choroidal neovascularization. (Top panel) Fluorescein angiography of a patient presenting with an occult choroidal neovascularization. Visual acuity at baseline was 20/2000. One single course of photodynamic therapy and intravitreal triamcinolone acetonide was performed at the baseline visit. (Bottom panel) Fluorescein angiography (FA) of this patient three months after combination treatment. The lesion appeared hypofluorescent in the early phase FA (Left image); leakage was absent during late phase FA (Right image) and had not recurred by the 24th month. Visual acuity improved to 20/200. tion free of solvent agents or other vehicles. The points were not included in the standard observation. In amount of administered TA was determined by high- case of CNV leakage, the patients were retreated at performance liquid chromatography measurement im- three-month intervals using the identical procedure. mediately following removal of the preservative. After The primary efficacy variable was defined as best- injection of TA, patients were clinically controlled refracted visual acuity measured using Snellen charts. including measurement of IOP at day one, two, and six, The primary efficacy time points were the follow up and six weeks after injection of TA. These safety time visits at twelve months and twenty-four months follow- VOL. 141, NO. 4 VERTEPORFIN PDT AND TRIAMCINOLONE IN OCCULT CNV 641
ing the initial treatment. The mean visual acuity data at these follow-up visits were compared with the mean 20/32–20/400 24 Months visual acuity at the baseline visit using the paired t test 20/81 20/38 20/63 TABLE. Mean Visual Acuity (Snellen Charts) of Patients With Occult Choroidal Neovascularization Attributable to Age-Related Macular Degeneration Following Combined to identify statistical significance. RESULTS 20/32–20/400 21 Months 20/82 20/38 20/63 A TOTAL OF 41 CONSECUTIVE PATIENTS SUFFERING FROM occult CNV secondary to AMD was included into the study. Twenty-four individuals were female and 17 male, and the mean age of the patients was 76.2 ⫾ 5.1 year Therapy With Photodynamic Therapy and Intravitreal Triamcinolone for Each Visit During a Two-year Follow-up 20/32–20/400 (mean ⫾ standard deviation, SD, range 66 to 87 years). 18 Months 20/83 20/39 20/63 VIP-criteria were met in all patients except that eyes presenting with a visual acuity lower than 20/200 were also included.4 Twenty-six (63.4%) of the study eyes were phakic and 15 (36.6%) were pseudophakic. The study eye 20/32–20/400 of each of the 41 patients was treated primarily and 15 Months documented as study eye, the fellow eye was treated in five 20/87 20/39 20/80 patients, but data were excluded from the study documen- tation for the second eye. Most of the study eyes, 34 of 41 eyes (82.9%) required one additional treatment at three months because of 20/32–20/400 *Patients who failed to read any letters (counting fingers or hand motion) are arbitrarily assigned to 20/2000.37 12 Months persistent leakage originating from the CNV lesion. Com- 20/84 20/39 20/80 plete resolution of leakage was seen in all eyes by three to six months, and no patient required additional retreat- ments after the 6-month interval. Thus, the mean number of treatments was 1.83 for the study eye. The median size 20/32–20/400 of lesions before first combination was 3600 m (range 800 9 Months 20/89 20/38 20/80 to 7100 m); 34 of 41 eyes showed persistent leakage after three months. The median size of lesions of these 34 patients was 3200 m (range 1200 to 4700 m). Figure 1 presents data on best-corrected visual acuity 20/32–20/400 (mean, SD) for the study eyes during the two-year fol- 6 Months 20/101 low-up period after the first treatment. The mean visual 20/39 20/80 acuity at baseline was 20/133 (SD 20/57) and significantly (P ⬍ .0001) improved to 20/84 at the twelve-month follow-up visit. The improvement in visual acuity was 20/40–20/2000* maintained throughout the twenty-four-month follow-up with a mean visual acuity of 20/81 (SD 20/38) at the final 3 Months 20/115 20/100 20/44 visit. Notably, the mean visual acuity at the twenty-four- month visit also represented a significant improvement in comparison with baseline values. The mean visual acuity of the study eye before treatment 20/40–20/2000* was 20/133 (range 20/40 to 20/2000). Visual acuity im- 20/133 20/100 Baseline proved gradually in all of the patients except for nine 20/57 patients. Mean visual acuity was 20/115, 20/101, 20/89, 20/83, and 20/81 at three, six, twelve, eighteen, and twenty- four months, respectively. At twelve months, 43% of the 18 patients remained Standard deviation stable (⫾1 line), after twenty-four months, 41.5% of the 17 patients remained stable. The percentage of patients who improved 3 or more lines was 29.3% (12 patients) at Median Range twelve months and 31.7% (13 patients) at twenty-four Mean months. The percentage of patients who gained 6 or more lines at twelve and twenty-four months was 9.8% (4 642 AMERICAN JOURNAL OF OPHTHALMOLOGY APRIL 2006
patients). No deterioration in visual acuity was observed in relatively high. For the subgroup of cases with occult with any of the patients during the two-year observation period. no classic CNV in the VIP trial, verteporfin-treated patients Figure 2 shows a characteristic finding in a patient suffering received an average of 3.1 treatments (of a possible total of from occult CNV treated with IVTA. The patient required four) before the follow-up at month twelve and an average one combination treatment, and during twenty-four month of 1.8 in the second twelve months.4 In comparison, a follow-up, the lesion became inactive. Accordingly, vision recently published study reports a mean number of 5.6 increased from 20/63 to 20/32 and remained stable. retreatments in patients with classic subfoveal CNV during Figure 3 shows a characteristic finding in a patient suffering a period of two years.2 from occult CNV treated with IVTA. The patient required There are several hypothesis for the persistence of CNV one combination treatment, and during twenty-four month and the need of retreatments after PDT monotherapy. One follow-up, the lesion became inactive. Accordingly, vision of the mechanisms of photodynamic action is the produc- increased from 20/2000 to 20/200 and remained stable. tion of oxidative radicals, thus enhancing a major patho- Generally, treatments were well tolerated. Eleven of 41 genic process of CNV induction. Following PDT, the acute treated study eyes (26.8%) underwent cataract surgery oxidative damage represents a much more powerful reac- between months 6 and 15 after the first treatment; 11 of tion than the chronic life-long photodynamic light-induced the 26 phakic study eyes (42.3%) underwent cataract process that eventually leads to CNV.6 Each PDT retreat- surgery. One of these patients was treated with Yttrium ment may acutely enhance the long lasting disease process Aluminum Garnet (YAG) laser capsulotomy six months and increase the amount of photoreceptor loss. After the after the cataract surgery. Three untreated fellow eyes also acute phase of the PDT reaction, oxidation- or ischemia- had cataract surgery at eighteen to twenty-one months and induced expression of VEGF, VEGF receptor 3, and one untreated fellow eye was treated with YAG laser pigment epithelium-derived factor was described in the capsulotomy. PDT-treated areas.6 This effect may represent another sub- A transient IOP-increase was observed in nine eyes, acute and longer lasting stimulus for neovascular growth and which was controlled by topical monotherapy in seven leakage and induce inflammatory reactions. In experimental patients. Two patients required intermittent systemic ther- studies, PDT was shown to induce a rapid inflammatory apy using carboanhydrase inhibitors. The median IOP was response including infiltration of leukocytes, increased ex- 15 at baseline visit (range 11 to 19 mm Hg), 16 at follow-up pression of cytokines for example, intracellular adhesion visit after three months (range 11 to 34 mm Hg), 15 at molecule (ICAM)-1 and interleukin (IL)-6.19 Following follow-up visit after 6 and 9 months (range 10 to 42 mm application of PDT using standard parameters to the Hg and 10 to 19 mm Hg, respectively), 16 at follow-up macula of human eyes, histologic studies have identified visit after twelve months (range 11 to 20 mm Hg), and 15 thrombotic occlusion of the choriocapillary layer; charac- at follow-up visits after twenty-four months (range 11 to 18 teristic hypofluorescence seen in indocyanine green (ICG) mm Hg). Complications attributable to the injection angiography was clearly consistent with a thrombosis of procedure such as pseudoendophthalmitis, retinal detach- choriocapillaries and individual larger vessels.20 Choroidal ment, retinal tears, or vitreous hemorrhage were not hypoperfusion and resulting tissue hypoxia may represent observed. an angiogenic stimulus responsible for CNV progression and may be enhanced by PDT-induced release of VEGF.6 Corticosteroids have antiproliferative, anti-inflamma- DISCUSSION tory and angiostatic effects and are known to decrease vascular permeability.21–23 The rationale for the present THE PRESENT STUDY ILLUSTRATES THE USEFULNESS OF study was to combine verteporfin PDT with an antiinflam- verteporfin PDT combined with IVTA in the treatment of matory and/or antiangiogenetic drug thus antagonizing occult CNV secondary to AMD. The treatment course VEGF-expression and inflammatory reactions in the sub- with a mean number of 1.8 treatments needed during a acute phase following PDT. IVTA alone has been used in two-year period is favorable. In addition, visual acuity a number of conditions, including AMD and macular improved in most of the patients, consistent with pilot edema of different origins.14,24 Several approaches have results from small studies using verteporfin PDT com- been employed to administer corticosteroids, for example, bined with IVTA in other CNV subgroups.17,18 This intravitreal injections, implants, periocular, or systemic study includes a well-defined population of eyes with administration. Although the mode of action is not fully purely occult lesions and clearly demonstrates that the clarified for IVTA, promising results have been obtained in improvement in visual acuity and absence of leakage the treatment of intraocular proliferative, edematous, and was maintained throughout the twenty-four-month fol- neovascular diseases.14 –16,25,26 Most studies have reported low-up visit. beneficial effects on visual acuity from the use of either 4 mg Verteporfin PDT alone is effective in the treatment of or 25 mg IVTA.14 –16,25,26 However, in the case of AMD occult CNV secondary to AMD, but the number of associated with CNV, the effect was mostly anatomical retreatments necessary for CNV closure was found to be and did not translate into functional improvement: IVTA VOL. 141, NO. 4 VERTEPORFIN PDT AND TRIAMCINOLONE IN OCCULT CNV 643
inhibited neovascular growth in an experimental model of intravitreal corticosteroid. This increase could be con- laser-induced CNV, a model of limited value for age- trolled by topical monotherapy or short-term systemic related CNV.23 In sub- and juxtafoveal CNV eyes, a single therapy. Published studies have reported elevation in IVTA resulted in 55% stabilization, but 33% of eyes intraocular pressure in 30% to 50% of patients treated with experienced vision loss.26 In predominantly occult lesions, IVTA during the first three months after the injection.31,32 CNV enlargement was reduced to 31% in the IVTA group The corticosteroid-induced elevation in intraocular pres- compared with 70% growth in the control group with only sure can usually be controlled with topical medication.31 In minor effects on vision outcome.25 A single IVTA course comparison, the incidence of cataracts in the Treatment of in predominantly classic lesions reduced lesion growth, but AMD in Photodynamic Therapy (TAP) investigation, was showed no difference in vision outcome at twelve 14.9% for verteporfin-treated patients compared with months.27 Following IVTA using a high dose of 25 mg, 15.0% for patients receiving placebo (P ⫽ 1.00); in the visual acuity increased after each injection, but the overall VIP AMD trial, the incidence of cataracts was 13.3% effect was transient during follow-up.28 Obviously, the and 8.8% in verteporfin- and placebo-treated patients, effects of IVTA alone are not appropriate to achieve respectively (P ⫽.285).36 persistent absence of CNV leakage together with vision This interventional case series had several limitations, stabilization or even improvement. including lack of standardized protocol refractions/visual Preliminary experience with combination of PDT and acuity testing, lack of randomization, and absence of a IVTA seems to promise improved visual outcome and control group. Without a control group, the number of lower retreatment rates. Spaide and associates18 found that patients who may have improved or remained stable in patients not pretreated with PDT alone, an increase of without treatment can not be determined. at least 3 lines was seen in 33% at six months, the mean In conclusion, there is a need for more effective new change in VA was 2.4 lines. treatments of occult CNV secondary to AMD. If vertepor- After a mean follow-up of eighteen months, combina- fin monotherapy is being used, the need for multiple tion therapy resulted in vision gain in 7%, stabilization in retreatments is a significant concern. Future treatments are 50%, and vision loss in 43% of all patients.17 Numbers or likely to include combinations of PDT with corticoste- retreatment needed to achieve absence of leakage using roids, angiostatic corticosteroids, or antiangiogenetic/anti combination therapy ranged from 1.2 to 2.7, significantly permeability drugs. Prospective, randomized, and controlled lower than with PDT monotherapy. studies are needed to further evaluate the benefit of combi- In our study population, verteporfin PDT combined nation strategies (Table). with IVTA was well tolerated. However, at the current state it must be highlighted that the use of IVTA in any condition still is experimental and that the experience from its use in various conditions is based on small REFERENCES uncontrolled studies.29 Potential complications of IVTA include cataract progression and increased intraocular 1. TAP Study Group. Photodynamic therapy of subfoveal cho- pressure.14,17,25,27,29 –32 Rare cases of endophthalmitis have roidal neovascularization in age-related macular degeneration with verteporfin. One-year results of two randomized clinical also been reported after IVTA.29,33 This side-effect might trials—TAP Report 1. Arch Ophthalmol 1999;117:1329 –1345. be related to the content of alcohol in the original 2. TAP Study Group. 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Biosketch Albert J. Augustin, MD, is a Professor of Ophthalmology and Chairman of the Department of Ophthalmology at Klinikum Karlsruhe, Medical Education Center of the University of Freiburg, Germany. His research interests include age-related macular degeneration, diabetic retinopathy, and retinal ischemia. Dr Augustin has been involved in many prospective clinical studies and is a member of numerous professional organizations, including the American Academy of Ophthalmology, the International Society of Eye Research, and the American Society of Retina Specialists. 645.e1 AMERICAN JOURNAL OF OPHTHALMOLOGY APRIL 2006
Biosketch Ursula Schmidt-Erfurth, MD, is a Professor in Ophthalmology and the Chairman of the Department of Ophthalmology and Optometry at the University of Vienna, Austria. Her clinical work includes general ophthalmology with a specific focus in medical and surgical retina. During her fellowship at the Harvard Medical School in Boston, she initiated research in photodynamic therapy for the treatment of ocular neovascular disease and became an inventor of verteporfin therapy. She is also one of the founders of the TAP (treatment of age-related macular degeneration using photodynamic therapy) and VIP (verteporfin in photodynamic therapy) study groups. Her research interests include the development of novel imaging modalities as well as pharmacologic strategies in the treatment of chorioretinal disease. Another focus of her research interest is retinal imaging and pharmacologic strategies to treat neovascular disease of retina and choroid. She is a principal investigator and member of the study advisory boards for the clinical trials using antiangiogenic agents such as Macugen and Lucentis. Dr Schmidt-Erfurth has published extensively in peer-reviewed journals and is a member of multiple national and international ophthalmological societies such as the American Academy of Ophthalmology, the Macula Society, the Retina Society, the Club Jules Gonin, Euretina, and others. She has received a number of prestigious research awards including the Roger Johnson Award, the Achievement Award of the American Academy, the Carl Zeiss Research Award, the Fight-for-Sight Award, and the Christiansen Award. VOL. 141, NO. 4 VERTEPORFIN PDT AND TRIAMCINOLONE IN OCCULT CNV 645.e2
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