Macular Degeneration: Yannuzzi LA

Yannuzzi LA, Freund KB, Takahashi BS. · No affiliation provided · Retina. · Pubmed #18327130 No free full text.

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Yannuzzi LA. · No affiliation provided · Retina. · Pubmed #17621173 No free full text.

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Ciardella AP, Donsoff IM, Huang SJ, Costa DL, Yannuzzi LA. · The LuEsther T Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York 10021, USA. · Surv Ophthalmol. · Pubmed #14711438 No free full text.

Abstract: Polypoidal choroidal vasculopathy was first described as a peculiar hemorrhagic disorder of the macula, characterized by recurrent sub-retinal and sub-retinal pigment epithelium bleeding in middle aged black women. The use of indocyanine green angiography and subsequently of optical coherent tomography has widened our ability to study and understand the pathophysiology of this disorder. The primary abnormality involves the choroidal circulation, and the characteristic lesion is an inner choroidal vascular network of vessels ending in an aneurysmal bulge or outward projection, visible clinically as a reddish orange, spheroid, polyp-like structure. We have also recognized that individuals of African-American and Asian descents are more at risk for developing polypoidal choroidal vasculopathy as the disorder seems to preferentially affect pigmented individuals. However, it has been shown that while that still holds true, patients of other racial backgrounds may be afflicted. Particularly, polypoidal choroidal vasculopathy has been found to be present in about 8-13% of white patients with clinical appearance of exudative age-related macular degeneration. Polypoidal choroidal vasculopathy has also been reported in Irish, French, German, and Italian patients. The natural course of the disease often follows a remitting-relapsing course, and clinically, it is associated with chronic, multiple, recurrent serosanguineous detachments of the retinal pigment epithelium and neurosensory retina with long-term preservation of good vision. Photodynamic treatment appears to be a promising alternative to conventional laser therapy, for the treatment of polypoidal choroidal vasculopathy. In conclusion, polypoidal choroidal vasculopathy seems to be a distinct clinical entity that should be differentiated from other types of choroidal neovascularization associated with age-related macular degeneration and other known choroidal degenerative, inflammatory, and ischemic disorders.

Ciardella AP, Donsoff IM, Guyer DR, Adamis A, Yannuzzi LA. · LuEsther T. Mertz Retinal Research Laboratory, Manhattan Eye, Ear and Throat Hospital, 210 E. 64th Street, New York, NY 10021, USA. · Ophthalmol Clin North Am. · Pubmed #12515077 No free full text.

Abstract: Although these preliminary results on the use of antiangiogenesis drugs for the treatment of neovascular AMD appear promising, double-masked, placebo-controlled, multicenter clinical trials are needed to demonstrate the therapeutic efficacy of such treatments. For example, the first antiangiogenesis drug tested in AMD, interferon alpha-2a, raised great enthusiasm. Indeed, interferon alpha-2a had been shown to be antiangiogenic in animal and in vitro models. It proved to be ineffective, however, in halting the progression of neovascular AMD in a double-masked, placebo-controlled clinical trial [28]. Another antivasogenesis drug tested in a phase 3 clinical trial is thalidomide [67]. Although the enrollment of patients is finished, the results are not yet known.

Borodoker N, Spaide RF, Maranan L, Murray J, Freund KB, Slakter JS, Sorenson JA, Yannuzzi LA, Guyer DR, Fisher YL. · Vitreous-Retina-Macula Consultants of New York, and the LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York 10021, USA. · Am J Ophthalmol. · Pubmed #11812424 No free full text.

Abstract: PURPOSE: To determine if oral hydration decreases the incidence of verteporfin infusion-associated pain and to find out if other factors play a role in predisposing to this undesired complication. METHODS: Nonrandomized clinical trial. We prospectively examined 250 consecutive patients who have been diagnosed with subfoveal choroidal neovascularization secondary to age-related macular degeneration and received photodynamic therapy using verteporfin. One hundred twenty-five patients were assigned to receive 500 ml of water orally administered 30 minutes before beginning the verteporfin infusion, and the remaining 125 consecutive patients were used as controls. Historical and clinical factors in these patients were evaluated for their association with the presence of verteporfin infusion-associated pain. RESULTS: Out of 125 patients receiving water before treatment 12 (9.6%) experienced verteporfin infusion-associated pain. Among the 125 patients who did not get hydration before therapy 12(9.6%) experienced verteporfin infusion-associated pain. There was no statistical difference between the incidence of pain in the two groups (P = 1.0). No statistically significant association was evidenced between the presence of pain and participant's baseline characteristics, except for pain on previous administration of verteporfin (P < .001). Out of 250 total patients 24 (9.6%) developed verteporfin infusion-associated pain. Back pain was the most common and occurred in 21 (8.4%) patients, but other sites included leg, groin, chest, buttock, arm, and shoulder pain concurrently or independently. All patients had resolution of their pain, including chest pain, on cessation of the infusion. CONCLUSIONS: Verteporfin infusion-associated pain may be more common than has been previously reported and is not limited to the back area. It appears to be an idiosyncratic reaction to the drug. It does not seem to be prevented by oral hydration before infusion of verteporfin, and no baseline characteristics, other than a history of pain on previous infusion, seem to be predictive of verteporfin infusion-associated pain.

Robison CD, Krebs I, Binder S, Barbazetto IA, Kotsolis AI, Yannuzzi LA, Sadun AA, Sebag J. · VMR Institute, Huntington Beach, California, USA. · Am J Ophthalmol. · Pubmed #19327744 No free full text.

Abstract: PURPOSE: To evaluate vitreomacular relations in different stages of age-related macular degeneration (AMD) without the influence of genetics and environmental factors. DESIGN: Retrospective, observational case series. METHODS: This was a multicenter study consisting of 29 previously untreated subjects with active exudative (wet) AMD in one eye and active nonexudative (dry) AMD in the fellow eye who were compared with 10 previously untreated subjects with end-stage geographic atrophy in one eye and an end-stage fibrotic (disciform) scar in the fellow eye. All subjects were studied with ultrasonography to identify the presence of posterior vitreous detachment (PVD) and by optical coherence tomography to detect vitreomacular adhesion (VMA). RESULTS: The incidence of PVD in eyes with nonexudative AMD was 20 (69%) of 29, compared with 6 (21%) of 29 with active exudative AMD (P = .002). VMA was present in 11 (38%) of 29 of eyes with exudative AMD and in only 3 (10%) of 29 eyes with nonexudative AMD (P = .008). The incidence of PVD in geographic atrophy was 7 (70%) of 10, compared with 4 (40%) of 10 with disciform scar (P = .44). VMA was present in 2 (20%) of 10 eyes with disciform scars and in 0 (0%) of 10 eyes with geographic atrophy (P = .48). CONCLUSIONS: PVD may protect against exudative AMD, whereas VMA may promote exudative AMD. This phenomenon is not evident in end-stage disease because of an increased incidence of PVD and a decreased incidence of VMA in eyes with disciform scars. Genetic and environmental factors do not seem to influence these observations.

Ferrara DC, Merriam JE, Freund KB, Spaide RF, Takahashi BS, Zhitomirsky I, Fine HF, Yannuzzi LA, Allikmets R. · LuEsther T. Mertz Retinal Research Center, New York, New York, USA. · Arch Ophthalmol. · Pubmed #19001225 No free full text.

Abstract: OBJECTIVE: To analyze the frequency of major age-related macular degeneration (AMD)-associated alleles in patients with multifocal choroiditis (MFC). METHODS: A cohort of 48 patients with MFC was compared with previously characterized cohorts of patients with advanced AMD (368 samples) and matched unaffected controls (368 samples). Allele and genotype frequencies of single nucleotide polymorphisms for the following AMD-associated alleles were evaluated: risk alleles in complement factor H (CFH) gene (Y402H and IVS14) and LOC387715/HTRA1 gene on 10q26 (A69S) and protective alleles in CFH (IVS1, IVS6, and delCFHR1-3) and complement factor B loci (H9L and R32Q). RESULTS: Frequencies of all major AMD-associated alleles in the CFH locus indicate a strong, statistically significant association of CFH gene single nucleotide polymorphisms and MFC. However, the same analysis for the single nucleotide polymorphisms in complement factor B and 10q26 loci matched the results in the control group. CONCLUSIONS: Like AMD, the MFC phenotype is strongly associated with the major alleles/haplotypes in the CFH locus. Clinical Relevance We report compelling evidence of a strong association between CFH polymorphisms and MFC, which contributes to the understanding of MFC pathogenesis and suggests new potential therapeutic targets.

Fine HF, Zhitomirsky I, Freund KB, Barile GR, Shirkey BL, Samson CM, Yannuzzi LA. · LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York, USA. · Retina. · Pubmed #18784620 No free full text.

Abstract: BACKGROUND: Multifocal choroiditis (MFC) is an inflammatory condition, occasionally associated with choroidal neovascularization (CNV). Bevacizumab (Avastin) and ranibizumab (Lucentis) are therapies that target vascular endothelial growth factor. Bevacizumab and ranibizumab have been used successfully to treat CNV in age-related and myopic macular degeneration. PURPOSE:: To describe the treatment of MFC-associated CNV with intravitreal bevacizumab and/or ranibizumab. DESIGN: Retrospective interventional case series. PARTICIPANTS: Six eyes of five patients with MFC-associated CNV were treated with intravitreal bevacizumab and/or ranibizumab. MAIN OUTCOME MEASURES: Visual acuity at 1, 3, and 6 months after the initial injection. RESULTS: Previous therapies (number of eyes treated) included sub-Tenon's corticosteroids (2), intravitreal corticosteroids (1), photodynamic therapy (1), and thermal laser (1). The mean number (range) of antivascular endothelial growth factor injections per eye was 2.3 (1-6). The mean duration (range) of follow-up per patient was 41.5 (25-69) weeks. Five of six eyes improved to 20/30 acuity or better at 6 months. One eye suffered a subfoveal rip of the retinal pigment epithelium with 20/400 acuity. There was a qualitative decrease in clinical and angiographic evidence of CNV. CONCLUSIONS: Bevacizumab and ranibizumab were effective at improving visual acuity over 6 months in a small series of patients with MFC-associated CNV. Tears of the retinal pigment epithelium may occur after intravitreal antivascular endothelial growth factor therapy in MFC-associated CNV.

Barbazetto IA, Room M, Yannuzzi NA, Barile GR, Merriam JE, Bardal AM, Freund KB, Yannuzzi LA, Allikmets R. · Department of Ophthalmology, Columbia University, New York, New York, USA. · Invest Ophthalmol Vis Sci. · Pubmed #18502988 No free full text.

Abstract: PURPOSE: To investigate the prevalence of sequence variants in the ATM gene and to determine the frequency of major age-related macular degeneration (AMD)-associated variants in CFH, CFB, and 10q26 loci in patients with idiopathic perifoveal telangiectasia (IPT). METHODS: Thirty patients with diagnoses of IPT underwent standard ophthalmologic evaluation that included visual acuity testing, fundus photography, and fluorescein angiography. DNA was screened for variations in the ATM gene by a combination of denaturing high-performance liquid chromatography and direct sequencing. Major AMD-associated alleles in CFH, CFB, and 10q loci were screened by PCR-restriction fragment-length polymorphism. RESULTS: Nineteen female and 11 male patients (average age, 59 years) with a median visual acuity of 20/50 were evaluated. Six patients were of Asian-Indian origin, one was Hispanic, and 23 were of European-American ancestry. Nine of 30 (30%) patients had diabetes mellitus, 18 of 30 (60%) patients had hypertension, and 12 of 30 (40%) patients had a history of smoking. Screening of the ATM gene revealed a null allele in 2 of 23 (8.7%) patients of European ancestry, previously disease-associated missense alleles in 4 of 23 (17.4%) patients, and common missense alleles in 7 of 23 (30.4%) patients. No variants were identified in the ATM gene in patients of Asian or Hispanic origin. Frequencies of major AMD-associated alleles in CFH, CFB, and 10q loci in the IPT cohort were similar to those in the ethnically matched general population. CONCLUSIONS: At least 26%, and maybe up to 57%, of IPT patients of European-American descent carried possibly disease-associated ATM alleles. Vascular risk factors such as hypertension, diabetes, and smoking may be associated with the pathogenesis of the disease.

Bhatnagar P, Spaide RF, Takahashi BS, Peragallo JH, Freund KB, Klancnik JM, Cooney MJ, Slakter JS, Sorenson JA, Yannuzzi LA. · Vitreous-Retina-Macula Consultants of New York, New York, USA. · Retina. · Pubmed #17891007 No free full text.

Abstract: PURPOSE: To evaluate the short-term outcomes after intravitreal ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA) injection in patients with neovascular age-related macular degeneration. METHODS: A review of data for consecutive patients who received intravitreal ranibizumab injection was conducted. The main outcome measures were mean visual acuity and central macular thickness at 3 months compared with those at baseline. Response to ranibizumab therapy was evaluated with particular attention to prior treatment with bevacizumab (Avastin; Genentech, Inc.). RESULTS: Mean baseline visual acuity of 231 eyes of 231 patients was 20/152, and 189 patients (81.8%) had undergone prior treatment, with 153 (65.4%) having received intravitreal bevacizumab. Mean visual acuity at 3 months, available for 203 patients (88%), was 20/126 (P = 0.004). Mean visual acuity for 98 patients treated with bevacizumab within 3 months before ranibizumab injection was 20/100 at baseline and 20/98 at 3 months (P = 0.35). Mean baseline central macular thickness was 278 microm for all patients and improved to 211 microm at 3 months (P < 0.001). Macular thickness decrease was noted irrespective of previous bevacizumab therapy. CONCLUSION: Ranibizumab therapy was associated with significant improvements in mean visual acuity and central macular thickness for the group of all patients. Patients who had received bevacizumab treatment within 3 months before initiating ranibizumab treatment had stability of, but no improvement in, visual acuity.

Eandi CM, Ober MD, Freund KB, Slakter JS, Yannuzzi LA. · The LuEsther T. Mertz Retina Research Center of Manhattan Eye, Ear and Throat Hospital, New York, New York 10021, USA. · Retina. · Pubmed #17891004 No free full text.

Abstract: PURPOSE: To evaluate the efficacy of selective treatment with indocyanine green (ICG) angiography-guided photodynamic therapy (PDT) with verteporfin for polypoidal choroidal vasculopathy (PCV). METHODS: In this retrospective consecutive series, 30 eyes of 30 patients with PCV were included. Complete ocular examination, digital fluorescein angiography (FA), ICG angiography, and optical coherence tomography were performed at baseline and at standard intervals thereafter. ICG angiography-guided PDT was performed on all eyes. Only the area of the active PCV or "hot spot" evident on the ICG angiogram was treated. A spot size was chosen to cover the active neovascular lesion with a 200-mum border. Retreatment was performed when angiography revealed a recurrent lesion. RESULTS: Thirty eyes with PCV were treated and followed for 1 year. Mean age of the patients was 75 years (range, 55-90 years). These patients were all classified as having occult choroidal neovascularization (CNV) with FA and polypoidal CNV with ICG angiography. Improvement of vision (>or=3 lines) was achieved in 15 eyes (50%). Nine eyes had stable vision (30%), and 6 eyes (20%) had a decrease in vision (>or=3 lines). Repeated treatment was required in 15 eyes (50%) for an average of 2.2 treatments in 1 year. CONCLUSION: This study indicates that stabilization or improvement of vision is achieved in most eyes (80%) with neovascular AMD from PCV after selected ICG angiography-guided PDT. These outcomes compare very favorably with those in previous reports on the treatment of occult CNV. Reduced collateral damage to the choriocapillaris and reduced upregulation of vascular endothelial growth factor are presumed to be the explanation for this apparently better outcome. Further studies with longer follow-up are warranted to investigate the long-term efficacy in these conditions.

Matsumoto Y, Freund KB, Peiretti E, Cooney MJ, Ferrara DC, Yannuzzi LA. · Vitreous-Retina-Macula Consultants of New York, and LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York 10022, USA. · Retina. · Pubmed #17420693 No free full text.

Abstract: BACKGROUND: Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), has been given via intravitreal injection as an off-label therapy for both neovascular age-related macular degeneration and for macular edema secondary to retinal vascular disease. The authors describe three patients with macular edema secondary to retinal venous occlusion whose edema initially responded to intravitreal bevacizumab but subsequently recurred in excess of that observed before treatment. METHODS: This is a retrospective case series of three patients with macular edema secondary to retinal vein occlusion treated with intravitreal bevacizumab. RESULTS: In all three patients, the rebound retinal edema observed was more pronounced than that present before treatment. CONCLUSION: These cases suggest a potential limitation of using relatively short-acting VEGF antagonists in retinal vascular disease of a chronic nature. Frequent repeated injections may be required to prevent a rebound effect with no clearly defined endpoint. Until the long-term safety of multiple injections of these agents is established, the authors recommend caution in using this treatment strategy.

Iranmanesh R, Eandi CM, Peiretti E, Klais CM, Garuti S, Goldberg DE, Slakter JS, Yannuzzi LA. · The LuEsther T. Mertz Retina Research Center of Manhattan Eye, Ear and Throat Hospital, New York, USA. · Eur J Ophthalmol. · Pubmed #17294386 No free full text.

Abstract: PURPOSE: This study was designed to evaluate the frequency and nature of neovascularization in age-related macular degeneration (ARMD) utilizing the combination of digital imaging techniques, fluorescein angiography (FA), indocyanine green (ICG) angiography, and optical coherence tomography (OCT). METHODS: A complete clinical examination was performed on 100 eyes of 93 consecutive newly diagnosed patients with neovascular ARMD. Digital fluorescein angiography, ICG angiography, and OCT were also used in evaluating those patients. Comparison of the imaging techniques to determine their value in studying the nature of the lesions. RESULTS: On the basis of existing fluorescein standards, 15 eyes were diagnosed with classic choroidal neovascularization (CNV), 15 with minimally classic CNV, and 70 with occult CNV. ICG angiography was superior for detecting the active vascular component in polypoidal CNV (16 eyes) and retinal angiomatous proliferation (14 eyes). OCT was more sensitive than FA for determining the presence of cystoid macular edema evident in the vast majority of eyes with retinal angiomatous proliferation (RAP). CONCLUSIONS: These results suggest that FA, ICG angiography, and OCT, when used in combination, will assist clinicians in best determining the precise nature of the neovascular process in ARMD.

Peiretti E, Iranmanesh R, Lee JJ, Klancnik JM, Sorenson JA, Yannuzzi LA. · The Vitreous-Retina-Macula Consultants of New York, the LuEsther T Mertz Retinal Research Center, and Manhattan Eye, Ear, and Throat Hospital, New York, NY 10022, USA. · Retina. · Pubmed #17151507 No free full text.

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Klais CM, Eandi CM, Ober MD, Sorenson JA, Sadeghi SN, Freund KB, Spaide RF, Slakter JS, Yannuzzi LA. · LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York 10021, USA. · Retina. · Pubmed #16963850 No free full text.

Abstract: PURPOSE: The purpose of this study was to evaluate anecortave acetate treatment of retinal angiomatous proliferation (RAP), a neovascular form of age-related macular degeneration, with specific regard to inhibition of neovascularization and maintenance of vision. METHODS: Thirty-four patients with RAP with any stage of neovascularization were randomized 1:1:1 for treatment with three different quantities (30 mg, 15 mg, 3 mg) of anecortave acetate sterile suspension for juxtascleral administration. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study chart), intraocular pressure measurement, biomicroscopy, funduscopy, digital fluorescein, and indocyanine green angiography were recorded at baseline and at 3 months. A 6-month retreatment interval was established for this study with a follow-up of 12 months. In selected patients optical coherence tomography was performed. The outcomes were mean changes in visual acuity and lesion size at 1 year. RESULTS: The detachment of the neurosensory retina and retinal pigment epithelium improved in all eyes, but all neovascular lesions increased in size. Vision loss occurred in the majority of study eyes (22 out of 34 eyes, 64.7%) independent of the concentration administered. CONCLUSION: The results suggest that a posterior juxtascleral injection of anecortave acetate reduces capillary permeability in patients with RAP. However, in spite of improvement of the exudation there is a progression of neovascularization and a significant loss of vision in all these patients. Like other monotherapeutic methods used to treat this variant of neovascular age-related macular degeneration, anecortave acetate alone does not appear to benefit these patients. Future studies should investigate a combination form of therapy.

Freund KB, Klais CM, Eandi CM, Ober MD, Goldberg DE, Sorenson JA, Yannuzzi LA. · LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, NY 10021, USA. · Arch Ophthalmol. · Pubmed #16606873 links to  free full text

Abstract: OBJECTIVE: To study sequenced combined therapy using intravitreal triamcinolone acetonide followed by photodynamic therapy for the treatment of retinal angiomatous proliferation. METHODS: Patients newly diagnosed as having retinal angiomatous proliferation underwent intravitreal triamcinolone injection to reduce intraretinal and subretinal exudation, followed 7 to 14 days later by indocyanine green angiography-guided photodynamic therapy with verteporfin. Complete ocular examination, fluorescein angiography, indocyanine green angiography, and optical coherence tomography were performed at baseline and at standard intervals thereafter. RESULTS: Twenty-seven eyes of 26 patients underwent this sequenced combined treatment and were followed up for 12 months. The triamcinolone injection reduced the cystoid edema before photodynamic therapy. Complete resolution of the angiographic leakage was achieved in 89% of eyes. Visual acuity improved in 37% and was stable in 52% of eyes. Eight eyes developed recurrent leakage after 3 to 11 months. Complete resolution of leakage was observed after subsequent treatment. CONCLUSIONS: This sequenced combined treatment in patients with retinal angiomatous proliferation was effective in reducing or eliminating the edema, achieving rapid regression of neovascularization, and stabilizing or improving visual acuity. To our knowledge, no study to date has achieved such promising results in the management of retinal angiomatous proliferation. A randomized clinical trial is under way to compare sequential and simultaneous combined therapy.

Spaide RF, Laud K, Fine HF, Klancnik JM, Meyerle CB, Yannuzzi LA, Sorenson J, Slakter J, Fisher YL, Cooney MJ. · Vitreous Retina Macula Consultants of New York and the LuEsther T. Mertz Retinal Research Center at Manhattan Eye, Ear & Throat Hospital, 460 Park Avenue, New York, NY 10022, USA. · Retina. · Pubmed #16603955 No free full text.

Abstract: PURPOSE: To describe the short-term anatomical and visual acuity responses after intravitreal injection of bevacizumab (Avastin, Genentech) in patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). METHODS: We conducted a retrospective study of patients with CNV secondary to AMD who were treated with intravitreal injection of bevacizumab (1.25 mg) during a 3-month period. Patients underwent best-corrected Snellen visual acuity testing, optical coherence tomography, and ophthalmoscopic examination at baseline and follow-up visits. RESULTS: There were 266 consecutive eyes of 266 patients who received injections, and follow-up information was available for 251 (94.4%). The mean age of the patients was 80.3 years, the mean baseline visual acuity was 20/184, and 175 (69.7%) had inadequate response to alternate methods of treatment. At the 1-month follow-up (data available for 244 patients), the mean visual acuity was 20/137 (P < 0.001 as compared with baseline), and 74 (30.3%) of patients had improvement in visual acuity as defined by a halving of the visual angle. At the 2-month follow-up (data available for 222 patients), the mean visual acuity was 20/122 (P < 0.001), and 78 (31.1%) of patients had visual improvement. At the 3-month follow-up (data available for 141 patients), the mean visual acuity was 20/109 (P < 0.001), and 54 (38.3%) of patients had visual acuity improvement. The mean central macular thickness at baseline was 340 mum and decreased to a mean of 247 microm at month 1 (P < 0.001) and 213 microm at month 3 (P < 0.001). At 1 month, two patients had mild vitritis, as did one patient at 2 months, who had a history of recurrent uveitis. No endophthalmitis, increased intraocular pressure, retinal tear, or retinal detachment occurred. The risk for thromboembolic disorders did not seem to be different than reported previously in studies concerning macular degeneration. CONCLUSION: There were no apparent short-term safety concerns for intravitreal bevacizumab injection for CNV. Treated eyes had a significant decrease in macular thickness and improvement in visual acuity. The follow-up was too short to make any specific treatment recommendations, but the favorable short-term results suggest further study is needed.

Iturralde D, Spaide RF, Meyerle CB, Klancnik JM, Yannuzzi LA, Fisher YL, Sorenson J, Slakter JS, Freund KB, Cooney M, Fine HF. · Vitreous, Retina, Macula Consultants of New York, NY, USA. · Retina. · Pubmed #16508427 No free full text.

Abstract: PURPOSE: To report the short term anatomic and visual acuity response after intravitreal injection of bevacizumab (Avastin, Genentech) in patients with macular edema due to central retinal vein occlusion (CRVO). METHODS: The authors conducted a retrospective study of patients with macular edema due to CRVO who were treated with at least one intravitreal injection of bevacizumab 1.25 mg in 0.05 mL. Patients underwent Snellen visual acuity testing, optical coherence tomography (OCT) imaging, and ophthalmoscopic examination at baseline and follow-up visits. RESULTS: There were 16 eyes of 15 consecutive patients with a mean age of 76.1 years (SD 9.8 years). Intravitreal triamcinolone had been previously administered to 9 patients, but all of these patients either had no improvement or had excessive intraocular pressure caused by the triamcinolone. The patients received a mean of 2.8 injections of bevacizumab per eye. No adverse events were observed, including endophthalmitis, clinically evident inflammation, increased intraocular pressure, retinal tears, retinal detachment, or thromboembolic events in any patient. The mean central macular thickness at baseline was 887 microm and decreased to a mean of 372 microm at month 1 (P < 0.001). The mean baseline acuity was 20/600 (logMAR = 1.48) and the mean acuity at month 1 was 20/200 (logMAR = 1.05), a difference that was highly significant (P = 0.001). At last follow-up, a mean of 3 months after the first injection, the mean visual acuity was 20/138 (logMAR = 0.84), which was significantly better than baseline (P < 0.001). Visual acuity improvement, defined as a halving of the visual angle, was seen in 14 of the 16 eyes. CONCLUSION: Initial treatment results of patients with macular edema secondary to CRVO did not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in a significant decrease in macular edema and improvement in visual acuity. The number of patients in this pilot study was limited and the follow-up is too short to make any specific treatment recommendations, but the favorable short-term results suggest further study is needed.

Gross NE, Aizman A, Brucker A, Klancnik JM, Yannuzzi LA. · LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear & Throat Hospital, New York, New York 10021, USA. · Retina. · Pubmed #16141858 No free full text.

Abstract: PURPOSE: To determine the nature and risk of neovascularization in the fellow eyes of patients with unilateral retinal angiomatous proliferation (RAP), a neovascular form of age-related macular degeneration (AMD). METHODS: A consecutive series of 52 patients diagnosed with unilateral RAP were studied retrospectively. Clinical biomicroscopic examination, fluorescein angiography, and indocyanine green angiography were used to evaluate all patients for the development of neovascular manifestations in the fellow eye. RESULTS: Neovascularization developed in the fellow eye in 52 patients over the follow-up period (range, 2-36 months). All patients developed neovascular manifestations of RAP in the fellow eye. Twenty-one patients (40%) developed a RAP lesion within 1 year; 29 (56%), within 2 years; and 52 (100%), within 3 years. At the time of diagnosis of neovascularization in the fellow eye, 8 patients (15%) had a stage I RAP lesion, 36 (70%) had a stage II RAP lesion, and 8 (15%) had a stage III RAP lesion. Other characteristic findings in these patients included the presence of preretinal, intraretinal, and subretinal hemorrhages in 49 patients (94%) and pigment epithelial detachments in 41 patients (79%). CONCLUSIONS: In patients diagnosed with unilateral RAP lesions, the form of neovascularization that develops in the fellow eye is virtually always RAP. The annual and accumulative risk of neovascularization in the fellow eye is higher in patients with RAP than in those with other forms of neovascular AMD. These new findings enhance our understanding of the clinical spectrum of RAP in terms of its natural course and visual prognosis and may possibly offer useful information to establish future treatment options.

Klais CM, Ober MD, Freund KB, Ginsburg LH, Luckie A, Mauget-Faÿsse M, Coscas G, Gross NE, Yannuzzi LA. · Vitreous-Retina-Macula Consultants of New York, 519 E 72nd Street, Ste. 203, New York, NY 10021, USA. · Arch Ophthalmol. · Pubmed #16087856 No free full text.

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Eandi CM, Klais CM, Freund KB, Yannuzzi LA. · University Eye Clinic, University of Torino, Torino, Italy. · Retina. · Pubmed #15933607 No free full text.

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Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman JL, Stockman HA, Borchardt JD, Gehrs KM, Smith RJ, Silvestri G, Russell SR, Klaver CC, Barbazetto I, Chang S, Yannuzzi LA, Barile GR, Merriam JC, Smith RT, Olsh AK, Bergeron J, Zernant J, Merriam JE, Gold B, Dean M, Allikmets R. · Department of Ophthalmology and Visual Sciences, Cell Biology and Functional Genomics Laboratory, University of Iowa, Iowa City, IA 52240, USA. · Proc Natl Acad Sci U S A. · Pubmed #15870199 links to  free full text

Abstract: Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Our previous studies implicated activation of complement in the formation of drusen, the hallmark lesion of AMD. Here, we show that factor H (HF1), the major inhibitor of the alternative complement pathway, accumulates within drusen and is synthesized by the retinal pigmented epithelium. Because previous linkage analyses identified chromosome 1q25-32, which harbors the factor H gene (HF1/CFH), as an AMD susceptibility locus, we analyzed HF1 for genetic variation in two independent cohorts comprised of approximately 900 AMD cases and 400 matched controls. We found association of eight common HF1 SNPs with AMD; two common missense variants exhibit highly significant associations (I62V, chi2 = 26.1 and P = 3.2 x 10(-7) and Y402H, chi2 = 54.4 and P = 1.6 x 10(-13)). Haplotype analysis reveals that multiple HF1 variants confer elevated or reduced risk of AMD. One common at-risk haplotype is present at a frequency of 50% in AMD cases and 29% in controls [odds ratio (OR) = 2.46, 95% confidence interval (1.95-3.11)]. Homozygotes for this haplotype account for 24% of cases and 8% of controls [OR = 3.51, 95% confidence interval (2.13-5.78)]. Several protective haplotypes are also identified (OR = 0.44-0.55), further implicating HF1 function in the pathogenetic mechanisms underlying AMD. We propose that genetic variation in a regulator of the alternative complement pathway, when combined with a triggering event, such as infection, underlie a major proportion of AMD in the human population.

Ergun E, Costa D, Slakter J, Yannuzzi LA, Stur M. · Department of Ophthalmology, University of Vienna Medical School, Vienna, Austria. · Retina. · Pubmed #15187662 No free full text.

Abstract: PURPOSE: To investigate the effect of photodynamic therapy (PDT) with verteporfin on patients with vitelliform lesions caused by cuticular drusen or adult-onset foveomacular vitelliform dystrophy (AOFVD). DESIGN: Observational case series. PATIENTS AND METHODS: Eight eyes of seven patients from two centers were examined prospectively. Each patient received PDT with verteporfin applied to the vitelliform lesions. RESULTS: Photodynamic therapy did not significantly affect the median visual acuity outcome (20/50 before PDT and 20/66 after PDT) in all seven treated patients. Of note, however, were four eyes of four patients who experienced a severe decrease in visual acuity after PDT with verteporfin. The temporary relationship of the vision loss to the treatment suggests that this may represent an adverse effect from therapy. The fluorescein angiographic appearance was virtually unchanged in all treated patients, whereas indocyanine green angiography showed typical PDT-associated reduction of choroidal perfusion in the treatment area. CONCLUSION: Photodynamic therapy does not have a positive influence on the visual outcome in patients with vitelliform lesions and may have a negative impact on vision in some treated patients. It is important for physicians using PDT to exercise caution in distinguishing between choroidal neovascular membranes and vitelliform lesions because the outcome in this latter group may be worse with application of PDT than with the natural course.

Iida T, Yannuzzi LA, Spaide RF, Borodoker N, Carvalho CA, Negrao S. · Department of Ophthalmology, Fukushima Medical University School of Medicine, Japan. · Retina. · Pubmed #12652224 No free full text.

Abstract: PURPOSE: To describe the optical coherence tomography (OCT) and fluorescein angiography findings in the macula of eyes with chronic central serous chorioretinopathy (CSC) and reduced central vision. METHODS: Using OCT, clinical examination, and fluorescein and indocyanine green (ICG) angiography, the authors examined eight eyes of seven patients with CSC, an attached macula, and reduced central vision of 20/200 or worse. All had a history of chronic CSC with resolution of the subretinal fluid in the macular area and poor vision. RESULTS: Patient ages ranged from 55 to 82 years (mean, 66 years). All eight eyes had some parafoveal, patchy RPE atrophy with corresponding transmission hyperfluorescence (window defect) on fluorescein angiography. Five eyes also had a window defect in the foveal area. With OCT, the foveal area revealed variable areas of cystoid change and atrophy in seven of the eight eyes. In four of these eyes, the cystoid changes were not seen on clinical examination or fluorescein angiography. The seven eyes with cystoid changes imaged with OCT had no intraretinal leakage of fluorescein in the foveal region. The authors categorized these eyes as having cystoid macular degeneration (CMD). One other eye had foveal thinning or atrophy without cystoid changes. CONCLUSIONS: Intraretinal cystoid spaces without intraretinal leakage, or CMD, was a common finding in eyes with chronic CSC and reduced central vision after resolution of subretinal fluid. OCT was useful to establish the presence of CMD and foveal atrophy, even when these changes were not clearly evident on clinical examination or fluorescein angiography. Chronic foveal detachment and antecedent intraretinal leakage were proposed to be the mechanisms for the development of the changes. CMD in conjunction with foveal atrophy was an important clinical finding to account for the poor visual outcome in patients with CSC.

Fernandes LH, Freund KB, Yannuzzi LA, Spaide RF, Huang SJ, Slakter JS, Sorenson JA. · LuEsther T Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, NY 10021, USA. · Retina. · Pubmed #12441720 No free full text.

Abstract: PURPOSE: To clarify the frequency and nature of ICG angiographic "hot spots" seen in patients with neovascular age-related macular degeneration (ARMD). METHODS: A consecutive series of newly diagnosed patients with neovascular ARMD and fluorescein angiographic evidence of occult choroidal neovascularization (occult CNV) was imaged with ICG angiography. Eyes with ICG angiographic "hot spots" were identified and further classified. A hot spot was defined as any area of abnormal hyperfluorescence, in the mid to late stages of ICG angiography, measuring less than 1 disk area in size. RESULTS: From a total of 190 patients (220 eyes) with neovascular ARMD, 30 patients and 34 eyes (16%) with hot spots were identified. Hot spots were noted to be of three distinct patterns: polypoidal choroidal neovascularization (polypoidal CNV) in 21 of 34 eyes, or 62%; retinal angiomatous proliferation (RAP) in 11 of 34 eyes, or 30%; and focal occult CNV in 2 of 34 eyes, or 8%. CONCLUSIONS: A focal area of intense hyperfluorescence or so-called hot spot seen on ICG angiography in neovascular ARMD is due to one of three possible forms of neovascularization: most frequently polypoidal CNV, less commonly RAP, and infrequently nonspecific, focal occult CNV. Since neovascular ARMD may be caused by different types of neovascularization, each with distinct clinical manifestations, natural course, visual prognosis, and response to treatment, it is important to identify the precise nature of hot spots to establish an accurate diagnosis and, when appropriate, a specific form of management.