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1. Cigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways.

Author

Giordano, L, Deceglie, S, d'Adamo, P, Valentino, ML, La Morgia, C, Fracasso, F, Roberti, M, Cappellari, M, Petrosillo, G, Ciaravolo, S, Parente, D, Giordano, C, Maresca, A, Iommarini, L, Del Dotto, V, Ghelli, AM, Salomao, SR, Berezovsky, A, Belfort, R, Sadun, AA, Carelli, V, Loguercio Polosa, P, and Cantatore, P

Subjects
Humans, Optic Atrophy, Hereditary, Leber, Reactive Oxygen Species, DNA, Mitochondrial, Smoking, Oxidative Phosphorylation, Female, Male, Optic Atrophy, Hereditary, Leber, DNA, Mitochondrial, Biochemistry and Cell Biology, Oncology and Carcinogenesis
Abstract

Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that modulate LHON penetrance must take into account also the exposure to environmental triggers such as tobacco smoke.

Published
2015

4. Efficacy and Safety of Abicipar in Neovascular Age-Related Macular Degeneration: 52-Week Results of Phase 3 Randomized Controlled Study

Author

Kunimoto D., Yoon Y. H., Wykoff C. C., Chang A., Khurana R. N., Maturi R. K., Agostini H., Souied E., Chow D. R., Lotery A. J., Ohji M., Bandello F., Belfort R., Li X. -Y., Jiao J., Le G., Schmidt W., Hashad Y., Kunimoto, D., Yoon, Y. H., Wykoff, C. C., Chang, A., Khurana, R. N., Maturi, R. K., Agostini, H., Souied, E., Chow, D. R., Lotery, A. J., Ohji, M., Bandello, F., Belfort, R., Li, X. -Y., Jiao, J., Le, G., Schmidt, W., and Hashad, Y.

Subjects
Male, Time Factors, Dose-Response Relationship, Drug, Recombinant Fusion Proteins, Visual Acuity, Drug Administration Schedule, Treatment Outcome, Double-Blind Method, Intravitreal Injections, Wet Macular Degeneration, Humans, Female, Macula Lutea, Tomography, Optical Coherence, Aged, Follow-Up Studies
Abstract

Purpose: To compare the efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) versus ranibizumab every 4 weeks in treatment-naïve patients with neovascular age-related macular degeneration (AMD). Design: Two randomized, multicenter, double-masked, parallel-group, active-controlled, phase 3 clinical trials (CEDAR, SEQUOIA) with identical protocols were conducted. Data from both trials were pooled for analysis. Participants: Patients with active choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) of 24–73 Early Treatment Diabetic Retinopathy Study letters in the study eye were enrolled. Methods: Patients (n = 1888) were randomized in a 1:1:1 ratio to study eye treatment with abicipar 2 mg every 8 weeks after 3 initial doses at baseline and weeks 4 and 8 (Q8), abicipar 2 mg every 12 weeks after 3 initial doses at baseline and weeks 4 and 12 (Q12), or ranibizumab 0.5 mg every 4 weeks (Q4). Main Outcome Measures: The primary efficacy end point was proportion of patients with stable vision (defined as

Published
2020

6. Colour vision defects in asymptomatic carriers of the Leber's hereditary optic neuropathy (LHON) mtDNA 11778 mutation from a large Brazilian LHON pedigree: a case-control study

Author

Quiros, P.A., Torres, R.J., Salomao, S., Berezovsky, A., Carelli, V., Sherman, J., Sadun, F., De Negri, A ., Belfort, R., and Sadun, A.A.

Subjects
Optic atrophy -- Development and progression, Optic atrophy -- Genetic aspects, Color blindness -- Causes of, Color blindness -- Research, Gene mutations -- Research, Health
Published
2006

16. Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative

Author

Dick, A. D., Rosenbaum, J. T., Al-Dhibi, H. A., Belfort, R., Brezin, A. P., Chee, S. P., Davis, J. L., Ramanan, A. V., Sonoda, K. -H., Carreno, E., Nascimento, H., Salah, S., Salek, S., Siak, J., Steeples, L., Accorinti, M., Acharya, N., Adan, A., Agrawal, R., Akkoc, N., Al Ghamdi, S., Al Ghamdi, T., Al Saati, A., Alsabaani, N., Al-Shamarani, M., Bachta, A., Barisani-Asenbauer, T., Beare, N., Porto, F. B. O., Blanco, R., Yee, A. C. S., Chandran, V., Chiquet, C., Chng, H. H., Cimbalas, A., Cimino, L., Cordero-Coma, M., Cristobal, C., Cuevas, M., Eurico da Fonseca, J., de Boer, J., de la Torre, A., De Schryver, I., Derzko-Dzulynsky, L., Diaz-Valle, D., Merino, C. E. D., Facsko, A., Figueira, L., Fonollosa, A., Fortin, E., Gale, R., Galeazzi, M., Garcia, S., Garcia Ruiz de Morales, J. M., Gaspersic, N., Goldstein, D., Guedes, M., Guex-Crosier, Y., Gul, A., Hamam, R., Haroon, M., Hasegawa, K., Heiligenhaus, A., Hooper, C., Hwang, Y. -S., Hwang, D. -K., Juanola, X., Kaburaki, T., Kadayifcilar, S., Kempen, J., Kezuka, T., Kherani, A., Kirsimae, M., Kotaniemi, K., Kraut, A., Kubicka-Trzaska, A., Kuffova, L., Lightman, S., Lim, L., Lim, W. K., Mccluskey, P., Mcguire, M., Mirabelli, P., Miserocchi, E., Misiuk-Hojlo, M., Muccioli, C., Munoz, S., Murphy, C., Murray, P., Nagy, Z., Namba, K., Neri, P., Nguyen, Q., O'Gradaigh, D., Omair, M., Otsa, K., Ozyazgan, Y., Pablo, F., Paroli, M. P., Pleyer, U., Poor, G., Proenca, R., Rabinovitch, T., Read, R., Rebrov, M., Recillas-Gispert, C., Rothova, A., Schwartzman, S., Seve, P., Sharma, S., Sims, J., Sohar, N., Suhler, E., Szanto, S., Szepessy, Z., Tappeiner, C., Thorne, J., Tugal Tutkun, I., Turno-Krecicka, A., Van Calster, J., van der Horst-Bruinsma, I., Vidovic Valentincic, N., Vitale, A., Voorduin Ramos, S., Vukojevic, N., Wakefield, D., Willermain, F., Yalcindag, N., Yamamoto, J. H., Yeh, S., Zemaitiene, R., and Ziouzina, O.

Published
2018

19. Ocular manifestations of Zika virus: What we do and do not know

Author

Benzekri, R., Belfort, R., Jr. {UNIFESP], Ventura, C. V. [UNIFESP], Freitas, B. de Paula, Maia, M. [UNIFESP], Leite, M., Labetoulle, M., and Rousseau, A.

Subjects
Uveitis, Zika, Maculopathy, Microcephaly, Conjunctivitis, Epidemics, Virus
Abstract

Zika virus (ZIKV) disease outbreak, which was declared by the end of 2015 inBrazil, has become the largest one to date. Being reported in the Americas and in certain islands of the Pacific, it has the potential to spread worldwide. Although ZIKV infections are mostly self-limiting and/or asymptomatic in the healthy adult, they are responsible for devastating congenital neurologic malformations ZIKV (mainly microcephaly) when contracted during the first months of pregnancy. Ocular manifestations during the acute adult infection include conjunctivitis and more rarely ocular inflammation. Congenital infection is associated with chorioretinal atrophy pigment mottling of the retina retinal vasculature abnormalities and optic nerve atrophy. Therefore, complete ophthalmological evaluation is recommended for suspected congenital infections. (C) 2017 Elsevier Masson SAS. All rights reserved. Univ Paris Sud, Hop Bicetre, Assistance Publ Hop Paris, Serv Ophtalmol,DHU Vis & Handicap, 78 Rue Gen Leclerc, F-94275 Le Kremlin Bicetre, France Univ Fed Sao Paulo, Dept Ophthalmol & Visual Sci, Paulista Sch Med, Sao Paulo, Brazil Vis Inst, Sao Paulo, Brazil Altino Ventura Fdn, Recife, PE, Brazil Pernambucos Eye Hosp HOPE, Dept Ophthalmol, Recife, PE, Brazil Hosp Geral Roberto Santos, Dept Ophthalmol, Salvador, BA, Brazil Commissariat Energie Atom & Energies Alternat, Immunol Infect Virales & Malad Autoimmunes, UMR 1184, Fontenay Aux Roses, France Univ Fed Sao Paulo, Dept Ophthalmol & Visual Sci, Paulista Sch Med, Sao Paulo, Brazil Web of Science

Published
2017

20. Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema: Subgroup analysis of the MEAD study

Author

Augustin, A. J., Kuppermann, B. D., Lanzetta, P., Loewenstein, A., X. -Y., Li, Cui, H., Hashad, Y., Whitcup, S. M., Abujamra, S., Acton, J., Ali, F., Antoszyk, A., Awh, C. C., Barak, A., Bartz-Schmidt, K. U., Baumal, C. R., Belfort, R. Jr., Bhende, M., Boyer, D. S., Bridges, W. Z. Jr., Brown, D. M., Carmichael, T., Carnevale, K., Casella, A. M., Chang, T., Chechik, D., Chen, S. -N., Chong, L. P., Chong, V., Corwin, J., Creuzot-Garcher, C., Cruess, A., Daniell, M., De Avila, M. P., De Moraes, H. V. Jr., Devenyi, R. G., Doft, B. H., Donaldson, M., Dreyer, R., Eliott, D., Engel, H. M., Ernest, J., Essman, T. F., Falcone, P. M., Fekrat, S., Ferencz, J. R., Ferreira, J. L., Figueira, J., Fiser, I., Foster, B., Fox, G. M., Freeman, W. R., Garg, S. P., Gillies, M., Glaser, D., Goldstein, B. G., Gomes, A. M. V., Gonder, J. R., Gopal, L., Gous, P., Gupta, A., Halperin, L., Han, D., Hariprasad, S. M., Holz, F. G., Kaiser, P., Kalvodova, B., Katz, B., Katz, R. S., Kecik, D., Kellaway, J., Klemperer, I., Lattanzio, R., Lee, W. -K., Lehr, J., Leys, M., Loose, I., Lotery, A., D. -W., Lu, Mccartney, P., Majji, A. B., Martinez, J. A., Massin, P., Maturi, R. K., Menchini, U., Menon, G., Michels, M., Midena, E., Miller, J. Jr., Mitchell, P., Moisseiev, J., Morse, L., Navarro, R., Nemeth, J., Newland, H., Newsom, R., Nichols, J., Orellana, J., Orzalesi, N., Paranhos, A. Jr., Park, R., Park, S., Parodi, M. B., Pavan, P. R., Peace, J., Perez-Ortiz, D. J., Pollack, A., Ramaswamy, K., Ratnakaram, R., Ravalico, G., Rehak, J., Rezaei, K., Rizzo, S., Rodriguez-Alvira, F. J., Romanet, J. -P., Rose, S., Rosen, R. B., Rossetti, L., Ruiz-Moreno, J. M., Sadda, S., Sall, K., Sandner, D., Sanz, A. F. -V., Sartani, G., Schmickler, S., Schwartz, S. D., Sharma, Y. R., Sheu, S. -J., Singer, M., Sivaprasad, S., Soubrane, G., Soucek, P., Souied, E. H., Staurenghi, G., Studnicka, J., Suarez-Figueroa, M., Takahashi, W. Y., Tognetto, D., Tsai, P. L., Ulanski, L. J., H. S., Uy, Varano, M., Veith, M., Vicha, I., Viola, F., Visser, L., Weinberger, D., Wing, G. L., Wong, E., Wong, T. Y., Wylegala, E., Yan, J., Yoon, Y. H., Young, L. H., H. G., Yu, Zimmer-Galler, I. E., Augustin, Aj, Kuppermann, Bd, Lanzetta, P, Loewenstein, A, Li, Xy, Cui, H, Hashad, Y, Whitcup, Sm, on behalf of for the Ozurdex MEAD Study, Group, Battaglia Parodi, M, Augustin, A. J., Kuppermann, B. D., Lanzetta, P., Loewenstein, A., Li, X. -Y., Cui, H., Hashad, Y., Whitcup, S. M., Abujamra, S., Acton, J., Ali, F., Antoszyk, A., Awh, C. C., Barak, A., Bartz-Schmidt, K. U., Baumal, C. R., Belfort, R., Bhende, M., Boyer, D. S., Bridges, W. Z., Brown, D. M., Carmichael, T., Carnevale, K., Casella, A. M., Chang, T., Chechik, D., Chen, S. -N., Chong, L. P., Chong, V., Corwin, J., Creuzot-Garcher, C., Cruess, A., Daniell, M., De Avila, M. P., De Moraes, H. V., Devenyi, R. G., Doft, B. H., Donaldson, M., Dreyer, R., Eliott, D., Engel, H. M., Ernest, J., Essman, T. F., Falcone, P. M., Fekrat, S., Ferencz, J. R., Ferreira, J. L., Figueira, J., Fiser, I., Foster, B., Fox, G. M., Freeman, W. R., Garg, S. P., Gillies, M., Glaser, D., Goldstein, B. G., Gomes, A. M. V., Gonder, J. R., Gopal, L., Gous, P., Gupta, A., Halperin, L., Han, D., Hariprasad, S. M., Holz, F. G., Kaiser, P., Kalvodova, B., Katz, B., Katz, R. S., Kecik, D., Kellaway, J., Klemperer, I., Lattanzio, R., Lee, W. -K., Lehr, J., Leys, M., Loose, I., Lotery, A., Lu, D. -W., Mccartney, P., Majji, A. B., Martinez, J. A., Massin, P., Maturi, R. K., Menchini, U., Menon, G., Michels, M., Midena, E., Miller, J., Mitchell, P., Moisseiev, J., Morse, L., Navarro, R., Nemeth, J., Newland, H., Newsom, R., Nichols, J., Orellana, J., Orzalesi, N., Paranhos, A., Park, R., Park, S., Parodi, M. B., Pavan, P. R., Peace, J., Perez-Ortiz, D. J., Pollack, A., Ramaswamy, K., Ratnakaram, R., Ravalico, G., Rehak, J., Rezaei, K., Rizzo, S., Rodriguez-Alvira, F. J., Romanet, J. -P., Rose, S., Rosen, R. B., Rossetti, L., Ruiz-Moreno, J. M., Sadda, S., Sall, K., Sandner, D., Sanz, A. F. -V., Sartani, G., Schmickler, S., Schwartz, S. D., Sharma, Y. R., Sheu, S. -J., Singer, M., Sivaprasad, S., Soubrane, G., Soucek, P., Souied, E. H., Staurenghi, G., Studnicka, J., Suarez-Figueroa, M., Takahashi, W. Y., Tognetto, D., Tsai, P. L., Ulanski, L. J., Uy, H. S., Varano, M., Veith, M., Vicha, I., Viola, F., Visser, L., Weinberger, D., Wing, G. L., Wong, E., Wong, T. Y., Wylegala, E., Yan, J., Yoon, Y. H., Young, L. H., Yu, H. G., and Zimmer-Galler, I. E.

Subjects
Male, Vascular Endothelial Growth Factor A, Visual acuity, Triamcinolone acetonide, genetic structures, medicine.medical_treatment, Visual Acuity, Angiogenesis Inhibitors, Drug Implant, Triamcinolone Acetonide, Dexamethasone, Immunosuppressive Agent, Glucocorticoid, Diabetic retinopathy, Dexamethasone Intravitreal Implant, Corticosteroid, Drug delivery, Implant, Macular edema, Aged, Diabetic Retinopathy, Drug Implants, Female, Glucocorticoids, Humans, Immunosuppressive Agents, Intravitreal Injections, Macular Edema, Middle Aged, Retreatment, Tomography, Optical Coherence, Ophthalmology, Tomography, General Medicine, medicine.symptom, medicine.drug, Angiogenesis Inhibitor, Human, Research Article, medicine.medical_specialty, Subgroup analysis, medicine, business.industry, Intravitreal Injection, Cataract surgery, medicine.disease, eye diseases, Optical Coherence, business
Abstract

Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34–68 Early Treatment Diabetic Retinopathy Study letters (20/200–20/50 Snellen equivalent), and central retinal thickness (CRT) ≥300 μm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was ≥15-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n = 261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had ≥15-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was −126.1 μm with DEX 0.7 versus −39.0 μm with sham (P

Published
2015

21. The Standardization of Uveitis Nomenclature (SUN) Project

Author

Trusko, B., Thorne, J., Jabs, D., Belfort, R. [UNIFESP], Dick, A., Gangaputra, S., Nussenblatt, R., Okada, A., Rosenbaum, J., Standardization Uveitis Nomenclatu, Mt Sinai Sch Med, Johns Hopkins Univ, Universidade Federal de São Paulo (UNIFESP), Univ Bristol, Univ Wisconsin, NEI, Kyorin Eye Ctr, and Oregon Hlth & Sci Univ

Subjects
medicine.medical_specialty, Pathology, Delphi Technique, 020205 medical informatics, Standardization, Classification criteria, Delphi method, Health Informatics, 02 engineering and technology, Health informatics, Article, Terminology, Uveitis, 03 medical and health sciences, 0302 clinical medicine, Health Information Management, Health informatics tools, Terminology as Topic, Delphi technique, 0202 electrical engineering, electronic engineering, information engineering, Humans, Medicine, Medical physics, 030212 general & internal medicine, Advanced and Specialized Nursing, Evidence-Based Medicine, business.industry, nominal group techniques, Nominal group, Evidence-based medicine, Group Processes, standardized terminology, Informatics, uveitis, business, Medical Informatics
Abstract

Background: Given the recent increased focus on evidence-based medicine, it is critical that diseases and syndromes have accurate and complete descriptions, including standardized and widely accepted terminologies. Standardizing these descriptions and terminologies is necessary to develop tools such as computerized data entry forms and classification criteria. This need is especially true for diseases that are relatively uncommon, such as uveitis.Objectives: To develop a standardized and internationally accepted terminology for the field of uveitis.Methods: the Standardization of Uveitis Nomenclature (SUN) Working Group (WG) is an international group of 79 uveitis experts from 18 countries and 62 clinical centers. Initial terminology was developed utilizing a modified green field approach, which was enhanced through web-based surveys and teleconferences via a modified Delphi technique. Terms were mapped provisionally into ontologic dimensions for each syndrome. the Working Group then met and utilized nominal group techniques as a formalized method of finalizing the mappings.Results: Mapping of terms into dimensions to describe 28 major uveitic diseases was confirmed using nominal group techniques (achieving super-majority consensus) for each of the diseases at a meeting of the entire WG.Conclusions: the SUN WG utilized an informatics-based approach to develop a standardized and internationally accepted terminology for the uveitides. Mt Sinai Sch Med, New York, NY 10029 USA Johns Hopkins Univ, Sch Med, Baltimore, MD USA Universidade Federal de São Paulo, Dept Ophthalmol, São Paulo, Brazil Univ Bristol, Bristol, Avon, England Univ Wisconsin, Madison, WI USA NEI, NIH, Bethesda, MD 20892 USA Kyorin Eye Ctr, Tokyo, Japan Oregon Hlth & Sci Univ, Portland, OR 97201 USA Universidade Federal de São Paulo, Dept Ophthalmol, São Paulo, Brazil Web of Science

Published
2013

22. Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy

Author

Giordano, C., Iommarini, L., Giordano, L., Maresca, A., Pisano, A., Valentino, M. L., Caporali, L., Liguori, R., Deceglie, S., Roberti, M., Fanelli, F., Fracasso, F., Ross Cisneros, F. N., D'Adamo, ADAMO PIO, Hudson, G., Pyle, A., Yu Wai Man, P., Chinnery, P. F., Zeviani, M., Salomao, S. R., Berezovsky, A., Belfort, R., Ventura, D. F., Moraes, M., Moraes Filho, M., Barboni, P., Sadun, F., De Negri, A., Sadun, A. A., Tancredi, A., Mancini, M., D'Amati, G., Loguercio Polosa, P., Cantatore, P., Carelli, V., Univ Rome, Univ Bologna, Univ Bari, Bellaria Hosp, USC, Univ Trieste, Newcastle Univ, Fdn Ist Neurol Carlo Besta IRCCS, MRC Mitochondrial Biol Unit, Universidade Federal de São Paulo (UNIFESP), Universidade de São Paulo (USP), Studio Oculist dAzeglio, Osped San Giovanni Evangelista, Azienda Osped San Camillo Forlanini, Giordano C, Iommarini L, Giordano L, Maresca A, Pisano A, Valentino ML, Caporali L, Liguori R, Deceglie S, Roberti M, Fanelli F, Fracasso F, Ross-Cisneros FN, D'Adamo P, Hudson G, Pyle A, Yu-Wai-Man P, Chinnery PF, Zeviani M, Salomao SR, Berezovsky A, Belfort R Jr, Ventura DF, Moraes M, Moraes Filho M, Barboni P, Sadun F, De Negri A, Sadun AA, Tancredi A, Mancini M, d'Amati G, Loguercio Polosa P, Cantatore P, Carelli V, C., Giordano, L., Iommarini, L., Giordano, A., Maresca, A., Pisano, M. L., Valentino, L., Caporali, R., Liguori, S., Deceglie, M., Roberti, F., Fanelli, F., Fracasso, F. N., Ross Cisnero, D'Adamo, ADAMO PIO, G., Hudson, A., Pyle, P., Yu Wai Man, P. F., Chinnery, M., Zeviani, S. R., Salomao, A., Berezovsky, R., Belfort, D. F., Ventura, M., Morae, M., Moraes Filho, P., Barboni, F., Sadun, A., De Negri, A. A., Sadun, A., Tancredi, M., Mancini, G., D'Amati, P., Loguercio Polosa, P., Cantatore, and V., Carelli

Subjects
Adult, Male, mitochondrial biogenesis, Adolescent, mtDNA copy number, Penetrance, and over, Medical and Health Sciences, LHON penetrance, Young Adult, 80 and over, Humans, mitochondrial biogenesi, Aged, Aged, 80 and over, DNA, Mitochondrial, Female, Middle Aged, Mitochondrial Turnover, Optic Atrophy, Hereditary, Leber, Pedigree, lhon, Leber, Neurology & Neurosurgery, Psychology and Cognitive Sciences, lhon penetrance, mtdna copy number, DNA, Mitochondrial, Optic Atrophy, Hereditary
Abstract

Telethon Associazione Serena Talarico per i giovani nel mondo and Fondazione Giuseppe Tomasello O.N.L.U.S. Mitocon Onlus Research to Prevent Blindness International Foundation for Optic Nerve Diseases (IFOND) Struggling Within Leber's Poincenot Family Eierman Foundation National Eye Institute Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies. Univ Rome, Dept Radiol Oncol & Pathol, Rome, Italy Univ Bologna, Dept Biomed & NeuroMotor Sci DIBINEM, Bologna, Italy Univ Bari, Dept Biosci Biotechnol & Biopharmaceut, Bari, Italy Bellaria Hosp, IRCCS Ist Sci Neurol Bologna, I-40139 Bologna, Italy USC, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA USA USC, Keck Sch Med, Dept Neurosurg, Los Angeles, CA USA Univ Trieste, Dept Reprod Sci Dev & Publ Hlth, Trieste, Italy Univ Trieste, IRCCS Burlo Garofolo Children Hosp, Trieste, Italy Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England Fdn Ist Neurol Carlo Besta IRCCS, Unit Mol Neurogenet, Milan, Italy MRC Mitochondrial Biol Unit, Cambridge, England Fed Univ São Paulo UNIFESP, Dept Ophthalmol, São Paulo, Brazil Univ São Paulo, Inst Psychol, Dept Expt Psychol, São Paulo, Brazil Studio Oculist dAzeglio, Bologna, Italy Osped San Giovanni Evangelista, Tivoli, Italy Azienda Osped San Camillo Forlanini, Rome, Italy Univ Rome, Dipartimento Metodi & Modelli Econ Finanza & Terr, Rome, Italy Univ Rome, Dept Mol Med, Rome, Italy Fed Univ São Paulo UNIFESP, Dept Ophthalmol, São Paulo, Brazil Telethon: GGP06233 Telethon: GGP11182 Telethon: GPP10005 National Eye Institute: EY03040 Web of Science

Published
2014

23. Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema: Subgroup analysis of the MEAD study

Author

Augustin, AJ, Kuppermann, BD, Lanzetta, P, Loewenstein, A, Li, XY, Cui, H, Hashad, Y, Whitcup, SM, Abujamra, S, Acton, J, Ali, F, Antoszyk, A, Awh, CC, Barak, A, Bartz-Schmidt, KU, Baumal, CR, Belfort, R, Bhende, M, Boyer, DS, Bridges, WZ, Brown, DM, Carmichael, T, Carnevale, K, Casella, AM, Chang, T, Chechik, D, Chen, SN, Chong, LP, Chong, V, Corwin, J, Creuzot-Garcher, C, Cruess, A, Daniell, M, De Avila, MP, De Moraes, HV, Devenyi, RG, Doft, BH, Donaldson, M, Dreyer, R, Eliott, D, Engel, HM, Ernest, J, Essman, TF, Falcone, PM, Fekrat, S, Ferencz, JR, Ferreira, JL, Figueira, J, Fiser, I, Foster, B, Fox, GM, Freeman, WR, Garg, SP, Gillies, M, Glaser, D, Goldstein, BG, Gomes, AMV, Gonder, JR, Gopal, L, Gous, P, Gupta, A, Halperin, L, Han, D, Hariprasad, SM, Holz, FG, Kaiser, P, Kalvodova, B, Katz, B, Katz, RS, Kecik, D, Kellaway, J, Klemperer, I, Lattanzio, R, Lee, WK, Lehr, J, Leys, M, Loose, I, Lotery, A, Lu, DW, McCartney, P, Majji, AB, Martinez, JA, Massin, P, Maturi, RK, Menchini, U, Menon, G, Michels, M, Midena, E, Miller, J, Mitchell, P, Moisseiev, J, Morse, L, Navarro, R, Nemeth, J, Newland, H, Newsom, R, Nichols, J, Orellana, J, and Orzalesi, N

Subjects
genetic structures, eye diseases
Abstract

© 2015 Augustin et al. Background: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods: Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34.68 Early Treatment Diabetic Retinopathy Study letters (20/200.20/50 Snellen equivalent), and central retinal thickness (CRT) ≥300 μm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was ≥15-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Results: Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n=261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had ≥15-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 μm with DEX 0.7 versus -39.0 μm with sham(P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. Conclusions: DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population.

Published
2015

24. Intravitreal Injection Technique Reply

Author

Haller JA, Belfort R, Gillies M, Loewenstein A, Yoon YH, Li XY, Whitcup SM, BANDELLO , FRANCESCO, Haller, Ja, Bandello, Francesco, Belfort, R, Gillies, M, Loewenstein, A, Yoon, Yh, Li, Xy, and Whitcup, Sm

Published
2012

27. Dexamethasone Intravitreal Implant in Patients with Macular Edema Related to Branch or Central Retinal Vein Occlusion

Author

Haller, Ja, Bandello, F, Belfort R., Jr, Blumenkranz, M. S., Gillies, M, Heier, J, Loewenstein, A, Yoon, Yh, Jiao, J, Li, Xy, Whitcup, S. M., Aaberg, Tm, Abraham, P, Abujamra, S, Acton, J, Adamczyk Ludyga, A, Adenwalla, M, Agahigian, Dd, Agoas, V, Aguilar Mendoza, M, Aisenbrey, S, Alam, S, Albiani, D, Alexandrescu, B, Alfaiate, Mm, Allam, S, Almeida, Hp, Anagnoste, S, Anand, R, Anderson, N, Antoszyk, A, Armogan, N, Arnold, J, Ash, D, Atlas, Wg, Augustin, Ja, de Ávila MP, Awh, C, Azzolini, C, Babkova, B, Bakri, Sj, Banach, Mj, Barak, A, Barile, G, Barker, D, Barnard, T, Bartz Schmidt KU, Battaglia Parodi, M, Baumal, C, Bedrich, P, Beer, P, Belfort Mattos Junior, R, Bellini, L, Benner, J, Benson, W, Benz, M, Berger, B, Bergren, R, Bharadwaj, A, Bhavan, S, Bhavsar, A, Binder, S, Biondi, A, Bishop, F, Blair, N, Blinder, K, Blumenkranz, M, Bohm, A, Boldrey, Ee, Bornfeld, N, Borrillo, Jl, Boyer, D, Bradford, R, Bridges, W, Brigatti, L, Briggs, M, Brooks HL Jr, Brown, D, Browning, A, Browning, D, Brunner, S, Brunnerova, R, Bryan, Js, Brydak Godowska, J, Buettner, H, Burns, J, Burrows, Af, Busbee, B, Butner, R, Butter, J, Byrnes, G, Callahan, C, Campochiaro, P, Cano Hildalgo RA, Canziani, T, Capaccioli, K, Capone, A, Carmichael, T, Carnevale, K, Casella, Am, Casey, R, Castanheira Dinis, A, Celis, B, Chambers, R, Chang, S, Chang, Yh, Chechik, D, Chee, Sp, Chen, E, Chen, Jt, Chen, Sn, Chen, S, Cheng, B, Chiquet, C, Chong, K, Chong, Lp, Chong, V, Chou, T, Chow, V, Chrapek, O, Chu, T, Chua, J, Chun, D, Chung, Hw, Cialdini, Ap, Ciancas, E, Cihelkova, I, Cisiecki, S, Clark, W, Cleary, T, Coco, R, Codenotti, M, Cohen, Bz, Cohen, Ja, Cohen, J, Connolly, B, Conway, B, Cook, H, Cooper, B, Coors, L, Corwin, J, Costa, Jr, Cottrell, D, Couvillion, S, Craig, J, Cruess, A, Dabbs, T, Danesh, S, Davidorf, F, Davis, J, De Cilla, S, De Fazio, R, de la Fuente MA, de la Rua ER, De Mattia, M, Deen, A, Del Priore, L, Delyfer, Mn, Deuter, C, Devadason, Ds, Devenyi, R, D'Heurle, D, Dickinson, J, Doft, B, Dooner, J, Doubell, D, Downie, J, Drenser, K, Dreyer, R, D'Sousa, Y, Du, T, Duarte, L, Dubiner, Hb, Dubovy, S, Dubska, Z, Dugel, P, Dunn, W, Dusova, J, Dvorak, J, Dyer, D, Dziegielewska, K, Earl, M, Egan, C, Eichenbaum, D, Eifrig, C, Ells, A, El Shabrawi, Y, Elsherbiny, S, Engel, H, Engelbrecht, N, Ernest, J, Essex, R, Eter, N, Evans, R, Fakadej, A, Falcone, P, Fan, D, Fan, Jt, Eid Farah, M, Farah, S, Feiner, L, Feldman, Rm, Ferencz, J, Fernandez Vega Sanz, A, Ferreira, Jl, Figueira, J, Fineman, M, Fiser, I, Fish, G, Fish, Rh, Fishburne, B, Fisher, Sj, Fitzsimons, R, Flaxel, C, Fletcher, E, Flores Aguilar, M, Florez, S, Flynn, H, Fogarty, S, Folgado, A, Foster, Bs, Fox, Gm, Frambach, D, Framme, C, Fransen, S, Fraser Bell, S, Frederick, A, Freeman, W, Freisberg, L, Friedman, E, Friedman, L, Fucik, M, Fuller, Dg, Gaitan, J, Gallemore, R, Gallogly, P, Arumi, Jg, Garg, S, Garretson, B, Gastaud, P, Gaudric, A, Gawrilow, P, Gehlbach, Pl, Geyer, O, Ghuman, At, Giansanti, F, Luiz Gil, A, Gilbert, Hd, Girmens, Jf, Giubilato, A, Glacet Bernard, A, Glaser, D, Glatzer, R, Goldstein, D, Gomes, Am, Gon Yu, H, Gonçalves, Fp, Gonzales, C, Googe, J, Gopal, L, Gordon, A, Gous, P, Grand, M, Cristina, P, Magro, G, Granero Riano, M, Grassi, M, Green, J, Green, S, Gregor, Z, Gregori, N, Grizzard, Ws, Groenewald, C, Gross, Jg, Gross, Ne, Gruber, A, Grutow, G, Guillet, E, Gupta, A, Gyorgyova, D, Haas, A, Haas, K, Hadden, P, Hagemann, L, Hainsworth, D, Haivala, D, Haller, J, Halperin, L, Hamer, P, Hammer, M, Han, D, Handa, Jt, Handelman, I, Handza, J, Harder, B, Harding, S, Hariprasad, Sm, Hartley, K, Hartman, P, Hartnett, Me, Harvey, P, Hassan, T, Headon, M, Hejsek, L, Higgins, P, Hillenkamp, J, Ho, A, Ho, T, Holekamp, N, Holz, E, Holz, F, Hooper, P, Hopkins, Jj, Hoskin Mott, A, Hoskins, J, Hrisomalos, N, Hsu, J, 3rd, Hubbard B., Hudson, H, Hughes, E, Hunt, A, Hunyor, A, Hwang, T, Hwang, Jf, Ibarra, M, Incarnato, N, Inhetvin Hutter, C, Introini, U, Isaacs, T, Islam, N, Iyer, Mn, Jablonski, C, Jack, Rl, Jager, R, Jahn, C, Jao, C, Jehan, F, Jonas, J, Joseph, D, Joshi, M, Jost, B, Jurklies, B, Kaincova, I, Kaiser, P, Kaiser, R, Kalvodova, B, Kamppeter, B, Kanann, Nb, Kang, K, Katz, Rs, Kaushal, S, Kecik, D, Kellaway, J, Kelly, K, Kelly, S, Khan, J, Kherani, A, Kim, R, Kim, I, Kim, J, Kim, Jg, Kim, N, Kim, Tw, Kingsley, R, Klein, R, Klemperer, I, Kociecki, J, Korbasova, M, Korda, V, Korobelnik, Jf, Koshy, Z, Kostamaa, H, Kovach, J, Kozak, I, Kozousek, V, Krasny, J, Kreiger, A, Krivosic, V, Krug JV Jr, Kruger, L, Kunimoto, D, Kuppermann, Bd, Kurtz, R, Kuznik Borkowska, A, Lai, J, Lai, W, Lake, S, Lalwani, G, Lam, Wc, Lanning, Rc, Lanzetta, Paolo, Lara, W, Larrison, Wi, Lattanzio, R, Lavina, A, Lavinsky, J, Lazzaroni, F, Lee, E, Yong Lee, J, Lee, M, Young Lee, S, Lee, V, Leff, S, Lehr, J, Lenfesty, P, Leonard, R, Levine, A, Levitan, M, Lewis, H, Liew, S, Lim, J, Lim, R, Lin, R, Lip, Pl, Liu, J, Lobes, La, Loose, I, Lotery, A, Lottenberg, Cl, Loutchkina, D, Lu, Dw, Lubczynska, A, Lujan, B, Lyssek Boron, A, Ma, C, Ma, P, Maberley, D, Maccumber, M, Madhusudhana, Kc, Madreperla, S, Magee, M, Magolan, J, Maia Junior Ode, O, Maia, A, Majji, A, Malthieu, D, Mango, C, Marmor, M, Marques, L, Martin, D, Martinez, Ja, Massaoutis, P, Mathai, A, Mathur, R, Mattioli, S, Maturi, Rk, Mazur Michalek, I, Mcallister, I, Mccabe, F, Mccannel, Ca, Mcgimpsey, S, Mchugh, Jd, Mckibbin, M, McLean WC Jr, Mcmillan, T, Meireles, R, de Melo CS, Menchini, U, Meredith, T, Merrill, P, Mian, U, Michels, M, Midena, E, Mieler, Wf, Migliavacca, L, Miller, D, Miller, J, Mincey, G, Mitchell, P, Katsuki Mizubuti, S, Mohamed, S, Mohammed, M, Moinfar, N, Moisseiev, J, Mones, J, Montemayor Lobo, R, Montero, J, de Moraes NI, Moreira CA Jr, Morely, M, Moreno, Jm, Moron, Jt, Morrison, Vl, Morse, L, Moshfeghi, A, Moshfeghi, D, Muccioli, C, Munshi, V, Murthy, Rc, Naing, T, Nair, R, Nascimento, J, Nascimento, Vp, Nawrocka, Z, Nawrocki, J, Newell, C, Newsom, R, Nguyen, J, Nguyen, Q, Nguyen, Rl, Nichols, J, Nilanjana, D, Noguchi, B, Noorily, S, Novack, R, Novak, M, Novalis, G, O'Brien, D, Offermann, I, Oguido, Ap, Oh, K, Okruszko, A, de Oliveira TL, Oliver, S, Ong, S, Orellana, J, Orzalesi, N, O'Toole, L, Ovando, Y, Paccione, J, Pach, J, Packo, K, Packowska, Ma, Palmer, J, Palmer, H, Palombi, K, Papp, A, Paques, M, Paranhos A., Jr, Park, D, Park, Ri, Park, S, Parke, D, Parravano, M, Pastor Jimeno JC, Patel, S, Patra, S, Pavan, Pr, Pearce, I, Pecold, K, Pedio, M, Peh, Kk, Pelosini, L, Pendergast, S, Perez, Br, Perez Ortiz DJ, Perkins, S, Peters, M, Pheasant, T, Pilat, J, Pilotto, E, Piltz Seymour, J, Pirracchio, A, Pollack, A, Portella, E, Pracharova, Z, Prati, M, Prensky, Jg, Preston, R, Prieto, F, Puls, S, Purohit, Ar, Quintao, T, Rahhal, F, Rahman, W, Ramos, Ar, Ramsey, S, Rani, A, Rao, Pk, Rapizzi, E, Raskauskas, P, Ratiglia, R, Ratnakaram, R, Rauser, Me, Regillo, C, Rehak, J, Reichel, E, Reid, Da, Rejmont, L, Rougier, Mb, Ribon, Ri, Ricarova, R, Rich, R, Riley, A, Ripandelli, G, Rishi, E, Rivett, K, Rogers, A, Romanet, Jp, Rosa, Pj, Rosberger, D, Rose, S, Rosenfeld, P, Ross, Rr, Rotberg, M, Roth, Cb, Roth, D, Rubaltelli, D, Rubsamen, P, Ruby, A, Ruiz Moreno JM, Ruiz, R, Russell Gonder, J, Russell, M, Ryu, Jw, Sachs, H, Sadda, S, Safar, A, Salinas, C, Sall, K, Samad, A, Samkova, K, Sanders, J, Sandhu, R, Sandhu, Ss, Sandner, D, Sanislo, Sr, Sartani, G, Saviano, S, Savy, O, Schechter, Ba, Schenker, Hi, Schiff, W, Schlichtenbrede, F, Schneider, B, Schneider, L, Schneiderman, T, Schocket, L, Schoenherr, U, Schoenleber, D, Scholl, Hp, Schreiber, J, Schwartz, Sd, Sears, J, Sedlakova, J, Seery, C, Sell, C, Shah, G, Shapiro, M, Sharma, A, Sheidow, T, Sheu, Sj, Sheufele, T, Shukla, D, Siewec Proscinska, J, Silva, Er, Singer, M, Singer, S, Singerman, Lj, Singh, M, Siow, Yc, Sipperley, Jo, Sivaprasad, S, Sjaarda, R, Snyder, W, Sobrin, L, Sodi, A, Solomon, S, Sonkin, P, Soubrane, G, Soucek, P, Spirn, B, Srivastava, S, Stannard, K, Staurenghi, G, Steinmetz, R, Stepien, K, Stern, W, Stevenson, Od, Stewart, D, Stewart, J, Stolba, U, Stoller, G, Stone, C, Stout, Jt, Stringfellow, G, Studnicka, J, Suarez Figueroa, M, Sung, J, Susini, A, Syracuse, R, Szaflik, J, Tabandeh, H, Tadayoni, R, Takahashi, Wy, Taleb, Ac, Talks, Sj, Tamayo, L, Tan, M, Taney, B, Tarnawska, D, Tassinari, G, Taylor, J, Telander, D, Territo, C, Thomas, El, Thomas, M, Thompson, Jt, Thompson, Ws, Tiedeman, Js, Topping, T, Trese, M, Truong, S, Tsang, Cw, Tufail, A, Ufret Vincenty, R, Uhmannova, R, 2nd, Ulanski L., Ulinska, M, Urminsky, J, Uy, H, Vaishnav, H, Varano, M, Vavvas, D, Vega Sanz BF, Veloso, A, Vicha, I, Viola, F, Visser, L, Vlkova, E, Voelker, M, Volkert, D, Vossmerbaumer, U, Vu, C, Vyas, S, Wald, Kj, Walker, J, Walter, A, Wang, R, Wasiak, K, Watt, Dr, Weger, M, 3rd, Weidman F., Weinberger, D, Weisz, Jm, 3rd, Wells J., Wheatley, M, Wickremasingh, S, Wiegand, T, Wieland, M, Will, D, Williams, G, Williams, Rg, Wilson, D, Win, Ph, Wing, Gl, Wirostko, W, Wirthlin, R, Wong, Al, Wong, T, Woo, J, Wu, Tt, Wylegala, E, Yan, J, Yang, Ch, Yang, Cm, Yang, Y, Yang, Yc, Yarian, D, Yates, P, Yedavally, S, Yoken, J, Young, L, Young, S, Zago, Rj, Zakov, Z, Zaras, M, Zegarra, H, Ziemianski, M, Zimmer Galler, I, Zourdani, A, and Zur, C.

Published
2011

29. Randomized, Sham-Controlled Trial of Dexamethasone Intravitreal Implant in Patients with Macular Edema Due to Retinal Vein Occlusion

Author

Haller, Ja, Bandello, F, Belfort R., Jr, Blumenkranz, Ms, Gillies, M, Heier, J, Loewenstein, A, Yoon, Yh, Jacques, Ml, Jiao, J, Li, Xy, Whitcup, Sm, OZURDEX GENEVA Study Group, Aaberg, Tm, Abraham, P, Abujamra, S, Acton, J, Adamczyk Ludyga, A, Adenwalla, M, Agahigian, Dd, Agoas, V, Aguilar Mendoza, M, Aisenbrey, S, Alam, S, Albiani, D, Alexandrescu, B, Alfaiate, Mm, Allam, S, Almeida, Hp, Anagnoste, S, Anand, R, Anderson, N, Antoszyk, A, Armogan, N, Arnold, J, Ash, D, Atlas, Wg, Augustin, Ja, de Avila MP, Awh, C, Azzolini, C, Babkova, B, Bakri, Sj, Banach, Mj, Barak, A, Barile, G, Barker, D, Barnard, T, Bartz Schmidt KU, Parodi, Mb, Baumal, C, Bedrich, P, Beer, P, Mattos RB Jr, Bellini, L, Benner, J, Benson, W, Benz, M, Berger, B, Bergren, R, Bharadwaj, A, Bhavan, S, Bhavsar, A, Binder, S, Biondi, A, Bishop, F, Blair, N, Blinder, K, Blumenkranz, M, Bohm, A, Boldrey, Ee, Bornfeld, N, Borrillo, Jl, Boyer, D, Bradford, R, Bridges, W, Brigatti, L, Briggs, M, Brooks HL Jr, Brown, D, Browning, A, Browning, D, Brunner, S, Brunnerova, R, Renata, Js, Brydak Godowska, J, Buettner, H, Burns, J, Burrows, Af, Busbee, B, Butner, R, Butter, J, Byrnes, G, Callahan, C, Campochiaro, P, Cano Hildalgo RA, Canziani, T, Capone, A, Carmichael, T, Carnevale, K, Casella, Am, Casey, R, Castanheira Dinis, A, Celis, B, Chambers, R, Chang, S, Chang, Yh, Chechik, D, Chee, Sp, Chen, E, Chen, Jt, Chen, Sn, Chen, S, Cheng, B, Chiquet, C, Chong, K, Chong, Lp, Chong, V, Chou, T, Chow, V, Chrapek, O, Chu, T, Chua, J, Chun, D, Chung, Hw, Cialdini, Ap, Ciancas, E, Cihelkova, I, Cisiecki, S, Clark, W, Cleary, T, Coco, R, Codenotti, M, Cohen, Bz, Cohen, Ja, Cohen, J, Connolly, B, Conway, B, Cook, H, Cooper, B, Coors, L, Corwin, J, Costa, Jr, Cottrell, D, Couvillion, S, Craig, J, Cruess, A, Cupo, G, Dabbs, T, Danesh, S, Davidorf, F, Davis, J, De Cilla, S, De Fazio, R, de la Fuente MA, de la Rua ER, De Mattia, M, Deen, A, Del Priore, L, Delyfer, Mn, Deuter, C, Devadason, Ds, Devenyi, R, D'Heurle, D, Dickinson, J, Doft, B, Dooner, J, Doubell, D, Downie, J, Drenser, K, Dreyer, R, D'Sousa, Y, Du, T, Duarte, L, Dubiner, Hb, Dubovy, S, Dubska, Z, Dugel, P, Dunn, W, Dusova, J, Dvorak, J, Dyer, D, Dziegielewska, K, Earl, M, Egan, C, Eichenbaum, D, Eifrig, C, Ells, A, El Shabrawi, Y, Elsherbiny, S, Engel, H, Engelbrecht, N, Ernest, J, Essex, R, Eter, N, Evans, R, Fakadej, A, Falcone, P, Fan, D, Fan, Jt, Farah, Me, Farah, S, Feiner, L, Feldman, Rm, Ferencz, J, Fernandez Vega Sanz, A, Ferreira, Jl, Figueira, J, Fineman, M, Fiser, I, Fish, G, Fish, Rh, Fishburne, B, Fisher, Sj, Fitzsimons, R, Flaxel, C, Fletcher, E, Flores Aguilar, M, Florez, S, Flynn, H, Fogarty, S, Folgado, A, Foster, Bs, Fox, Gm, Frambach, D, Fransen, S, Fraser Bell, S, Frederick, A, Freeman, W, Freisberg, L, Friedman, E, Friedman, L, Fucik, M, Fuller, Dg, Gaitan, J, Gallemore, R, Gallogly, P, Garcia Arumi, J, Garg, S, Garretson, B, Gastaud, P, Gaudric, A, Gawrilow, P, Gehlbach, Pl, Geyer, O, Ghuman, At, Giansanti, F, Gil, Al, Gilbert, Hd, Girmens, Jf, Giubilato, A, Glacet Bernard, A, Glaser, D, Glatzer, R, Goldstein, D, Gomes, Am, Gon Yu, H, Gonçalves, Fp, Gonzales, C, Googe, J, Gopal, L, Gordon, A, Gous, P, Grand, M, Grandao Magro PC, Granero Riano, M, Grassi, M, Green, J, Green, S, Gregor, Z, Gregori, N, Grizzard, Ws, Groenewald, C, Gross, Jg, Gross, Ne, Gruber, A, Grutow, G, Guillet, E, Gyorgyova, D, Haas, A, Haas, K, Hadden, P, Hagemann, L, Hainsworth, D, Haivala, D, Haller, J, Halperin, L, Hamer, P, Hammer, M, Han, D, Handa, Jt, Handelman, I, Handza, J, Harder, B, Harding, S, Hariprasad, Sm, Hartley, K, Hartman, P, Hartnett, Me, Harvey, P, Hassan, T, Headon, M, Hejsek, L, Higgins, P, Hillenkamp, J, Ho, A, Ho, T, Holekamp, N, Holz, E, Holz, F, Hooper, P, Hopkins, Jj, Hoskin Mott, A, Hoskins, J, Hrisomalos, N, Hsu, J, 3rd, Hubbard B., Hudson, H, Hughes, E, Hunt, A, Hunyor, A, Hwang, T, Hwang, Jf, Ibarra, M, Incarnato, N, Inhetvin Hutter, C, Introini, U, Isaacs, T, Islam, N, Iyer, Mn, Jablonski, C, Jack, Rl, Jager, R, Jahn, C, Jao, C, Jehan, F, Jonas, J, Joseph, D, Joshi, M, Jost, B, Jurklies, B, Kaincova, I, Kaiser, P, Kaiser, R, Kalvodova, B, Kamppeter, B, Kanann, Nb, Kang, K, Katz, Rs, Kaushal, S, Kecik, D, Kellaway, J, Kelly, K, Kelly, S, Khan, J, Kherani, A, Kim, R, Kim, I, Kim, J, Kim, Jg, Kim, N, Kim, Tw, Kingsley, R, Klein, R, Klemperer, I, Kociecki, J, Korbasova, M, Korda, V, Korobelnik, Jf, Koshy, Z, Kostamaa, H, Kovach, J, Kozak, I, Kozousek, V, Krasny, J, Kreiger, A, Krivosic, V, Krug JV Jr, Kruger, L, Kunimoto, D, Kuppermann, Bd, Kurtz, R, Kuznik Borkowska, A, Lai, J, Lai, W, Lake, S, Lalwani, G, Lam, Wc, Lanning, Rc, Lanzetta, Paolo, Lara, W, Larrison, Wi, Lattanzio, R, Lavina, A, Lavinsky, J, Lazzaroni, F, Lee, E, Lee, Jy, Lee, M, Lee, Sy, Lee, V, Leff, S, Lehr, J, Lenfesty, P, Leonard, R, Levine, A, Levitan, M, Lewis, H, Liew, S, Lim, J, Lim, R, Lin, R, Lip, Pl, Liu, J, Lobes, La, Loose, I, Lottenberg, Cl, Loutchkina, D, Lu, Dw, Lubczynska, A, Lujan, B, Lyssek 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Published
2010

32. Nonspecific provocation of target organs in allergic diseases: EAACI-GA(2)LEN consensus report

Author

Bonini S. Rasi G, Brusasco V, Carlsen KH, Crimi E, Popov T, Schultze-Werninghaus G, Gramiccioni C, Bonini M, Passali D, Bachert C, van Cauwenberge PB, Bresciani M, Bonini S, Calonge M, Montan PG, Serapiao Dos Santos M, Belfort R Jr, Lambiase A, and Sacchetti M.

Subjects
allergic diseases, nonspecific challenges, rhinitis, conjunctivitis, asthma
Abstract

It is widely accepted that nonspecific tissue reactivity is a distinct pathophysiological hallmark of allergic diseases, influenced by genetic and environmental factors different from those involved in causing sensitization and allergen response of target organs. This consensus document aims at reviewing procedures currently used for nonspecific provocation of the bronchi, nose and eye and for measuring their responsiveness to nonspecific stimuli.

Published
2007

35. Randomized dose-comparison studies of intravitreous fomivirsen for treatment of cytomegalovirus retinitis that has

Author

Boyer, D. S., Cowen, S. J., Danis, R. P., Diamond, J. G., Fish, R. H., Goldstein, D. A., Jaffe, G. J., Lalezari, J. P., Lieberman, R. M., Belfort, R., Muccioli, C., Palestine, A. G., Perez, J. E. A., Territo, C., Andreu-Andreu, D., Deschennes, J. G., de Smet, M. D., Fisher, M., Gastaut, J. A., Gazzard, B. G., Lightman, S., Johnson, M. A., Klauss, V., Gumbel, H., Knospe, V., Mallolas-Masferrer, J., Cornish, M. J., Holland, G. N., Ransome, S. S., Tufail, A., Weisz, J. M., Crooke, S. T., Kishner, D. L., Frost, K. R., Hutscherson, S. L., Whitley, R. J., Chandler, J. W., Grillone, L. R., Hutcherson, S. L., Lanz, R., and Ophthalmology

Published
2002

36. Safety of intravitreous fomivirsen for treatment of cytomegalovirus retinitis in patients with AIDS

Author

Boyer, D. S., Cowen, S. J., Danis, R. P., Diamond, J. G., Fish, R. H., Goldstein, D. A., Jaffe, G. J., Lalezari, J. P., Lieberman, R. M., Belfort, R., Muccioli, C., Palestine, A. G., Perez, J. E. A., Territo, C., Andreu-Andreu, D., Deschennes, J. G., de Smet, M. D., Fisher, M., Gastaut, J. A., Gazzard, B. G., Lightman, S., Johnson, M. A., Klauss, V., Gumbel, H., Knospe, V., Mallolas-Masferrer, J., Cornish, M. J., Holland, G. N., Ransome, S. S., Tufail, A., Weisz, J. M., Crooke, S. T., Kishner, D. L., Frost, K. R., Hutscherson, S. L., Whitley, R. J., Chandler, J. W., Grillone, L. R., Hutcherson, S. L., Lanz, R., and Ophthalmology

Published
2002

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