Joan Miller

Joan Whitten Miller is a Canadian-American ophthalmologist and scientist who has made notable contributions to the treatment and understanding of eye disorders (particularly diseases of the retina). She is credited for developing photodynamic therapy (PDT) with verteporfin (Visudyne), the first pharmacologic therapy for retinal disease. She also co-discovered the role of vascular endothelial growth factor (VEGF) in eye disease and demonstrated the therapeutic potential of VEGF inhibitors, forming the scientific basis of anti-VEGF therapy for age-related macular degeneration (AMD), diabetic retinopathy, and related conditions.

For the choreographer, see Joan Miller (choreographer).
Joan Miller
Born
Toronto, Ontario, Canada
Alma materMIT (SB Biology)
Harvard Medical School (MD)
Known forDevelopment of Visudyne (verteporfin photodynamic therapy)
Scientific basis of anti-VEGF therapy for eye disease
AwardsChampalimaud Vision Award (2014)
Mildred Weisenfeld Award (2015)
Scientific career
FieldsOphthalmology (vitreo-retinal surgery)
Angiogenesis
Neuroscience
Genetics
InstitutionsHarvard Medical School
Massachusetts Eye and Ear
Massachusetts General Hospital

Early life and education

Joan Miller (née Whitten) was born in Toronto, Canada, and attended Bishop Strachan School.[1] She received her SB in biology from Massachusetts Institute of Technology, where she also rowed crew for four years, taking 2nd place in the Head of the Charles Regatta in 1978 and 3rd nationally in 1980.[2] She received her MD at Harvard Medical School in 1985[3] and interned at Newton-Wellesley Hospital; she then completed residency training in ophthalmology in the Harvard Medical School Department of Ophthalmology in 1989, and a research and clinical fellowship in vitreoretinal surgery at Massachusetts Eye and Ear (the primary affiliate hospital of the Harvard Medical School Department of Ophthalmology) in 1991.[4]

Medical and academic career

In 1991, Miller joined Mass. Eye and Ear as an assistant in ophthalmology. She became an assistant surgeon in 1992, an associate surgeon in 1996, and a surgeon in 2002. Miller became chief of ophthalmology at Mass. Eye and Ear in 2003, and in 2009 she also became chief of ophthalmology at Massachusetts General Hospital.[5] Miller is the first woman to serve as chief of either department.

Miller is a faculty member of Harvard Medical School (HMS) in the Department of Ophthalmology, beginning with her 1991 appointment as an instructor in ophthalmology. She was promoted to assistant professor of ophthalmology in 1994, associate professor of ophthalmology in 1998, and professor of ophthalmology in 2002. In 2003, Miller became chair of the HMS Department of Ophthalmology and Henry Willard Williams Professor of Ophthalmology. In 2017, she was promoted to David Glendenning Cogan Professor of Ophthalmology. Miller is the first female ophthalmologist to achieve the rank of Professor at HMS and the first woman to chair the Department of Ophthalmology.[6]

Research and clinical innovations

Verteporfin Photodynamic Therapy (Visudyne)
Verteporfin

In the 1990s, through a series of preclinical[7][8][9][10][11][12] and clinical studies,[13][14][15][16] Miller, Evangelos Gragoudas, and colleagues at Mass. Eye and Ear and Mass General Hospital (in collaboration with QLT PhotoTherapeutics Inc. and Novartis) developed photodynamic therapy (PDT) with verteporfin (Visudyne). Verteporfin, a light-sensitive dye, is injected systemically, and a laser specifically activates the drug in the choroidal vessels, blocking vessel leakage and preventing further vessel growth.[17] On April 12, 2000, verteporfin became the first drug approved by the Food and Drug Administration (FDA) for treating AMD.[18][19]

In 2000, Visudyne was selected by Popular Science magazine for the "Best of What's New" Award,[20] and by Business Week as one of the "Best Products of 2000."[21] For her role in pioneering the pharmacologic treatment of retinal disease, Miller delivered the 2002 Jules Gonin Lecture,[22] an award that recognizes individuals "for making a significant contribution to the understanding and treatment of eye diseases."[23]

Anti-VEGF therapy for ocular disease

During the development of Visudyne, Miller and colleagues also examined the molecular mechanisms of ocular neovascularization. In 1994, using a primate model, Miller (along with Anthony Adamis, Patricia D'Amore, and others) were the first to correlate VEGF with ocular neovascularization in vivo.[24] That same year, Miller and colleagues (including Adamis and Judah Folkman) were the first to report increased levels of VEGF in the eyes of patients with vascular eye disease (diabetic retinopathy).[25] These findings were replicated in a larger study by Lloyd Paul Aiello and George King of Joslin Diabetes Center and Napoleone Ferrara of Genentech.[26] Drs. Miller, Gragoudas, Ferrara, and Adamis also demonstrated that introducing VEGF into normal primate eyes could cause several intraocular vascular disorders, such as retinal ischemia[27] and neovascular glaucoma.[28] These studies strongly correlated VEGF protein with pathological ocular neovascularization both in patients and in experimental models.

In a series of parallel and collaborative preclinical studies, Miller and colleagues effectively blocked ocular neovascularization with a VEGF-neutralizing antibody (bevacizumab),[29] a VEGF-neutralizing antibody fragment (ranibizumab),[30][31] and a VEGF-neutralizing aptamer EYE001 (later known as pegaptanib).[32] These studies not only reinforced VEGF's key role in ocular pathology, but also provided the scientific foundation for clinical trials of multiple anti-VEGF therapies. In July 2005, Miller presented data from the Phase III MARINA trial of ranibizumab (Lucentis) at the 23rd Annual Meeting of the American Society of Retina Specialists (ASRS) in Montreal, Canada.[33]

In the annual Breakthrough of the Year awards by the journal Science, anti-VEGF therapy for AMD was recognized as one of the top ten scientific distinctions of the year 2006.[34] In 2014, the Champalimaud Foundation awarded the António Champalimaud Vision Award to Napoleone Ferrara, Joan Miller, Evangelos Gragoudas, Patricia D'Amore, Anthony Adamis, George L. King, and Lloyd Paul Aiello "for the development of anti-angiogenic therapy for retinal disease."[35][36] Considered the highest distinction in ophthalmology and visual science, the €1 million Champalimaud Vision Award is among the world's largest scientific and humanitarian prizes and often referred to as the "Nobel Prize for Vision."[37][38]

Publications

Miller's scholarly contributions include more than 150 original research articles, 20 clinical trial reports (as a member of the investigative team), 40 reviews, and 30 book chapters.[39] Miller is an editor of the journal Ophthalmology[40] and several textbooks, including Albert and Jakobiec's Principles and Practice of Ophthalmology (3rd ed),[41] Retinal Disorders: Genetic Approaches to Diagnosis and Treatment,[42] and Endophthalmitis.[43]

Selected awards and honors
Joan W. Miller speaking at the 2014 António Champalimaud Vision Award ceremony in Lisbon, Portugal, 10 September 2014.

Personal life

Miller is married to John B. Miller, a construction attorney and 2014 Republican candidate for Massachusetts Attorney General.[64]

References
  1. "Distinguished Old Girl 2007: Joan WHITTEN Miller '76 - Pioneering Cures for Blindness" (PDF). The Bishop Strachan School. Retrieved 3 June 2016.
  2. Maxwell, Jill Hecht. "Joan Whitten Miller '80: Retina specialist advances her field—and the women in it". MIT Technology Review. Retrieved 3 June 2016.
  3. "I Am Harvard Medicine: Joan W. Miller, MD '85". Harvard Medical School. Retrieved 3 June 2016.
  4. "Joan W. Miller, M.D." Massachusetts Eye and Ear. Retrieved 3 June 2016.
  5. "Joan Whitten Miller, MD". Massachusetts General Hospital. Retrieved 3 June 2016.
  6. Colby, Kathryn (December 2002). "Now We Number 33: Women in Ophthalmology at the Massachusetts Eye and Ear Infirmary in 2002". Archives of Ophthalmology. 120 (12): 1738–1740. doi:10.1001/archopht.120.12.1738. PMID 12470151.
  7. Miller, JW; Walsh, AW; Kramer, M; Hasan, T; Michaud, N; Flotte, TJ; Haimovici, R; Gragoudas, ES (June 1995). "Photodynamic therapy of experimental choroidal neovascularization using lipoprotein-delivered benzoporphyrin". Arch Ophthalmol. 113 (6): 810–818. doi:10.1001/archopht.1995.01100060136048. PMID 7540388.
  8. Kramer, M; Miller, JW; Michaud, N; Moulton, RS; Hasan, T; Flotte, TJ; Gragoudas, ES (1996). "Liposomal benzoporphyrin derivative verteporfin photodynamic therapy. Selective treatment of choroidal neovascularization in monkeys". Ophthalmology. 103 (3): 427–438. doi:10.1016/s0161-6420(96)30675-1. PMID 8600419.
  9. Husain, D; Miller, JW; Michaud, N; Connolly, E; Flotte, TJ; Gragoudas, ES (1996). "Intravenous infusion of liposomal benzoporphyrin derivative for photodynamic therapy of experimental choroidal neovascularization". Arch Ophthalmol. 114 (8): 978–985. doi:10.1001/archopht.1996.01100140186012. PMID 8694734.
  10. Haimovici, R; Kramer, M; Miller, JW; Hasan, T; Flotte, TJ; Schomacker, KT; Gragoudas, ES (1997). "Localization of lipoprotein-delivered benzoporphyrin derivative in the rabbit eye". Current Eye Research. 16 (2): 83–90. doi:10.1076/ceyr.16.2.83.5088. PMID 9068937.
  11. Reinke, MH; Canakis, C; Husain, D; Michaud, N; Flotte, TJ; Gragoudas, ES; Miller, JW (1999). "Verteporfin photodynamic therapy retreatment of normal retina and choroid in the cynomolgus monkey". Ophthalmology. 106 (10): 1915–1923. doi:10.1016/s0161-6420(99)90401-3. PMID 10519585.
  12. Husain, D; Kramer, M; Kenny, AG; Michaud, N; Flotte, TJ; Gragoudas, ES; Miller, JW (1999). "Effects of photodynamic therapy using verteporfin on experimental choroidal neovascularization and normal retina and choroid up to 7 weeks after treatment". Invest Ophthalmol Vis Sci. 40 (10): 2322–2331. PMID 10476799.
  13. Schmidt-Erfurth, U; Miller, J; Sickenberg, M; et al. (1998). "Photodynamic therapy of subfoveal choroidal neovascularization: clinical and angiographic examples". Graefes Arch Clin Exp Ophthalmol. 236 (5): 365–374. doi:10.1007/s004170050092. PMID 9602321. S2CID 32104788.
  14. Miller, JW; Schmidt-Erfurth, U; SIckenberg, M; et al. (1999). "Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of a single treatment in a phase 1 and 2 study". Arch Ophthalmol. 117 (9): 1161–1173. doi:10.1001/archopht.117.9.1161. PMID 10496388.
  15. Schmidt-Erfurth, U; Miller, JW; Sickenberg, M; et al. (1999). "Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study". Arch Ophthalmol. 117 (9): 1177–1187. doi:10.1001/archopht.117.9.1177. PMID 10496389.
  16. Treatment of age-related macular degeneration with photodynamic therapy (TAP) Study Group (1999). "Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials--TAP report". Arch Ophthalmol. 117 (10): 1329–1345. doi:10.1001/archopht.117.10.1329. PMID 10532441.
  17. EyeSmart — American Academy of Ophthalmology. "Photodynamic Therapy PDT Treatment [video]". www.youtube.com. Retrieved 8 June 2016.
  18. "Drug Approval Package: Visudyne (Verteporfin) Injection". U.S. Food and Drug Administration (FDA). Retrieved 28 June 2016.
  19. Pollack, Andrew (April 14, 2000). "Agency Approves First Therapy For a Major Cause of Blindness". The New York Times. Retrieved 7 June 2016.
  20. "New Products". Optometry and Vision Science. 78 (1): 5. 2001. doi:10.1097/00006324-200101010-00003.
  21. "BUSINESS WEEK SELECTS VISUDYNE™ THERAPY AS ONE OF THE "BEST PRODUCTS OF 2000" [press release]" (PDF). CIBA Vision and QLT Inc—Partners in developing Visudyne therapy. December 12, 2000. Retrieved 8 June 2016.
  22. Miller, JW (2003). "Photodynamic therapy for choroidal neovascularization. The Jules Gonin Lecture, Montreux, Switzerland, 1 September 2002". Graefes Arch Clin Exp Ophthalmol. 241 (4): 258–262. doi:10.1007/s00417-003-0623-y. PMID 12719985. S2CID 29648721.
  23. "Jules Gonin Lecturer of the Retina Research Foundation". Retina Research Foundation. Retrieved 22 June 2016.
  24. Miller, JW; Adamis, AP; Shima, DT; D'Amore, PA; et al. (1994). "Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model". American Journal of Pathology. 145 (3): 574–584. PMC 1890317. PMID 7521577.
  25. Adamis, AP; Miller, JW; Bernal, MT; D'Amico, DJ; Folkman, J (1994). "Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy". American Journal of Ophthalmology. 118 (4): 445–450. doi:10.1016/s0002-9394(14)75794-0. PMID 7943121.
  26. Aiello, LP; et al. (1994). "Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders". New England Journal of Medicine. 331 (22): 1480–1487. doi:10.1056/NEJM199412013312203. PMID 7526212.
  27. Tolentino, MJ; Miller, JW; Gragoudas, ES; Jakobiec, FA; Flynn, E; Chatzistefanou, K; Ferrara, N; Adamis, AP (1996). "Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate". Ophthalmology. 103 (11): 1820–1828. doi:10.1016/s0161-6420(96)30420-x. PMID 8942877.
  28. Tolentino, MJ; Miller, JW; Gragoudas, ES; Chatzistefanou, K; Ferrara, N; Adamis, AP (1996). "Vascular endothelial growth factor is sufficient to produce iris neovascularization and neovascular glaucoma in a nonhuman primate". Arch. Ophthalmol. 114 (8): 964–970. doi:10.1001/archopht.1996.01100140172010. PMID 8694732.
  29. Adamis, AP; Shima, DT; Tolentino, MJ; Gragoudas, ES; Ferrara, N; Folkman, J; D'Amore, PA; Miller, JW (1996). "Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate". Archives of Ophthalmology. 114 (1): 66–71. doi:10.1001/archopht.1996.01100130062010. PMID 8540853.
  30. Krzystolik, MG; Afshari, MA; Adamis, AP; Gaudreault, J; Gragoudas, ES; Michaud, N; Li, W; Connolly, E; O'Neill, CA; Miller, JW (2002). "Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment". Archives of Ophthalmology. 120 (3): 338–346. doi:10.1001/archopht.120.3.338. PMID 11879138.
  31. Husain D; Kim I; Gauthier D; Lane AM; Tsilimbaris MK; Ezra E; Connolly EJ; Michaud N; Gragoudas ES; O'Neill CA; Beyer JC; Miller, JW (2005). "Safety and efficacy of intravitreal injection of ranibizumab in combination with verteporfin PDT on experimental choroidal neovascularization in the monkey". Archives of Ophthalmology. 123 (4): 509–516. doi:10.1001/archopht.123.4.509. PMID 15824225.CS1 maint: multiple names: authors list (link)
  32. Carrasquillo, KG; Ricker, JA; Rigas, IK; Miller, JW; Gragoudas, ES; Adamis, AP (2003). "Controlled delivery of the anti-VEGF aptamer EYE001 with poly(lactic-co-glycolic)acid microspheres". Invest Ophthalmol Vis Sci. 44 (1): 290–9. doi:10.1167/iovs.01-1156. PMID 12506087.
  33. Helzner, Jerry (September 1, 2005). "Inside Genentech's Lucentis Strategy: The company had no experience in ophthalmic drugs, but has moved its wet AMD treatment ahead quickly". Retinal Physician. Retrieved 6 June 2016.
  34. "Breakthrough of the year. The runners-up". Science. 314 (5807): 1850–1855. 2006. doi:10.1126/science.314.5807.1850a. PMID 17185566. S2CID 220098939.
  35. "2014 António Champalimaud Vision Award". Champalimaud Foundation. Retrieved 17 June 2016.
  36. "2014 Champalimaud Vision Award". Association for Research in Vision and Ophthalmology (ARVO). Retrieved 17 June 2016.
  37. "ARVO members honored with world's largest prize in eye research". Association for Research in Vision and Ophthalmology (ARVO). September 10, 2014. Retrieved 22 June 2016.
  38. Malamut, Melissa (September 11, 2014). "Harvard Medical School Researchers Awarded $1.3 Million Prize". Boston Magazine. Retrieved 22 June 2016.
  39. "Joan W. Miller". Google Scholar. Retrieved 22 June 2016.
  40. Editor's Biographies. Ophthalmology (journal) Retrieved 3 June 2016
  41. Albert, Daniel M.; Miller, Joan W.; Azar, Dimitri T.; Blodi, Barbara A. (2008). Albert & Jakobiec's Principles & Practice of Ophthalmology (3 ed.). Philadelphia: Saunders/Elsevier. ISBN 978-1416000167.
  42. Pierce, Eric A.; Masland, Richard H.; Miller, Joan W. (2014). Retinal Disorders: Genetic Approaches to Diagnosis and Treatment (1 ed.). Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press. ISBN 978-1621820178.
  43. Durand, Marlene L.; Miller, Joan W.; Young, Lucy H. (2016). Endophthalmitis. Switzerland: Springer. ISBN 978-3319292298.
  44. "Awards & Lectures". Macula Society. Retrieved 17 June 2016.
  45. "Jules Gonin Lecturer of the Retina Research Foundation". Retina Research Foundation. Retrieved 22 June 2016.
  46. Miller, JW (2003). "Photodynamic therapy for choroidal neovascularization. The Jules Gonin Lecture, Montreux, Switzerland, 1 September 2002". Graefes Arch Clin Exp Ophthalmol. 241 (4): 258–262. doi:10.1007/s00417-003-0623-y. PMID 12719985. S2CID 29648721.
  47. "Past Grant Recipients of the Alcon Research Institute". myalcon.com. Retrieved 17 June 2016.
  48. "2006 ARVO Annual Award Winners". Retina Today. June 2006. Retrieved 17 June 2016.
  49. "Distinguished Old Girl 2007: Joan WHITTEN Miller '76 - Pioneering Cures for Blindness" (PDF). The Bishop Strachan School. Retrieved 3 June 2016.
  50. Miller, JW (2008). "Higher irradiance and photodynamic therapy for age-related macular degeneration (an AOS thesis)". Trans Am Ophthalmol Soc. 106: 357–382. PMC 2646424. PMID 19277246.
  51. "Awards & Lectures". Macula Society. Retrieved 17 June 2016.
  52. "Joan Miller, MD, receives Harvard leadership award". Ophthalmology Times. June 9, 2010. Retrieved 17 June 2016.
  53. "Paul Henkind Memorial Lecture". Macula Society. Retrieved 17 June 2016.
  54. Miller, J.W. (2014). "The Harvard Angiogenesis Story". Survey of Ophthalmology. 59 (3): 361–364. doi:10.1016/j.survophthal.2013.07.003. PMID 24138892.
  55. Reidy, Chris (December 14, 2011). "Pinnacle Awards honor local women leaders". The Boston Globe. Retrieved 23 June 2016.
  56. Miller, J.W. (2013). "Age-related macular degeneration revisited--piecing the puzzle: the LXIX Edward Jackson memorial lecture". American Journal of Ophthalmology. 155 (1): 1–35. doi:10.1016/j.ajo.2012.10.018. PMID 23245386.
  57. "Cless Best of the Best Award". Department of Ophthalmology & Visual Sciences, University of Illinois College of Medicine at Chicago. Retrieved 17 June 2016.
  58. "Members by Name". Academia Ophthalmologica Internationalis. Retrieved 22 June 2016.
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  61. "2015 ARVO Fellows". Association for Research in Vision and Ophthalmology (ARVO). Retrieved 17 June 2016.
  62. "2015 Achievement Award recipients". Association for Research in Vision and Ophthalmology (ARVO). Retrieved 17 June 2016.
  63. "Directory: IOM Member- Dr. Joan W. Miller M.D., FARVO". National Academy of Medicine. Archived from the original on 10 June 2016. Retrieved 17 June 2016.
  64. Lehigh, Scot (July 25, 2014). "John Miller, the GOP's noteworthy AG hopeful". The Boston Globe. Retrieved 6 June 2016.
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