Rama Paolo Professore OrdinarioMedicineMED/30
Place of Birth: Feltre (BL), Italy
High School "Classics"
1985: Degree in Medicine, University of Padua
1989: Residency in Ophthalmology, University of Modena.
1986: one-month internship on strabismus with Prof. Paliaga in Como (Itay)
1987: one-month internship on retina with George Blankenship at Bascom Palmer Institute, Miami
1988: one-month internships on cataract surgery with Philippe Sourdille at Sourdille Institute, Nantes (France)
1989-2000: repeated internships on oculoplastic surgery with Serge Morax at Rothschild Foundation, Paris (France)
1990-2000: repeated internships on oculoplastic surgery with Richard Collin at Moorfields Eye Hospital, London
1992-2000: repeated internships on cornea with John Dart at Moorfields Eye Hospital, London
1991/1992: Research Fellowship and clinical activities on cornea with Walter Stark, John Gottsch, Oliver Schein, and Dimitri Azar, Wilmer Institute, Johns Hopkins University, Baltimore
1989-1990 : Instructor (Ophthalmology) Nurses School ULSS 36 Venice-Mestre
1992-1993 : Research fellow, Johns Hopkins University, Baltimore (USA)
1999-2001 : contract professor (Surgery of the anterior segment) Ophthalmology Residency Course University of "Tor Vergata", Rome
2002-2006 : contract professor (Surgery of the anterior segment) Ophthalmology Residency Course University "Campus Bio-Medico", Rome
2000-2009 : contract professor (Cornea and Ocular Surface Diseases) Ophthalmology Residency Course University "Vita e Salute", Milan
2014-2017 : contract professor (Cornea and Ocular Surface Disease) Ophthalmology Residency Course University of Milan, Milan
2020-present day : full professor in Opthalmology at the University Vita-Salute San Raffaele, Milan
1988-1993 : Assistant at the Ophthalmology Unit, General Hospital in Mestre-Venice
1993-2000 : Head of the Cornea and Ocular Surface Service and of Reconstructive Plastic Surgery, General Hospital Venice
2000-2005 : Head of the Cornea and Ocular Surface Service, San Raffaele Scientific Institute
2005-2009 : Director of the Ophthalmology Department, San Raffaele Scientific Institute
2009-present day : Director of the Cornea and Ocular Surface Unit, San Raffaele Scientific Institute
2020-present day : Full professor in Ophthalmology at the University Vita-Salute San Raffaele
Surgical activity :
1986-Decembre 2020, more than 10.000 surgical procedures including more than 5,000
cornea transplants (lamellar, penetrating and endokeratoplasties)
Main fields of research
1991-1994: animal study for a new medium for tissue preservation for corneal grafting, in collaboration with Chen CH, Johns Hopkins University, Baltimore. The medium was later acquired and commercialized by Baush & Lomb.
1996-present day: first application of Nerve Growth Factor (NGF) in ocular diseases, in collaboration with Luigi Aloe, CNR (National Research Centre)- Neurobiology and Molecular Medicine Institute, Roma, Alessandro Lambiase and Stefano Bonini, "Campus Biomedico" University of Rome. The first clinical results on the treatment of neurotrophic keratitis were published in the New England of Medicine in 1998. Dompè Pharmaceutical recently acquired the rights to develop and commercialize NGF in ocular diseases, and a Multicentric European phase I-II study was started in November 2012.
1997-present day: clinical application of ex-vivo expanded limbal stem cells, in collaboration with Michele De Luca and Graziella Pellegrini, University of Modena.
The long-term clinical results were published in the New England Journal of Medicine in 2010.
2002-present day: studies on corneal and scleral biomechanics, in collaboration with Ahmed Elsheikh, School of Engineering, University of Liverpool.
2004-2009: studies on retinal progenitor cells, in collaboration with Vania Broccoli, Stem Cells and Neurogenesis Research Unit, San Raffaele Scientific Institute, Milano.
2010-present day: translational studies on corneal angiogenesis, in collaboration with Roberta Mazzieri and Luigi Naldini, Angiogenesis and Tumor Targeting Research Unit, San Raffaele Scientific Institute.
Clinical Studies and Project
2004-2007 : Work package Leader “Clinical testing” of the European Project “Three Dimensional Reconstruction of Human Corneas by tissue engineering” Sixth Framework Programme NMP2-CT-2003-504017
- : Project Responsible “Analisi delle potenzialità rigenerative delle cellule staminali
retiniche derivate dalla glia di Muller in topi Rds (Retinal slow degeneration) con retinopatia”, Award for the Research project of the Italian Ophthalmological Society – SOI 2006
2006-2008: Study Coordinator AIFA, "Multicenter, randomized, double-blind study on the efficacy of topical cyclosporine for the treatment of mucous membrane pemphigoid
2008-2013 : Principal Investigator ‘‘Retrospective Evaluation of the Clinical Management of Patients Affected by Acanthamoeba Keratitis’ – 038/SI - Sponsor : SIFI S.p.A.
2009-2010 : Principal Investigator ‘Retrospective evaluation of the efficacy and safety of autologous cultivated limbal stem cells transplantation for restoration of corneal epithelium in patients with limbal stem cell deficiency due to ocular burns’ – HLSTM01 – Chiesi Farmaceutici S.p.A. This study allowed EMA approval of the limbal stem cells transplantation (Holoclar®).
2011-2016 : Director of Unit involved in the study ‘Valutazione della microscopia confocale corneale, degli esami elettrofisiologici e della biopsia cutanea nella clinica delle neuropatie periferiche sensitive’ – CONFONEUR
2013-2013 : Responsible of the research ‘NGF eye drops potential effects on retinal ganglion cells survival and axon regeneration after optic nerve crush’ – Dompè S.p.A.
2013-2016 : Principal Investigator ‘An 8 week phase I/II, multicenter randomized, double-masked, vehicle controlled parallel group study with a 48 or 56 week follow-up period to evaluate the safety and efficacy of two doses (10 µg/ml and 20 µg/ml) of recombinant human nerve growth factor eye drop solution versus vehicle in patient with Stage 2 and 3 of Neurotrophic Keratitis’ – REPARO – This study allowed EMA approval, in 2017, of the Oxervate® eyedrops for the treatment of neurotrophic keratities; in 2018 in the USA, in 2019 in Canada and Israel.
2013-2015 Principal Investigator study ‘Modificazione dei livelli di neuro mediatori lacrimali dopo chirurgia corneale in pazienti con cheratocono’- NMCONO
2014-2018 Principal Investigator Study ‘Markers infiammatori in pazienti con infiammazione oculare attiva e correlazione con qualità di vita e grading clinic di flogosi oculare’
2015-2016 : Scientict Project Responsible ‘Nerve Growth Factor in collirio come trattamento innovativo per la Perdita visive nei pazienti con retinite pigmentosa : dalla sperimentazione preclinica allo studio clinico di fase II’ – Studio NEMO, financed by the Italian Ministry of University and Research (MIUR) and Dompè S.p.A.
2015-2019 Principal Investigator study ‘Ricerca di nuovi markers e di potenziali target terapeutici associati a vascolarizzazione corneale’ – NEOVASI
2015-2020 : Principal Investigator study ‘Multinational, multicenter, prospective, open-label, uncontrolled clinical trial to assess the efficacy and safety of Autologous Cultivated Limbal Stem Cells Transplantation (ACLSCT) for restoration of corneal epithelium in patients with limbal stem cell deficiency due to ocular burns’ – CCD-GPLSCD01-03 (HOLOCORE) - Chiesi Farmaceutici S.p.A.
2016-ongoing : Project Responsible ‘Prevenzione della retinopatia diabetica mediante trattamento topico con NGF’ - Dompè S.p.A.
2016-ongoing : Principal Investigator study ‘Long-term safety after Holoclar® implant for restoration of corneal epithelium in patients with limbal stem cell deficiency due to ocular burns : observational study of routine clinical practice’ – CCD-GPLSCD-05 (HOLOSIGHT) – Holostem Terapie Avanzate S.p.A.
2017-ongoing : Principal Investigator study ‘Randomized, Assessor-Masked, Active-Controlled, Phase 3 Study to Evaluate Efficacy, Safety and Tolerability of 0.08% Polyhexamethylene Biguanide (PHMB) Ophthalmic Solution in Comparison with 0.02% PHMB + 0.1% Propamidine Combination Therapy in Subjects Affected by Acanthamoeba Keratitis’ – 043/SI (ODAK) – SIFI S.p.A.
2017-2018 : Principal Investigator study ‘Observational follow-up study to evaluate the long term efficacy of autologous cultivated limbal stem cells transplantation for restoration of corneal epithelium in patients with limbal stem cells deficiency due to ocular burns – CCD-GPLSCD01-07 (HOLO-UP) – Chiesi Farmaceutici S.p.A.
2017-ongoing : Principal Investigator study ‘Multinational, multicentre, prospective, long-term safety and efficacy follow-up study after autologous cultivated limbal stem cells transplantation (ACLSCT) for restoration of corneal epithelium in patients with limbal stem cell deficiency due to ocular burns’ – CCD-GPLSD01-03-FU (HOLOCORE-FU) – Holostem Terapie Avanzate S.p.A.
2017-2018 : Unit Director study ‘Elettroterapia per la sindrome da occhio secco’ – RESONO17
Sponsor : Resono Ophthalmics
Awards and Honors
1991 Grant Foundation G.B. Bietti for research activities at ‘The Johns Hopkins University
School of Medicine’ in Baltimore, Cornea and Cataract Unit of Prof. Walter J. Stark
2000 Award and grant AIRCMO Society for the scientific paper "Topical treatment with nerve
growth factor for corneal neurotrophic ulcers", N Engl J Med. 1998; 338(17): 1174-80
2006 Award and grant for the best Research project of the Italian Ophthalmological Society
2011 Award and grant “Best paper 2010” Clinical Science Category, San Raffaele Scientific
Institute for the paper "Limbal stem-cell therapy and long-term corneal regeneration",
N Engl J Med. 2010; 363(2): 147-55
2011 Award for the second best Research Projects of the Italian Ophthalmological Society
2011 Award and grant AIRCMO Society for the scientific paper "Limbal stem-cell therapy and
long-term corneal regeneration", N Engl J Med. 2010; 363(2): 147-55
2015 Award ‘Meibom Mooren Medal’, Lecture “The studies on ocular surface reconstruction
using eyedrops(NGF) and cells (cultivated limbal stem cells) instead of corneal
2016 Award ‘EUCORNEA GOLD MEDAL’, Lecture ‘Study on the application of cultivated
limbal stem cells for the treatment of corneal limbal deficiency’ (EuCornea Congress, 9/10 September 2016, Copenhagen/Denmark)
Major Peer-reviewed bibliography
- Deng S. X., Kruse F., Gomes J. A. P., Chan C. C., Daya S., Dana R., Figueiredo F. C., Kinoshita S., Rama P., Sangwan V., Slomovic A. R., Tan D. (2020).
Global Consensus on the Management of Limbal Stem Cell Deficiency.
CORNEA, vol. 39, p. 1291-1302
- Papa V., Rama P., Radford C., Minassian D. C., Dart J. K. G. (2020).
Acanthamoeba keratitis therapy: Time to cure and visual outcome analysis for different antiamoebic therapies in 227 cases.
BRITISH JOURNAL OF OPHTHALMOLOGY, vol. 104, p. 575-581
- Bonini S, Lambiase A, Rama P, Filatori I, Allegretti M, Chao W, Mantelli F (2018).
Phase I Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis. OPHTHALMOLOGY, vol. 125, p. 1468-1471
- Bonini S, Lambiase A, Rama P, Sinigaglia F, Allegretti M, Chao W, Mantelli F (2018). Phase II Randomized, Double-Masked, Vehicle-Controlled Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis.
OPHTHALMOLOGY, vol. 125, p. 1332-1343
- Dua HS, Said DG, Messmer EM, Rolando M, Benitez-Del-Castillo JM, Hossain PN, Shortt AJ, Geerling G, Nubile M, Figueiredo FC, Rauz S, Mastropasqua L, Rama P, Baudouin C (2018).
PROGRESS IN RETINAL AND EYE RESEARCH, vol. 66, p. 107-131
- Sacchetti M, Rama P, Bruscolini A, Lambiase A (2018).
Limbal stem cell transplantation : clinical results, limits, and perspectives.
STEM CELLS INTERNATIONAL
- Rama P, Ferrari G, Pellegrini G (2017).
Cultivated limbal epithelial transplantation.
CURRENT OPINION IN OPHTHALMOLOGY, vol. 28, p. 387-389
- Ferrari Giulio, Giacomini Chiara, Bignami Fabio, Moi Davide, Ranghetti Anna, Doglioni C, Naldini Luigi, Rama Paolo, Mazzieri Roberta (2016).
Angiopoietin 2 expression in the cornea and its control of corneal neovascularisation. BRITISH JOURNAL OF OPHTHALMOLOGY, vol. 100, p. 1005-1010
- Pellegrini G, Rama P, Di Rocco A, Panaras A, De Luca M (2014).
Concise Review: Hurdles in a Successful Example of Limbal Stem Cell-based Regenerative Medicine.
STEM CELLS, vol. 32, p. 26-34
- Pellegrini G, Rama P, Matuska S, Lambiase A, Bonini S, Pocobelli A, Colabelli RG, Spadea L, Fasciani R, Balestrazzi E, Vinciguerra P, Rosetta P, Tortori A, Nardi M, Gabbriellini G, Traverso CE, Macaluso C, Losi L, Percesepe A, Venturi B Corradini F, Panaras A, Di Rocco A, Guatelli P, De Luca M (2013). Biological parameters determining the clinical outcome of autologous cultures of limbal stem cells. REGENERATIVE MEDICINE, vol. 8, p. 553-567
- Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G (2010).
Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration.
NEW ENGLAND JOURNAL OF MEDICINE, vol. 363, p. 147-155
- Pellegrini G, Rama P, Mavilio F, De Luca M (2009).
Epithelial stem cells in corneal regeneration and epidermal gene therapy.
JOURNAL OF PATHOLOGY, vol. 217, p. 217-228
- Rama P, Bonini S, Lambiase A, Golisano O, Paterna P, De Luca M, Pellegrini G (2001).
Autologous fibrin-cultured limbal stem cells permanently restore the corneal surface of
patients with total limbal stem cell deficiency.
TRANSPLANTATION, vol. 72, p. 1478-1485
- Pellegrini G, Golisano O, Paterna P, Lambiase A, Bonini S, Rama P, De Luca M (1999).
Location and clonal analysis of stem cells and their differentiated progeny in the human ocular surface.
THE JOURNAL OF CELL BIOLOGY, vol. 145, p. 769-782
- Lambiase A, Rama P, Bonini S, Caprioglio G, Aloe L (1998).
Topical treatment with Nerve Growth Factor for Corneal Neurotrophic Ulcers.
N Engl J Med. 1998 Apr 23;338(17):1174-80
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