INTRAVITREAL INJECTION OF PHARMACOLOGICAL AGENTS: FROM CLINICAL TRIAL TO CLINICAL PRACTICE

Authors

  • Rufino Martins Silva 1 Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC) - Coimbra, Portugal 2 Faculty of Medicine, University of Coimbra (FMUC) – Coimbra, Portugal 3 Association for Innovation and Biomedical Research on Light and Image (AIBILI) – Coimbra, Portugal
  • João Pedro Marques 1 Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC) - Coimbra, Portugal 3 Association for Innovation and Biomedical Research on Light and Image (AIBILI) – Coimbra, Portugal

DOI:

https://doi.org/10.48560/rspo.7161

Keywords:

CNV, DME, Macular edema, intravitreal injections, anti-VEGF, intravitreal implants, corticosteroids, AMD, DR.

Abstract

Intravitreal delivery bypasses the blood-retinal barrier, leading to a higher intraocular drug concentration for a longer period of time, while lessening the systemic toxicity. A wide variety of intravitreal pharmacological agents has been used: anti-infective  (antibiotic, antifungal, and antiviral), anti-inflammatory (nonsteroidal anti-inflammatory agents, steroids and immunomodulators), anticancer agents, gas, anti-vascular endothelium growth factor (VEGF), among others1. Over the last decade, intravitreal corticosteroids and/or anti-VEGF have become the therapeutic backbone of several retinal disorders, including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal vein occlusions (RVO) and myopic neovascularization. Industry supported clinical research has helped propelling several drugs with encouraging visual and anatomic outcomes. With numerous novel therapies currently being investigated in clinical trials, the number of available drugs will likely continue to rise. High-quality imaging and the application of pharmacogenomic principles are probably guiding future therapies that through a comprehensive approach will hopefully meet the patients’ needs and expectations.

We should keep in mind that everyday clinical practice differs greatly from a clinical trial setting and this inevitably affects the treatment results. The dependence on the center’s resources (public or private) and agenda may delay the beginning of treatment, the interval between injections, between evaluations and injections (when performed separately), and even follow-up appointments. This usually leads to poorer than expected visual outcomes, patient dissatisfaction and physician frustration. Lack of patient motivation directly disturbs compliance and a vicious circle ensues. In order to provide the best possible treatment to our patients in a clinical setting, a balance between cost, effectiveness, compliance and agenda needs to be found.

The purpose of this paper is (1) to review the available drugs for intravitreal use, (2) to explore their approved indications and off-label use in the management of retinal diseases and (3) to present the treatment protocols currently being used at the Retinal Department of the Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal.

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Author Biographies

Rufino Martins Silva, 1 Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC) - Coimbra, Portugal 2 Faculty of Medicine, University of Coimbra (FMUC) – Coimbra, Portugal 3 Association for Innovation and Biomedical Research on Light and Image (AIBILI) – Coimbra, Portugal

Prof. Rufino Silva. 56 years old, is the head of the Medical Retina Unit at the Ophthalmology Department, Coimbra University Hospital, Portugal, Invited professor of Ophthalmology at the Faculty of Medicine of the University of Coimbra, Portugal and Investigator at the Association for Innovation and Biomedical research on Light and Image (AIBILI). His main field of clinical practice is Medical retina.  His research interests are focused on age-related macular degeneration, diabetic retinopathy, pathologic myopia and central serous chorioretinopathy.  He presents his contribution  to the medical literature publishing in such journals as Ophthalmology, Retina, Graefe´s Archive of Ophthalmology, Bristish Journal or  Ophtalmologica

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-Participation in humanitarian missions in Guine Bissau –Program Guiné Vision–  2010, 2011, 2012

-Principal investigator in 48 clincial trials  (28 as Principal Investigator, 20 as Sub-Investigator)

Reviewer for International Scientific journals like Ophthalmology, Bristih Journal of Ophthalmology, Retina, Greafe´s Archives of Ophthalmology, Ophthalmologica.

- Member of the International Ophthalmological Society Club Jules Gonin

- Member of the European Retinal Society (Euretina)

- Member of the Scientific Committee of the Euretina

- Member of the European Eye Epidemiology Network (E3)

- Member of the AMD Scientific Committee of the EVIcrNET

- Member of the American Academy of Ophthalmology

- Member of the ARVO

 

 

-  43 publications in international peer review journals

- 10 book chapters

- Invited speaker at International Congress - 87 presentations

-Coordinator of the Clinical Trial ATLANTIC, a multicentre, internacional, randomised clinical trial on polypoidal choroidal vasculopathy.

João Pedro Marques, 1 Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC) - Coimbra, Portugal 3 Association for Innovation and Biomedical Research on Light and Image (AIBILI) – Coimbra, Portugal

1. PERSONAL INFORMATIONNAMEJoão Pedro MarquesDATE OF BIRTH15th December 1986SEXMaleNATIONALITYPortugueseRua José Castilho, lote 17, 3º esquerdo frente, 3030-301 Coimbra+351 239718821 +351 918791157marquesjoaopedro@gmail.com2. WORK EXPERIENCEChief Resident – from October 2014 to PresentCoimbra Hospital and University Centre (CHUC)Grader at Coimbra Ophthalmology Reading Centre (CORC) – from Jul 2012 to PresentAssociation for Innovation and Biomedical Research on Light and Image (AIBILI)3000-548 Coimbra, Portugal• Grader in the following Clinical Trials/Projects- 2014 – 2014 RETRIAL Project- 2014 – 2014 Diabetic Retinopathy Screening – North Region of Portugal: 391 images graded- 2013 – 2014 Coimbra Eye Study: Epidemiologic Study on Age-Related Maculopathy(ClinicalTrials.gov NCT01298674): general analysis (785 graded images) and differentiated analysis(602 graded images)- 2012 – 2012 AMD Markers (ClinicalTrials.gov NCT00801541)Sub investigator at the Centre for Clinical Trials (CEC) – from Jan 2012 to PresentAssociation for Innovation and Biomedical Research on Light and Image (AIBILI)3000-548 Coimbra, Portugal• Participation in the following Clinical Trials/Projects- 2013 – 2014 Project Gullstrand (EVICR.net), Protocol ECR-CCRS-2010-01Member of the Eye Bank of the Coimbra University Hospital – from Jan 2012 to December 2013Coimbra Hospital and University Centre (CHUC)3000-075 Coimbra, Portugal• Eye harvesting and tissue storage for corneal transplantationOphthalmology Resident – from Jan 2012 to PresentCoimbra Hospital and University Centre (CHUC)3000-075 Coimbra, PortugalPoliclinical Practice – from Jan 2011 to Dec 2011Unidade Local de Saúde de Matosinhos EPE – Hospital Pedro Hispano4464-513 Senhora da Hora, Portugal• Medical practice in General Surgery, Internal Medicine, Paediatrics, Public Health, Primary Care,Gynaecology23. EDUCATION AND TRAININGWeb-based Examination “ICH-GCP in English” – Apr 2014 (valid through Apr 2016)Covering all aspects of Good Clinical Practice as laid down in the International Committee on HarmonisationGuidelines, the EU GCP Directives (2001/20 & 2005/28) and the UK Clinical Trials Regulations 2004 (SI 1031) andamendments of 2006 and 2008. The Faculty of Pharmaceutical Medicine of The Royal College of Physicians of theUnited Kingdom has accreditted this course.Certificate no 002984232834th Ophthalmology Basic Sciences Course (CCBO) – Mar 2012Ophthalmology Department of UNIFESP, Sao Paulo, BrazilIntegrated Master in Medicine – from 2004 to 2010Faculty of Medicine University of Coimbra (FMUC)Coimbra Hospital and University Centre (CHUC)IFMSA Professional Exchange in the Ophthalmology Department of Reykjavik, Iceland – Aug2009Department of Ophthalmology, National Hospital of Reykjavik, University of IcelandHringbraut 101, Reykjavík, IcelandERASMUS at Charles University Prague (4th year Medical Training) – From September 2007 toJune 2008First Faculty of Medicine, Charles University Prague121 08 Praha 2, Czech Republic4. PUBLICATIONSMANUSCRIPTSRetinal Angiomatous Proliferation - A Quantitative Analysis Of The Fundoscopic FeaturesOf The Fellow EyeMarques JP, Laíns I, Costa M, Pires I, Cachulo ML, Figueira J, Silva RAccepted for publication on 15/03/2015Retina. 2015Ocular Risk Factors for Exudative AMD: A Novel Semiautomated Grading SystemMarques JP, Costa M, Melo P, Oliveira CM, Pires I, Cachulo ML, Figueira J, Silva R.ISRN Ophthalmol. 2013 Jul 30;2013:464218doi: 10.1155/2013/464218. eCollection 2013BOOK CHAPTERSSubretinal FluidMarques JP, Silva REncyclopedia of Ophthalmology, Springer Reference 2014 Article ID: 433057, Chapter ID: 1056Accepted on 12/12/2014Goldmann-Favre DystrophyMarques JP, Silva RManual de Retina LIDEL 2015Teacher at Academia da Especialidade – January 2011 – PresentAcademia da Especialidade (http://www.academiadaespecialidade.com)Coimbra, Porto, Lisboa, Braga, Covilhã• Coordinator of Academia da Especialidade Coimbra• Classes on multiple areas of Medicine (Hematology, Cardiology, Gastroenterology, Pneumology andNephrology) based on Harrison’s Principles of Internal Medicine, intended for 6-year medical studentspreparing for the final national medical exam3Neovascular Phenotypes of AMD: RAP and PCVMarques JP, Silva RManual de Retina LIDEL 2015Capillary HemangiomaMarques JP, Silva RManual de Retina LIDEL 2015Ranibizumab in RAPNovartis Clinical Cases Book, 2013, pp 161-170PHOTOGRAPHIESAn Incredible CRAO: a magnificent image of a maleficent manifestationMarques JPThe Ophthalmologist July/August 20145. AWARDSBEST SURGICAL VIDEO OF THE POSTERIOR SEGMENTPORTUGUESE SOCIETY OF OPHTHALMOLOGY/ALCONCombined macular buckling, 23Ga vitrectomy and inverted ILM flap technique for macular hole withassociated foveoschisis in a highly myopic eyeMarques JP, Cardoso P, Rego M, Ferreira L, Figueira J, Alfaiate M57th Congress of the Portuguese Society of OphthalmologyDecember 2014, Vilamoura, PortugalBEST FREE PAPER PRESENTATIONThe distance monocular telescope in low-vision rehabilitation: a multidisciplinary chalangeMarques JP, Costa J, Gil JQ, Gil P, Mesquita T, Paiva CXXVI Reunião Anual de Pediatria do Centro Materno-Infantil Do Norte – CHP: NASCER E CRESCERNovember 2014, Porto, PortugalBEST FREE PAPER PRESENTATION OF YOUNG OPHTHALMOLOGISTSPORTUGUESE SOCIETY OF OPHTHALMOLOGY/MERCKRAP vs Typical Exudative AMD: incidence of neovascularization and fundoscopic findings of the felloweyeMarques JP, Costa M, Pires I, Cachulo ML, Figueira J, Silva R56th Congress of the Portuguese Society of OphthalmologyDecember 2013, Vilamoura, PortugalHONORABLE MENTIONPORTUGUESE SOCIETY OF OPHTHALMOLOGYAMD: ocular risk factors and the risk of neovascularization of the fellow eyeMarques JP, Costa M, Melo P, Pires I, Cachulo ML, Figueira J, Faria de Abreu JR, Silva R55th Congress of the Portuguese Society of OphthalmologyDecember 2012, Lisbon, Portugal6. CONGRESS PRESENTATIONS (Free Papers, Posters and Videos)2015RETICULAR PSEUDODRUSEN AND THE FIVE-YEAR RISK OF PROGRESSION FOR LATE AMDMarques JP, Gil JQ, Lains I, Costa M, Nunes S, Cachulo ML, Silva R2015 ARVO Annual Meeting – Accepted for poster presentationPresentation Number 3779 / Posterboard Number C00213-7 May 2015, Denver, Colorado, United States of America4VISUAL REHABILITATION WITH DISTANCE MONOCULAR TELESCOPE IN PRE-SCHOOLAND SCHOOL-AGED VISUALLY IMPAIRED CHILDRENMarques JP, Cost J, Gil JQ, Gil P, Mesquita T, Paiva C3rd WSPOS – Accepted for presentation4-6 September 2015, Barcelona, Spain2014OBJECTIVE EVALUATION OF VISUAL FUNCTION TWELVE MONTHS AFTER BILATERALIMPLANTATION OF A TRIFOCAL DIFFRACTIVE IOLMarques JP, Rosa AM, Quendera B, Silva F, Mira J, Lobo C, Castelo-Branco M, Murta JN57th Congress of the Portuguese Society of Ophthalmology4-6 December 2014, Vilamoura, PortugalVISUAL REHABILITATION WITH DISTANCE MONOCULAR TELESCOPE IN CHILDREN ANDADOLESCENTS WITH LOW-VISIONMarques JP, Costa J, Gil JQ, Mesquita T, Paiva C57th Congress of the Portuguese Society of Ophthalmology4-6 December 2014, Vilamoura, PortugalLARGE MACULAR HOLE FOUND IN LOCO AFTER COMPLICATED CATARACT SURGERY:MISFORTUNES NEVER COME SINGLYMarques JP, Rocha T, Cardoso P, Rego M, Oliveira N, Henriques F, Alfaiate M57th Congress of the Portuguese Society of Ophthalmology4-6 December 2014, Vilamoura, PortugalCOMBINED MACULAR BUCKLING, 23GA VITRECTOMY AND INVERTED ILM FLAPTECHNIQUE FOR MACULAR HOLE WITH ASSOCIATED FOVEOSCHISIS IN A HIGHLYMYOPIC EYEMarques JP, Cardoso P, Rego M, Ferreira L, Figueira J, Alfaiate M57th Congress of the Portuguese Society of Ophthalmology4-6 December 2014, Vilamoura, PortugalENZIMATIC VITREOLYSIS WITH OCRIPLASMIN: FIRST EXPERIENCES IN PORTUGALMarques JP, Rego M, Lains I, Nascimento J, Flores R, Sampaio A, Roque JG, Figueira J14th ESASO Retina Academy14-15 November 2014, Istambul, TurquiaTHE RETINAL RIDDLEMarques J, Costa J, Cachulo ML, Silva R14th ESASO Retina Academy14-15 November 2014, Istambul, TurquiaOBJECTIVE EVALUATION OF VISUAL FUNCTION 12 MONTHS AFTER BILATERALIMPLANTATION OF A TRIFOCAL DIFFRACTIVE IOL (PHYSIOL FINEVISION®)Marques JP, Rosa AM, Silva F, Quendera B, Lobo C, Mira J, Murta JNXXXII Congress of the ESCRS13-17 September 2014, London, United KingdomBRVO ASSOCIATED CHANGES IN THE PERIFOVEAL RNFL THICKNESS ANALYZED BYSPECTRALIS® SD-OCTMarques JP, Costa J, Pires I, Cachulo ML, Silva R, Figueira J14th EURETINA Congress11-14 September 2014, London, United KingdomPOLYPOIDAL CHOROIDAL VASCULOPATHY – CAN SD-OCT OVERTAKE INDOCYANINEGREENANGIOGRAPHY?Marques JP, Lains I, Figueira J, Farinha C, Cachulo ML, Costa M, Silva R14th EURETINA Congress11-14 September 2014, London, United Kingdom5COMBINED ANIRIDIA RING IMPLANTATION AND IOL IMPLANTATION TO CORRECT POSTTRAUMATICANIRIDIA AND APHAKIAMarques JP, Fonseca P, Quadrado MJ, Póvoa JXXXII Congress of the ESCRS13-17 September 2014, London, United KingdomNEW TECHNIQUE FOR CATARACT SURGERY AFTER IMPLANTATION OF IRIS-FIXATEDPHAKIC INTRAOCULAR LENSMarques JP, Rego M, Póvoa J, Lobo C, Murta JN1st European Meeting of Young Ophthalmologists (EMYO)12-13 July 2014, Porto, PortugalILM STAINING WITH RETIDYNE: THE GREEN EFFECTMarques JP, Brito S, Lencart J, Sousa-Martins D, Ferreira L, Figueira J14th EURETINA Congress11-14 September 2014, London, United KingdomTYPICAL EXUDATIVE AMD VS. RAP: CAN WE PREDICT THE NEOVASCULAR PHENOTYPE OFTHE FELLOW EYE?Marques JP, Costa M, Pires I, Cachulo ML, Figueira J, Silva RThe 5th World Congress on Controversies in Ophthalmology (COPHy)20-23 March 2014, Lisboa, Portugal2013OBJECTIVE EVALUATION OF VISUAL FUNCTION AFTER BILATERAL IMPLANTATION OFTRIFOCAL IOLMarques JP, Rosa AM, Quendera B, Silva F, Mira J, Lobo C, Castelo-Branco M, Murta JN56th Congress of the Portuguese Society of Ophthalmology5-7 December 2013, Vilamoura, PortugalIDIOPATHIC UVEAL EFFUSION SYNDROMEMarques JP, Araujo R, Pires I, Cachulo ML, Figueira J, Silva R56th Congress of the Portuguese Society of Ophthalmology5-7 December 2013, Vilamoura, PortugalRAP VS TYPICAL EXUDATIVE AMD: INCIDENCE OF NEOVASCULARIZATION ANDFUNDOSCOPIC FINDINGS OF THE FELLOW EYEMarques JP, Costa M, Pires I, Cachulo ML, Figueira J, Silva R56th Congress of the Portuguese Society of Ophthalmology5-7 December 2013, Vilamoura, PortugalBRVO RELATED MACULAR EDEMA TREATED WITH RANIBIZUMAB: LONG TERM RESULTSAND PREDICTIVE FACTORS FOR FUNCTIONAL IMPROVEMENTMarques JP, Farinha C, Almeida E, Melo P, Costa M, Pires I, Silva R56th Congress of the Portuguese Society of Ophthalmology5-7 December 2013, Vilamoura, PortugalVISUAL FUNCTIONAL OUTCOMES AFTER BILATERAL IMPLANTATION OF A TRIFOCALDIFFRACTIVE INTRAOCULAR LENSMarques JP, Rosa AM, Silva F, Quendera B, Lobo C, Mira J, Murta JNXXXI Congress of the ESCRS5-9 October 2013, Amsterdam, The NetherlandsMACULAR EDEMA DUE TO BRVO TREATED WITH RANIBIZUMAB: LONG TERM RESULTSAND PREDICTIVE FACTORS FOR FUNCTIONAL IMPROVEMENTMarques JP, Farinha C, Almeida E, Melo P, Costa M, Pires I, Silva R13th EURETINA Congress26-29 September 2013, Hamburg, GermanyDIABETIC RETINOPATHY SCREENING USING TELE-OPHTHALMOLOGYMarques JP, Ribeiro L, Silva RSeminario de Investigación Aplicada en las Patologías Retinianas16-18 April 2013, IOBA, Valladolid, Spain6POLYPOID CHOROIDAL VASCULOPATHY – CASE REPORTSMarques JP, Lains I, Silva RII Jornadas Oftalmologia Hospital de Braga “To the macula and beyond...”8 - 9 March 2013, Braga, Portugal2012AGE-RELATED AMD: OCULAR RISK FACTORS AND THE RISK OF NEOVASCULARIZATIONOF THE FELLOW EYEMarques JP, Costa M, Melo P, Pires I, Cachulo ML, Figueira J, Faria de Abreu JR, Silva R55th Congress of the Portuguese Society of Ophthalmology6-8 December 2012, Lisbon, PortugalACANTHAMOEBA KERATITIS: TREATMENT DIFFICULTIESMarques JP, Beselga D, Oliveira R, Costa E, Rosa A, Quadrado MJ, Murta JN55th Congress of the Portuguese Society of Ophthalmology6-8 December 2012, Lisbon, PortugalSEVERE BILATERAL GRAVES ORBITOPATHY – A THERAPEUTIC CHALLENGEMarques JP, Cardoso L, Ribeiro JC, Jacobetty M, Carrilho F55th Congress of the Portuguese Society of Ophthalmology6-8 December 2012, Lisbon, Portugal7. SCIENTIFIC SOCIETIESPortuguese Society Of Ophthalmology (SPO)European Society of Cataract and Refractive Surgery (ESCRS)Association for Research in Vision and Ophthalmology (ARVO)European Society of Retina Specialists (EURETINA)Pan-American Association of Ophthalmology (PAAO)

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Published

2015-12-25

How to Cite

Silva, R. M., & Marques, J. P. (2015). INTRAVITREAL INJECTION OF PHARMACOLOGICAL AGENTS: FROM CLINICAL TRIAL TO CLINICAL PRACTICE. Revista Sociedade Portuguesa De Oftalmologia, 39(2), 76–90. https://doi.org/10.48560/rspo.7161

Issue

Vol. 39 No. 2 (2015)

Section

Review Article

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CC BY

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