Newer Technologies for Ocular Drug Development and Deployment

  • Sahil Thakur
Part of the Current Practices in Ophthalmology book series (CUPROP)


There are around 285 million visually impaired people in the world with 39 million blind and 256 million with low vision. The main disorders responsible for this disease burden are age-related macular degeneration (AMD), diabetic retinopathy/macular edema (DR/DME), and glaucoma. There are several effective medications that are used to treat these conditions, but it is still a challenge to provide this treatment with a sustained release profile, minimum side effects, and cost-effective rates. In this chapter we will review the ocular drug development process and highlight developments that can potentially improve the efficiency of the current ocular drug discovery industry.


  1. 1.
    Kamb A, Wee S, Lengauer C. Why is cancer drug discovery so difficult? Nat Rev Drug Discov. 2007;6(2):115–20.CrossRefGoogle Scholar
  2. 2.
    Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014;32(1):40–51.CrossRefGoogle Scholar
  3. 3.
    Sams-Dodd F. Is poor research the cause of the declining productivity of the pharmaceutical industry? An industry in need of a paradigm shift. Drug Discov Today. 2013;18(5–6):211–7.CrossRefGoogle Scholar
  4. 4.
    Bowes J, Brown AJ, Hamon J, et al. Reducing safety-related drug attrition: the use of in vitro pharmacological profiling. Nat Rev Drug Discov. 2012;11(12):909–22.CrossRefGoogle Scholar
  5. 5.
    Wilson JL, Racz R, Liu T, et al. PathFX provides mechanistic insights into drug efficacy and safety for regulatory review and therapeutic development. PLoS Comput Biol. 2018;14(12):e1006614.CrossRefGoogle Scholar
  6. 6.
    Gehrs KM, Anderson DH, Johnson LV, Hageman GS. Age-related macular degeneration--emerging pathogenetic and therapeutic concepts. Ann Med. 2006;38(7):450–71.CrossRefGoogle Scholar
  7. 7.
    Bandello F, Sacconi R, Querques L, et al. Recent advances in the management of dry age-related macular degeneration: a review. F1000Res. 2017;6:245.CrossRefGoogle Scholar
  8. 8.
    Salvi M. Immunotherapy for Graves’ ophthalmopathy. Curr Opin Endocrinol Diabetes Obes. 2014;21(5):409–14.CrossRefGoogle Scholar
  9. 9.
    Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748–61.CrossRefGoogle Scholar
  10. 10.
    Smith TJ, Tsai CC, Shih MJ, et al. Unique attributes of orbital fibroblasts and global alterations in IGF-1 receptor signaling could explain thyroid-associated ophthalmopathy. Thyroid. 2008;18(9):983–8.CrossRefGoogle Scholar
  11. 11.
    Ezra DG, Krell J, Rose GE, et al. Transcriptome-level microarray expression profiling implicates IGF-1 and Wnt signalling dysregulation in the pathogenesis of thyroid-associated orbitopathy. J Clin Pathol. 2012;65(7):608–13.CrossRefGoogle Scholar
  12. 12.
    Zeiss CJ. Translational models of ocular disease. Vet Ophthalmol. 2013;16(Suppl 1):15–33.CrossRefGoogle Scholar
  13. 13.
    Drake DR III, Singh I, Nguyen MN, et al. In vitro biomimetic model of the human immune system for predictive vaccine assessments. Disruptive Sci Technol. 2012;1(1):28–40.CrossRefGoogle Scholar
  14. 14.
    Chavent M, Duncan AL, Sansom MSP. Molecular dynamics simulations of membrane proteins and their interactions: from nanoscale to mesoscale. Curr Opin Struct Biol. 2016;40:8–16.CrossRefGoogle Scholar
  15. 15.
    Edington CD, Chen WLK, Geishecker E, et al. Interconnected microphysiological systems for quantitative biology and pharmacology studies. Sci Rep. 2018;8(1):4530.CrossRefGoogle Scholar
  16. 16.
    Russell S, Bennett J, Wellman JA, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65 mediated inherited retinal dystrophy: a randomised, controlled, open-label, Phase 3 trial. Lancet. 2017;390(10097):849–60.CrossRefGoogle Scholar
  17. 17.
    Constable IJ, Pierce CM, Lai C-M, et al. Phase 2a Randomized Clinical Trial: safety and post hoc analysis of subretinal rAAV.sFLT-1 for wet age-related macular degeneration. EBioMedicine. 2016;14:168–75.CrossRefGoogle Scholar
  18. 18.
    Constable IJ, Lai CM, Magno AL, et al. Gene therapy in neovascular age-related macular degeneration: three-year follow-up of a phase 1 Randomized Dose Escalation Trial. Am J Ophthalmol. 2017;177:150–8.CrossRefGoogle Scholar
  19. 19.
    Lores-Motta L, de Jong EK, den Hollander AI. Exploring the use of molecular biomarkers for precision medicine in age-related macular degeneration. Mol Diagn Ther. 2018;22(3):315–43.CrossRefGoogle Scholar
  20. 20.
    Friedlaender MH, Protzko E. Clinical development of 1% azithromycin in DuraSite, a topical azalide anti-infective for ocular surface therapy. Clin Ophthalmol. 2007;1(1):3–10.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Barar J, Aghanejad A, Fathi M, Omidi Y. Advanced drug delivery and targeting technologies for the ocular diseases. Bioimpacts. 2016;6(1):49–67.CrossRefGoogle Scholar
  22. 22.
    Shafiee A, Bowman LM, Hou E, Hosseini K. Aqueous humor penetration of ketorolac formulated in DuraSite or DuraSite 2 delivery systems compared to Acular LS in rabbits. J Ocul Pharmacol Ther. 2013;29(9):812–6.CrossRefGoogle Scholar
  23. 23.
    Hamalainen KM, Kananen K, Auriola S, Kontturi K, Urtti A. Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera. Invest Ophthalmol Vis Sci. 1997;38(3):627–34.PubMedGoogle Scholar
  24. 24.
    Janagam DR, Wu L, Lowe TL. Nanoparticles for drug delivery to the anterior segment of the eye. Adv Drug Deliv Rev. 2017;122:31–64.CrossRefGoogle Scholar
  25. 25.
    Aggarwal D, Kaur IP. Improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal ophthalmic drug delivery system. Int J Pharm. 2005;290(1–2):155–9.CrossRefGoogle Scholar
  26. 26.
    Kompella UB, Kadam RS, Lee VH. Recent advances in ophthalmic drug delivery. Ther Deliv. 2010;1(3):435–56.CrossRefGoogle Scholar
  27. 27.
    Jo DH, Kim JH, Yu YS, Lee TG, Kim JH. Antiangiogenic effect of silicate nanoparticle on retinal neovascularization induced by vascular endothelial growth factor. Nanomedicine. 2012;8(5):784–91.CrossRefGoogle Scholar
  28. 28.
    Huu VA, Luo J, Zhu J, et al. Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye. J Control Release. 2015;200:71–7.CrossRefGoogle Scholar
  29. 29.
    Stewart MW. Extended duration vascular endothelial growth factor inhibition in the eye: failures, successes, and future possibilities. Pharmaceutics. 2018;10(1):pii: E21.CrossRefGoogle Scholar
  30. 30.
    Ghasemi M, Alizadeh E, Saei Arezoumand K, Fallahi Motlagh B, Zarghami N. Ciliary neurotrophic factor (CNTF) delivery to retina: an overview of current research advancements. Artif Cells Nanomed Biotechnol. 2018;46(8):1694–707.PubMedGoogle Scholar
  31. 31.
    Khanna I. Drug discovery in pharmaceutical industry: productivity challenges and trends. Drug Discov Today. 2012;17(19–20):1088–102.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Sahil Thakur
    • 1
  1. 1.Singapore Eye Research InstituteSingaporeSingapore

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