Home » Research & Development » Unmet Clinical Needs in Anti-angiogenic Ocular Therapy

Unmet Clinical Needs in Anti-angiogenic Ocular Therapy

Anti-angiogenesis therapy has revolutionized patient care in the treatment of ocular neovascular diseases such as wet age related macular degeneration (wet AMD) and permeability disorders such as diabetic macular oedema (DMO) and retinal vein occlusion (RVO), which all severely impair vision and can lead to blindness. Currently, therapy includes use of various classes of biologics that block VEGF-A including nucleic acid based aptamers, monoclonal antibodies and receptor-based traps (1).

The impressive impact of anti-VEGF therapy on wet AMD patients coupled the prevention of vision deterioration in up to 90% of patients with an improvement of vision in 30-40% receiving treatment compared to laser therapy (2, 3). This is thought to be due to the inhibition of vascular proliferation and the reduction of vessel permeability through the antagonism of VEGF. However, due to their systemic toxicity, administration of anti-VEGFs is via intravitreal injection and must be on a monthly basis to prevent vision loss, which is burdensome for both patient and practitioner. Furthermore, patient responses to anti-VEGFs vary greatly with between 30-45% showing modest or unexpectedly poor response to treatment as a consequence of underlying disease aggressiveness or the development of a progressive resistance to the drug (3). Anti-VEGF therapy is also less effective in wet AMD patients of African or Asian descent who often (30-55%) present with a distinct form of the disease called idiopathic polypoidal choroidal vasculopathy (4).

Therefore, there is a pressing need for new anti-angiogenic drugs that target distinct, non-VEGF, promoters of pathological angiogenesis offering the potential for combination therapy to deliver improved clinical outcomes. These new anti-angiogenics should:

  • Target patient groups that respond sub-optimally to anti-VEGFs as a consequence of a novel mechanism of action or via promoting a therapeutic synergy if used in combination with anti-VEGFs.
  • Reduce the number of injections needed to maintain the efficacy of anti-VEGF therapy by inducing a therapeutic synergy when used in combination with anti-VEGFs.
  • Show reduced systemic toxicity allowing for potential administration via an alternative route to intravitreal injection e.g. systemic administration or topical application.


  1. Carmeliet P., Jain R.K. (2011). Molecular mechanisms and clinical applications of angiogenesis. Nature. 473(7347):298–307.
  2. Anderson OA, Bainbridge JW, Shima DT. (2010). Delivery of anti-angiogenic molecular therapies for retinal disease. Drug Discov Today. 15(7-8):272-82
  3. Lux, A., Llacer, H., Heussen, FMA and Joussen, AM (2007). Non‐responders to bevacizumab (Avastin) therapy of choroidal neovascular lesions Br J Ophthalmol. 91(10): 1318–1322.
  4. Koh A, Lee WK, Chen LJ, Chen SJ, Hashad Y, Kim H, Lai TY, Pilz S, Ruamviboonsuk P, Tokaji E, Weisberger A, Lim TH. (2012). EVEREST STUDY: Efficacy and Safety of Verteporfin Photodynamic Therapy in Combination with Ranibizumab or Alone Versus Ranibizumab Monotherapy in Patients with Symptomatic Macular Polypoidal Choroidal Vasculopathy. Retina. 32(8):1453-1464.