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Monday / April 15.
HomemiophthalmologyExperiences of Anti-VEGF in a European Setting

Experiences of Anti-VEGF in a European Setting

Swiss ophthalmologist Professor Stephan Michels has shared his experience on the use of the anti-VEGF inhibitor aflibercept (Eylea) in treating central retinal vein occlusion (CRVO), diabetic macular edema (DME) and neovascular age related macular degeneration (AMD) in a European setting with ophthalmologists in Australia.The Head of Medical Retina and Vice Chair of the Department of Ophthalmology at the City Hospital Triemli in Zurich, began by outlining the specifics of the Swiss medical system that allow ophthalmologists under certain circumstances to gain early access to off label drugs to treat diseases such as DME and CRVO. As a result, in Switzerland, several patients had received treatment for DME and CRVO with aflibercept before other countries, which had provided opportunities for early clinical observation and data collection.

Central Retinal Vein Occlusion

Professor Michels analysed the Galileo and Copernicus studies and said these phase III approval studies for aflibercept had shown patients with macular edema secondary to CRVO to experience a rapid and extensive vision gain of three lines at one year follow-up; with the strongest reduction in edema after the first injection. He mentioned that the edema reduction had been “able to be more or less maintained through one year”. However, he said, “these studies are of limited help with providing good guidance on how to treat our patients in daily clinic. The protocols and approved regiments are actually quite different from Galileo and Copernicus studies throughout many countries. In Australia a loading of three aflibercept injections followed by a treat and extend protocol is the approved treatment regimen. An additional key information from the studies is that not all vision may be recovered if initial treatment is delayed,” he said.

The Swiss ophthalmic surgeon, who has been the principal or co-investigator in more than 20 clinical studies, spoke of his own preliminary experience treating CRVO. He highlighted that most cases of edema in CRVO are part of a chronic recurrent disease. The recurrence interval is quite different from patient to patient. He said “the key was to find the individual recurrence interval using spectral domain optical coherence tomography (SD-OCT)… Over time under an individualised treatment you are able to get a little more of an extension (between injections)”.

For Professor Michels a pro re nata approach (PRN) is not ideal for managing patients with central retinal vein occlusion, especially if extended follow-up intervals are used. Instead “we not only need to individualise the number of treatments but also the follow-up intervals as in a treat and extend regimen”.

Over time under an individualised treatment you are able to get a little more of an extension (between injections)…

He presented his “personal pearls” in relation to treating CRVO:

  • In many cases we are treating a chronic disease;
  • Each eye has its own, individual recurrence-free interval;
  • This individual recurrence-free interval is:
  • difficult to predict based on findings prior to start of treatment (fundus, FA, OCT);
  • is quite stable over years
  • can be easily found by a ‘treat and

extend’ approach

  • Is dependent on the anti-VEGF drug used
  • There is no fixed regimen that fits all patients (PRN, 1-2 monthly)
  • The best tool to currently detect recurrence is SD-OCT
  • As in AMD: function follows early anatomic changes.

Diabetic Macular Edema

According to Professor Michels anti-VEGF drugs in general have a “stunning effect” on diabetic macular edema and diabetic retinopathy, as evidenced also by the VIVID and VISTA studies using aflibercept.

In his experience the number of patients showing edema despite an intravitreal anti-VEGF injection four weeks prior (frequently called VEGF non-responders) has decreased with the availability of aflibercept, decreasing the need for alternative treatment strategies (e.g. steroids). In his experience the “the recurrence free interval can be extended with aflibercept in selected cases”. In his own retrospective analysis on 27 patients with DME being under intensive treatment with ranbizumab or off-label bevacizumab the switch to aflibercept achieved a significant reduction in central retinal thickness (CRT) and significant improvement in best corrected visual acuity (BCVA) of 1.7 letters at three months. But he also clearly outlined that long term follow up is necessary to determine clinically relevant improvements in vision and to evaluate a potential extended durability of aflibercept.

Professor Michels said patients with diabetic macular edema and diabetic retinopathy had “a chronic disease which required a careful watch”. Even when the macula is dry it is worth considering continuing injections on a very low number of injections per year. His arguments for this approach are improved diabetic retinopathy, avoiding the chance of vision loss and a better patient control in the context of a chronic disease.

Macular Degeneration

Four case studies of patients treated for neovascular age related macular degeneration (AMD) were presented, that had shown a long term benefit of switching to aflibercept. Professor Michels presented his one year results on insufficiently-responding patients being switched to aflibercept. His definition of insufficient response was persistent or increasing intra- or subretinal fluid by SD-OCT despite three injections over a period of four months. Over one year the 96 patients in Professor Michels’ cohort experienced:

  • Significant reduction in central retinal thickness;
  • Significant reduction in maximum PED height;
  • Visual acuity maintained over one year (on average fourth year of treatment).

Additionally he said outcomes appeared independent of the number of prior injections given.

Reducing the Patient Burden

“We have realised that neovascular AMD under anti-VEGF treatment is, in most cases, a chronic recurrent disease. In addition to trying to avoid under-treatment (the key reason for unfavourable outcomes for AMD patients in many European countries) we have to make patient’s visits in our clinics as convenient and short as possible to maintain a good compliance.” At his clinic several steps have been taken to achieve this, including bilateral injections the same day if needed and dilation for AMD patients only in case of symptoms. The comment was met with some surprise, generating significant discussion about different methodologies in countries around the world.