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ust fifteen years ago, there were no good treatments for major eye diseases like diabetic macular edema (DME), retinal vein occlusion (RVO), and wet age-related macular degeneration (wAMD). Even patients receiving the best care available at the time had to resign themselves to progressive vision loss and probable blindness. The discovery of new treatments that combat vascular endothelial growth factor (VEGF) has changed that.

For many years, the only treatment for wAMD was laser-based, either through direct laser photocoagulation or through photodynamic therapy. Although these were able to slow down the progression of the disease, they were unable prevent itmaking neither laser-based therapies an ideal solution.

Within the last decade, two new anti-VEGF treatments (ranibizumab and afliberecpet) have been approved by Health Canada for use in the eye – these have had dramatic benefits for patients with retinal diseases. During this time, a third anti-VEGF treatment (bevacizumab) has been added to the mix, despite the fact that it is not approved for use in the eye. “These drugs are all in a class called anti-VEGF,” explains Dr. David Wong, Ophthalmologist in Chief at St. Michael's Hospital. “VEGF is the primary system that grows blood vessels and when that happens in the eye, it can be a big problem.”

The success of these drugs has been described as miraculous, preserving and even improving vision for a great many Canadians who would otherwise have lost their sight. That has provided a great boon to the large population of older Canadians, as age is one of the most important risk factors for these diseases of the eye. “In Canada, people are living longer, but most importantly making significant contribution to Canadian society in paid employment as well as volunteering in many capacities,” says Dr. Jane Barratt, Secretary General of the International Federation on Ageing. “Healthy ageing is about being enabled to do what you value, and vision is a critical factor.”

Not All Drugs Are Created Equal

Though the three drugs all have a similar mechanism, there are differences between them that can be very important. Most significantly, bevacizumab has only been approved by Health Canada for use in the treatment of cancer, while ranibizumab and aflibercept have been specifically approved for use in the eye. This means that all uses of bevacizumab to treat eye disease are off-label – the drug has also not been subjected to the rigorous safety testing required for the specific application of injection into the eye.

On the other hand, bevacizumab is much cheaper than the other two options. Because bevacizumab is manufactured for use in other contexts than the eye, it is sold in much larger vials and each injection into the eye only uses a fraction of a vial. This is not all up-side though. “When we use bevacizumab in ophthalmology, we have to rely on a compounding pharmacist to take that large vial and break it up into appropriate dosages,” says Dr. Robert Devenyi, Ophthalmologist in Chief and Director of Retinal Services at the University Health Network. “So, regardless of which drug is better, the fact that you need that extra step means that patients are unnecessarily being put at an increased risk of infection. Infection in the eye is a surgical problem and lots of patients lose their eyes completely. It's an absolutely catastrophic complication.”

Between ranibizumab and aflibercept, the line is a little fuzzier. “There are differences,” says Dr. Wong. “Studies show that one has a little bit more durability, but the other has the longer track record. For treating diabetic retinopathy specifically, there is some evidence from a study called Protocol T that aflibercept performs better than the others in the first year. By the second year both aflibercept and ranibizumab were better than bevacizumab which is not approved for use in the eye.”

The important thing is that patients be aware of the choice that exists between these treatments and be empowered to ask the hard questions about safety and why one is being chosen over another. “What we're looking for is a way to optimize the functional ability and contributions of older Canadians, says Dr. Barratt. “Part of that is ensuring that people are well educated and informed about the treatment options available to them to improve their sight.”