GLAUCOMA RESEARCH

Sir Peng Tee Khaw is an optimist. He foresees a time in the not too distant future when patients with glaucoma can receive a treatment that takes 10 minutes, lowers intraocular pressure (IOP) to 10mmHg, and lasts for 10 years. This would have an enormous impact on the management of glaucoma worldwide if it could be achieved.

Dr Khaw, Professor of Glaucoma and Ocular Healing at the UCL Institute of Ophthalmology and Consultant Ophthalmic Surgeon at Moorfields Eye Hospital, London, UK, outlined progress in glaucoma treatment that may help get to that goal during a talk at the World Ophthalmology Congress in Tokyo.

“We are still far from this goal. In the 21st Century, whatever surgery you are doing, whether in the suprachoroidal space, subconjunctival, or anywhere else, they all rely on tissue scarring. And they all fail because of tissue scarring, particularly when you fail to achieve a low pressure,” he noted.

What is needed is nothing less than perfect surgical technique, along with perfect healing. Fortunately, there has been considerable progress on both fronts. The traditional problems of glaucoma surgery of hypotony and complications are both occurring less frequently with better surgical techniques.

He cited as an example a success story involving a young patient with advanced congenital glaucoma.. Following successful surgery in this particularly challenging condition, she has maintained an IOP of 10mmHg for the past 10 years.

“She scored us 10/10 because she has had a good life. The important thing is to get the pressure low, and I mean to around 10mmHg if you can do this safely. If you keep the pressure low for most patients over a prolonged period of five to 10 years, most of them don’t progress. It is very important to get this right,” he emphasised. (Image 1: Long-term diffuse non-cystic bleb, pressure 10mmHg)

Recent years have seen incremental improvements in surgical technique that are already making a difference. For example, simple changes in trabeculectomy have made the use of antimetabolites safer, and are producing better looking blebs compared with before.

Hypervascularity and leakage are problems linked with poor outcomes. Treatments that take this into consideration could make a difference.

“We see in the clinic that people are very different. You see the same surgeon using the same device, and same anti-scarring agent, yet the outcomes are very different. We have seen that hypervascularity is a very bad sign. A patient with a very red eye post-op on the Moorfields scale at two weeks has a hazard ratio of 2.89; if still very red at 6 weeks, the hazard ratio is six. There are not many things in medicine that have a hazard ratio of six.” (Image 2: Severely inflamed bleb - Grade 5, Moorfields bleb grading at week 6. This eye is six times more likely to fail. http://www.blebs.net )

Vascular leakage

Vascular leakage can negate the effects of intraoperative mitomycin-C and other agents used at the time of surgery. It may be necessary to deploy these agents in the longer term, otherwise the surgery could fail, or pressures will not be as good as they should be.

“We are finding in laboratory research that inflammation is very important. We tend to use steroids, or non-steroidal anti-inflammatory drugs if steroids are not sufficient. What we really need is a new generation of anti-inflammatory agents without the troubling side effects.

“We are seeing signs in translational research of new agents that do not have the side effects of steroids. We are very excited. But in the meantime, we continue to use more anti-inflammatory agents than in the past.”

Anti-VEGF antagonists like bevacizumab (Avastin) are also likely to have an important role in treatment. High-resolution angiography imaging studies show that it is leakage that is the problem, not neovascularisation. VEGF inhibition tends to stabilise the leakage, which is important from the point of view of wound healing. (Image 3: High-resolution angiography showing bleb leakage rather than neovascularisation)

Another line of approach involves pain control. Better pain control reduces leakage and the release of cytokines and the cascade of fibroblasts and other inflammatory factors. Simple pain control may provide significant anti-scarring effects.

“We all learn in medical school - calor dolor, rubor. That is, heat, pain, and redness in inflammation. We are sticking needles in people’s eyes, and it hurts. I always use local anaesthetic in the injection when giving postoperative agents. Patients like it, and when they come back for a second injection, they are not jumping up the wall. You may also be improving their outcome as well by preventing scarring,” said Dr Khaw.

Peng Tee Khaw: p.khaw@ucl.ac.uk