EuCornea Medal Lecture charts ongoing progress and latest challenges in keratoconus research

François Malecaze receiving the 2017 EuCornea Medal from EuCornea president Friedrich Kruse   While keratoconus remains a mysterious disease with a complex pathophysiology, significant progress has been made in recent years in the diagnosis and management of the condition, François Malecaze said in the keynote EuCornea Medal Lecture at the opening ceremony of the 8th EuCornea Congress. “We still have much to learn about how this disease develops, but the good news is that the technological advances of recent years have transformed the decision tree of keratoconus patients and given us more options for effective treatment,” he said. In a wide-ranging lecture entitled “Keratoconus: what we have accomplished and what is still left to do”, Prof Malecaze said that his first encounter with the disease came when he was still a medical student. “I heard this lecture on keratoconus and I had the impression of taking a grim stroll among a host of frightening animals, because keratoconus was a very serious disease for which the only treatment was a corneal graft, which was a very risky treatment at the time,” he said. Several causes have been proposed in keratoconus pathophysiology, including genetics, collagen-related issues, inflammation, oxidative stress and reduced keratocyte proliferation, said Prof Malecaze. He noted that while a large number of studies from different labs have led to the identification of genome regions or “putative loci” situated on different chromosomes that contain the gene implicated, the overall results have still been somewhat disappointing. “The candidate genes approach has mostly failed to identify genes with major effect, which strengthens the idea that keratoconus is a complex multigenic and multifactorial disease. In addition to the genetic mutations, other contributory factors – and eye rubbing in particular – are necessary in order for the disease to develop,” he said. Studies on collagen and in particular the role of matrix metalloproteases in the development of keratoconus are contradictory and non-conclusive, said Prof Malecaze. Likewise, theories implicating inflammation, oxidative stress and reduced keratocyte proliferation in the aetiology of keratoconus are interesting but necessitate a lot more research before any conclusions can be drawn, he said. In terms of diagnosis, significant progress has been made in earlier detection of the disease, thanks to advances in technology such as reflective topography and the groundbreaking work by Yaron Rabinowitz in identifying “at-risk” topographic patterns, he said. For non-surgical management of the disease, Prof Malecaze noted that a recent consensus report from leading keratoconus experts stressed one of the most important measures as giving verbal guidance to the patient regarding the importance of avoiding eye rubbing. “The experts also agreed that in cases of allergy or if there is any allergic component that patients should be treated with topical anti-allergic medication and lubricants,” he said. For patients intolerant of rigid contact lenses, Prof Malecaze said the new generation of hybrid and scleral lenses may provide a viable alternative. In terms of surgical interventions, corneal collagen crosslinking (CXL) has proven its efficacy and safety over time for progressive keratoconus, while corneal rings have also been used effectively, often in tandem with CXL, to stabilise keratoconic corneas. For patients with stable or non-progressive keratoconus, treatment will depend on the status of the cornea, said Prof Malecaze. “If there are no opacities, we can propose glasses, then rigid lenses. If optical correction is inefficient we can use rings to correct astigmatism or phakic toric implantation to treat astigmatism or high myopia. If there is opacity and other strategies have failed, we can propose a corneal graft, usually with deep anterior lamellar keratoplasty as the preferred option,” he said.               EuCornea Medal Lecture charts ongoing progress and latest challenges in keratoconus research   While keratoconus remains a mysterious disease with a complex pathophysiology, significant progress has been made in recent years in the diagnosis and management of the condition, François Malecaze said in the keynote EuCornea Medal Lecture at the opening ceremony of the 8th EuCornea Congress. “We still have much to learn about how this disease develops, but the good news is that the technological advances of recent years have transformed the decision tree of keratoconus patients and given us more options for effective treatment,” he said. In a wide-ranging lecture entitled “Keratoconus: what we have accomplished and what is still left to do”, Prof Malecaze said that his first encounter with the disease came when he was still a medical student. “I heard this lecture on keratoconus and I had the impression of taking a grim stroll among a host of frightening animals, because keratoconus was a very serious disease for which the only treatment was a corneal graft, which was a very risky treatment at the time,” he said. Several causes have been proposed in keratoconus pathophysiology, including genetics, collagen-related issues, inflammation, oxidative stress and reduced keratocyte proliferation, said Prof Malecaze. He noted that while a large number of studies from different labs have led to the identification of genome regions or “putative loci” situated on different chromosomes that contain the gene implicated, the overall results have still been somewhat disappointing. “The candidate genes approach has mostly failed to identify genes with major effect, which strengthens the idea that keratoconus is a complex multigenic and multifactorial disease. In addition to the genetic mutations, other contributory factors – and eye rubbing in particular – are necessary in order for the disease to develop,” he said. Studies on collagen and in particular the role of matrix metalloproteases in the development of keratoconus are contradictory and non-conclusive, said Prof Malecaze. Likewise, theories implicating inflammation, oxidative stress and reduced keratocyte proliferation in the aetiology of keratoconus are interesting but necessitate a lot more research before any conclusions can be drawn, he said. In terms of diagnosis, significant progress has been made in earlier detection of the disease, thanks to advances in technology such as reflective topography and the groundbreaking work by Yaron Rabinowitz in identifying “at-risk” topographic patterns, he said. For non-surgical management of the disease, Prof Malecaze noted that a recent consensus report from leading keratoconus experts stressed one of the most important measures as giving verbal guidance to the patient regarding the importance of avoiding eye rubbing. “The experts also agreed that in cases of allergy or if there is any allergic component that patients should be treated with topical anti-allergic medication and lubricants,” he said. For patients intolerant of rigid contact lenses, Prof Malecaze said the new generation of hybrid and scleral lenses may provide a viable alternative. In terms of surgical interventions, corneal collagen crosslinking (CXL) has proven its efficacy and safety over time for progressive keratoconus, while corneal rings have also been used effectively, often in tandem with CXL, to stabilise keratoconic corneas. For patients with stable or non-progressive keratoconus, treatment will depend on the status of the cornea, said Prof Malecaze. “If there are no opacities, we can propose glasses, then rigid lenses. If optical correction is inefficient we can use rings to correct astigmatism or phakic toric implantation to treat astigmatism or high myopia. If there is opacity and other strategies have failed, we can propose a corneal graft, usually with deep anterior lamellar keratoplasty as the preferred option,” he said.