“For most people, seeing a “cone” for the first time is quite surprising. They ask: How can the eye of someone be that shape? What is keratoconus doing to these people’s eyes?”, says Swiss eye surgeon, Prof. Dr. Dr. Farhad Hafezi, Medical Director of the ELZA Institute, Dietikon, Zurich. “To answer that, we need to understand two things: the eye is pressurised with fluid (in order to keep its shape), and that the cornea needs to not only be transparent, but also strong enough to resist that internal eye – intraocular – pressure, and what happens when the cornea isn’t strong enough to resist that pressure: it bulges, and instead of looking circular, the eye’s cornea starts to look like a cone instead. Understanding what makes the cornea strong – what researchers call ‘corneal biomechanics’ and what causes it to lose strength is central to not only our understanding of diseases like keratoconus, but actually most of refractive surgery”.
Presenting to the Swiss Optometrists Association (SBAO) Annual Meeting, Hafezi identified the single biggest villain in the development of keratoconus: eye rubbing. “It’s clear: rubbing your eyes is simply bad for your eyes. It’s not 100% clear whether rubbing your eyes causes keratoconus, or whether some other genetic or environmental factor needs to be present, it is 100% clear that rubbing your eyes can damage your cornea, and make the disease far worse.” But rubbing your eyes when you’re tired or they are sore is a natural thing to do, right? “I understand that, and if you do have to rub your eyes, rub them with your fingertips, not your knuckles. It’s just as satisfying, and you apply far less trauma to the eye when you do that.”
As he told the SBAO members, it turns out hormones can weaken your cornea too. “Pregnancy is a classic example. Pregnant women’s bodies release more progesterone, which has one major benefit in late pregnancy: it softens ligaments, which enables the baby to be delivered more easily during childbirth.” But progesterone also softens the cornea — and that can be a problem. “If the mother has had LASIK prior to pregnancy, or already has a weakened cornea thanks to a latent keratoconus (or even a history of vigorous eye rubbing) then the cornea is already weakened, and pregnancy can reveal the problem. It’s the same story for women trying to conceive using IVF – the hormones they administer during the process can soften the cornea too. If your vision changes, it’s worth getting screened to exclude the possibility of it being keratoconus or a related disease.”
It’s not just sex hormones: thyroid hormones are important too. The incidence of keratoconus is ten times higher in people with under-active thyroid glands – that is, hypothyroidism – and there are many cases reported of patients who have had thyroid surgery developing keratoconus. In fact, I think it’s important that any patient with keratoconus should be screened for hypothyroidism, and any patient with hypothyroidism be screened for keratoconus.”
There is now an effective treatment for keratoconus that can strengthen the cornea and stop the disease from progressing: corneal cross-linking (CXL), in which ultraviolet light and vitamin B2 (riboflavin) eye drops can be combined to “cross-link” the collagen molecules in the cornea and making it mechanically stronger. It helps flatten the cones to a certain extent. It’s effective, but it doesn’t necessarily improve patients’ vision – and its effect on the cornea varies from patient to patient.
Why? Corneal biomechanics. Every person’s cornea is different. Hafezi notes, “If eye care professionals could map the strength of a person’s cornea like they can currently map its shape, this would have profound consequences. Those patients with underlying, but undiscovered weaknesses in their corneas might be able to be identified. Understanding where the strong and weak areas of a patient’s cornea are could help to customise CXL treatment and give them not just a stronger cornea that stops keratoconus disease progression, but possibly one that could be used to improve their vision too.”
The problem is that it has been impossible to determine the strength of the cornea in a live patient – either it has had to be done indirectly (by blowing a puff of air into the eye, and using high-speed video filming to map how the cornea changes shape and bounces back in response to the air puff) or post-mortem (or post-transplant surgery on the diseased bit of tissue that’s removed). But this is changing. “There is now a new device that non-invasively can map corneal strength in patients: the Brillouin microscope. It’s a machine that’s still under development, but our ELZA laboratory in the USA has one, and is being used under the supervision of my colleague J. Bradley Randleman, and the early results are promising.”
But there’s another important application for the Brillouin microscope: predicting the effects of laser refractive surgery too. “Laser refractive surgery has never been safer or more predictable,” explains Hafezi. “We can, today, routinely get within 0.5 diopters of what we target, which means patients are easily spectacle-free afterwards. But laser refractive surgery does mean that the laser does vaporise some of the cornea to reshape it. This does weaken the cornea to some extent. Successful clinical use of Brillouin microscopy would mean that those patients who appear normal, but have an underlying weakness in their cornea can be identified and excluded more easily. But it also means that we can more accurately predict the effect of even a single laser pulse in any given region of a patient’s cornea. That would enable fine-tuning of laser refractive surgery to what we hope, will approach perfection.”