Eyeworld

26 January 2018 EW NEWS & OPINION Research highlight by Maxine Lipner EyeWorld Senior Contributing Writer you more carefully," Dr. Markoulli said. It might even be possible to screen for peripheral neuropathy. With peripheral neuropathy, there can be recurrent wounds, like re- current ulcers of the feet that may ultimately end up in extreme cases with amputation. "If we can identify those at risk for peripheral neuropa- thy earlier and manage them earlier, we could potentially prevent these downstream effects," Dr. Markoulli said, adding that currently the way peripheral neuropathy is assessed involves an invasive biopsy of the skin. If the tears could be used instead, that might offer a non-inva- sive option. "It's a long stretch, but that's what we're looking at now," Dr. Markoulli said. Investigators with a group at the Prince of Wales Hospital are collect- ing tears and taking confocal images in conjunction with peripheral neuropathy assessments and looking for a possible association. Dr. Markoulli is also looking into expanding the sample size for the current study. "We're including type 1 and type 2 diabetes as well as the different healthy controls, and we're collecting more variables re- lated to peripheral neuropathy," she said. "We will be looking at other proteins. There may be others in the tear film as well as other neuro- mediators." EW Reference 1. Markoulli M, et al. Corneal nerve morphol- ogy and tear film substance P in diabetes. Optom Vis Sci. 2017;94:726–731. Editors' note: Dr. Markoulli has no financial interests related to her comments. Contact information Markoulli: m.markoulli@unsw.edu.au Clinical possibilities The potential clinical implications are two-fold, Dr. Markoulli thinks. "This gives an idea of what changes in the tear film with diabetes and potentially can give us an under- standing as to the mechanisms that result in the poor wound-healing that happens in diabetes," Dr. Mark- oulli said. "If we can understand that, we can potentially supplement the cornea with whatever it is that's missing." For example, if there is a lower concentration of substance P, it might be possible to provide an eye drop that contains this to enable the wound healing process, Dr. Markoulli explained, adding that there has been some work already done in Italy where substance P in the form of a drop was administered to neurotrophic ulcers and showed an improvement in wound healing. The second clinical possibility is that substance P might be used as a marker for corneal nerve damage. "The idea is that if we were to collect someone's tears and analyze them, we could say this indicates that you've got a reduction of nerves in your cornea, you're at risk for this condition, and we need to monitor Included in the study were nine patients with type 2 diabetes and 17 healthy control subjects. "Par- ticipants came for a single visit and at that visit they had their corneal nerve density examined. Confocal microscopy was performed on their eyes and tears collected," Dr. Mark- oulli said. "We first compared the nerve fiber density between the control group and the diabetic group, and as expected, the diabetic group had less corneal nerves present," she said. "When we analyzed the tears, we found that the diabetic group had a lower concentration of substance P compared to the control group, and that was what we had hypothesized." Investigators then compared the concentration of substance P against the corneal nerve fiber density. "We found a significant but weak to moderate correlation suggesting that the more nerves you have, the more substance P you have in the tear film," Dr. Markoulli said. However, the sample size was small and there was a lot of variabil- ity among the patients. Examining tears for possible diabetic neuropathy cues F or patients with diabetes, corneal neuropathy can oc- cur all too commonly. Up to approximately 64% of those with diabetes have some form of corneal damage, but not all of this involves nerve damage, according to Maria Markoulli, PhD, University of New South Wales, Sydney, Australia. "Those who have corneal nerve damage are those who also have diabetic peripheral neuropathy. That tends to be about 70% of people with diabetes," Dr. Markoulli said. A study published in Optometry and Vision Science indicates that tear samples from patients with diabe- tes show lower levels of a protein known as substance P than those of normal controls, Dr. Markoulli noted. 1 Investigators set out to deter- mine whether there was a relation- ship between substance P and the sub-basal nerve plexus in diabetic patients. Substance P properties Looking into substance P seemed to be a natural step. "We know that people with diabetes have reduced density of corneal nerves," Dr. Markoulli said, adding that corneal nerves release various factors such as substance P into the tear film as part of the wound-healing process. "We hypothesized that if you have less corneal nerves because of diabetes, you also have a lower concentration of substance P." Dr. Markoulli said that it is known that people with diabetes have poorer wound healing in the cornea and thus are more prone to recurrent corneal erosions and neurotrophic ulcers. Substance P and nerve fibers Diabetic patients tend to have fewer corneal nerves than their non-diabetic counterparts. Source: Maria Markoulli, PhD allow the use of a lid speculum may have trouble achieving microker- atome suction. "It can be challeng- ing to get clearance," Dr. Randle- man. "You have to get good suction, but not unlike femtosecond lasers, once you get fixation you should be OK. One thing from the surgeon/ patient perspective is the battle between the lid speculum being wide enough open for the surgeon, but too wide and somewhat uncom- fortable for the patient. From my perspective as the surgeon, when necessary, I would prefer the patient to have 30–45 seconds of discomfort and a good outcome, rather than have a relatively comfortable but terrible outcome. That has always been my bias." "I think refractive surgeons know about the complications they can have with microkeratomes, but we don't talk about them as much anymore. However, many surgeons still use mechanical devices in their practices, so it is very important to be aware of these complications and how we can work around them," Dr. Randleman said. EW Editors' note: Dr. Randleman has no financial interests related to his comments. Contact information Randleman: randlema@usc.edu Bad continued from page 25

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