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126 | EYEWORLD | APRIL 2019 C ORNEA density of the corneal nerves, in vivo, even in patients with minimal signs of peripheral neurop- athy. 3 Other studies have shown that both quan- titative and qualitative analyses are possible using confocal microscopy of the cornea, which can be repeated over time to evaluate disease progres- sion 4 ," he said. Neurotrophic keratitis Corneal damage through diabetes ultimately re- sults in what is called neurotrophic keratitis, which is a corneal degeneration characterized by the reduction or absence of corneal sensitivity, due to an impairment of corneal innervation of the tri- geminal nerve. The sensory and trophic function- al impairments lead to the consequent breakdown of the corneal epithelium, affecting the health and integrity of the tear film, epithelium, and stroma. Seventy percent of diabetic patients have altered corneal nerves. These individuals are at a high risk of developing neurotrophic keratitis, according to Dr. Nubile, particularly if they have suffered corneal injuries, have other corneal comorbidities, or have had surgery. 5 Neurotrophic keratitis is classified into differ- ent stages: mild, moderate, or severe. Mild is when the epithelial is altered, moderate is when there is persistent epithelial defects without stromal defects that include hypo-anesthesia/anesthesia, and severe is when the stroma is involved from ulcers to lysis. 6 As diabetic patients may request LASIK, clinicians should be aware that refractive laser sur- gery should be avoided in individuals with diabe- tes that fail to demonstrate tight glycemic control and have any evidence of ocular or peripheral complications. There is also a greater risk of ocular surface complications following pars plana vitrectomy, cataract surgery, and keratoplasty. Treatments of diabetes-related ocular surface abnormalities include: systemic therapy for dia- betes (blood glucose level control), artificial tears, antibiotics, bandage contact lens, tarsorrhaphy, and AMT, most of which are implemented to repair the ocular surface, not address the etiology of the disorder. The treatment of neurotrophic keratitis has shown progress. New approaches in the treatment of diabetes-related ocular surface abnormalities are both systemic and topical. Their aim is to regenerate the corneal nerves. Dr. Nubile observed that collagen may also be affected, altering the mechanical properties of the cornea in diabetic patients. "There is an increased corneal stiffness resulting from hyper- glycemia. We have to expect an overestimation of IOP measurements in these patient and other effects when dealing with ectatic disease, which is a consideration in refractive surgery candidates," he said. Keratopathy Diabetic keratopathy relies on two main mecha- nisms: One is damage to the corneal unmyelinated nerves due to axonal degeneration from hypergly- cemia, and the other is the reduced wound healing capability of the corneal epithelium, related to the alteration of the equilibrium between the epitheli- al cells and the basal membrane. Clinical manifestations of keratopathy in- clude: punctate keratopathy, poor wound healing, recurrent corneal epithelial defects, ulcers, or a propensity to corneal infections. Additionally, stress to the ocular surface in the form of refrac- tive or corneal surgery or contact lens wear can play a role in destabilizing the already compro- mised ocular surface. Corneal neuropathy "Corneal neuropathy involves a mechanism of damage to the corneal nerves that is related to hyperglycemia in diabetic patients, through dif- ferent mechanisms. One is the oxidative stress/ age products, and the other involves metabolic pathways like the protein kinase C pathway and others. All of them lead to damage of the corneal nerves," he said. Diabetic neuropathy has a 50% prevalence in diabetic patients and constitutes 27% of the U.S. annual cost of diabetes ($66 billion), raising the importance of diagnostics and disease prevention, according to Dr. Nubile. Traditional methods of evaluating the peripheral nerve fibers of the cor- nea include biothesiometry (vibration perception), skin punch, and sural/peroneal nerve biopsy. 2 Also, confocal microscopy is a good diagnostic modality to follow disease progression in diabet- ic-related peripheral neuropathy. "It has been proven that with confocal microscopy, which is a non-invasive tool with relatively low expenses, we can assess different degrees of alteration in the morphology and continued from page 124 References 1. Shih KC, et al. A systematic review on the impact of diabetes mellitus on the ocular surface. Nutr Diabetes. 2017;7:e251. 2. Petropoulos IN, et al. Diag- nosing diabetic neuropathy: something old, something new. Diabetes Metab J. 2018;42:255– 269. 3. Patel DV, McGhee CNJ. Mapping of the normal human corneal sub-basal nerve plexus by in vivo laser scanning confocal microscopy. Invest Ophthalmol Vis Sci. 2005;46:4485–8. 4. Wang EF, et al. In vivo con- focal microscopy of the human cornea in the assessment of peripheral neuropathy and systemic disease. Biomed Res Int. 2015;2015:951081. 5. Mastropasqua L, et al. Understanding the pathogenesis of neurotrophic keratitis: the role of corneal nerves. J Cell Physiol. 2017;232:717–724. 6. Dua HS, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018;66:107–131. Financial interests Nubile: None

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