US adults visit eye care providers more often than primary healthcare providers, placing these doctors in a prime position to help identify and manage patients with prediabetes and diabetes. Currently, diabetes is identified in eye clinics in an advanced stage, only after visible signs of diabetic retinopathy. Recent ophthalmic research has identified multiple subclinical and clinical changes that occur in the anterior segment of the eye with metabolic disease. The corneal epithelium exhibits increased defects and poor healing, including an increased risk of neurotrophic keratitis. Increased thickness and stiffness of the cornea artificially alters intraocular pressure. There is damage to the endothelial cells and changes to the bacterial species on the ocular surface, both of which can increase risk of complications with surgery. Decreased corneal sensitivity due to a loss of nerve density predispose patients with metabolic disease to further neurotrophic complications. Patients with diabetes have increased Meibomian gland dysfunction, blepharitis and reduced tear production, resulting in increased rates of dry eye disease and discomfort. Early detection of metabolic disease may allow eye care providers to be more proactive in recommending referral and intervention in order to reduce the risk of blindness and other diabetes-related morbidity. Continued research is needed to better understand the time course of changes to the anterior segment and what can be done to better detect and diagnose patients with prediabetes or undiagnosed diabetes and provide improved care for these patients.

Purpose: Decreased corneal nerve fiber density and higher corneal epithelial dendritic cells have been reported in established patients with type 2 diabetes; however, alterations in the subbasal nerve plexus in prediabetes with healthy subjects or subjects with diabetes is limited. The study aimed to determine corneal nerve fiber density and morphology and dendritic cell density between healthy subjects and those with prediabetes or type 2 diabetes. Methods: Fifty-two subjects (aged 30–70 years) were recruited. Blood samples and body metrics were taken. Subjects were grouped as: healthy controls (hemoglobin A1c [HbA1c] < 5.7%), prediabetes (5.7–6.4%), and type 2 diabetes (> 6.4% or physician diagnosis). Central corneal subbasal nerve plexus was imaged using in vivo confocal microscopy. Corneal nerve fiber density and morphology, including interconnections and tortuosity, and dendritic cell density were assessed. Kruskal-Wallis tests were carried out to compare differences in the examined variables between groups. Spearman correlations were carried out to examine the associations between body metrics with HbA1c and corneal findings. Results: Seventeen healthy controls, 20 subjects with prediabetes, and 15 subjects with type 2 diabetes completed this study. Central corneal nerve fiber density was significantly lower in type 2 diabetes compared to prediabetes (P = 0.045) and healthy controls (P = 0.001). No differences were found in central corneal nerve fiber interconnections, tortuosity, or dendritic cell density between groups. There was a significant association between HbA1c and corneal nerve fiber density (rho = −0.45, P = 0.001) and body mass index (BMI; rho = −0.30, P = 0.04). Conclusions: Increased HbA1c values are associated with decreased corneal nerve fiber density across the spectrum of type 2 diabetes.

Purpose LASIK causes corneal nerve damage and may affect the neuro-immune crosstalk. This study examined the effects of LASIK on corneal epithelial dendritic cells (CEDC) density and morphology and explored their relationships with corneal nerves and tear neuropeptides. A grading system was developed to assess CEDC morphology. Methods Intra- and inter-observer repeatability of the CEDC morphology grading system was established using kappa (kappa). In vivo confocal microscope images of the central cornea were captured from 20 participants who had undergone LASIK 12-16 months earlier and 20 controls (age 18-32 years, 55%F). CEDC density was counted manually, and CEDC morphology was assessed using a new grading system. CEDC sub-types (contacting nerves [CEDCc] and not contacting nerves [CEDCnc]) were also assessed. Differences in CEDC density and morphology were examined using mixed models and chi-squared test. Relationships between CEDC and corneal nerve parameters and tear substance P were explored using Spearman's correlation. Results Excellent intra- and inter-observer repeatability was demonstrated for the grading system (kappa = 0.82-0.97). In post-LASIK participants, CEDC density was lower compared with controls (5 [0-34] vs. 21 [7-77] cells/mm(2); p = 0.01), and the proportion of CEDC with thick dendrites was higher (55%-73% vs. 11%-21%, p < 0.003). Higher tear substance P levels were associated with higher CEDC density (rho = 0.48, p = 0.003). Fewer nerve interconnections were observed in participants in whom CEDC had dendrites (p = 0.03). CEDC sub-types followed a similar pattern to CEDC. Conclusions The findings suggest that CEDC may remain altered more than 12 months post-LASIK. The association with substance P suggests a role for CEDC in corneal neurogenic inflammation.