Diabetic keratopathy (DK) is a common, but underdiagnosed, ocular complication of diabetes mellitus (DM) that has a significant economic burden. It is characterised by progressive damage of corneal nerves, due to DM-induced chronic hyperglycaemia and its associated metabolic changes. With advances in corneal nerve imaging and quantitative analytic tools, studies have shown that the severity of diabetic corneal neuropathy correlates with the status of diabetic peripheral neuropathy. The corneal nerve plexus is, therefore, considered as an important surrogate marker of diabetic peripheral neuropathy and helps in the evaluation of interventional efficacy in the management of DM. The clinical manifestations of DK depend on the disease severity and vary from decreased corneal sensitivity to sight-threatening corneal infections and neurotrophic ulcers. The severity of diabetic corneal neuropathy and resultant DK determines its management plan, and a step-wise approach is generally suggested. Future work would focus on the exploration of biomarkers for diabetic corneal neuropathy, the development of new treatment for corneal nerve protection, and the improvement in the clinical assessment, as well as current imaging technique and analysis, to help clinicians detect diabetic corneal neuropathy earlier and monitor the sub-clinical progression more reliably.

Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus, affecting nerves in all parts of the body including corneal nerves and peripheral nervous system, leading to diabetic corneal neuropathy and diabetic peripheral neuropathy, respectively. Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies, clinical scoring, and skin biopsies. However, these diagnostic methods have limited sensitivity in detecting small-fiber disease, hence they do not accurately reflect the status of diabetic neuropathy. More recently, analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy. In this review, we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy, elaborating on the foundational aspects of each: pathogenesis, clinical presentation, evaluation, and management. We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy, particularly early diabetic peripheral neuropathy; the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy; and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.

The tear proteomics and neuromediators are associated with clinical dry eye parameters following refractive surgery. To investigate and compare the tear proteomic and neuromediator profiles following small incision lenticule extraction (SMILE) versus laser-assisted in-situ keratomileusis (LASIK). In this randomized controlled trial with paired-eye design, 70 patients were randomized to receive SMILE in one eye and LASIK in the other eye. Tear samples were collected preoperatively, and 1 week, 1, 3, 6 and 12 months postoperatively, and were examined for protein concentration changes using sequential window acquisition of all theoretical fragment ion mass spectrometry (SWATH-MS). The data were analyzed with DAVID Bioinformatics Resources for enriched gene ontology terms and over-represented pathways. Tear neuromediators levels were correlated with clinical parameters. Post-SMILE eyes had significantly better Oxford staining scores and tear break-up time (TBUT) than post-LASIK eyes at 1 and 3 months, respectively. Tear substance P and nerve growth factor levels were significantly higher in the LASIK group for 3 months and 1 year, respectively. SMILE and LASIK shared some similar biological responses postoperatively, but there was significant up-regulation in leukocyte migration and wound healing at 1 week, humoral immune response and apoptosis at 1 month, negative regulation of endopeptidase activity at 3 to 6 months, and extracellular structure organization at 1 year in the post-LASIK eyes. Tear mucin-like protein 1 and substance P levels were significantly correlated with TBUT (r = -0.47, r = -0.49, respectively). Significant differences in the tear neuromediators and proteomics were observed between SMILE and LASIK, even though clinical dry eye signs have subsided and became comparable between 2 procedures.

Neural Regen Res, Official publication of Publishing House of Neural Regeneration Research China Association of Rehabilitation Medicine,China

To compare the aqueous oxidative stress, prostaglandin E2 (PGE2), and cytokine levels after low-energy femtosecond laser-assisted cataract surgery versus conventional phacoemulsification, and to evaluate the effect of a nonsteroidal antiinflammatory drug (NSAID) on the aqueous profiles. Singapore National Eye Center, Singapore. Randomized controlled trial. Thirty-five patients were randomized to receive conventional phacoemulsification in one eye and femtosecond laser-assisted cataract surgery in the fellow eye. Another matched prospective cohort of 35 patients was included to receive femtosecond laser-assisted cataract surgery with a preoperative NSAID. Aqueous humor was collected after the laser was used or at the beginning of surgery (conventional phacoemulsification), and at the end of phacoemulsification. The levels of aqueous malondialdehyde (MDA), PGE2, and cytokines, chemokines, and growth factors were analyzed. The postoperative aqueous flare levels were evaluated. Compared with the conventional group, the femtosecond-assisted group had a significantly higher PGE2 (P = .01) and interleukin-1 receptor antagonist levels (P = 0.04). The preoperative NSAID significantly reduced the PGE2 surge (P = .002) and the mean reduction in pupil diameter (P = .02). The MDA concentrations before phacoemulsification were 0.24 μmol/L ± 0.18 (SD), 0.51 ± 0.41 μmol/L and 0.59 ± 0.52 μmol/L for the conventional, femtosecond-assisted, and femtosecond-assisted NSAID groups, respectively (P = .42). After phacoemulsification, the PGE2 and MDA levels increased in all groups. The MDA induction was significantly correlated with the phacoemulsification time (P = .002). The postoperative flare was insignificantly higher in the femtosecond-assisted group than the conventional group. Compared with conventional phacoemulsification, the femtosecond laser-assisted cataract surgery performed with the Femto LDV Z8 laser platform induced a significantly higher PGE2 level. The MDA and postoperative aqueous flare level were insignificantly higher. The preoperative NSAID reduced the PGE2 surge and occurrence of intraoperative miosis. The oxidative stress induced during phacoemulsification was strongly correlated with phacoemulsification time.

PURPOSE: To compare long-term corneal nerve status following small incision lenticule extraction (SMILE) versus laser in situ keratomileusis (LASIK). METHODS: Twenty-four patients were randomized to receive SMILE in one eye and LASIK in the other eye. In vivo confocal microscopy examination and dry eye assessments were performed at a mean of 4.1 years postoperatively. The patients were further divided into two groups based on the mean assessment time: 2.7 years postoperatively (2.7 years group) and 5.5 years postoperatively (5.5 years group). Another 6 age-matched normal patients were recruited. RESULTS: At 4.1 years, LASIK eyes had significantly less corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and corneal total branch density and significantly more nerves with beading than SMILE eyes. The CNFD, CNBD, CNFL, and number of nerves with sprouting were significantly higher in the 5.5 years group than in the 2.7 years group, in both types of surgery, suggesting persistent nerve regeneration. The CNBD and CNFD in the 5.5 years group, regardless of surgical types, were significantly lower than those in the control group, indicating the nerve status had not recovered to normal ranges even at 5.5 years. High myopic treatment resulted in significantly reduced CNFD with LASIK but not with SMILE. There were no significant differences in the dry eye parameters between the two procedures at 4.1 years postoperatively. CONCLUSIONS: The impact on corneal nerves following refractive surgery is long-lasting. SMILE had better nerve preservation and regeneration than LASIK, but neither procedure had recovered nerve status to normal levels even at 5.5 years. [ J Refract Surg . 2020;36(10):653–660.]