Comparison of Novel Wide-Field In Vivo Corneal Confocal Microscopy With Skin Biopsy for Assessing Peripheral Neuropathy in Type 2 Diabetes.

Diabetic peripheral neuropathy (DPN) is a serious complication of diabetes, where skin biopsy assessing intraepidermal nerve fiber density (IENFD) plays an important diagnostic role. In vivo confocal microscopy (IVCM) of the corneal subbasal nerve plexus has been proposed as a noninvasive diagnostic modality for DPN. Direct comparisons of skin biopsy and IVCM in controlled cohorts are lacking, as IVCM relies on subjective selection of images depicting only 0.2% of the nerve plexus. We compared these diagnostic modalities in a fixed-age cohort of 41 participants with type 2 diabetes and 36 healthy participants using machine algorithms to create wide-field image mosaics and quantify nerves in an area 37 times the size of prior studies to avoid human bias. In the same participants, and at the same time point, no correlation between IENFD and corneal nerve density was found. Corneal nerve density did not correlate with clinical measures of DPN, including neuropathy symptom and disability scores, nerve conduction studies, or quantitative sensory tests. Our findings indicate that corneal and intraepidermal nerves likely mirror different aspects of nerve degeneration, where only intraepidermal nerves appear to reflect the clinical status of DPN, suggesting that scrutiny is warranted concerning methodologies of studies using corneal nerves to assess DPN. ARTICLE HIGHLIGHTS: Comparison of intraepidermal nerve fiber density with automated wide-field corneal nerve fiber density in participants with type 2 diabetes revealed no correlation between these parameters. Intraepidermal and corneal nerve fibers both detected neurodegeneration in type 2 diabetes, but only intraepidermal nerve fibers were associated with clinical measures of diabetic peripheral neuropathy. A lack of association of corneal nerves with peripheral neuropathy measures suggests that corneal nerve fibers may be a poor biomarker for diabetic peripheral neuropathy.

Schematic sectioning approaches for corneal and retinal surfaces used in ophthalmology and vision-related clinical practice and research.

Schematically, the corneal surface area and other similar surfaces such as the retinal surface and the visual field area have been represented by a circle. While there are different types of schematic sectioning patterns in use, not all patterns are recognized or referred to with their respective appropriate terminology. In scientific communications, as well as in clinical practice, when dealing with corneal or retinal surfaces, it is imperative to have the ability to refer to specific areas with an as high degree of accuracy as possible. The necessity arises in many situations, either when performing tests such as corneal surface staining, corneal sensitivity test, scanning the corneal surface, reporting of the findings related to any specific corneal surface area, or using a sectioning pattern for parts of the retinal surface when locating retinal lesions, or when referring to loci with changes in the visual field. Applying the appropriate geometric terms when any pattern is used for sectioning of surfaces such as cornea or retina, for precise localization and description of the findings or changes with a high degree of accuracy using the correct terminology is a sine qua non. Hence, the idea for this work is to gain an overview of the sectioning methods that are available and in use as methodological guidance in different sectioning patterns related to the corneal, retinal, and visual field.

Alterations in meibomian glands in patients treated with intensity-modulated radiotherapy for head and neck cancer.

Patients undergoing intensity-modulated radiotherapy (IMRT) for head and neck cancer may have increased incidence of dry eye disease and the exact mechanism is unclear. The present study aims to assess tear film and meibomian gland (MG) features in patients who received IMRT for head and neck cancer not involving the orbital area. Twenty-seven patients (64.7 ± 9.8 years) and 30 age-matched controls (61.4 ± 11.0 years) underwent a comprehensive dry eye work-up. Compared to the control group, the patients had more lid margin abnormalities, and worse meibum quality. The MG loss, calculated as (tarsal area-MG area)/tarsal area, was higher in the patient group in both the upper (53.0 ± 12.0% vs. 35.1 ± 10.3%, p < 0.001) and lower lids (69.5 ± 12.6% vs. 48.5 ± 12.5%, p < 0.001). In the patient group, more MG loss in the lower lids correlated with worse meibum quality (r = 0.445, p = 0.029). In contrast, there was no significant difference in aqueous tear production level, measured with Schirmer test. Patients treated with IMRT for head and neck cancer seemed to have comparable lacrimal gland function to the controls despite more dry eye symptoms. However, the patients had MG functional and morphological changes, which may present a higher risk for developing dry eye disease.

Temporal redistribution of cap and residual stromal thickness after SMILE.

PURPOSE: To investigate corneal sublayer alterations during the postoperative period after small-incision lenticule extraction (SMILE). SETTING: Synslaser clinic, Oslo, Norway. STUDY DESIGN: Retrospective. METHODS: Patients who underwent SMILE for treating myopia were included. The thicknesses of the corneal epithelium, cap, stromal part of the cap (StromaCap), residual stromal bed (StromaRes), and total stroma (StromaTot) were measured using spectral-domain optical coherence tomography at 1 day, 1 week, 1 month, 3 months, and 6 months postoperatively. Postoperative changes in the corneal sublayer thicknesses were analyzed and correlated with changes in spherical equivalence and anterior and posterior keratometry (K). RESULTS: The study was based on analyses of the right eyes of 51 patients. From 1 day to 6 months postoperatively, the corneal epithelium, cap, StromaCap, StromaRes, and StromaTot thicknesses increased from 54.4 ± 4.0 µm to 57.3 ± 5.2 µm; 137.1 ± 5.5 µm to 140.3 ± 5.1 µm; 82.7 ± 5.9 µm to 82.8 ± 6.3 µm; 375.0 ± 40.8 µm to 381.4 ± 30.6 µm; and 457.6 ± 41.1 µm to 462.1 ± 36.7 µm, respectively. Between 1 month and 6 months postoperatively, the increase in anterior K correlated significantly with the thickening of the cap (r = 0.37, P = .03) and the stromal component of the cap (r = 0.36, P = .04) within the central cornea. CONCLUSIONS: The post-SMILE remodeling behavior between the anterior (StromaCap) and posterior (StromaRes) stroma were dissimilar. There was a significant correlation between changes in anterior K and the central cap and the stromal component of the cap. This might be because of biomechanical changes, tissue remodeling, and wound healing or a combination of some or all of the aforementioned processes.

Dendritic cell maturation in the corneal epithelium with onset of type 2 diabetes is associated with tumor necrosis factor receptor superfamily member 9.

Type 2 diabetes mellitus is characterized by a low-grade inflammation; however, mechanisms leading to this inflammation in specific tissues are not well understood. The eye can be affected by diabetes; thus, we hypothesized that inflammatory changes in the eye may parallel the inflammation that develops with diabetes. Here, we developed a non-invasive means to monitor the status of inflammatory dendritic cell (DC) subsets in the corneal epithelium as a potential biomarker for the onset of inflammation in type 2 diabetes. In an age-matched cohort of 81 individuals with normal and impaired glucose tolerance and type 2 diabetes, DCs were quantified from wide-area maps of the corneal epithelial sub-basal plexus, obtained using clinical in vivo confocal microscopy (IVCM). With the onset of diabetes, the proportion of mature, antigen-presenting DCs increased and became organized in clusters. Out of 92 plasma proteins analysed in the cohort, tumor necrosis factor receptor super family member 9 (TNFRSF9) was associated with the observed maturation of DCs from an immature to mature antigen-presenting phenotype. A low-grade ocular surface inflammation observed in this study, where resident immature dendritic cells are transformed into mature antigen-presenting cells in the corneal epithelium, is a process putatively associated with TNFRSF9 signalling and may occur early in the development of type 2 diabetes. IVCM enables this process to be monitored non-invasively in the eye.

Tissue Harvesting Site and Culture Medium Affect Attachment, Growth, and Phenotype of Ex Vivo Expanded Oral Mucosal Epithelial Cells.

Transplantation of cultured oral mucosal epithelial cells (OMECs) is a promising treatment strategy for limbal stem cell deficiency. In order to improve the culture method, we investigated the effects of four culture media and tissue harvesting sites on explant attachment, growth, and phenotype of OMECs cultured from Sprague-Dawley rats. Neither choice of media or harvesting site impacted the ability of the explants to attach to the culture well. Dulbecco's modified Eagle's medium/Ham's F12 (DMEM) and Roswell Park Memorial Institute 1640 medium (RPMI) supported the largest cellular outgrowth. Fold outgrowth was superior from LL explants compared to explants from the buccal mucosa (BM), HP, and transition zone of the lower lip (TZ) after six-day culture. Putative stem cell markers were detected in cultures grown in DMEM and RPMI. In DMEM, cells from TZ showed higher colony-forming efficiency than LL, BM, and HP. In contrast to RPMI, DMEM both expressed the putative stem cell marker Bmi-1 and yielded cell colonies. Our data suggest that OMECs from LL and TZ cultured in DMEM give rise to undifferentiated cells with high growth capacity, and hence are the most promising for treatment of limbal stem cell deficiency.