In Vivo Confocal Microscopy of the Corneal Sub-Basal Nerve plexus in Medically Controlled Glaucoma

The present study investigated the corneal sub-basal nerve plexus (SNP) modifications in glaucoma. Ninety-five glaucomatous patients were enrolled and divided into Group 1 and 2, preserved and preservative-free mono-therapy (30 and 28 patients), and Group 3, multi-therapy (37). Thirty patients with dry eye disease (DED) and 32 healthy subjects (HC) served as controls. In vivo confocal microscopy evaluated the nerve fibers density (CNFD), length (CNFL), thickness (CNFT), branching density (CNBD), and dendritic cell density (DCD). CNFD, CNFL, and CNBD were reduced in Group 3 and DED compared to HC (p < 0.05). CNFL was reduced in Group 3 compared to Group 2 (p < 0.05), and in Group 1 compared to HC (p < 0.001). CNFD, CNBD, and CNFT did not differ between glaucomatous groups. DCD was higher in Group 3 and DED compared to HC and Group 2 (p < 0.01). Group 3 showed worse ocular surface disease index (OSDI) scores compared to Group 1, 2, and HC (p < 0.05). CNFL and DCD correlated with OSDI score in Group 3 (r = −0.658, p < 0.001; r = 0.699, p = 0.002). Medical therapy for glaucoma harms the corneal nerves, especially in multi-therapy regimens. Given the relations with the OSDI score, SNP changes seem features of glaucoma therapy-related OSD and negatively affects the patient's quality of life.

Evaluation of Corneal Nerves and Dendritic Cells By in Vivo Confocal Microscopy After Descemet’s Membrane Keratoplasty For Bullous Keratopathy

This study evaluated changes in corneal nerves and the number of dendritic cells (DCs) in corneal basal epithelium following Descemet membrane endothelial keratoplasty (DMEK) surgery for bullous keratopathy (BK). Twenty-three eyes from 16 consecutive patients that underwent DMEK for BK were included. Eyes of age-matched patients that underwent pre-cataract surgery (12 eyes) were used as controls. In vivo confocal microscopy was performed pre- and postoperatively at 6, 12, and 24 months. Corneal nerve length, corneal nerve trunks, number of branches, and the number of DCs were determined. The total corneal nerve length of 1634.7 ± 1389.1 μm /mm2 before surgery was significantly increased in a time-dependent manner to 4485.8 ± 1403.7 μm /mm2, 6949.5 ± 1477.1 μm /mm2, and 9389.2 ± 2302.2 μm /mm2 at 6, 12, and 24 months after DMEK surgery, respectively. The DC density in BK cornea pre- and postoperatively at 6 months was significantly higher than in the controls, and decreased postoperatively at 12 and 24 months and was significantly lower than that at 6 months postoperatively. Thus, our results suggest that DMEK can repair and normalize the corneal environment.

The Clinical Guiding Role of the Distribution of Corneal Nerves in the Selection of Incision for Penetrating Corneal Surgery in Canines

The cornea is one of the regions with the highest density of nerve terminals in the animal body and it bears such functions as nourishing the cornea and maintaining corneal sensation. In veterinary clinical practice, the corneoscleral limbus incision is frequently applied in cataract surgery, peripheral iridectomy, and other procedures for glaucoma. Inevitably, it would cause damage to the nerve roots that enter the cornea from the corneal limbus, thus inducing a series of complications. In this paper, the in vitro cornea (39 corneas from 23 canines, with ages ranging from 8 months old to 3 years old, including 12 male canines and 11 female canines) was divided into 6 zones, and the whole cornea was stained with gold chloride. After staining, corneal nerves formed neural networks at different levels of cornea. There was no significant difference in the number of nerve roots at the corneoscleral limbus between different zones (F = 1.983, p = 0.082), and the nerve roots at the corneoscleral limbus (mean value, 24.43; 95% CI, 23.43–25.42) were evenly distributed. Additionally, there was no significant difference in the number of corneal nerve roots between male and female canines (p = 0.143). There was also no significant difference in the number of corneal nerve roots between adult canines and puppies (p = 0.324). The results of the above analysis will provide a reasonable anatomical basis for selecting the incision location and orientation of penetrating surgery for the canine cornea in veterinary practice.

In vivo confocal microscopy qualitative investigation of the relationships between lattice corneal dystrophy deposition and corneal nerves

Background To investigate the corneal neurotropic phenomenon in patients with lattice corneal dystrophy (LCD) with in vivo laser scanning confocal microscopy (IVCM). Methods IVCM was performed on a total of 15 patients (28 eyes) with LCD annually at a follow-up. A collection of the data was acquired to be analyzed. Results As indicated by the analysis, the LCD patients’ normal corneal stromal nerves (Grade 0) presented a decline with the prolongation of the follow-ups, corresponding to a gradual increase in grade I and II involving amyloid-wrapped nerve fibers, which demonstrated that the growing amount of amyloid deposit due to the corneal nerve invasion increased slowly over time. Conclusions The neurotropic phenomenon could increase with its severity in the corneal lesion of the patients with LCD, and also reflect the distribution of the corneal nerves, to some extent. IVCM provides a rapid, noninvasive way to observe the corneal nerves, which can be an efficient means of better understanding the development of LCD.

New Possibilities of Refractive Modeling of the Cornea by the Radiation of an Argon-fluorine Excimer Laser

Purpose: To consider new possibilities of refractive modeling of the cornea by the radiation of an argon-fluorine excimer laser in ablative and subablative modes after saturation of the stroma with riboflavin. Materials and Methods: Experimental (20 pork, 90 rabbit eyes) and clinical studies on photorefractive and phototherapeutic operations with saturation of the corneal stroma with riboflavin (610 operations) were analyzed. To activate riboflavin, secondary radiation induced by exposure to ablative and subablative energy densities was used. A quick transition to energy densities below the ablation threshold without additional calibrations was carried out using a “Microscan Visum-500” excimer laser (Optosystems, Russia). An objective assessment of the refractive keratomodelling effect and visual results was carried out according to the data of complex optometric studies. Results: Experimental and clinical studies have shown the advantages of refractive keratomodeling by theradiation of an argon-fluorine excimer laser in ablative and subablative modes after saturation of the stroma with riboflavin. Isotonic 0.25% riboflavin solution did not affect the accuracy of refractive ablation and blocked the negative effect of induced secondary radiation on keratocytes and corneal nerves. This reduced the aseptic inflammatory response and the risk of developing an irreversible form of fibroplasia. Ablation with riboflavin initiated a damped crosslinking effect, which increased the photoprotective and strength properties of the thinned cornea. A refractive keratomodelling effect was found when energy densities were applied below the stromal ablation threshold. The magnitude of this refractive effect depended on the total radiation dose and the topography of the affected area. This approach made it possible to implement laser-induced refractive keratomodeling without ablation of the corneal stroma. Conclusion: Refractive modeling of the cornea by the radiation of an argon-fluorine excimer laser in ablative and subablative modes after saturation of the stroma with riboflavin opens up new possibilities in laser correction of ametropia.

Artificial intelligence utilising corneal confocal microscopy for the diagnosis of peripheral neuropathy in diabetes mellitus and prediabetes

Aims/hypothesis We aimed to develop an artificial intelligence (AI)-based deep learning algorithm (DLA) applying attribution methods without image segmentation to corneal confocal microscopy images and to accurately classify peripheral neuropathy (or lack of). Methods The AI-based DLA utilised convolutional neural networks with data augmentation to increase the algorithm’s generalisability. The algorithm was trained using a high-end graphics processor for 300 epochs on 329 corneal nerve images and tested on 40 images (1 image/participant). Participants consisted of healthy volunteer (HV) participants (n = 90) and participants with type 1 diabetes (n = 88), type 2 diabetes (n = 141) and prediabetes (n = 50) (defined as impaired fasting glucose, impaired glucose tolerance or a combination of both), and were classified into HV, those without neuropathy (PN−) (n = 149) and those with neuropathy (PN+) (n = 130). For the AI-based DLA, a modified residual neural network called ResNet-50 was developed and used to extract features from images and perform classification. The algorithm was tested on 40 participants (15 HV, 13 PN−, 12 PN+). Attribution methods gradient-weighted class activation mapping (Grad-CAM), Guided Grad-CAM and occlusion sensitivity displayed the areas within the image that had the greatest impact on the decision of the algorithm. Results The results were as follows: HV: recall of 1.0 (95% CI 1.0, 1.0), precision of 0.83 (95% CI 0.65, 1.0), F1-score of 0.91 (95% CI 0.79, 1.0); PN−: recall of 0.85 (95% CI 0.62, 1.0), precision of 0.92 (95% CI 0.73, 1.0), F1-score of 0.88 (95% CI 0.71, 1.0); PN+: recall of 0.83 (95% CI 0.58, 1.0), precision of 1.0 (95% CI 1.0, 1.0), F1-score of 0.91 (95% CI 0.74, 1.0). The features displayed by the attribution methods demonstrated more corneal nerves in HV, a reduction in corneal nerves for PN− and an absence of corneal nerves for PN+ images. Conclusions/interpretation We demonstrate promising results in the rapid classification of peripheral neuropathy using a single corneal image. A large-scale multicentre validation study is required to assess the utility of AI-based DLA in screening and diagnostic programmes for diabetic neuropathy. Graphical abstract

The Role of Neuropeptides in Pathogenesis of Dry Dye

Neuropeptides are known as important mediators between the nervous and immune systems. Recently, the role of the corneal nerve in the pathogenesis of various ocular surface diseases, including dry eye disease, has been highlighted. Neuropeptides are thought to be important factors in the pathogenesis of dry eye disease, as suggested by the well-known role between the nervous and immune systems, and several recently published studies have elucidated the previously unknown pathogenic mechanisms involved in the role of the neuropeptides secreted from the corneal nerves in dry eye disease. Here, we reviewed the emerging concept of neurogenic inflammation as one of the pathogenic mechanisms of dry eye disease, the recent results of related studies, and the direction of future research.