Background Many studies in multiple sclerosis (MS) have investigated the retina. Little however is known about the effect of MS on the cornea, which is innervated by the trigeminal nerve. It is the site of neural-immune interaction with local dendritic cells reacting in response- to environmental stimuli. Objective This study aims to investigate the effect of MS on- corneal nerve fibres and dendritic cells in the subbasal nerve plexus using in vivo confocal microscopy (IVCM). Methods We measured the corneal nerve fibre and dendritic cell density in 26 MS patients and matched healthy controls using a Heidelberg Retina Tomograph with Cornea Module. Disease severity was assessed with the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale, visual acuity and retinal optical coherence tomography. Results We observed significant reduction in total corneal nerve fibre density in MS patients compared to controls. Dendritic cell density was similar in both groups. Reduced total nerve fibre density was associated with worse clinical severity, but not with previous clinical trigeminal symptoms, retinal neuroaxonal damage, visual acuity, or disease duration. Conclusion Corneal nerve fibre density is a promising new imaging marker for the assessment of disease severity in MS and should be investigated further.

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The use of femtosecond lasers has created an evolution in modern corneal and refractive surgery. With accuracy, safety, and repeatability, eye surgeons can utilize the femtosecond laser in almost all anterior refractive procedures; laser in situ keratomileusis (LASIK), small incision lenticule extraction (SMILE), penetrating keratoplasty (PKP), insertion of intracorneal ring segments, anterior and posterior lamellar keratoplasty (Deep anterior lamellar keratoplasty (DALK) and Descemet's stripping endothelial keratoplasty (DSEK)), insertion of corneal inlays and cataract surgery. As the technology matures, it will push surgical limits and open new avenues for ophthalmic intervention in areas not yet explored. As we witness the transition from femto-LASIK to femto-cataract surgery it becomes obvious that this innovation is here to stay. This article presents some of the most relevant advances of femtosecond lasers to modern corneal and refractive surgery.

Purpose To investigate the longitudinal alterations of subbasal corneal nerves in patients with infectious keratitis (IK) during acute phase, cessation of treatment and recovery phase by in vivo confocal microscopy (IVCM). Design Prospective, longitudinal, case-control, single-center study. Subjects Fifty-six eyes of 56 patients with the diagnosis of bacterial (n=28), fungal (n=15), and Acanthamoeba (n=13) keratitis were included in the study. Thirty eyes of 30 normal volunteers constituted the control group. Methods Corneal sensation and serial IVCM of the central cornea were performed prospectively, by using the Heidelberg Retina Tomograph 3/Rostock Cornea Module (Heidelberg Engineering, Germany). IVCM images were assessed at 3 time points: at the first visit of the patient to the cornea service, at cessation of antimicrobial treatment, and up to six months after the resolution of infection. Main outcome measures Total nerve number and length, main nerve trunks, branching and corneal sensation were assessed during the follow-up period. Results Corneal nerves were significantly reduced during the acute phase in eyes with IK compared with controls across all subgroups, with total nerve length of 5.47 ± 0.69 vs. 20.59 ± 1.06 mm/mm2; p<0.0001. At the cessation of treatment, corneal nerves in patients with IK had regenerated, including total nerve length (8.49 ± 0.94; p=0.02) and nerve branch length (4.80 ± 0.37; p=0.005). During the recovery phase, after resolution of infection, corneal nerves further regenerated, including total nerve length (12.13 ± 1.97; p=0.005), main nerve trunk length (5.80 ± 1.00; p=0.01) and nerve branch length (6.33 ± 0.76; p=0.003) as compared to the acute phase, but were still significantly lower when compared to controls (p<0.05 for all parameters). Corneal degeneration and regeneration correlated with corneal sensation (r=0.47, p=0.0009). Conclusion Patients with IK, suffering from profound loss of corneal nerves during the acute phase of infection, demonstrate an increase of corneal nerve density during the first six months after the resolution of infection. However, despite significant nerve regeneration, corneal nerve density does not fully recover and remains low as compared to controls. By providing an objective methodology to monitor corneal re-innervation, IVCM adds potentially important findings that may have implications for clinical management and surgical planning.

PURPOSE. To evaluate whether the densities of corneal subbasal nerves and epithelial immune dendritiform cells (DCs) are comparable between a set of three representative standard images of in vivo confocal microscopy (IVCM) and the wide-field mapped composite IVCM images.METHODS. This prospective, cross-sectional, and masked study included 110 eyes of 58 patients seen in a neurology clinic who underwent laser-scanning IVCM (Heidelberg Retina Tomograph 3) of the central cornea. Densities of subbasal corneal nerves and DCs were compared between the average of three representative standard images and the wide-field mapped composite images, which were reconstructed by automated mapping.RESULTS. There were no statistically significant differences between the average of three representative standard images (0.16 mm 2 each) and the wide-field composite images (1.29 6 0.64 mm 2 ) in terms of mean subbasal nerve density (17.10 6 6.10 vs. 17.17 6 5.60 mm/mm 2 , respectively, P ¼ 0.87) and mean subbasal DC density (53.2 6 67.8 vs. 49.0 6 54.3 cells/mm 2 , respectively, P ¼ 0.43). However, there were notable differences in subbasal nerve and DC densities between these two methods in eyes with very low nerve density or very high DC density.CONCLUSIONS. There are no significant differences in the mean subbasal nerve and DC densities between the average values of three representative standard IVCM images and wide-field mapped composite images. Therefore, these standard images can be used in clinical studies to accurately measure cellular structures in the subbasal layer.

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Our results demonstrate that although corneal nerve regeneration occurs in patients with HSV keratitis, this change is not clinically significant and does not results in changes of corneal sensation. Therefore, these patients need to be followed closely for complications of neurotrophic keratopathy and might benefit from neuro-regenerative therapies.

IVCM has a moderate sensitivity and a high specificity for diagnosis of AK. Although clinical parameters do not affect this diagnostic accuracy, a higher sensitivity is seen when images are interpreted by experienced observers.