Background: Presence of corneal cystine crystals is the main ocular manifestation of cystinosis, although controversial findings concerning the corneal layer with the highest density have been reported. The aim of this study was the analysis of the characteristics of crystal arrangement in different corneal layers and the assessment of corneal morphological changes with age. Methods: A cross sectional study was carried out in three children and three adults who had nephropathic cystinosis and corneal cystine depositions. All patients underwent a comprehensive ophthalmological examination including best corrected distance visual acuity, slit-lamp examination, in vivo confocal microscopy and anterior segment optical coherence tomography. An evaluation of the depth of crystal deposits and crystal density in different corneal layers was also performed. Due to the low number of subjects no statistical comparison was performed. Results: Anterior segment optical coherence tomography images revealed deposition of hyperreflective crystals from limbus to limbus in each patient. Crystals appeared as randomly oriented hyperreflective, elongated structures on in vivo confocal microscopy images in all corneal layers except the endothelium. In children the deposits occurred predominantly in the anterior stroma, while in adults, the crystals were mostly localized in the posterior corneal stroma with the depth of crystal deposition showing an increasing tendency with age (mean depth of crystal density was 353.17 ± 49.23 μm in children and it was 555.75 ± 25.27 μm in adults). Mean crystal density of the epithelium was 1.47 ± 1.17 (median: 1.5; interquartile range: 0.3-2.4). Mean crystal density of the anterior and posterior stroma of children and adults was 3.37 ± 0.34 (median: 3.4; interquartile range: 3.25-3.55) vs. 1.23 ± 0.23 (median: 1.2; interquartile range: 1.05-1.35) and 0.76 ± 0.49 (median: 0.7; interquartile range: 0.4-1.15) vs. 3.63 ± 0.29 (median: 3.7; interquartile range: 3.45-3.8), respectively. Endothelium had intact structure in all cases. Some hexagonal crystals were observed in two subjects. Conclusions: In vivo confocal microscopy and anterior segment optical coherence tomography confirmed an agerelated pattern of crystal deposition. In children, crystals tend to locate anteriorly, while in adults, deposits are found posteriorly in corneal stroma.
The purpose of our study was to analyze abnormal neural regeneration activity in the cornea through means of confocal microscopy in rheumatoid arthritis patients with concomitant dry eye disease. We examined 40 rheumatoid arthritis patients with variable severity and 44 volunteer age- and gender-matched healthy control subjects. We found that all examined parameters were significantly lower (p < 0.05) in rheumatoid arthritis patients as opposed to the control samples: namely, the number of fibers, the total length of the nerves, the number of branch points on the main fibers and the total nerve-fiber area. We examined further variables, such as age, sex and the duration of rheumatoid arthritis. Interestingly, we could not find a correlation between the above variables and abnormal neural structural changes in the cornea. We interpreted these findings via implementing our hypotheses. Correspondingly, one neuroimmunological link between dry eye and rheumatoid arthritis could be through the chronic Piezo2 channelopathy-induced K2P-TASK1 signaling axis. This could accelerate neuroimmune-induced sensitization on the spinal level in this autoimmune disease, with Langerhans-cell activation in the cornea and theorized downregulated Piezo1 channels in these cells. Even more importantly, suggested principal primary-damage-associated corneal keratocyte activation could be accompanied by upregulation of Piezo1. Both activation processes on the periphery would skew the plasticity of the Th17/Treg ratio, resulting in Th17/Treg imbalance in dry eye, secondary to rheumatoid arthritis. Hence, chronic somatosensory-terminal Piezo2 channelopathy-induced impaired Piezo2–Piezo1 crosstalk could result in a mixed picture of disrupted functional regeneration but upregulated morphological regeneration activity of these somatosensory axons in the cornea, providing the demonstrated abnormal neural corneal morphology.
Our objective in this study was to analyze the aberrant neural regeneration activity in the cornea by means of in vivo confocal microscopy in systemic lupus erythematosus patients with concurrent dry eye disease. We examined 29 systemic lupus erythematosus patients and 29 age-matched healthy control subjects. Corneal nerve fiber density (CNFD, the number of fibers/mm2) and peripheral Langerhans cell morphology were lower (p < 0.05) in systemic lupus erythematosus patients compared to the control group. Interestingly, corneal nerve branch density, corneal nerve fiber length, corneal nerve fiber total branch density, and corneal nerve fiber area showed a negative correlation with disease duration. A negative correlation was also demonstrated between average corneal nerve fiber density and central Langerhans cell density. This is in line with our hypothesis that corneal somatosensory terminal Piezo2 channelopathy-induced impaired Piezo2–Piezo1 crosstalk not only disrupts regeneration and keeps transcription activated, but could lead to Piezo1 downregulation and cell activation on Langerhans cells when we consider a chronic path. Hence, Piezo2 containing mechanosensory corneal nerves and dendritic Langerhans cells could also be regarded as central players in shaping the ocular surface neuroimmune homeostasis through the Piezo system. Moreover, lost autoimmune neuroinflammation compensation, lost phagocytic self-eating capacity, and lost transcription regulation, not to mention autoantibodies against vascular heparin sulfate proteoglycans and phospholipids, could all contribute to the progressive fashion of dry eye disease in systemic lupus erythematosus.
the crystalline lens. The most common clinical test is the slit-lamp measurement 4 , in which cataract is quantified by illuminating the eye obliquely with a narrow line-shaped light-source, while the ophthalmologist inspects the crystalline lens from the front through a microscope. Visual observation is then compared to a standard reference image sequence to determine the grade of progression; e.g. in the case of nuclear cataract there are six categories (plus the scatter-free case). In addition to this coarse figure, the method is also strongly subjective, since the diagnosis is affected by the personal judgement and specific experience of the examiner. Further drawbacks are that by using a slit-lamp only backward scattering can be examined instead of the physically relevant effect, and the provided metric is not directly related to the visual loss of the patient 5. The latter problems are eliminated in case of the C-Quant 6 equipment, which investigates how a disturbing source affects the visibility of a target viewed by the patient. Although it provides a better way of quantification, subjectivity (in this case that of the subject) is still an issue. Fully objective and quantitative testing solutions also exist. A double-pass setup was commercialized to examine the image of a retinal point source distorted by ocular scattering 7, 8. The method needs to be carefully corrected for refractive errors and only measures overall cataract without providing a spatial map of the pupil. Scheimpflug-camera 9, 10 is also a common tool in ophthalmology with a long history of cataract detection, however the method shares the disadvantage of slit-lamp measurements that examine backward scattered light. Optical Coherence Tomography 11-13 (OCT) was also suggested as a potential tool for cataract examination. A comparison of all these methods can be found in Kamiya et. al. 's paper 14. An interesting approach found in the literature 15 quantifies cataract by using a Shack-Hartmann wavefront sensor 16. Diagnostic apparatuses applying such a device have been developed and are widely available for the measurement of monochromatic wavefront aberration of the eye. In their study, Donelly at al. attempted to correlate visual acuity with the scattering properties of the eye by using a custom equipment, but no reassuring correspondence was found. They pointed out that their optical system was unable to detect all scattered light, concluding that this may have been one of the reasons of the negative result. The method was also tested on clinical (Zeiss-made WASCA) aberrometers 17 as well, using C-Quant as a reference. The study could reveal some correlation between the two measurements, though the lack of exposure control possibility strongly reduced the interpretability of the captured images. Our aim was to develop an objective and quantitative method to characterize cataract by measuring forward scattering in the eye with a Shack-Hartmann wavefront sensor. In order to have complete control over design parameters as well as operationa...
Background Our aim was to determine associations of pachymetry, keratometry, and their changes with haze formation and corneal flattening after collagen cross-linking, and to analyse the relationship between postoperative haze and visual outcome. Methods Retrospective analysis was performed on 47 eyes of 47 patients with keratoconus using the Pentacam HR Scheimpflug camera before and 1, 3, 6 and 12 months after cross-linking. Corneal backscattered light values in grey scale unit were recorded in the anterior, center and posterior corneal layers and in four concentric rings. Surface area- and thickness-corrected grey scale unit values were assessed with an additional calculation. Friedman test with post hoc Wilcoxon signed-rank test was used to analyse changes in visual acuity, pachymetry, keratometry and densitometry. Spearman’s rank correlation test was used to detect correlations of haze formation and corneal flattening with pachymetry, keratometry and their postoperative change. Generalized estimating equations analysis was used to investigate the influence of densitometry values on postoperative visual acuity after controlling for the effect of preoperative keratometry. Results One year after treatment, significant flattening was observed in maximum and mean keratometry readings (p < 0.001). Significantly increased densitometry values were observed in three central rings compared to baseline (post hoc p < 0.0125). According to receiver operating characteristic curve, densitometry value of the anterior layer of 0–2 mm ring was the most characteristic parameter of densitometry changes after cross-linking (area under the curve = 0.936). Changes in haze significantly correlated with preoperative maximum keratometry (R = 0.303, p = 0.038) and with the changes in maximum keratometry (R = -0.412, p = 0.004). Changes in maximum keratometry correlated with preoperative maximum keratometry (R = -0.302, p = 0.038). Postoperative haze had a significant impact on uncorrected and best corrected distance visual acuity (β coefficient = 0.006, p = 0.041 and β coefficient = 0.003, p = 0.039, respectively). Conclusions Our findings indicate that in more advanced keratoconus more significant corneal flattening effect parallel with haze formation can be observed after cross-linking. Despite significant reduction of keratometry, postoperative corneal haze may limit final visual acuity.
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