Corneal stromal repair and regeneration

The cornea is a specialized, transparent, avascular, immune-privileged, and heavily innervated tissue that affords 2/3rd of refraction to the eye. Ocular injuries, infections, and genetic factors affect corneal function and cause vision impairment. Presently, a variety of laser/non-laser surgeries, immunosuppressants, and/or corneal transplants are predominantly used to revive sight in human patients. The development of novel, precision-guided, and tissue-targeted non-surgical therapies promoting corneal repair and regeneration based on mechanistic understanding is of paramount importance to reduce the impact of global blindness. Research over the past decade revealed that modulation of pathological signaling pathways and factors by a variety of therapeutic delivery methods effectively treats corneal disorders including corneal scar/haze, inflammation, and angiogenesis in various pre-clinical animal models and are primed for human translation. This review discusses recent advances in the areas of corneal repair, restoration, and regeneration. Herein, we provide an overview of evolving approaches and therapeutic modalities that have shown great promise in reviving corneal transparency and function through the use of small drug molecules, gene therapy, nanomedicine, stem cells, trophic factors, exosomes, stromal equivalents, bioengineered stromal scaffolds, tissue adhesives, and 3D bioprinting.     

角膜内皮细胞移植

角膜内皮细胞在体外培养的条件下可以在同种异体或异种角膜后弹力层上成功生长,培养的上皮细胞的生长情况及特性与供体年龄、内皮细胞来源部位、载体材料、培养条件、以及是否应用生长因子有密切关系。人角膜内皮细胞培养的成功,以及在非人类的灵长目动物眼上的成功移植,为内皮移植技术的治疗作用提供了实验基础。培养传代的角膜内皮细胞移植到活体上后具有正常内皮细胞的功能,可以作为穿透性角膜移植的替代方法之一加以选择。     

组织工程角膜内皮移植的研究进展

随着组织工程技术和细胞工程技术的不断发展,组织工程角膜的研究已经取得一定进展,其中体外培养角膜内皮细胞技术的成熟为组织工程角膜内皮移植奠定了基础.通过将不同来源的角膜内皮种子细胞种植于合适的载体上得到重构的角膜内皮,应用其取代失代偿角膜内皮细胞,这种技术的成熟将会为角膜内皮损害而致盲患者带来新的希望.     

Corneal bee sting-induced endothelial changes

PURPOSE: To report the acute management and clinical findings of a case of corneal bee sting and to report the outcome of corneal endothelial cell analysis 1 year after trauma. METHODS: Clinical findings, anterior segment photographs, corneal endothelial images, and medical treatment of a case of right corneal bee sting are presented. Right and left central corneal endothelial cell analysis was performed by noncontact specular microscopy. RESULTS: The stinger was removed from the cornea. Systemic, subconjunctival, and topical steroids and systemic and topical antibiotics were given. One year later, a corneal scar and anterior capsular opacity of the lens in the right eye were shown by slit-lamp examination. Endothelial cell analysis determined that the endothelial cell density of the right eye was substantially decreased compared with the left eye. CONCLUSION: Corneal infiltration gradually decreased, presumably because of the systemic, topical, and subconjunctival steroids. Late complications observed in this case included a substantial decrease in cornea endothelial cell density, a corneal scar, and anterior capsular opacity.     

超声乳化术后角膜内皮的变化

评价是超声乳化对角膜内皮的损伤。方法４８例白内障超声乳化病人在术前及术后１月在非接触式角膜内皮镜下进行计数检查。结果浅前房下超声对角膜内皮损伤最重,前房内超声次之,在稳定的前方下行囊袋内超声对角膜内皮损伤最轻。     

激光角膜屈光手术后的神经修复

干眼症是激光角膜屈光手术后常见的并发症之一,与角膜神经损伤密切相关。角膜神经损伤修复缓慢,术后6个月仍未恢复至术前水平。不同的激光角膜屈光手术带来的神经损伤亦不相同。角膜神经修复涉及角膜细胞分泌细胞因子、角膜细胞的分化、角膜缘血管内淋巴细胞和巨噬细胞的迁移、角膜中心部基质下神经丛中性粒细胞的迁移及其生长因子的分泌等复杂过程。一些细胞因子、信号素、自体血清等参与角膜神经的修复,但目前多为动物实验,临床研究较少。（国际眼科纵览,2019, 43： 405-410)     

Corneal endothelial changes in diabetic dogs

The corneal endothelium of alloxan diabetic dogs was examined by wide-field specular microscopy and compared to that of age-matched non-diabetic dogs. Computer-assisted morphometry of individual cells showed that the diabetic dog endothelium had marked polymegethism and pleomorphism similar to that previously described in diabetic patients. There also appeared to be a positive correlation between the degree of these endothelial changes and the diabetic control as demonstrated by HbA1 concentration.     

Corneal endothelial density in glaucoma patients

PURPOSE: To asses mean endothelial cell density in glaucoma patients. MATERIAL AND METHODS: Examinations were conducted and registered using the Noncon Robo (Konan) non-contact specular microscope between years 2000 and 2004, in Tadeusz Krwawicz Chair of Ophthalmology and 1st Eye Hospital, Medical University of Lublin. The results of 159 patients (233 eyes) with glaucoma and 37 patients (44 eyes) with pseudoexfoliation syndrome were analyzed. Patients, 22-91 years old, were divided into 8 groups according to the clinical diagnosis and for each group an adequate control group was matched. Statistical analysis was carried out to compare the examined and control groups using the non-parametric U Mann-Whitney test. RESULTS: Corneal endothelial cell density were significantly lower in all groups of glaucoma patients. There was a significant reduction in cell count in patients with chronic angle-closure glaucoma: 2333 +/- 476/mm2, control group (C): 2809 +/- 378/mm2, p< 0.001), acute angle-closure glaucoma 2136 +/- 620/mm2, C. 2780 +/- 384/mm2, p< 0.001, pigmentary glaucoma 2537 +/- 355/mm2, C. 3003 +/- 335/mm2, p< 0.05, juvenile glaucoma 2337 +/- 277/mm2, C. 3001 +/- 168/mm2, p< 0.001, primary open angle glaucoma 2326 +/- 231/mm2, C. 2779 +/- 398/mm2, p< 0.001, normal tension glaucoma 2343 +/- 394/mm2, C. 2732 +/- 356/mm2, p< 0.01, capsular glaucoma 2128 +/- 483/mm2, C. 2753 +/- 354/mm2, p< 0.001 and in patients with pseudoexfoliation syndrome 2255 +/- 299/mm2, C. 2721 +/- 352/mm2, p< 0.001. CONCLUSIONS: Patients with glaucoma have lower mean corneal endothelial cell density than control groups. The density of corneal endothelial cells depends on the type of glaucoma.     

Corneal transplantation for endothelial pigmentation.

Endothelial pigmentation does not usually interfere with vision. This case report documents a dense and extensive deposition of uveal pigment in corneal endothelial cells of a patient who had undergone 2 previous grafts subsequent to an alkali burn injury. The previous graft in which the pigmentation occurred remained compensated, but vision was impaired secondary to dense endothelial pigmentation. A combination of the initial chemical injury, recurrent iritis, chronic glaucoma, and multiple intraocular procedures may have resulted in the stimulus for the uveal tract to disperse a large amount of pigment onto the cornea and its subsequent phagocytosis by the endothelium. Endothelial pigmentation may become a more commonly seen complication in attempts to treat the severely damaged anterior segment.     

Corneal endothelial examination of pseudoexfoliation syndrome

Specular microscopic observation of corneal endothelial changes in pseudoexfoliation syndrome was performed. The images of corneal endothelium were recorded by a video camera, traced and put into an image analyzer to obtain cell density, coefficient of variation in cell area (C.V.), and hexagonality. In both affected eyes and fellow eyes with pseudoexfoliation syndrome, cell density and hexagonality were significantly decreased and C.V. value had a tendency to be higher than normal subjects. Corneal endothelium was damaged morphologically and quantitatively not only in affected eyes but also in unaffected fellow eyes in case of pseudoexfoliation syndrome. The necessity to assess the corneal endothelium in the patients of pseudoexfoliation syndrome before intraocular surgery was emphasised.     

Corneal endothelial assessment after ICL implantation

PURPOSE: To evaluate the 3- to 4-year effects of the Implantable Contact Lens (ICL) on the corneal endothelium. SETTING: Multicenter study. METHODS: Noncontact specular microscopy was performed as a subgroup study in a Phase III U.S. Food and Drug Administration clinical trial. Endothelial cell images were collected in the central region of the cornea before surgery and 3, 12, 24, and 36 months after surgery, with a few at 48 months. The images were recorded and analyzed later by a central reading center. The cell density, coefficient of variation, and percentage of hexagonal cells were determined. RESULTS: The cumulative endothelial cell loss was between 8.4% and 8.9% over the first 3 years and between 8.4% and 9.5% over the first 4 years depending on the method of calculation. The cell loss between baseline and 3 months was 2.1%; 3 months and 1 year, 0.9%; 1 year and 2 years, 2.3%; 2 years and 3 years, 3.2%; and 3 years and 4 years, -0.1%. The coefficient of variation decreased over the course of the study, and the proportion of cases with hexagonal cells increased slightly. CONCLUSIONS: The cell loss between 1 year and 3 years in the absence of an increase in the coefficient of variation and/or a decrease in the percentage of hexagonal cells is most readily explained by prolonged corneal remodeling following the surgical procedure rather than ongoing cell loss. The cell loss observed between 3 years and 4 years (0.1% gain) was negligible. Regardless of the cause of the change in endothelial cell density over the first 3 years, the available 4-year data suggest there was no ongoing chronic loss.     

Corneal endothelial cell density after trabeculoplasty

Central corneal endothelial photographs were taken with a specular microscope. The cell density was calculated with a computerized image analyzer. No difference between the treated and control eyes could be found. The laser energy level delivered in trabeculoplasty seems to be too small to induce any permanent changes in the endothelial cells.     

Corneal endothelial changes in pseudoexfoliation syndrome

Using specular microscopy and computer-assisted morphometry, we studied 27 eyes with pseudoexfoliation syndrome, 17 apparently normal fellow eyes, and 15 eyes of matched normal subjects with no ocular disease other than senile cataract. Endothelium of the eyes with pseudoexfoliation syndrome showed significantly lower cell density than did the endothelium from control eyes. Endothelium of both eyes of patients with unilateral pseudoexfoliation syndrome showed significant morphologic changes in cell size (polymegethism) and shape variability (pleomorphism); these changes were essentially the same in overtly affected and apparently normal fellow eyes. The results suggested that the corneal endothelial changes are consistent and might serve as an early sign of the disorder.     

Corneal endothelial cell density in iridocyclitis

The endothelial cells of both eyes of 60 unilateral iridocyclitic patients were photographed with a specular microscope to establish the possible effect of iridocyclitis on corneal endothelial cells. Chronic severe iridocyclitis with mutton-fat keratic precipitates (KP) lowered the central endothelial cell count. Five patients out of the seven with mutton-fat KPs had a distinctly lower central cell density in the affected eye. In the remaining patients, no significant difference in cell densities could be demonstrated between affected and healthy eyes. Neither the inflammatory process itself nor the round white KPs had a deleterious effect on the central corneal endothelial cell densities.     

Corneal endothelial dysfunction in Pearson syndrome

Mitochondrial disorders are associated with well recognized ocular manifestations. Pearson syndrome is an often fatal, multisystem, mitochondrial disorder that causes variable bone marrow, hepatic, renal and pancreatic exocrine dysfunction. Phenotypic progression of ocular disease in a 12-year-old male with Pearson syndrome is described. This case illustrates phenotypic drift from Pearson syndrome to Kearns-Sayre syndrome given the patient’s longevity. Persistent corneal endothelial failure was noted in addition to ptosis, chronic external ophthalmoplegia and mid-peripheral pigmentary retinopathy. We propose that corneal edema resulting from corneal endothelial metabolic pump failure occurs within a spectrum of mitochondrial disorders.