Shu-Wen Chang

The cornea in young myopic adults.

AIMS To further understand the effect of refractive error on the corneal dimensions and function. METHODS Corneal curvature, corneal thickness, and axial length measurements were performed, as well as specular microscopy and fluorophotometry, on patients with various refractive statuses. 216 subjects, mean age 22.2 (SD 4.2) years, were examined. Patients with previous contact lens wear history, external eye diseases, as well as previous ocular surgeries, were excluded. RESULTS The corneas were flatter in eyes with longer axial length (r = −0.22, p = 0.003). Eyes with more myopic spherical equivalent had longer axial length (r = −0.90, p <0.001) as well as less corneal endothelial density (r = 0.20, p = 0.037). Corneal endothelial density decreased in eyes with longer axial length (r = 0.24, p = 0.019); however, it correlated neither with corneal thickness (r= −0.06, p = 0.59) nor with corneal curvature (r = −0.07, p = 0.52). The corneas had a mean corneal thickness of 533 (SD 29) μm and were thinner in more myopic eyes (r = 0.16, p = 0.021). The corneas tended to be thinner in eyes with longer axial length. However, the correlation did not reach statistical significance (r = −0.11, p = 0.14). Besides, there was no significant correlation between the corneal thickness and the corneal curvature (r = −0.13, p = 0.093) and the endothelial permeability (r = 0.042, p = 0.69). The corneas with higher endothelial density had larger corneal transfer coefficient (r = 0.26, p = 0.024) and higher permeability to fluorescein molecules (r = 0.28, p = 0.014). Nevertheless, the corneal endothelial permeability did not correlate significantly with either the axial length (r = −0.18, p = 0.11) or the degree of myopia (r = 0.12, p = 0.26). CONCLUSION Changes in the anterior segments as the eyeball elongates in myopia progression included flatter corneal curvature, decreased corneal thickness, as well as decreased endothelial density. These factors should be considered in refractive surgery.

Changes in corneal autofluorescence and corneal epithelial barrier function with aging.

Corneal epithelial permeability studies using fluorophotometers were performed on 90 eyes of 51 normal subjects. After recording the autofluorescence of the cornea (AFC) and of the lens (AFL), we applied 20 µl of 2% sodium fluorescein to the conjunctival sac. The corneal fluorescence 45 min later (F45), which paralleled the corneal epithelial permeability to fluorescein, was measured by fluorophotometer and analyzed. All parameters of the two eyes of each subject correlated well with each other. There was positive correlation between AFL and patient age and between AFC and patient age (r=0.78, p<0.001, and r=0.74, p<0.001, respectively). The F45 increased exponentially with advancing age ( r= 0.67, p<0.001). The strong correlation between AFC and AFL in each eye (r=0.79, p<0.001) indicated corresponding aging processes in both the cornea and the lens. The increase in epithelial permeability with age possibly represents a subclinical breakdown of barrier function, rendering the corneas more vulnerable to insults.

Corneal Autofluorescence and Epithelial Barrier Function in Diabetic Patients

Corneal autofluorescence and corneal epithelial barrier function of 146 diabetic patients and 121 controls were examined using anterior segment fluorophotometry. Corneal autofluorescence in diabetic patients was significantly higher when compared with that of controls (14.6 +/- 3.7 vs. 10.9 +/- 2.7 ng/ml, p < 0.001), and was increased in patients with more severe diabetic retinopathy (r = 0.23, p = 0.005), higher postprandial blood glucose level (r = 0.25, p = 0.009), and higher glycosylated hemoglobin (r = 0.21, p = 0.047). No correlation existed between corneal autofluorescence and the duration of diabetes mellitus. The corneal fluorescein concentration 45 min after topical application of 20 microliters of 2% sodium fluorescein was also significantly higher in diabetics than in controls (1,373.2 +/- 1,081.5 vs. 363.0 +/- 308.3 ng/ml, p < 0.001). No correlation existed with postprandial blood sugar (r = -0.19, p = 0.056) nor with glycosylated hemoglobin (r = -0.13, p = 0.20). The corneas in diabetics became more hypesthetic with longer duration of diabetes mellitus (r = -0.19, p = 0.02), although the mean corneal sensitivity threshold was not statistically higher in the diabetic group (p = 0.57). There was no correlation of the epithelial barrier function with the duration of diabetes (r = -0.07, p = 0.38), the severity of diabetic retinopathy (r = 0.07, p = 0.38), and the corneal sensitivity threshold (r = -0.06, p = 0.43).

Outcomes of penetrating keratoplasty with imported donor corneas.

PURPOSE To analyze factors influencing the surgical success of penetrating keratoplasty and long-term graft survival when using imported donor corneas. METHODS Sixty-three donor corneas imported to Taipei from the Cincinnati Eye Bank from July 1992-June 1993 were used for penetrating keratoplasty. The corneal endothelium was examined using specular microscopy on arrival in Taiwan. The endothelial morphology and endothelial cell density (ECD) were compared with the photograph of the same cornea taken in the United States. The relationships of the surgical success rate with donor age, death to enucleation time, death to surgery time, and ECD were analyzed. The long-term graft survival and ECD of clear grafts were analyzed 4 years after surgery. RESULTS On specular microscopic examination. the imported corneas showed diminished endothelial reflection, blurred cellular borders, and increased dark areas, which were markedly different from the pictures of the corneal endothelium taken in the United States. The average ECD before transportation was 2,525+/-267/mm2 and decreased to 1,934+/-250/mm2 after transportation (p < 0.001), with an average endothelial cell loss of 590+/-247/mm2. The overall surgical success rate was 89% and did not correlate with any of the donor factors tested except death to surgery time. The surgical success rate decreased when the time from death to surgery was >7 days (p = 0.05), mainly because of poor reepithelialization. Four years after surgery, 24 grafts remained clear. The ECD had decreased by 72+/-5% in the clear grafts. CONCLUSIONS Our findings show that endothelial changes in imported donor corneas do occur after transportation, but the surgical success rate may not be influenced significantly if the penetrating keratoplasty is performed within 7 days after donor death. However, the ECD in the clear grafts 4 years after surgery is low.

Effects of Contact Lenses on Corneal Endothelium – A Morphological and Functional Study

Purpose: To study the corneal endothelial morphological changes and endothelial barrier function in contact lens wearers. Methods: Specular microscopy and anterior segment fluorophotometry were performed on 116 controls (group 1) and 76 daily wear soft contact lens wearers. Group 2 patients (n = 34) had been wearing contact lenses for less than 5 years and group 3 (n = 42) for more than 5 years. The relationship of corneal thickness, endothelial cell density, hexagonal cell percentage, coefficient of variation in cell area, corneal autofluorescence and corneal endothelial permeability to the contact lens wear duration was studied. Results: The average corneal thickness of contact lens wearers did not differ significantly from controls (0.533 ± 0.031, 0.538 ± 0.044, 0.532 ± 0.031 mm for groups 1, 2 and 3, respectively; p = 0.89). However, there was a significant tendency toward corneal thinning with a longer history of contact lens wear (r = –0.31, p = 0.002 in groups 2 and 3). The percentage of hexagonal cells decreased with both increasing hours of contact lens wear per day (r = –0.36, p < 0.001) and the duration of contact lens wear in years (r = –0.33, p < 0.001), but there was no significant change in endothelial cell density in contact lens wearers. The coefficient of variation in cell size correlated more closely with increased hours of contact lens wear per day (r = 0.35, p = 0.002) than with the duration of contact lens wear in years (r = 0.12; p = 0.31). In the functional study, corneal autofluorescence increased in contact lens wearers (5.13 ± 0.71 ng/ml in group 1, 6.45 ± 2.03 ng/ml in group 2 and 7.21 ± 1.51 ng/ml in group 3, respectively, p < 0.001) and the mean endothelial permeability decreased in contact lens wearers (3.89 ± 0.95 ×10–4/cm in group 1, 2.71 ± 0.73 × 10–4/cm in group 2 and 2.95 ± 0.91 × 10–4/cm in group 3, respectively, p = 0.003). Conclusions: Daily wear soft contact lenses caused morphological changes in the corneal endothelium. With an increasing span of contact lens wear, there was a significantly increased variation in cell size, a decreased hexagonal cell percentage, an evident intercellular dark area and rosette formation. The corneal autofluorescence increased and the overall endothelial permeability decreased as a consequence of contact lens wear. Contact lens wear also caused corneal thinning, and the cornea became thinner with increasing duration of contact lens wear.

Enhanced corneal wound healing with hyaluronic acid and high‐potassium artificial tears

The aim of this study was to investigate the therapeutic role of preservative‐free artificial tears containing hyaluronic acid and high potassium ion concentration (HA/high‐K artificial tears) on mechanically scraped or alkali‐induced corneal epithelial defects in rats.

Corneal epithelial recovery following photorefractive keratectomy.

AIMS: To further understand the morphological and functional recovery of corneal epithelium following excimer laser photorefractive keratectomy (PRK). METHODS: The right eyes (group 1) of 15 male, New Zealand white rabbits weighing 2-3 kg underwent PRK. The left eye of each rabbit (group 2) underwent simple mechanical de-epithelialisation and were examined as treated controls. Both eyes of another eight rabbits (group 3) served as untreated controls. All eyes underwent a corneal epithelial permeability study by fluorophotometry at 2, 4, and 8 weeks after surgery. Five animals in groups 1 and 2 were sacrificed at 9, 10, and 12 weeks after surgery. The animals in group 3 were sacrificed at the end of the 12 week experimental period. Both eyes of each sacrificed animal were enucleated immediately and processed for both haematoxylin and eosin stain and electron microscopic study. The electron micrograph was magnified to 14,000x and the extent of hemidesmosome formation was quantified and analysed. RESULTS: The corneal epithelial barrier to sodium fluorescein was subnormal and returned to a normal barrier state 4 weeks after PRK in group 1 whereas it was normal in group 2 throughout the examination period. The extent of hemidesmosome formation was abundant yet subnormal in both groups 1 and 2 up to 12 weeks, when compared with that in group 3. CONCLUSION: The corneal epithelium regained its functional barrier 4 weeks after PRK in rabbits while the extent of hemidesmosome formation was still subnormal 12 weeks after mechanical de-epithelialisation, with or without PRK.

Acyclovir treatment for linear endotheliitis on grafted corneas.

Two patients with previous corneal transplants developed unusual rejection-like episodes of the grafted cornea. Both had a migrating line of keratic precipitates and stromal edema involving both the donor and recipient corneas. Intensive steroid treatment attained little effect, but oral acyclovir treatment dramatically suppressed the disease process. The facts suggest that a virus-related immune mechanism against both the donor and recipient endothelia, rather than simple allograft rejection, may have been responsible for the clinical presentations. Oral acyclovir therapy might be considered in patients with steroid-nonresponsive corneal endotheliitis mimicking allograft rejection.

The Epithelial Barrier Function in Clear Corneal Grafts

We conducted a corneal epithelial permeability study using a fluorophotometer on 93 eyes of 79 patients with clear corneal grafts. There were 45 males and 34 females, aged 61.6 +/- 10.2 years. All eyes received penetrating keratoplasty at least 1 year (mean 40.4 +/- 31.3 months) before examination. The normal fellow eyes of 65 subjects were examined as controls. The averaged corneal epithelial permeability of grafted corneas was significantly higher than that of controls (p < 0.001). In the 65 individuals having an otherwise healthy fellow eye, the grafted corneas were significantly more permeable than their control fellow eyes verified by paired t test (n = 65, p = 0.006). Concomitant corneal sensitivity test revealed a significantly hypesthetic cornea. These results show that in spite of a clinically normal clear graft, there is usually a subnormal epithelial barrier function and reinnervation, even years after corneal transplantation.

In Vitro and In Vivo Models to Study Corneal Endothelial-mesenchymal Transition

Corneal endothelial cells (CECs) play a crucial role in maintaining corneal clarity through active pumping. A reduced CEC count may lead to corneal edema and diminished visual acuity. However, human CECs are prone to compromised proliferative potential. Furthermore, stimulation of cell growth is often complicated by gradual endothelial-mesenchymal transition (EnMT). Therefore, understanding the mechanism of EnMT is necessary for facilitating the regeneration of CECs with competent function. In this study, we prepared a primary culture of bovine CECs by peeling the CECs with Descemets membrane from the corneal button and demonstrated that bovine CECs exhibited the EnMT process, including phenotypic change, nuclear translocation of β-catenin, and EMT regulators snail and slug, in the in vitro culture. Furthermore, we used a rat corneal endothelium cryoinjury model to demonstrate the EnMT process in vivo. Collectively, the in vitro primary culture of bovine CECs and in vivo rat corneal endothelium cryoinjury models offers useful platforms for investigating the mechanism of EnMT.