David H. Ren

Effects of rigid and soft contact lens daily wear on corneal epithelium, tear lactate dehydrogenase, and bacterial binding to exfoliated epithelial cells☆

OBJECTIVE To determine the effects of lens type and oxygen transmissibility on human corneal epithelium during daily lens wear (DW). DESIGN Prospective, randomized, double-masked, single-center, parallel treatment groups clinical trial. PARTICIPANTS Two hundred forty-six patients fitted with: (1) high oxygen-transmissible soft lenses (n = 36), (2) hyper oxygen-transmissible soft lenses (n = 135), and (3) hyper oxygen-transmissible rigid gas-permeable (RGP) lenses (n = 75). INTERVENTION Irrigation chamber to collect exfoliated epithelial surface cells, confocal microscopy, and tear collection at baseline, 2 weeks, and 4 weeks of DW. MAIN OUTCOME MEASURES (1) Pseudomonas aeruginosa (PA) binding to exfoliated corneal epithelial surface cells, (2) central epithelial thickness, (3) superficial epithelial cell area, (4) epithelial surface cell exfoliation, and (5) tear lactate dehydrogenase (LDH). RESULTS Four weeks of DW with the high oxygen-transmissible soft lens significantly increased PA binding from baseline 6.55 +/- 3.01 to 8.75 +/- 3.05 bacteria per epithelial cell (P < 0.01). By contrast, hyper oxygen-transmissible soft lens wear increased binding significantly less (6.13 +/- 2.45 to 7.62 +/- 3.06; P < 0.01), whereas hyper oxygen-transmissible RGP lens wear demonstrated no significant changes (5.91 +/- 2.40 to 6.13 +/- 2.17; P = 0.533). No significant change in central epithelial thickness was found after 4 weeks of DW in either soft lens; however, the epithelial thickness decreased by 9.8% (P < 0.001) with RGP lens wear. Epithelial cell surface area increased 3.3% and 4.1% with the high and hyper oxygen-transmissible soft lenses, respectively, and 10.5% with the hyper oxygen-transmissible RGP lens (P < 0.001). Epithelial desquamation significantly decreased in all groups (P < 0.001). Tear LDH levels increased for all test lenses (P < 0.001). CONCLUSIONS Increased PA binding induced by wear of a conventional soft lens material is significantly greater than that induced by the new hyper oxygen-transmissible soft silicone hydrogel lens during DW. However, both soft materials showed significant increases in PA binding as compared with baseline controls. By contrast, hyper oxygen-transmissible RGP lens DW did not increase PA binding significantly. Taken together, these findings suggest for the first time both an oxygen effect as well as a difference between soft and rigid lens types on PA binding in DW.

Adaptive effects of 30-night wear of hyper-O2 transmissible contact lenses on bacterial binding and corneal epithelium: A 1-year clinical trial☆

OBJECTIVE To determine effects of lens type and oxygen transmissibility on human corneal epithelium during extended wear (EW). DESIGN Prospective, randomized, double-masked, single-center, parallel treatment groups, 1-year clinical trial. PARTICIPANTS One hundred seventy-eight patients completed the study: (1) high-O(2) soft lens (6-night [N] EW) (n = 27); (2) hyper-O(2) soft lens (6N-EW, n = 33) or (30N-EW, n = 66); and (3) hyper-O(2) rigid gas-permeable lens (RGP) (30N-EW, n = 52). INTERVENTION Irrigation chamber to collect exfoliated corneal surface cells, confocal microscopy, and tear collection at baseline, 1, 3, 6, 9, 12 months of EW. MAIN OUTCOME MEASURES (1) Pseudomonas aeruginosa (PA) binding to exfoliated corneal surface cells; (2) central epithelial thickness; (3) superficial epithelial cell area; (4) epithelial surface cell exfoliation; and (5) tear lactate dehydrogenase. RESULTS Quantitative evidence demonstrated increased binding of PA to human exfoliated corneal epithelial cells during the first 3 months of soft lens EW; the control high-O(2) test lens showed significantly higher bacterial binding (P < 0.05). Binding activity gradually decreased thereafter and returned to baseline after 9 and 12 months. The corneal epithelium demonstrated enlargement of surface cell size, thinning of central epithelium, and a significant decrease in surface cell shedding (P < 0.05). Remarkably, there was subsequent partial adaptive recovery in cell shedding and epithelial thickness but not surface cell size. There was no significant difference between 6N and 30N continuous wear of the hyper-O(2) soft lens for all outcome measures. Importantly, hyper-O(2) RGP lens wear did not show significantly increased PA binding during 1 year. CONCLUSIONS This study establishes three important new findings: (1) hyper-O(2) soft lens EW produces significantly less PA binding than the lower O(2) soft lens with no significant difference in PA binding with 6N versus 30N EW of the hyper-O(2) soft lens; (2) there is a remarkable adaptive recovery after 6 months with all soft lens wear with gradual return to prelens PA binding levels and partial recovery of other outcome measures for all test lenses EW except surface cell size; (3) 30N EW of the hyper-O(2) RGP lens produced no significant increases in PA binding over 1 year. Taken together, these results suggest that introduction of new hyper-O(2) transmissible lens materials into clinical use may offer safer EW, and future epidemiologic studies of ulcerative infectious keratitis should consider both lens type and time in lens EW in any incidence/risk analysis.

Effects of daily and overnight wear of a novel hyper oxygen-transmissible soft contact lens on bacterial binding and corneal epithelium: A 13-month clinical trial

OBJECTIVE To test prospectively a new biologic rationale for an advanced hyper oxygen-transmissible lens (HOTL) providing prospects for safer daily (DW) or extended (EW) contact lens wear. DESIGN Prospective, randomized, double-masked, single-center, 13-month clinical trial. PARTICIPANTS One hundred sixty-eight patients completed the DW study (1 month): control lens (n = 70); HOTL (n = 98). One hundred thirty-six patients finished 1 year of EW: controls (n = 56), HOTL (n = 25, 6 nights; n = 55, 30 nights). TESTING Irrigation chamber to collect corneal surface cells, confocal microscopy, tear collection at baseline, 2, and 4, weeks of DW, and 24 hours, 1, 3, 6, 9, and 12 months of EW. MAIN OUTCOME MEASURES (1) Pseudomonas aeruginosa (PA) binding to exfoliated corneal surface cells; (2) central epithelial thickness (CET); (3) superficial cell area (SCA); (4) epithelial surface cell exfoliation (DESQ); and (5) tear lactate dehydrogenase (LDH). RESULTS Daily wear with control lens increased PA binding from 5.90 +/- 2.60 to 7.81 +/- 3.04 bacteria per cell (P < 0.01); HOTL wear increased PA binding significantly less (5.31 +/- 1.87-5.98 +/- 2.26; P < 0.01). Daily wear produced no significant changes in CET or SCA. Significant decreases in DESQ were seen with both lenses with no significant intergroup differences. Tear LDH increased significantly in DW with HOTL wear versus control (P = 0.0017), but not after 1 month of subsequent EW (P = 0.533). One to 3 months of EW with control lens showed significantly higher PA binding than HOTL wear (P < 0.01); binding adaptively decreased thereafter, returning to baseline at 9 to 12 months. Lens EW produced significantly enlarged SCA, thinning of CET (except 6-night HOTL wear), and decreased DESQ (P < 0.01). Some adaptive recovery was seen with CET and DESQ, but not SCA; importantly, the data indicated no significant difference between 6- or 30-night EW for all outcomes. CONCLUSIONS Hyper oxygen-transmissible lens wear (DW or EW) produced significantly decreased PA binding compared with control lens wear, with no significant difference in wearing schedule (6 nights vs. 30 nights); additionally, there was a remarkable and unexpected adaptive recovery in the first 6 months of all soft lens wear, with a return to baseline PA binding levels and partial recovery for the other outcomes except SCA at 1 year. These results suggest that HOTL use should result in a decrease in the incidence of and risk(s) for lens-related microbial keratitis and that further epidemiologic studies should consider time in adapted EW in future risk and incidence analyses.

Effect of eyelid closure and overnight contact lens wear on viability of surface epithelial cells in rabbit cornea.

Purpose. To determine the effects of open, closed eye, and overnight contact lens wear on homeostatic epithelial surface cell death in the rabbit cornea. Methods. One eye of each rabbit was either closed by eyelid suture or fitted with one of the following test contact lenses: (1) low Dk/t rigid gas permeable (RGP) lens, (2) hyper Dk/t RGP lens, (3) hyper Dk/t soft lens. The other eye served as a control. After 24 hours, whole corneas were carefully excised and immediately stained with a calcein-acetoxymethyl ester–ethidium homodimer viability assay to quantify the number of nonviable surface epithelial cells. In addition, exfoliated corneal epithelial cells were collected with an eye irrigation chamber to determine cell viability. Results. In the normal cornea, open-eye conditions showed significantly more nonviable surface cells in the central cornea than in the periphery (p < 0.05). Overnight wear of all test lenses and eyelid closure induced significant decreases in the number of nonviable cells on the central corneal surface compared with controls (p < 0.05). All exfoliated corneal epithelial cells collected by eye irrigation were nonviable. Conclusion. In the rabbit model, overnight contact lens wear significantly down-regulated spontaneous epithelial surface cell death independent of lens rigidity or material oxygen transmissibility. These effects were similar to eyelid closure without lens wear. Taken together, these results suggest that eyelid closure and the physical presence of the contact lens may protect against the shear stress forces exerted by eyelid blinking, which are believed to cause central surface cell death and subsequent exfoliation.

Corneal epithelial homeostasis following daily and overnight contact lens wear

This report reviews and integrates our recent clinical and laboratory findings of the effects of daily (DW)/overnight (EW) contact lens wear on corneal epithelial homeostasis. In a prospective, double-masked human clinical study, three lens types (high and hyper Dk/t soft; hyper Dk/t RGP) were used to assess the effects of daily and overnight lens wear on corneal epithelial thickness, cell surface size, Pseudomonas aeruginosa (PA) binding to exfoliated epithelial cells and exfoliation rates. Concomitantly, we studied in a rabbit model, the effects of overnight lens wear on corneal epithelial surface cell viability (live/dead assay, TUNEL-labeling, Annexin-V staining, Bcl-2 expression), basal cell proliferation and migration patterns. The comprehensive results obtained yield important new insights on both the normal homeostasis of the corneal epithelium and the biological changes induced by contact lens wear.

Recovery time of corneal epithelial proliferation in the rabbit following rigid gas-permeable extended contact-lens wear

Purpose. To determine recovery time needed for the corneal epithelium to return to a normal proliferation rate following 24-hour rigid gas-permeable (RGP) lens wear. Methods. An RGP lens (Dk/t = 10) was fitted at 9:00 am on one randomly chosen eye of each rabbit (N = 16) and removed 24 hours later while the other eye served as a control. Following contact lens removal, the rabbits were injected at four different time intervals (1,2, 4, and 7 days) with 5-bromo-deoxyuridine (BrdU) at 9:00 am to label dividing corneal epithelial cells. All animals were sacrificed 24 hours after BrdU injection, and corneas were stained for BrdU. A series of continuously adjacent digital images of the whole-mount epithelium was collected from superior limbus to central cornea, and all BrdU-labeled epithelial cell pairs on each digitized image were counted. Results. On day 1 following lens removal, the number of BrdU-labeled corneal epithelium cells was reduced by 50% centrally (C) and 36% peripherally (P) (P < 0.001) compared with control eyes. At day 2, there was no statistically significant difference between control and experimental corneas (P = 0.675). At day 4, a marked significant increase in BrdU-labeled cells was noted, averaging 83% (C) and 96% (P) (P < 0.001). At day 7, BrdU-labeling returned to control values, although it was still slightly elevated (14% [C] and 5% [P], P = 0.045). Conclusions. The corneal epithelium in the rabbit required at least 1 full week to recover to its stable baseline proliferation rate following only 24 hours of RGP lens wear. Interestingly, hyperproliferation was noted within the limbal, peripheral, and mid-peripheral corneal epithelium 4 days after lens removal.

Effects of O2 Transmissibility on Corneal Epithelium After Daily and Extended Contact Lens Wear in Rabbit and Man

Exocrine cells respond to a battery of neurotransmitters and hormones that act on G protein-coupled and G protein-independent receptors. Receptors transmit their signals by activation of biochemical pathways that change the concentration of second messengers, the most common of which are cAMP and intracellular Ca2+ ions ([Ca2+] i ). Many G protein-coupled receptors (GPCR) expressed in a given cell, activate the same biochemical pathway changing the concentration of the same second messengers. With the development of techniques that measure the concentration of second messengers in single cells and subcellular compartments, it became clear that different receptors using the same biochemical pathway could generate receptor-specific signals. In this short review, we summarize the current knowledge regarding a central question in cell signaling (Hunter, 2000: Weng et al., 1999) of how signaling specificity is achieved by GPCR expressed in a given cell using the same signaling pathway.