The distribution of strain in the human cornea.

Experimental data on the mechanics of human cornea is meager and sometimes flawed. Moreover, questions regarding the correct material symmetry and the role of the fibrous microstructure are usually glossed over when mechanical models of the cornea and corneal shape changing procedures are presented. Accordingly, the deformation of 14 intact human corneas was measured for five pressures in the physiologic range (0, 5, 10, 25 and 45 cmH2O) by tracking small, self-adherent particles placed on their anterior surfaces. The meridional strains, calculated in five regions assuming axisymmetric deformation, are small; the average strain in the apical region being 1.14% at 45 cmH2O. Results also indicate that the strain distribution is unexpectedly nonuniform with statistically significant (p < 0.01, typical) variations between regions and a minimum occurring approximately half-way between apex and limbus. To better understand these results, a finite-element model (FEM) of the cornea was constructed and used to simulate the experiment. The heterogeneous model shows that our data may reflect the changing fiber orientation along a meridian suggested in the literature. The implications of a link between microstructure and mechanics are discussed in light of clinical procedures, such as radial keratotomy, the outcomes of which are dependent on corneal mechanical properties.

Corneal endothelial damage by air bubbles during phacoemulsification.

OBJECTIVE: To characterize the mechanism by which air bubbles damage the corneal endothelium during phacoemulsification. MATERIALS AND METHODS: A series of experiments was conducted to expose the corneal endothelium of New Zealand white rabbit and human eyes that were obtained from an eye bank to air under different conditions. Phacoemulsification at different power settings and irrigation with and without the introduction of air into the anterior chamber were performed. Corneal endothelial perfusion experiments were conducted with air bubbles that were introduced into the perfusion chamber for 2 seconds to 1 hour. Air was also injected into the anterior chambers of anesthetized rabbits for 2 minutes to 3 hours. Corneas were stained with nitrobenzo-xadiazole-phallacidin and examined with fluorescence microscopy. Selected corneas were also examined with scanning and transmission electron microscopy. RESULTS: Intracameral air bubbles during phacoemulsification, irrigation, and perfusion studies resulted in a severe injury to the corneal endothelium in as little as 20 seconds. Intracameral air bubbles in a living rabbit resulted in a slower injury that was morphologically different from the more rapid injury. CONCLUSIONS: Air bubbles in intraocular fluids with a high surface tension can cause a ring-shaped pattern of damage to the corneal endothelium. The mechanism that caused this pattern of damage appears to be a surface tension phenomenon.

Effect of tear lubricating solutions on in vivo corneal epithelial permeability.

PURPOSE: The rabbit corneal epithelial permeability was measured noninvasively following exposure to commercially available tear lubricating solutions. METHODS: The normal unanesthetized rabbit's corneal surface was either bathed in the tear lubricating solution for 5 min or received multiple applications of 2 drops per 30 min for 6 h for one or five days. The corneal epithelial permeability to carboxyfluorescein after a 5-min bath was measured with the Fluorotron Master. Fifteen commercially available tear preparations were tested. RESULTS: The baseline corneal epithelial permeability was 0.0455 +/- 0.0114 nm/s. The epithelial permeability values for the corneas bathed for 5 min in control solution (BSSplus) was 0.0798 +/- 0.0074 nm/s, in the preservative-free tear lubricating solutions the range was 0.512 to 0.542 nm/s, and in the preserved tear lubricating solutions the range was 0.3518 to 11.8873 nm/s. The preservative-free tear lubricating solutions had epithelial cell permeabilities up to 6 times greater than the control solution. Whereas, the preserved tear lubricating solutions had epithelial cell permeabilities up to 149 times greater than the control solution. Multiple applications of the tear lubricating solutions for 5 days were less damaging to the epithelial permeability than the 5 min bath applications. The resulting epithelial permeabilities were up to 2 fold greater than the control with the corresponding preservative-free solution and up to 29 fold greater than control with the corresponding preserved solution. CONCLUSION: An extended exposure of 5 min to various tear lubricating solutions demonstrated significant differences in epithelial cell permeability between preserved solutions and unpreserved solutions, whereas the multiple drop application technique demonstrated all of the preservative-free solutions and some of the preserved solutions to be insignificantly different from the control solution.

The illuminated high contrast macular grid: a pilot study.

BACKGROUND: Analysis of visual disturbances in the central 10 degrees provides valuable data for the low vision clinician. Amsler grid testing in the visually impaired can be poorly visible and it can be difficult to transcribe results. Automated perimeters will accurately map retinal defects, but the equipment is expensive and this technique is time consuming. An Amsler grid was modified using principles of luminance and contrast to improve its accuracy, and its efficacy was compared to an automated perimeter. METHODS: Eighteen visually impaired patients (28 eyes) were prospectively evaluated at the Emory Low Vision Laboratory. Each patient had three central threshold visual field tests: automated perimetry (Humphrey model 690), conventional Amsler Grid, and Illuminated High Contrast Macular Grid (IHCMG). The Humphrey central 10-2 threshold automated visual field examination was performed to map the patient's retinal function. RESULTS: The Humphrey analysis identified (mean +/- one standard deviation) 2.4 +/- 1.4 defects per patient with an average percent defect area of 33.4 +/- 14.8 degrees. The IHCMG technique was not significantly different from the Humphrey technique for identifying the number of defects (2.25 +/- 1.5) (p > 0.05) or the percent defect area (26 degrees +/- 20 degrees) (p > 0.05). The conventional Amsler grid technique significantly under-evaluated the retinal defects compared to the Humphrey analysis of the number of defects (p < 0.01) and percent area of defects (p > 0.001). CONCLUSIONS: The IHCMG technique can be used as a simple, rapid and accurate analysis of the central 10 degrees visual field in the low vision patient.

Noninvasive measurement of corneal epithelial permeability.

The Fluorotron Master fluorophotometer was used to measure the corneal epithelial permeability to carboxyfluorescein in the normal unanesthetized rabbit. This was related to the epithelial fluorescein staining grade as assessed with a slit lamp. The carboxyfluorescein concentration in the cornea was measured at 3, 60 and 120 min after bathing the cornea in 2.7 x 10(-3) M carboxyfluorescein for 5 min. The epithelial cell layer permeability was calculated from the corneal carboxyfluorescein concentration immediately after a balanced salt solution rinse (initial technique) and from the time zero intercept value extrapolated from the 60 and 120 min data (intercept technique). The slit lamp demonstrated 69% of the nonpaired rabbit eyes were free of epithelial defects, whereas, 46% of the paired rabbit eyes were free of defects. Epithelial permeability values determined from the initial or intercept technique were similar (p = 0.77, unpaired 2 tailed t-test for data < 0.165 nm/s). The initial analysis permeability values ranged from 0.0154 to 4.309 nm/s., n = 29 There was a Gaussian distribution of data between 0.015 and 0.144 nm/s with a mean of 0.0646 +/- 0.0070 nm/s. The larger values correlated with the naturally occurring epithelial defects observed with the slit lamp. The epithelial permeability values were independent of the contralateral eye or subsequent day measurements.

Corneal wound healing strength with topical antiinflammatory drugs.

The objective of this study was to compare the force required to separate corneal wounds after topical applications of nonsteroidal antiinflammatory drugs (NSAIDs) or corticosteroids. Bilateral central 8-mm long corneal full-thickness incisions in 50 NZW rabbits were closed with five interrupted 10-0 nylon sutures. There were four paired-eye groups: (a) control/control, (b) control/diclofenac sodium (0.1%), (c) control/flurbiprofen sodium (0.03%), and (d) control/prednisolone acetate (1%) treated six times per day for 7 or 21 days. The wound strength was measured by determining the force necessary to separate the incision along its length. The eyes did not differ statistically from their contralateral eye for each group except control/diclofenac (7.98 g/12.32 g) and control/flurbiprofen (6.96 g/11.67 g) at 21 days. The strongest scars occurred after treatment with diclofenac and flurbiprofen, which were similar (p = 0.74). The weakest wounds for each time period were with prednisolone (1.74 g/3.21 g). The diclofenac and flurbiprofen were stronger than prednisolone-treated eyes at 7 days (p = 0.028 and p = 0.023, respectively) and at 21 days (p < 0.001). The bilateral controls were stronger than the prednisolone controls (p = 0.008 at 7 days and p = 0.001 at 21 days). Steroid treatment caused weaker corneal wound scars than did the NSAIDs. Unilateral steroid treatment adversely affected their untreated contralateral eyes. The NSAID-treated wounds were the strongest and stronger than their contralateral control eyes.

Topographic evaluation of toric soft contact lens correction.

The anterior surface of the eye provides the greatest refracting surface to the optical system of the eye because of the large difference in refractive index between air and tissue. When a contact lens is placed on the eye, its anterior surface becomes the greatest refracting surface. Toric soft contact lenses have been designed to neutralize ocular astigmatism. We observed that topographic analysis of toric soft contact lenses on an astigmatic eye demonstrated residual astigmatism on the anterior surface of soft toric contact lenses. In this paper we show toric soft contact lens surface astigmatism by videokeratoscopy and interpret the origins of the astigmatism.

Nicotine on the revascularization of bone graft. An experimental study in rabbits.

STUDY DESIGN: In 24 rabbits, the authors transplanted autologous cancellous bone to the anterior chamber of the eye. Half of the rabbits received nicotine and half received placebo (albumin) from mini-osmotic pumps that were implanted subcutaneously. Revascularization of the bone graft was evaluated postoperatively using ophthalmology slit-lamp and fluorescein angiography, and after sacrifice using microvascular silicone injection and histology. OBJECTIVES: The hypothesis that nicotine inhibits the revascularization of bone graft because of its pharmacologic action on the microvasculature was tested. SUMMARY OF BACKGROUND DATA: Pseudoarthrosis after spinal fusion occurs more frequently in smokers as compared with nonsmokers. METHODS: Observations of the bone graft were made regarding the time after implantation when vessels within the graft were noted and the pattern of these vessels. Revascularization of the graft was graded based on the observed percent area of fluorescence after injection of fluorescein. Serum levels of nicotine were measured weekly. Colored silicone was injected at sacrifice to fix the vasculature of the bone graft. Histologic analysis of undecalcified sections was performed. RESULTS: Nicotine, as compared with placebo, was associated with delayed revascularization within the graft, a smaller percent area of revascularization, and a larger number of grafts showing necrosis. CONCLUSIONS: Nicotine inhibits, but does not prevent, the revascularization of cancellous bone grafts. Inhibition of early revascularization by nicotine is proposed as the pathophysiologic mechanism by which smoking may adversely affect the healing of spinal fusions.

Surface topography of soft contact lenses for neutralizing corneal astigmatism.

We compared the surface topography of 38 soft contact lenses in situ to the corneal topography of 17 patients. The analyzed lenses consisted of patients' spherical and toric lenses as well as additional spherical lenses of various thicknesses. Thirteen brands of contact lenses were worn; corneal astigmatism ranged from 0.12 to 3.81 D. Our hypothesis was that toric soft contact lens neutralization of corneal surface astigmatism occurred through the creation of a more spherical anterior surface. Videokeratoscopy was used to analyze corneal surface changes with contact lens wear. The correction of astigmatism for toric corneas (toricity > 0.75 D) fit with toric lenses (i.e., the difference between the surfaces of the cornea and anterior lens) showed surface astigmatism neutralization of only 34 +/- 38%. The greater the astigmatism, the greater the neutralization. Spherical lenses not only failed to mask corneal toricity, but actually increased it. The topographic map can be a valuable asset for analyzing and possibly improving contact lens fitting of toric contact lenses.

Assessment of the long-term corneal response to hydrogel intrastromal lenses implanted in monkey eyes for up to five years.

The biocompatibility of hydrogel intracorneal lenses (ICLs) implanted in monkey eyes was evaluated for periods ranging up to five years. Seventy-three plus or minus powered ICLs made of Lidofilcon A (68% water) or Lidofilcon B (79% water) were implanted following lamellar dissection with a microkeratome. Ten sham surgical procedures were performed without ICL implantation as controls. Eyes were followed for up to five years by slitlamp biomicroscopy and specular microscopy. Light and transmission electron microscopic evaluations of enucleated eyes were performed at various intervals. Minimal tissue reaction was noted; both hydrogel materials appeared to be equally well tolerated. Failures usually occurred as a result of microkeratome problems encountered during surgery. Histopathological changes to the cornea included epithelial thinning anterior to the thickest portion of the ICL, fibroblastic activity along the ICL-stromal interface, and deposition of an amorphous extracellular material adjacent to the ICL. These observations did not appear to be clinically significant as the eyes were quiet by slitlamp examination. Removal of three ICLs eight to ten months prior to enucleation restored the normal histological characteristics of the cornea. The endothelial cell density of ICL-implanted eyes decreased by 4.3% (n = 17) six months after surgery but remained stable thereafter. The variation in endothelial cell area and percentage of hexagonal cells did not change over 50 months. The results appear to demonstrate that high water content synthetic ICLs can be well tolerated in the monkey cornea for up to five years.

Intrastromal crystalline deposits following hydrogel keratophakia in monkeys.

Intrastromal corneal crystals developed in 11 of 49 monkey eyes with hydrogel intracorneal lenticules followed over a 4 year period. All of the eyes, except one, underwent synthetic keratophakia via a microkeratome incision. The diagnosis of crystal formation was initially made by slit-lamp examination and confirmed with specular microscopy (from 21 to 150 days post-hydrogel keratophakia). The crystals were noted to lie in a plane adjacent to the hydrogel lenticule and specular microscopy revealed polychromatic, hyperrefringent crystals with either a rectangular or linear morphology. Prior to intrastromal crystal formation, these corneas developed early postoperative stromal edema (< 3 weeks). We hypothesize that early stromal edema in combination with the hydrogel intracorneal lenticule induced the production of lipid crystals by stromal keratocytes.

A biomechanical evaluation of rabbit corneas in M-K and Dexsol.

We compared the average force required to separate normal corneas at a 50% stromal depth, with the force required to separate corneas stored for 2, 5, 7, 10, and 14 days in either McCarey-Kaufman or Dexsol corneal storage medium. The required interlamellar separation force was calculated by standardizing the width of the test strips. The average required force for 35 fresh rabbit corneas (no storage) was 9.1 +/- 1.5 g/mm. There was no significant change in the required separation force after storage in either medium for up to 14 days.

Practical aspects of a corneal topography system.

We used the EyeSys Corneal Topography System to examine several issues relating to corneal topography systems and the interpretation of their results. Interferometry measurements of EyeSys calibration spheres indicated that they deviated from suggested values by 0.05 +/- 0.13 D (mean +/- 1 standard deviation). The EyeSys unit reliably determined the calibration spheres to be spherical with differences between the flat and steep axis of 0.10 +/- 0.09 D. The data for the 3 mm chord circle was the least reliable. The spherical equivalent values for the calibration spheres were constantly greater than the 0.25 D reproducibility suggested by the manufacturer. Furthermore, the precision of the outputted values (0.01 D) is beyond the capability of the instrument. This gives the impression that the topography unit cannot consistently reproduce measurements of the calibration objects or chrome plated steel spheres. Image centralization and focus were found to be critical in obtaining accurate results. A target off center by more than 0.25 mm resulted in unreliable data; increasing the focal distance by greater than 1 mm beyond the focal point resulted in a sharp decrease in accuracy (a decrease in the focal distance was even more critical). When measuring aspheric contact lenses, it was found that the keratometer and EyeSys unit provided a close approximation of the surface characteristics of the lenses. A realistic view of the limitations of the topography system being used is critical for proper interpretation of the data.

Eight years experience with Permalens intracorneal lenses in nonhuman primates.

BACKGROUND: For the past 8 years, three independent laboratories have been researching the biocompatibility and performance of Permalens intracorneal lens implants in the corneas of nonhuman primates. Both myopic and hyperopic corrections have been achieved. This article describes the evolution of the intracorneal lens design and manufacturing process. METHODS: During this time period, 63 surgeries were performed on various species of nonhuman primates. Follow-up examination extended between 30 months and 8.2 years. Objective measures of refractive performance, as well as biocompatibility were made using slit lamp, retinoscopy, autorefractor, specular microscope, etc. Additionally, histopathology was performed on many of the specimens, both acute and chronic. RESULTS: Surgically successful implants were achieved in between 60% and 100% of eyes in the various series of lens implants outlined in the article. Levels of contamination in the preparation of hydrogels were felt to be responsible for many of the surgical failures. The removal of silicone and other contaminants seems to have significantly improved the biocompatibility of these materials within the cornea. The major histopathological finding was that there appeared to be some epithelial thinning over the implants, but in general excellent biocompatibility was obtained over the 8-year period outlined in this paper. CONCLUSIONS: Although extensive studies of biocompatibility have been completed, the future of the performance of these materials remains to be proven in the human subject. Additionally, empirical relationships between lens implant power and refractive results will have to be determined in humans, prior to their general clinical usage.

Hydrogel keratophakia: long-term morphology in the monkey model.

After 8.5 years a rhesus monkey with bilateral hydrogel (Permalens) intracorneal implants was evaluated by light microscopy and transmission electron microscopy to determine the long-term effects of a synthetic plastic upon the primate cornea. Light microscopy revealed that the hydrogel lenticules were implanted between 80 and 90% of stromal depth, causing posterior bulging of the stroma into the anterior chamber; this was also seen clinically with slit-lamp biomicroscopy. Some minor pathologic changes were also found elsewhere in the cornea, including epithelial remodelling anterior to the hydrogel implant and a few vacuolated endothelial cells posterior to the edges of the implant. Histologically, no inflammatory reaction was seen in either cornea. This primate demonstrates the long-term biocompatibility of hydrogel intracorneal lenses.

Modeling glucose distribution in the cornea.

The central cornea obtains its glucose by diffusion through the cornea from the aqueous humor to the epithelium. The diffusion of glucose in the cornea is analogous to the flow of current in an electrical resistance network. The cellular consumption of glucose can be compared to shunting a portion of the charge to electrical ground. An electrical analog model of the cornea was developed to predict the availability of glucose to the epithelium and the distribution of glucose in the stroma. The glucose constant concentration lines in the normal stroma are parallel to the corneal surface and have decreasing values from 880 to 580 micrograms/ml. The effects on epithelial glucose concentration by implanting an intracorneal lens (ICL) of varying diameter, depth, permeability and thickness can be modeled. Glucose permeability through the intracorneal lens has the most significant effect on glucose availability. The ICL profile i.e. power, can also be an important fact in determining glucose availability. A minus power design requires a thin central lens zone with a thick peripheral zone. The design results in relatively more glucose flux through the optical zone of the lens and thus improves central epithelial glucose availability.

Refractive predictability of myopic hydrogel intracorneal lenses in nonhuman primate eyes.

The refractive predictability of myopic hydrogel intracorneal lenses made of lidofilcon A was evaluated in 24 monkey eyes following a microkeratome dissection. All eyes were examined monthly for refractive alteration and clinical appearance during a follow-up period of 7 to 33 months. The refractive yield was measured by retinoscopy and found to be a function of the implant depth. The mean +/- SD percent of the desired correction achieved averaged 70% +/- 24% at a 36% to 60% depth (n = 8), 54% +/- 22% at a 61% to 79% depth (n = 7), and 12% +/- 14% in implants deeper than at a 79% depth (n = 9). For eyes with implants at a 36% to 60% depth, the predicted vs achieved refractive alteration yielded a correlation coefficient of .97 (88% within +/- 3 diopters of the correlation). The refractive outcome remained stable throughout 7 months of follow-up, whereas deeply placed lenses (greater than or equal to 80%) exhibited significant regression in power during this time.

Interlamellar adhesive strength in human eyebank corneas.

The interlamellar biomechanical properties of stromal collagen are relatively unknown, yet may be highly significant with respect to wound healing and the efficacy of certain keratorefractive surgical procedures. Interlamellar adhesive strength was measured as the tearing force required to separate corneal lamellae at a 50% stromal depth in 16 human eyebank corneas. The mean value for the central cornea was found to be 14.2 (+/- 0.5 SEM) g-wt/mm of tissue width. Histology showed a smooth separation between the lamellae along the tearing plane in the central cornea. We believe that the adhesive strength measured in the central cornea may be primarily the force needed to break interlamellar proteoglycan bonds between collagen lamellae, because no torn lamellae were found in this region. The mean adhesive strength and the SEM increased toward the periphery in a symmetrical fashion. The mean adhesive strength in the far periphery was 31.6 (+/- 3.7 SEM) g-wt/mm at 5 mm nasally, and 28.4 (+/- 3.2 SEM) g-wt/mm at 5 mm temporally, and was approximately twice the mean central value. The rising value of the mean adhesive strength with increasing distance from the central cornea was believed to be due to a more highly disorganized collagen network in which greater numbers of lamellae passed obliquely in depth through the tearing plane. These lamellae would contribute their tensile strength to the adhesive strength measurement along the tearing plane. Histology from the peripheral cornea confirmed the existence of depth-varying collagen lamellae and the torn ends of lamellae that passed across the tearing plane.

Lipid deposits posterior to impermeable intracorneal lenses in rhesus monkeys: clinical, histochemical, and ultrastructural studies.

Synthetic materials are being evaluated for their potential long-term use in corneal refractive surgery. Clinical and histopathologic studies were performed with polymethylmethacrylate (PMMA) and polysulfone intracorneal lenses in rhesus monkey eyes that were followed for up to 3 years. The 5 mm diameter lenses were placed in the deep posterior corneal stroma of four eyes. Fine, polychromatic crystalline deposits formed a layer posterior to the implants. Enucleated eyes had the corneas either frozen for histochemistry or fixed for electron microscopy. Special stains included oil red 0 and filipin on fresh frozen tissue. The cornea, with a PMMA intracorneal lens showed myriad crystalline aggregates in the deep corneal stroma behind the implant. These crystalline deposits stained positively with oil red 0 and with filipin indicating the presence of neutral fat as well as unesterified cholesterol. The polysulfone implant showed no evidence of crystalline deposits histologically but was surrounded by homogeneous aggregates that could represent nonspecific reaction to the lens material or protein deposits. Electron microscopy of all four corneas revealed dissolved lipid aggregates and laminated electron dense material that were most abundant posterior to the implant where the keratocytes appeared disintegrated. The PMMA lens appeared to induce lipid keratopathy.