Jay W. McLaren

Effect of myopic laser in situ keratomileusis on epithelial and stromal thickness: a confocal microscopy study.

PURPOSE To determine changes in central epithelial and stromal thickness in human corneas in vivo after laser in situ keratomileusis (LASIK). DESIGN Prospective, nonrandomized, comparative trial. PARTICIPANTS Eighteen eyes of 12 patients received LASIK (performed using the VISX Star laser [VISX, Santa Ana, CA]) with a planned 180- micro m flap (created using an automated Hansatome microkeratome [Bausch & Lomb, Irvine, CA]) to correct refractive errors between -2.0 diopters (D) and -11.0 D. METHODS Corneas were examined by using confocal microscopy in vivo before LASIK and at 1 week and 1, 3, 6, and 12 months after LASIK. Epithelial thickness was the distance between images of the surface epithelium and subbasal nerve plexus or, when nerves were not visible, the subbasal peak (if present in the light intensity profile). Total flap thickness was the distance between images of the surface epithelium and interface debris (or peak), and total stromal thickness was the distance between images of the most anterior keratocytes and endothelium. MAIN OUTCOME MEASURES Corneal epithelial and stromal thickness. RESULTS Epithelial thickness before LASIK was 46 +/- 5 micro m (mean +/- standard deviation) and increased 22% by 1 month after LASIK (56 +/- 5 micro m; P = 0.01). Thereafter, epithelial thickness did not change, but remained thicker at 12 months after LASIK (54 +/- 8 micro m) than before LASIK (P = 0.02). Total flap thickness at 1 month after LASIK was 160 +/-28 micro m and did not change thereafter. Changes in total stromal thickness between 1 and 12 months after LASIK were not significant. CONCLUSIONS The central corneal epithelium was thicker in the first year after LASIK than before LASIK. There was no change in central stromal thickness between 1 month and 12 months after LASIK.

Variations in human corneal endothelial cell morphology and permeability to fluorescein with age

Fluorophotometry with topically applied fluorescein and endothelial cell photography were performed on 80 normal subjects (age 5-79 yr). Variations in endothelial cell morphology and function, flow of aqueous humor, and intraocular pressure were recorded. The mean endothelial cell size was 332.3 +/- 46.3 micron 2. A 28% increase in endothelial cell size was measured over the eight decades (r = 0.53, P less than 0.001). The coefficient of variation of cell size also increased with age (r = 0.41, P less than 0.001). The percentage of hexagonal endothelial cells decreased by 14% (r = -0.48, P less than 0.001), while the percentage of pentagonal and heptagonal cells increased by 50% (r = 0.44, P less than 0.001) and 40% (r = 0.33, P less than 0.002), respectively, with age. The mean endothelial permeability to fluorescein was 4.03 +/- 0.63 x 10(-4) cm min-1. A 23% increase in endothelial permeability with age was observed (r = 0.44, P less than 0.001). No change in central corneal thickness or endothelial pump rate was found. Flow of aqueous humor remained stable with age, despite a 25% increase in intraocular pressure (r = 0.50, P less than 0.001). Polarization of fluorescence of fluorescein in the corneal stroma decreased with age (r = -0.46, P less than 0.001). We conclude that with age the human corneal endothelium becomes morphologically less regular and may become more permeable to fluorescein.

The effect of corneal light scatter on vision after descemet stripping with endothelial keratoplasty

OBJECTIVE To establish an association between corneal light scatter and vision after Descemet stripping with endothelial keratoplasty (DSEK). METHODS Twenty eyes of patients with Fuchs endothelial dystrophy were examined before and at 1, 3, and 6 months after DSEK in a prospective study. Main outcome measures were high-contrast best-corrected visual acuity, intraocular forward light scatter, and corneal backscatter. RESULTS One eye was excluded because of endothelial graft failure within 1 month. Best-corrected visual acuity improved at 3 months after DSEK (mean [standard deviation], 0.31 [0.20] logarithm of the minimum angle of resolution [logMAR]; Snellen equivalent, 20/41) relative to before DSEK (0.46 [0.26] logMAR; Snellen equivalent, 20/58; P = .03). Posterior corneal backscatter decreased 1 month after DSEK (P < .001), but backscatter from the anterior, middle, and posterior cornea did not return to normal by 6 months (P < or = .02). At 6 months, best-corrected visual acuity correlated with recipient age (r = 0.84, P < .001) and with intraocular forward light scatter (r = 0.67, P < .001); forward light scatter also correlated with recipient age (r = 0.67, P < .001). CONCLUSIONS Six months after DSEK, corneal light scatter remained greater in eyes with Fuchs endothelial dystrophy than in normal eyes and correlated with recipient age and visual acuity. Recipient age might be the best preoperative predictor of vision after DSEK.

Mechanism of Action of Bimatoprost, Latanoprost, and Travoprost in Healthy Subjects: A Crossover Study

PURPOSE To study the effects of 3 prostaglandin analogs, bimatoprost, latanoprost, and travoprost, on aqueous dynamics in the same subjects and to compare techniques of assessing outflow facility. DESIGN Experimental study (double-masked, placebo-controlled, randomized paired comparison, 4-period crossover). PARTICIPANTS Thirty healthy adult subjects. METHODS Bimatoprost, latanoprost, travoprost, or a placebo was administered to the left eye once a day in the evening for 7 days, after a minimum 4-week washout period between each session. Tonographic outflow facility was measured by Schiøtz tonography and pneumatonography on day 7. On day 8, the aqueous humor flow rate and fluorophotometric outflow facility were measured by fluorophotometry. Uveoscleral outflow was calculated from the aqueous humor flow rate and outflow facility using the Goldmann equation. MAIN OUTCOME MEASURES Facility of outflow, aqueous humor flow rate, intraocular pressure (IOP), and calculation of uveoscleral outflow. RESULTS All medications lowered IOP relative to a placebo. None of the drugs affected aqueous humor production. All medications increased outflow facility compared with placebo when measured by Schiøtz and 2-minute pneumatonography (P< or =0.02); the apparent increase of outflow facility measured with fluorophotometry and 4-minute pneumatonography did not reach statistical significance. In contrast, uveoscleral outflow was significantly increased by all medications when calculated from 4-minute pneumatonography data, and fluorophotometry and Schiøtz data at higher episcleral venous pressures. The apparent increase found with 2-minute pneumatonography did not reach statistical significance. These differing results in the same patients indicate that differences in measurement techniques, and not differences in mechanism of action, explain previous conflicting published reports on the mechanism of action of the prostaglandins. CONCLUSIONS Bimatoprost, latanoprost, and travoprost have similar mechanisms of action. All 3 drugs reduce IOP without significantly affecting the aqueous production rate. All drugs increase aqueous humor outflow, either by enhancing the pressure-sensitive (presumed trabecular) outflow pathway or by increasing the pressure-insensitive (uveoscleral) outflow, but the assessment of the amount of flow through each pathway depends upon the measurement technique.

Confocal microscopy in ophthalmology.

PURPOSE To describe the principles, capabilities, and applications of confocal microscopy in vivo in ophthalmology. DESIGN Perspective, literature review, and commentary. METHODS Review and synthesis of selected recent literature, with interpretation and perspective. RESULTS Confocal microscopy imaging has led to a better understanding of the cellular microstructure in the normal, postsurgical, and diseased cornea by enabling quantitative analysis of the cellular response in the human cornea in vivo. At present, the major role of confocal microscopy is in research of corneal surgery and disease. Clinical applications are limited to facilitating the diagnosis of Acanthamoeba and deep fungal keratitis, measuring residual bed thickness after laser in situ keratomileusis, and measuring endothelial cell density in high-light-scattering situations. CONCLUSIONS In addition to providing qualitative data, confocal microscopy is valuable for quantitative analysis of the cornea and will enable the investigation of pharmacologic and surgical modifications of corneal wound healing, nerve regeneration, and cellular responses. Prospective, quantitative analyses require individual calibration of confocal microscopes for lateral and axial dimensions of images, for image depth, and for light intensity.

Keratocyte density in keratoconus. A confocal microscopy study

PURPOSE To estimate keratocyte density in human corneas with keratoconus by confocal microscopy. DESIGN Prospective, observational cohort study. METHODS Twenty-nine unscarred corneas of 19 patients with keratoconus and 29 corneas of 19 controls matched for age (+/-3 years) and contact lens wear were examined by using confocal microscopy. Images were recorded from the full-thickness central cornea. A masked observer manually counted bright objects (keratocyte nuclei) in images without motion blur. Cell densities in anteroposterior stromal layers of keratoconus corneas were compared with densities in corresponding layers of control corneas. RESULTS In keratoconus patients, age 40 +/- 15 years (mean +/- standard deviation), keratocyte density was 19% lower in those who wore contact lenses (16,894 +/- 4032 cell/mm(3), n = 12) than in those who did not wear contact lenses (20,827 +/- 4934 cell/mm(3), n = 17, P =.03). In control patients, age 39 +/- 16 years, there was no difference in keratocyte density between those who wore contact lenses (n = 12) and those who did not wear contact lenses (n = 17, P =.80). Among contact lens wearers, keratocyte density was 25% lower in keratoconus corneas (16,894 +/- 4, 032 cell/mm(3), n = 12 [9 = rigid gas-permeable lenses, 3 = soft lenses]) than in control corneas (22,579 +/- 2, 387 cell/mm(3), n = 12 [3 = rigid gas-permeable lenses, 9 = soft lenses], P =.002), the result of cell density being lower in the most anterior keratocyte layer (P =.001) and the layers between 0% to 10% (P <.001), 67% to 90% (P <.001), and 91% to 100% (P <.001) of stromal thickness. Among noncontact lens wearers, there was no difference in cell density between keratoconus and controls (P =.41). CONCLUSION Keratocyte density is decreased in the anterior and posterior stroma of keratoconus patients who wear contact lenses.

Keratocyte density of central human cornea after laser in situ keratomileusis

PURPOSE To determine changes in keratocyte density in the first year after laser in situ keratomileusis (LASIK). DESIGN Prospective interventional cohort study. METHODS Seventeen eyes of 11 patients received LASIK with a planned 180-microm flap to correct refractive errors between -2.0 diopters and -11.0 diopters. Images of the full-thickness cornea were obtained by using confocal microscopy in vivo before LASIK and at 1 week, 1, 3, 6, and 12 months after LASIK. Bright objects (that resembled keratocytes) in images without motion blur were manually counted by one observer. Cell densities were determined in anterior and posterior halves of the stromal flap, anterior and posterior halves of the layer 100 microm-thick immediately deep to the ablation (retroablation layer), and in the posterior third of the stroma. The region of stroma that was ablated (as measured 1 month after LASIK) was omitted from the preoperative analysis. RESULTS Keratocyte density in the anterior flap was 28,978 +/- 5849 cells/mm(3) (mean +/- SD) pre-LASIK, and was decreased at all postoperative examinations, but the difference was not significant until 12 months after LASIK (22% decrease). Keratocyte densities in the posterior flap were 20,397 +/- 4215 cells/mm(3) pre-LASIK and were decreased by 20%-40% at all postoperative examinations 1 week to 1 year after LASIK. Keratocyte densities in the anterior half of the retroablation layer were 16,605 +/- 3595 cells/mm(3) pre-LASIK and decreased by 16%-30% between 3 and 12 months after LASIK. Keratocyte densities in the posterior half of the retroablation layer and posterior stroma did not change. CONCLUSIONS Keratocyte densities in the posterior flap and anterior retroablation layer (regions adjacent to the lamellar cut) decrease at 1 week and 3 months, respectively, after LASIK and remain decreased in these regions at 12 months after LASIK. In the anterior flap, keratocyte density decreases 1 year after LASIK. The long-term effects of these cellular deficits, if any, require further study.

Circadian variation of aqueous dynamics in young healthy adults.

PURPOSE Recent research indicates that intraocular pressure (IOP) does not decrease significantly during the nocturnal period, although aqueous humor flow decreases by 50% or more at night. This study was undertaken to investigate whether changes in outflow facility, episcleral venous pressure, or uveoscleral flow at night could account for the nocturnal IOP. METHODS Sixty-eight eyes of 34 healthy subjects (age, 18-44 years; mean, 29) were studied. Aqueous humor flow rate, IOP, and outflow facility were measured with pneumatonometry, anterior chamber fluorophotometry, and Schiotz tonography respectively, in each eye during the mid-diurnal (2-4 PM) and mid-nocturnal (2-4 AM) periods. Nocturnal IOP, flow rate, and outflow facility were compared to the same variables during the diurnal period. Mathematical models based on the modified Goldmann equation were used to assess the conditions under which these results could be reconciled. RESULTS Supine IOP decreased slightly from 18.9 +/- 2.7 mm Hg in the mid-diurnal period to 17.8 +/- 2.5 mm Hg in the mid-nocturnal period (mean +/- SD, P = 0.001). Aqueous flow rate decreased from 2.26 +/- 0.73 to 1.12 +/- 0.75 microL/min (mean +/- SD, P < 0.001). There was a nonsignificant trend toward a nocturnal decrease of outflow facility (diurnal, 0.27 +/- 0.11 microL/min/mm Hg; nocturnal, 0.25 +/- 0.08 microL/min/mm Hg; mean +/- SD, P = 0.13). CONCLUSIONS Outflow facility measured by tonography does not decrease enough during the nocturnal period to compensate for the decreased aqueous humor flow rate. Modeling results indicate that the experimental results could be reconciled only if nocturnal changes in episcleral venous pressure and/or uveoscleral flow occurred.

The Effect of Age on the Corneal Subbasal Nerve Plexus

Purpose: To measure subbasal nerve density and orientation in normal human corneas across a broad age range. Methods: Sixty-five normal corneas of 65 subjects were examined by using tandem scanning confocal microscopy. Ages of subjects ranged from 15 to 79 years (mean 46 ± 19 years), with 5 subjects from each hemidecade. Subbasal nerve fiber bundles appeared as bright, well-defined linear structures in confocal images of the central cornea. Images from 3 to 8 scans per eye (mean 4.6 ± 1.8 scans) were randomly presented to a masked observer for analysis. The mean subbasal nerve density (total nerve length [μm] within a confocal image [area = 0.166 mm2]), the mean nerve number per confocal scan, and the mean nerve orientation were determined by using a custom software program. Correlations between age and nerve density and age and nerve orientation were assessed by using Pearson correlation coefficients. Results: The subbasal nerve plexus was visible in the central cornea of all subjects. The mean subbasal nerve density was 8404 ± 2012 μm/mm2 (range 4735 to 14,018 μm/mm2). The mean subbasal nerve number was 4.6 ± 1.6 nerves (range 1 to 8 nerves). The mean subbasal nerve orientation was 94 ± 16 degrees (range 58 to 146 degrees). There was no correlation between age and subbasal nerve density (r = 0.21, P = 0.09) or between age and subbasal nerve orientation (r = −0.19, P = 0.12). Conclusion: The density and orientation of the subbasal nerve plexus in the central human cornea does not change with age.

Analysis of postoperative glare and intraocular lens design

Purpose: To assess the potential for reflected glare images from commonly used intraocular lens (IOL) materials and designs. Setting: Mayo Clinic, Rochester, Minnesota, USA. Methods: The interaction of reflected light rays from 3 commonly used IOLs (Bausch & Lomb LI61U and P359UV; Alcon AcrySof® MA60BM) with different optic designs (equi‐biconvex: 10.0 and 15.0 mm anterior radius of curvature; unequal biconvex: 32.0 mm anterior radius of curvature) and optic materials (silicone, poly[methyl methacrylate], and acrylic) were examined in an eye model using the Zemax optical design program. The potential of each IOL model to produce subjective glare was determined from the size of the defocused reflected glare image at the retina. Results: The unequal biconvex design concentrated reflected light on a retinal area that was 60‐fold smaller than that of the equi‐biconvex design. Increasing the refractive index of the IOL material from 1.43 (silicone) to 1.55 (acrylic) increased the amount of reflected light 5‐fold. Compared to an equi‐biconvex design composed of a lower refractive index material, the unequal biconvex design with a higher refractive index material increased the relative intensity of reflected light at the retina 300‐fold, and for eyes with low corneal power the intensity increased 3500‐fold. Similarly, for external glare apparent to an outside observer, the intensity of reflected light increased 400‐fold and for low corneal power it increased 6000‐fold. Conclusion: An unequal biconvex IOL design (32.0 mm anterior radius of curvature) composed of a higher refractive index material increased the potential for postoperative glare and external reflections.