Patient-Reported Visual Disability in Fuchs' Endothelial Corneal Dystrophy Measured by the Visual Function and Corneal Health Status Instrument.

PURPOSE: Measuring patient-reported visual disability in Fuchs' endothelial corneal dystrophy (FECD) may be helpful in determining when to intervene and for understanding the outcomes of intervention. In this study, we aimed to validate a new patient-reported visual disability questionnaire, the Visual Function and Corneal Health Status (V-FUCHS) instrument, in FECD before and after endothelial keratoplasty (EK). DESIGN: Cross-sectional study with instrument readministration at 6 weeks. PARTICIPANTS: Patients with a range of severity of FECD, including after EK, and patients with healthy corneas. METHODS: The V-FUCHS instrument was developed based on patient interviews, expert consultations, and pretesting. Psychometric methods of classic test theory were applied to estimate reliability and validity, including testing V-FUCHS against Catquest-9SF, a cataract-specific visual disability questionnaire. Ordered polytomous Rasch-based partial credit models and item response theory diagnostics were used to define the response patterns. MAIN OUTCOME MEASURES: Reliability (primary) and validity (secondary). RESULTS: The final instrument was completed by 65% of patients with a range of severity of FECD (n = 41), after undergoing EK for FECD (n = 70), and with healthy corneas (n = 28). Participants were phakic or pseudophakic. Exploratory factor analysis among FECD and patients who underwent EK showed 2 independent factors of visual disability: 7 items related to visual acuity and 8 items related to glare or diurnal variation. Retest reliability was substantial (intraclass correlation coefficient, ≥0.8, both factors). Among all patients, the visual acuity factor was correlated with Catquest-9SF scores (r = 0.65; P < 0.001; n = 96). The glare or diurnal variation factor increased with FECD severity (P < 0.001, n = 69) and was higher in FECD than healthy participants (P < 0.001). Diagnostics revealed that both factors were well calibrated and met Rasch model expectations. CONCLUSIONS: The V-FUCHS instrument is valid and reliable for assessing visual disability in FECD. The instrument allows for standardized, comprehensive, and rapid assessment of disease-specific visual disability and may be useful in clinical practice and research as a patient-reported outcome measure.

Vision-related quality of life before and after keratoplasty for Fuchs' endothelial dystrophy.

PURPOSE: To assess vision-related quality of life in Fuchs' dystrophy and changes in vision-related quality of life after 3 types of keratoplasty (penetrating keratoplasty [PK], deep lamellar endothelial keratoplasty [DLEK], and Descemet stripping endothelial keratoplasty [DSEK]). DESIGN: Prospective, observational case series. PARTICIPANTS: Sixty-three subjects with Fuchs' endothelial dystrophy: 12 subjects (12 eyes) received PK, 11 subjects (11 eyes) received DLEK, and 40 subjects (40 eyes) received DSEK. METHODS: Subjects were examined before keratoplasty and at regular intervals through 3 years after keratoplasty. At each examination, vision-related quality of life was assessed using the 25-item National Eye Institute Visual Functioning Questionnaire; best spectacle-corrected and uncorrected visual acuities were measured by using the electronic Early Treatment of Diabetic Retinopathy Study protocol; keratometric cylinder was measured by a manual keratometer. Disability glare was measured with a straylight meter. MAIN OUTCOME MEASURES: Vision-related quality of life composite score. RESULTS: Vision-related quality of life composite score for all eyes with Fuchs' dystrophy before keratoplasty was 72 ± 11 (n = 63) and did not differ between groups (P = 0.88). Vision-related quality of life improved by 6 months (PK, P = 0.008; DLEK, P = 0.03; DSEK, P < 0.001), with continued improvement between 6 months and 3 years after PK (P = 0.01) and DSEK (P = 0.004). At 6 months, the composite score was higher after DSEK than after PK (P = 0.006). At 3 years, there were no differences in composite scores between the 3 treatments (P = 0.33; mean minimum detectable difference, 8 [α = 0.05; ß = 0.20]). After keratoplasty, quality of life was correlated with uncorrected visual acuity at 1 year (r = -0.38; P = 0.001) and at 3 years (r = -0.36; P = 0.02), with disability glare at 3 years (r = -0.41; P = 0.02), and with best-corrected visual acuity at 6 months (r = -0.34; P = 0.03), but not thereafter. CONCLUSIONS: Vision-related quality of life in patients with Fuchs' endothelial dystrophy is significantly impaired but improves after keratoplasty, irrespective of the technique. The improvement is faster after DSEK than after PK, and this might be explained in part by rapid improvement in uncorrected visual acuity after DSEK. This study affirms an advantage of endothelial keratoplasty over PK with respect to patient-reported outcomes.

Corneal endothelium--past, present, and future.

OBJECTIVE: To review the history of the growth in knowledge about the corneal endothelium. METHODS: Publications concerning the corneal endothelium were reviewed. RESULTS: Highpoints in the growth of knowledge about the corneal endothelium include discovery of barrier and pump functions, specular microscopy, reduction in surgical trauma, corneal preservation, and future advances. CONCLUSIONS: The highpoints in the history of the growth in knowledge about the corneal endothelium were elucidated.

Corneal subbasal nerve density: a comparison of two confocal microscopes.

PURPOSE: To compare subbasal nerve densities estimated from images recorded by the tandem scanning and the ConfoScan 4 confocal microscopes. METHODS: Confocal microscopy was used to estimate subbasal nerve density in 62 corneas of 40 subjects (18 corneas of 18 normal subjects and 44 corneas of 22 patients between 1 and 12 months after LASIK). At each examination, corneas were scanned first by using tandem scanning and then by using a ConfoScan 4 confocal microscope. Subbasal nerves from 2 to 4 scans per cornea were traced by using a semi-automated nerve analysis program. Nerve density was expressed as total nerve length divided by the sample area (microm/mm2). Differences in nerve density between instruments were examined by using paired tests. RESULTS: In normal corneas, subbasal nerve density was 10,658 +/- 5,581 microm/mm2 (mean +/- SD) with the ConfoScan 4 and 5,534 +/- 1,850 microm/mm2 with the tandem scanning microscope (P<0.0001). One to 12 months after LASIK, mean subbasal nerve density was 2,477 +/- 3,514 microm/mm2 estimated with the ConfoScan 4 and 844 +/- 983 microm/mm2 estimated with the tandem scanning (P =0.0003). Estimates of nerve density were correlated between instruments (r = 0.71, P<0.0001), although the mean difference between instruments was 2,308 +/- 3,885 microm/mm2 (P<0.0001). CONCLUSIONS: Mean subbasal nerve density estimated with the ConfoScan 4 was 2 to 3 times higher than density estimated with the tandem scanning confocal microscope. These differences must be considered when comparing subbasal nerve densities between studies that use different confocal microscopes.

Objective measurement of backscattered light from the anterior and posterior cornea in vivo.

PURPOSE: To develop an objective and repeatable method of measuring corneal backscattered light from different depths of the cornea in vivo. METHODS: A modified slit lamp ("scatterometer"), with a video camera and synchronous white strobe light, was used to capture images of a 0.1-mm-wide slit beam through the cornea. Image analysis software was developed to measure backscatter from digitized high-magnification images of 82 normal corneas of 41 subjects. Forty eyes of 20 of the same subjects were examined again after 1 month. Mean backscatter from the anterior, middle, and posterior thirds of the cornea was compared between repeated measurements, and expressed in arbitrary scatter units (SU). RESULTS: Backscatter in the anterior third of the cornea was 451 +/- 42 SU (mean +/- SD, n = 82), from the middle third was 274 +/- 29 SU (n = 82), and from the posterior third was 242 +/- 28 SU (n = 82). The difference in backscatter measured a month apart was 5 +/- 27 SU (P = 0.34), 2 +/- 17 SU (P = 0.42), and 0 +/- 15 SU (P = 0.95) in the anterior, middle, and posterior thirds of the cornea, respectively. Minimum detectable differences between measurements were 12, 8, and 7 SU in the anterior, middle and posterior thirds, respectively (alpha = 0.05, beta = 0.20, n = 40). CONCLUSIONS: Backscatter can be measured at different depths of the cornea from high-magnification digitized images of a narrow slit beam through the cornea. The method is objective and repeatable and can be applied in prospective studies of deep and posterior lamellar keratoplasty.

Femtosecond laser versus mechanical microkeratome for LASIK: a randomized controlled study.

PURPOSE: To compare corneal haze (backscattered light) and visual outcomes between fellow eyes randomized to LASIK with the flap created by a femtosecond laser (bladeless) or with the flap created by a mechanical microkeratome. DESIGN: Randomized, controlled, paired-eye study. PARTICIPANTS: Twenty-one patients (42 eyes) received LASIK for myopia or myopic astigmatism. METHODS: One eye of each patient was randomized to flap creation with a femtosecond laser (IntraLase FS, IntraLase Corp., Irvine, CA) with intended thickness of 120 microm, and the fellow eye to flap creation with a mechanical microkeratome (Hansatome, Bausch & Lomb, Rochester, NY) with intended thickness of 180 microm. Patients were examined before and at 1, 3, and 6 months after LASIK. MAIN OUTCOME MEASURES: Corneal backscatter, high-contrast visual acuity, manifest refractive error, contrast sensitivity, and intraocular forward light scatter were measured at each examination. Flap thickness was measured by confocal microscopy at 1 month, and patients were asked if they preferred the vision in either eye at 3 months. RESULTS: Corneal backscatter was 6% higher after bladeless LASIK than after LASIK with the mechanical microkeratome at 1 month (P = 0.007), but not at 3 or 6 months. High-contrast visual acuity, contrast sensitivity, and forward light scatter did not differ between treatments at any examination. Flap thicknesses at 1 month were 143+/-16 microm (bladeless, mean +/- standard deviation) and 138+/-22 microm (mechanical microkeratome), with no statistical difference in variances. At 3 months, 5 patients preferred the bladeless eye, 7 patients preferred the microkeratome eye, and 9 patients had no preference. CONCLUSIONS: The method of flap creation did not affect visual outcomes during the first 6 months after LASIK. Although corneal backscatter was greater early after bladeless LASIK than LASIK with the mechanical microkeratome, patients did not perceive a difference in vision.

Keratocyte density and recovery of subbasal nerves after penetrating keratoplasty and in late endothelial failure.

OBJECTIVE: To determine central keratocyte and subbasal nerve densities in clear and failed grafts after penetrating keratoplasty. METHODS: Clear grafts and grafts with late endothelial failure (LEF) were examined using confocal microscopy 1 to 31 years after penetrating keratoplasty. Keratocyte density, number of keratocytes in a full-thickness column of stroma, and subbasal nerve density were determined from images. Comparisons were made with normal corneas. RESULTS: The mean +/- SD keratocyte density in clear grafts (22 101 +/- 3799 cells/mm(3)) was lower than that in normal corneas (26 610 +/- 3683 cells/mm(3); P < .001) but did not differ from that in grafts with LEF (21 268 +/- 3298 cells/mm(3); P = .47). The mean +/- SD number of keratocytes in clear grafts (10 325 +/- 1708 cells) was lower than that in normal corneas (11 466 +/- 1503 cells; P < .001) but did not differ from that in grafts with LEF (10 778 +/- 1760 cells; P = .39). Median subbasal nerve density in clear grafts (150 microm/mm(2)) was lower than that in normal corneas (7025 microm/mm(2); P < .001), and nerve recovery correlated with time after surgery (r = 0.36; P < .001). CONCLUSIONS: Keratocyte density and number are decreased in penetrating grafts compared with normal corneas. Subbasal nerve density does not recover to normal through 3 decades.

Confocal microscopy of a femtosecond laser LASIK flap before separation.

PURPOSE: To describe stromal changes after a femtosecond laser laser-assisted in situ keratomileusis (LASIK) flap was created but not separated. DESIGN: Case report. METHODS: As part of a randomized paired-eye study comparing LASIK flap creation by a femtosecond laser to a mechanical microkeratome, a femtosecond laser flap was successfully created on one eye of one patient, but the flap was not separated because of a flap-related complication in the fellow eye. Confocal microscopy of the femtosecond laser flap was performed before and at intervals after it was created. RESULTS: Activated keratocytes and interface haze were visible at one day after femtosecond laser treatment, with gradual resolution toward normal over two months. The femtosecond laser flap was easily separated four months after it was created. CONCLUSIONS: Corneal photodisruption by the femtosecond laser is associated with transient keratocyte activation and corneal haze, but marked wound healing does not occur to hinder flap separation several months later.

Confocal microscopy changes in epithelial and stromal thickness up to 7 years after LASIK and photorefractive keratectomy for myopia.

PURPOSE: To determine the long-term changes in epithelial, stromal, and corneal thickness after LASIK and photorefractive keratectomy (PRK). METHODS: In two prospective observational case series, 11 patients (16 eyes) received LASIK and 12 patients (18 eyes) received PRK to correct myopia or myopic astigmatism. None of the corneas had retreatment procedures. Corneas were examined using confocal microscopy before and at 1 month, and at 1, 2, 3, 5, and 7 years after surgery. Central thicknesses were measured from reflected light intensity profiles recorded by confocal microscopy. Postoperative epithelial thickness was compared to preoperative, and postoperative stromal and corneal thicknesses were compared to thickness at 1 month after surgery. RESULTS: In LASIK, epithelial thickness at 1 month (51 +/- 4 microm, n = 11) was greater than before surgery (41 +/- 4 microm, n = 16; P < .001) and remained thicker through 7 years (52 +/- 6 microm, n = 13; P < .001). Stromal and corneal thickness did not change between 1 month and 7 years after LASIK. After PRK, corneal thickness at 1 year (464 +/- 44 microm, n = 17) was greater than at 1 month (442 +/- 39 microm, n = 15; P = .001) and remained thicker at 7 years after PRK (471 +/- 45 microm, n = 17; P > .001). CONCLUSIONS: The early increase in central epithelial thickness after myopic LASIK persists for at least 7 years and is probably the result of epithelial hyperplasia. Central corneal thickness increases during the first year after PRK and remains stable thereafter up to 7 years.

Corneal keratocyte deficits after photorefractive keratectomy and laser in situ keratomileusis.

PURPOSE: To measure changes in keratocyte density up to five years after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). DESIGN: Prospective, nonrandomized clinical trial. METHODS: Eighteen eyes of 12 patients received PRK to correct a mean refractive error of -3.73 +/- 1.30 diopters, and 17 eyes of 11 patients received LASIK to correct a mean refractive error of -6.56 +/- 2.44 diopters. Corneas were examined by using confocal microscopy before and six months, one year, two years, three years, and five years after the procedures. Keratocyte densities were determined in five stromal layers in PRK patients and in six stromal layers in LASIK patients. Differences between preoperative and postoperative cell densities were compared by using paired t tests with Bonferroni correction for five comparisons. RESULTS: After PRK, keratocyte density in the anterior stroma decreased by 40%, 42%, 45%, and 47% at six months, two years, three years, and five years, respectively (P < .001). At five years, keratocyte density decreased by 20% to 24% in the posterior stroma (P < .05). After LASIK, keratocyte density in the stromal flap decreased by 22% at six months (P < .02) and 37% at five years (P < .001). Keratocyte density in the anterior retroablation zone decreased by 18% (P < .001) at one year and 42% (P < .001) at five years. At five years, keratocyte density decreased by 19% to 22% (P < .05) in the posterior stroma. CONCLUSIONS: Keratocyte density decreases for at least five years in the anterior stroma after PRK and in the stromal flap and the retroablation zone after LASIK.

Changes in corneal thickness in patients with treated and untreated ocular hypertension.

PURPOSE: The elevated intraocular pressure (IOP) in eyes with ocular hypertension is often accompanied by increased corneal thickness. We tested the hypotheses that chronically elevated IOP causes a slow increase in corneal thickness and that lowering the IOP reverses this slow increase. METHODS: Fifty patients with ocular hypertension were randomized to medication and observation groups in the Mayo Clinic site of the Ocular Hypertension Treatment Study. Central corneal thickness was measured using an optical pachymeter at baseline and annually for 6 years. The rates of change of corneal thickness was compared between the groups. Epithelial thickness was measured by confocal microscopy 8 years after the baseline examination. RESULTS: Corneal thickness increased 1.5 +/- 3.3 microm/yr in the observation group (n = 23) and decreased -1.3 +/- 2.8 microm/yr in the medication group (n = 27, P = 0.002). Both rates were significantly different from zero (P = 0.04 and P = 0.02, respectively). Epithelial thickness was 46.4 +/- 4.9 microm in the observation group and 41.3 +/- 4.4 microm in the medication group (P = 0.008). CONCLUSION: Results of this single-center series imply that corneal thickness increases slowly in eyes with ocular hypertension and decreases slowly if the IOP is lowered by topical medications. These phenomena could be explained by a causal relationship between elevated IOP and a slow increase in corneal thickness. A decrease in epithelial thickness accounts for a portion of the thinning that occurs with treatment. If confirmed in a larger series, these findings indicate that the effects of previous treatment on thickness should be considered if corneal thickness is to be used as a discriminant factor in the management of patients with ocular hypertension.

Effects of glaucoma medications on corneal endothelium, keratocytes, and subbasal nerves among participants in the ocular hypertension treatment study.

PURPOSE: To compare subbasal corneal nerve and keratocyte density and endothelial characteristics of ocular hypertensive patients treated with medications or observation. METHODS: Participants in the Ocular Hypertensive Treatment Study (OHTS) randomized at Mayo Clinic to medication or observation were evaluated with specular microscopy annually for 6 years. Confocal microscopy was performed 78 to 108 months after enrollment. Subbasal nerve density was calculated by manual tracing and digital image analysis. Keratocyte density was determined by manual counting methods. Data were compared using a t test and a rank sum test. RESULTS: After 6 years, corneal endothelial cell density, percent hexagonal cells, and coefficient of variation of cell area for the observation (n = 21) and medication groups (n = 26) were similar (2415 +/- 300 vs. 2331 +/- 239 cells/mm; 63% +/- 11% vs. 65% +/- 10%; and 0.32 +/- 0.07 vs. 0.30 +/- 0.06, respectively). Of 38 participants undergoing confocal examination, the medication group (n = 19) had fewer nerves (3.8 +/- 2.1 vs. 5.9 +/- 2.0 nerves/frame; P = 0.02) and a lower nerve density (5643 +/- 2861 vs. 9314 +/- 3743 mum/mm; P = 0.007) than the observation patients (n = 10). An additional 9 patients in the observation group, who began medication before confocal scanning, had intermediate nerve densities. Full-thickness keratocyte density was similar, with 22,257 +/- 2419 and 23,430 +/- 3285 cell/mm in the observation and medication groups, respectively. CONCLUSIONS: Chronic administration of glaucoma medications causes a decrease in the number and density of corneal subbasal nerve fiber bundles but does not affect keratocyte density or corneal endothelial characteristics.

Effect of Graft Thickness on Visual Acuity After Descemet Stripping Endothelial Keratoplasty: A Systematic Review and Meta-Analysis.

PURPOSE: To assess the relationship between graft thickness and best-corrected visual acuity (BCVA) after Descemet stripping endothelial keratoplasty (DSEK). DESIGN: Systematic review and meta-analysis. METHODS: PubMed, EMBASE, Web of Science, and conference abstracts were searched for studies published up to October 2015 with standard systematic review methodology. Eligibility criteria included studies evaluating graft thickness in primary DSEK and visual outcomes. There were no restrictions to study design, study population, or language. Correlation coefficients were pooled using random-effects models. RESULTS: Of 480 articles and conference abstracts, 31 met inclusion criteria (2214 eyes) after full-text review. Twenty-three studies assessed correlations between BCVA and graft thickness, and 8 studies used different statistical methods. All associations were reported dimensionless. Studies generally had small sample sizes and were heterogeneous, especially with respect to data and analysis quality (P = .02). Most studies did not measure BCVA in a standardized manner. The pooled correlation coefficient for graft thickness vs BCVA was 0.20 (95% CI, 0.14-0.26) for 17 studies without data concerns; this did not include 7 studies (815 eyes) that used different statistical methods and did not find significant associations. CONCLUSIONS: There is insufficient evidence that graft thickness is clinically important with respect to BCVA after DSEK, with meta-analysis suggesting a weak relationship. Although well-designed longitudinal studies with standardized measurements of visual acuity and graft thickness are necessary to better characterize this relationship, current evidence suggests that graft thickness is not important for surgical planning.

Corneal endothelium and postoperative outcomes 15 years after penetrating keratoplasty.

PURPOSE: To determine changes in the central endothelium and thickness of grafted corneas and the cumulative probability of developing glaucoma, of graft rejection, and of graft failure 15 years after penetrating keratoplasty. DESIGN: Longitudinal cohort study of 500 consecutive penetrating keratoplasties by one surgeon. METHODS: Regrafted eyes, fellow eyes of bilateral cases, and patients not granting research authorization were excluded, leaving 388 grafts for analysis. At intervals after surgery, we photographed the endothelium and measured corneal thickness using specular microscopy. The presence of glaucoma, graft rejection, and graft failure were recorded. RESULTS: The 67 patients examined at 15 years represented 30% of the available clear grafts. Endothelial cell loss from preoperative donor levels was 71 +/- 12% (mean +/- standard deviation, n = 67), endothelial cell density was 872 +/- 348 cells/mm(2), and corneal thickness was 0.59 +/- 0.06 mm. Endothelial cell density was unchanged between 10 and 15 years, whereas corneal thickness increased (P = .001, n = 55). The mean annual rate of endothelial cell loss from 10 to 15 years after surgery was 0.2 +/- 5.7% (n = 54). The cumulative probability of developing glaucoma, graft rejection, or graft failure was 20%, 23%, and 28%, respectively, and 6 of the 8 graft failures after 10 years resulted from late endothelial failure. CONCLUSIONS: From 10 to 15 years after penetrating keratoplasty, the annual rate of endothelial cell loss was similar to that of normal corneas, corneal thickness increased, and late endothelial failure was the major cause of graft failure.

Recovery of corneal subbasal nerve density after PRK and LASIK.

PURPOSE: To measure and compare the return of corneal innervation up to 5 years after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). DESIGN: Prospective, nonrandomized clinical trial. METHODS: Eighteen eyes of 12 patients received PRK to correct a mean refractive error of -3.73 +/- 1.30 diopters, and 16 eyes of 11 patients received LASIK to correct a mean refractive error of -6.56 +/- 2.44 diopters. Corneas were examined by confocal microscopy before and at 1, 2, 3, and 5 years after the procedures. Subbasal nerve fiber bundles were measured to determine density (visible length of nerve/frame area) and expressed as micrometers per square millimeters. Differences were compared by Friedman's test and adjusted for multiple comparisons by the Student-Newman-Keuls procedure. RESULTS: After PRK, mean subbasal nerve density was reduced by 59% at 1 year (2764 +/- 1321 microm/mm(2) [+/-SD]) when compared with preoperative (6786 +/- 1948 microm/mm(2); P < .001). By 2 years, subbasal nerve density (6242 +/- 1763 microm/mm(2)) was not significantly different from density before PRK and remained unchanged to 5 years (5903 +/- 3086 microm/mm(2)). After LASIK, subbasal nerve density was reduced by 51%, 35%, and 34% at 1, 2, and 3 years, respectively (P < .001). By 5 years, subbasal nerves had returned to densities (4441 +/- 2819 microm/mm(2)) that were not significantly different from densities before LASIK (5589 +/- 2436 microm/mm(2)). CONCLUSION: Corneal subbasal nerve density does not recover to near preoperative densities until 5 years after LASIK, as compared with 2 years after PRK.

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 [microm] within a confocal image [area = 0.166 mm]), 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 microm/mm (range 4735 to 14,018 microm/mm). 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.

Comparison of corneal endothelial cell images from a noncontact specular microscope and a scanning confocal microscope.

PURPOSE: We compared endothelial cell density (ECD) from images recorded by the ConfoScan 3 confocal microscope and a noncontact specular microscope. METHODS: Endothelial micrographs of 50 normal corneas of 25 subjects were acquired by a Konan Noncon Robo noncontact specular microscope (Konan Medical, Inc., Hyogo, Japan) and a ConfoScan 3 confocal microscope (Nidek Technologies, Inc, Greensboro, NC). ECD was determined in images from both instruments by using the HAI CAS System Corners Method (HAI Labs, Inc., Lexington, MA). Distances in the images from both machines were calibrated from images of an external scale. Images from the ConfoScan 3 were also assessed using the automated endothelial analysis software provided by the manufacturer, with and without manual correction. RESULTS: The ECD was 2634 +/- 186 cells/mm(2) (mean +/- SD) and 2664 +/- 173 cells/mm(2) by the Robo and ConfoScan 3 Corners methods, respectively. Differences between these 2 methods were not significant. When the automated analysis software was used, however, significant differences were found (P = 0.001). The uncorrected analysis program provided with the ConfoScan 3 indicated a higher ECD (2742 +/- 284 cells/mm(3)) than the Corners method did with images from the Robo and ConfoScan 3. The ECD from the manually corrected ConfoScan 3 method was 2716 +/- 229 cells/mm(3), not significantly different from the ConfoScan 3 Corners method but significantly different from the Robo Corners method. CONCLUSIONS: The ConfoScan 3 can be used interchangeably with the Robo when the Corners method is used to assess ECD and the magnification of both microscopes is calibrated with an external scale. If the proprietary software provided with the ConfoScan 3 is used, it should be manually corrected.

Changes in Keratocyte Density and Visual Function Five Years After Laser In Situ Keratomileusis: Femtosecond Laser Versus Mechanical Microkeratome.

PURPOSE: To determine the effects of keratocyte loss on optical properties and vision after laser in situ keratomileusis (LASIK) with the flap created with a femtosecond laser or a mechanical microkeratome. DESIGN: Randomized clinical paired-eye study. METHODS: Both eyes of 21 patients received LASIK for myopia or myopic astigmatism. One eye of each patient was randomized by ocular dominance to flap creation with a femtosecond laser and the other eye to flap creation with a mechanical microkeratome. Before LASIK and at 1, 3, and 6 months and 1, 3, and 5 years after LASIK, keratocyte density was measured using confocal microscopy, and high-contrast visual acuity and anterior corneal wavefront aberrations were measured by standard methods. At each visit, all variables were compared between methods of creating the flap and to the same variable before treatment using paired tests with Bonferroni correction for multiple comparisons. RESULTS: Keratocyte density in the flap decreased by 20% during the first year after LASIK and remained low through 5 years (P < .001). High-order wavefront aberrations increased and uncorrected visual acuity improved immediately after surgery, but these variables did not change further to 5 years. There were no differences in any variables between treatments. CONCLUSIONS: A sustained reduction in keratocyte density does not affect vision or optical properties of the cornea through 5 years after LASIK. The method of creating a LASIK flap does not influence the changes in keratocyte density in the flap.

Predicting endothelial cell loss and long-term corneal graft survival.

PURPOSE: To evaluate a biexponential decay model for describing the loss of corneal endothelial cells with age as well as the increased loss of cells after cataract surgery and penetrating keratoplasty. METHODS: Data from previous studies were identified and the sum of two exponentials, d = p. exp(-at) + q. exp(-bt) (where d is cell density at time t, p and q are constants the sum of which is equal to the initial cell density, and a and b are exponential rate constants), fitted to each data set by a nonlinear least-squares algorithm. Goodness of fit was indicated by the residual standard deviation. Half times were calculated from the exponential rate constants. RESULTS: The model identified in each instance a rapid and a slow component to the cell loss. The half time for the slow component of the loss with age was 224 years, underlining the excess endothelial capacity in normal eyes. After surgery, the rapid component of the cell loss was probably due to surgical trauma and, after penetrating keratoplasty, cell-mediated rejection and other complications. The half times of the slow component were only 26 years after cataract surgery and 21 years after penetrating keratoplasty. DISCUSSION: The loss of endothelial cells followed a biexponential decay and could thus be described by a single equation. The half times of the slow component of the cell loss after surgery were substantially less than for the loss with age, indicating a markedly increased rate of cell loss that persisted for many years after surgery. A mechanism for this accelerated cell loss is suggested that involves a nonspecific, innate response initiated by the breakdown of the blood-ocular barrier. The model was used to calculate endothelial cell loss in the long term after penetrating keratoplasty and to predict when cell density would reach levels that are incompatible with maintenance of transparency and graft function. Thus, a rationale is presented for the setting of minimum donor cell densities by eye banks.

Reinnervation in the cornea after LASIK.

PURPOSE: Nerve fibers in the cornea are disrupted by photorefractive procedures. In this study, the denervation and reinnervation of human central corneas were evaluated by sequential, quantitative measurements of nerves viewed by confocal microscopy in vivo during the first year after LASIK. METHODS: Seventeen eyes were studied of 11 patients who had undergone LASIK to correct myopia from -2.0 D to -11.0 D. Eyes were treated with an excimer laser with a planned 180- micro m flap. Central corneas were scanned throughout their full thicknesses by confocal microscopy before and at 1 week and 1, 3, 6, and 12 months after LASIK. Nerve fiber bundles appeared as bright, well-defined, linear structures that were sometimes branched and usually appeared in several consecutive frames. The number of nerve fiber bundles per scan in two to eight scans per eye per visit was determined in the subbasal region, the full-thickness stroma, the stromal flap (layer between the most anterior keratocyte and the flap interface), and the stromal bed (layer between the flap interface and the endothelium). RESULTS: In the subbasal region, the number of nerve fiber bundles decreased by more than 90% 1 week after LASIK and was significantly lower at all times after surgery than it was before surgery (P < 0.001). It increased 6 and 12 months after LASIK, but remained less than half of the preoperative value. In the stromal flap, the number of nerves at all times after surgery was also significantly less than before surgery (P < 0.001) and did not increase significantly by 1 year. In the stromal bed, there were no significant differences among any of the nerve measurements before and after LASIK (P = 0.24). CONCLUSIONS: In the corneal flap, the number of subbasal and stromal nerve fiber bundles decreases by 90% immediately after LASIK. During the first year after LASIK, subbasal nerve fiber bundles gradually return, although by 1 year their number remains less than half of that before LASIK.