Eye Dynamics and Engineering Network Consortium: Baseline Characteristics of a Randomized Trial in Healthy Adults.

PURPOSE: To improve understanding of intraocular pressure (IOP) and its variance, this project identifies systemic and ocular characteristics of healthy eyes of adult volunteers including IOP variation, ocular biometrics, and aqueous humor dynamics (AHDs). These data serve as baseline controls for further studies from the Eye Dynamics and Engineering Network (EDEN) Consortium. DESIGN: Multicenter open-label clinical trial in healthy adults randomized to 1 week treatment with 2 approved glaucoma drugs in a crossover design. PARTICIPANTS: Among 135 healthy participants, 122 participants (aged 55.2 ± 8.8 years; 92 females, 30 males) completed the protocol. METHODS: Participants from the University of Michigan, Mayo Clinic, and University of Nebraska Medical Center underwent measurements of ocular biometrics, AHD, and IOP using 4 tonometers. Intraocular pressure data during 3 study visits without glaucoma medications were used in the analysis. The PhenX Toolkit survey acquired standardized data on medical history, surgical history, medications, smoking and alcohol exposures, and physical measures. MAIN OUTCOME MEASURES: The variability of IOP measurements within eyes was assessed as visit-to-visit IOP variation, within-visit IOP variation, and within-visit positional IOP variation. The concordance (or correlation) between eyes was also assessed. RESULTS: Average positional change of > 4.7 mmHg was detected with a range of 0.5-11.0 mmHg. Pearson correlation of IOP between eyes within a visit was 0.87 (95% confidence interval [CI], 0.82-0.91) for Goldmann applanation tonometry, 0.91 (95% CI, 0.88-0.94) for Icare rebound tonometry, and 0.91 (95% CI, 0.88-0.94) for pneumatonometry. There was a 4% to 12% asymmetric fluctuation of 3 mmHg or more between eyes between visits using rebound tonometry, 9% with Goldmann applanation tonometry, and 3% to 4% by pneumotonometry. The coefficient of variation between visits for the same eye ranged from 11.2% to 12.9% for pneumatonometry, from 13.6% to 17.4% for rebound tonometry, and 15.8% to 16.2% for Goldmann applanation tonometry. CONCLUSIONS: The current study from the EDEN Consortium describes measurement methods and data analyses with emphasis on IOP variability. Future papers will focus on changes in ocular biometrics and AHD with timolol or latanoprost treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Tear Exchange, Intraocular Pressure, and Wear Characteristics of Quadrant-specific Versus Spherical Haptic Scleral Lenses.

OBJECTIVES: To compare scleral lenses (SLs) with a quadrant-specific (study lens) or a spherical (habitual lens) landing zone in a crossover study. METHODS: Seven participants (eight eyes) wore each of two lenses for 2 weeks before measurements. We measured visual acuity, contrast sensitivity, intraocular pressure (IOP), fluid reservoir clearance, corneal thickness, tear exchange, and lens experience. Variables were compared between lenses and before and after 2 hr of wear. RESULTS: The visual acuity was not different between the study lens, 0.12 logarithm of the minimum angle of resolution (logMAR), and habitual lens, 0.18 logMAR (median, P = 1.0). Contrast sensitivity was 1.3% under the study lens and 1.6% under the habitual lens ( P = 0.94). IOP did not change after 2 hr of wear for either lens (study lens, P = 0.33 and habitual lens, P = 0.74), and corneal thickness did not change during wear of either lens ( P = 0.44). The fluorescein concentration under the study lens did not change after 2 hr (99% of initial concentration; P = 0.84) but decreased to 46% of initial concentration under the habitual lens ( P = 0.008). Lens comfort was slightly better with the study lens (5.0 vs. 4.0, respectively; P = 0.05). CONCLUSIONS: SLs with spherical or quadrant-specific landing zones provide good vision and do not affect IOP or corneal thickness. However, tear exchange is greater under spherical lenses than under quadrant-specific lenses. The quadrant-specific lens provides greater patient comfort.

Effect of Topical Phenylephrine 2.5% on Episcleral Venous Pressure in Normal Human Eyes.

Purpose: Phenylephrine has been shown to affect intraocular pressure (IOP) but the mechanism of action is poorly understood. However, its action as a vasoconstrictor suggests possible effects on episcleral venous pressure (EVP). In this study, we evaluated the effect of phenylephrine on EVP and IOP in healthy subjects. Methods: Forty eyes of 20 subjects were included. Each subject received 3 drops of phenylephrine 2.5% in one eye at 1-minute intervals. The fellow eye served as control. Blood pressure, heart rate, and IOP and EVP of both eyes were measured at baseline, 15 minutes, and 60 minutes after instillation of phenylephrine. IOP was measured by pneumatonometry. EVP was assessed by using a computer-controlled episcleral venomanometer. Changes in IOP, EVP, blood pressure, and heart rate at 15 and 60 minutes were analyzed by paired t-tests. Results: IOP increased 15 minutes after instillation of phenylephrine in both treated (P = 0.001) and control eyes (P = 0.01) and returned to baseline at 60 minutes. The change in IOP at 15 minutes was not significantly different between the 2 groups. EVP in treated eyes was unchanged at 15 minutes (P = 0.8) but decreased significantly at 60 minutes (P < 0.001). In control eyes, there was no change in EVP at any time (P > 0.6). There were no significant changes from baseline in systolic and diastolic blood pressure and heart rate after instillation of phenylephrine. Conclusions: IOP elevation associated with topical phenylephrine is not caused by an increase in EVP in healthy subjects. Instead, EVP decreases with phenylephrine, but the mechanism remains to be determined.

Effect of Timolol on Aqueous Humor Outflow Facility in Healthy Human Eyes.

PURPOSE: Hyposecretion of aqueous humor has been postulated to adversely affect the health of the trabecular meshwork and outflow resistance. However, the effect of medications that reduce aqueous humor production on outflow facility in living human eyes is unclear. This study evaluated the effect of timolol, an aqueous humor flow suppressant, on outflow facility in healthy eyes. DESIGN: Prospective, before-and-after study. METHODS: In a multicenter study, 113 healthy participants over 40 years of age were included. Intraocular pressure (IOP) was measured with the participant in the sitting position by using a pneumatonometer. The outflow facility was measured with the participant in the supine position by 2-minute pneumatonography. After participants self-administered drops of timolol 0.5% for 1 week, twice daily in each eye, both measurements were repeated. RESULTS: Mean IOP decreased from 15.1 ± 3.0 mm Hg at baseline to 12.4 ± 2.4 mm Hg (P < 0.001) after 1 week of timolol use. Mean outflow facility decreased from 0.23 ± 0.08 µL/min/mm Hg at baseline to 0.18 ± 0.08 µL/min/mm Hg (P < 0.001) after timolol. The change in outflow facility was negatively correlated with baseline outflow facility (r = -0.51; P < 0.001). CONCLUSIONS: Timolol reduces outflow facility in healthy human eyes, and this effect is greater in eyes with higher baseline outflow facility. This phenomenon may be related to reduced aqueous humor flow, but the precise mechanism remains to be determined.

The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a Randomized Study in Humans.

PURPOSE: Netarsudil, an inhibitor of Rho kinase and a norepinephrine transporter, has been shown to lower elevated intraocular pressure (IOP) in controlled studies of patients with open-angle glaucoma and ocular hypertension, and in healthy volunteers. The mechanism of this ocular hypotensive effect in humans is unknown. METHODS: The objective of this study was to evaluate the effect of netarsudil 0.02% on aqueous humor dynamics (AHD) parameters. In this double-masked, vehicle-controlled, paired-eye comparison study, 11 healthy volunteers received topical netarsudil ophthalmic solution 0.02% or its vehicle once daily for 7 days (morning dosing). The primary endpoints were the change in AHD parameters, compared between active and vehicle-treated eyes. RESULTS: In netarsudil-treated eyes, diurnal outflow facility increased from 0.27 ± 0.10 µL/min/mmHg to 0.33 ± 0.11 µL/min/mmHg (+22%; P = 0.02) after 7 days of treatment. In placebo-treated eyes, diurnal outflow facility did not significantly change (P = 0.94). The difference between netarsudil and placebo eyes in diurnal change of outflow facility was 0.08 µL/min/mmHg (P < 0.001). Diurnal episcleral venous pressure (EVP) in netarsudil-treated eyes decreased from 7.9 ± 1.2 mmHg to 7.2 ± 1.8 (-10%; P = 0.01). Diurnal EVP was not significantly different between netarsudil- and placebo-treated eyes. There was a trend toward decreasing aqueous humor flow rate (-15%; P = 0.08). No treatment changes were seen in uveoscleral outflow rate. CONCLUSIONS: Once-daily dosing of netarsudil ophthalmic solution 0.02% lowered IOP through increasing trabecular outflow facility and reducing EVP. This suggests a combination of mechanisms that affect both the proximal and distal outflow pathways.

Corneal Optical Changes Associated with Induced Edema in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: Patients with Fuchs endothelial corneal dystrophy (FECD) often notice poor vision in the morning that improves as the day progresses. In this study, we determined changes in corneal optical properties associated with induced corneal edema. METHODS: Twenty-three phakic eyes (23 participants) with FECD (grades 1-6, modified Krachmer scale) and 8 normal eyes (8 participants) were examined by Scheimpflug photography. Central corneal thickness, high-order aberrations from anterior and posterior corneal surfaces, and backscatter from the anterior, mid-, and posterior cornea were determined from the Scheimpflug images. A low-oxygen permeable contact lens was placed on the eye, and eyes were closed for 2 hours, after which the lens was removed and Scheimpflug photography was repeated for up to 5 hours to determine changes in backscatter and high-order aberrations. RESULTS: Corneas swelled by 10% [95% confidence interval (CI), 9-10]. Backscatter from the anterior cornea increased by 416 scatter units (SU, 95% CI, 344-488; P < 0.001), independent of the presence and severity of FECD. Recovery of anterior backscatter was slower in advanced FECD (81 SU/h, 95% CI, 60-120) compared with normal (123 SU/h, 95% CI, 95-150; P = 0.019). Anterior and posterior corneal high-order aberrations, and mid and posterior backscatter, did not increase with induced swelling. CONCLUSIONS: Inducing corneal edema increases anterior corneal backscatter but not high-order aberrations. Subjective poor vision in the morning in FECD is probably caused by scattered light rather than by high-order aberrations, suggesting that these patients experience more disability glare than decreased visual acuity.

Effect of Body Position on Epsicleral Venous Pressure in Healthy Subjects.

Purpose: The mechanism of IOP change during a body position change is poorly understood. In this study, we investigated changes in episcleral venous pressure (EVP) between two body positions, sitting and inclined, and compared this with changes in IOP. Methods: This study was a prospective, comparative case series of 43 eyes of 24 healthy volunteers. IOP was measured using a pneumatonometer in the seated position. EVP was then measured in a selected episcleral vein by using an automated, slit-lamp-mounted venomanometer. Thirty minutes later, the subject was placed in an inclined position with the neck extended and the head resting on the chin rest of the slit lamp. After 5 minutes, IOP and EVP in the same vein were remeasured. EVP in the inclined position was compared with EVP in the seated position, and the change in IOP was compared with the change in EVP. Statistical significance was determined using generalized estimating equation models. Results: Mean IOP increased from 11.4 ± 3.0 mm Hg (mean ± SD) in the sitting position to 13.1 ± 3.4 mm Hg in the inclined position (P < 0.001). Mean EVP increased from 6.4 ± 1.4 mm Hg in the sitting position to 7.8 ± 1.7 mm Hg in the inclined position (P < 0.001). The postural rise in IOP was not different from the rise in EVP (P = 0.18). Conclusions: In the inclined position, IOP and EVP are higher than they are in the sitting position. The posture-induced rise in IOP can be attributed to an increase in EVP.

In Vivo Noninvasive Measurement of Young's Modulus of Elasticity in Human Eyes: A Feasibility Study.

PURPOSE: Abnormal ocular biomechanical properties may be important for understanding the risk of glaucoma. However, there are no clinical methods for measuring standard material properties in patients. In this feasibility study we demonstrated proof-of-principle for a novel method, ultrasound surface wave elastography (USWE), to determine the in vivo Young's modulus of elasticity of corneas in normal human eyes. METHODS: In total, 20 eyes of 10 healthy subjects (mean age, 51.4±7.2; ±SD; range, 43 to 64 y) were studied. A spherical-tipped probe (3-mm diameter) was placed on closed eyelids and generated a gentle harmonic vibration at 100 Hz for 0.1 second. Wave speed propagation in the cornea was measured by USWE, and Young's modulus was calculated from the wave speed. Associations between Young's modulus and intraocular pressure (IOP), age, central corneal thickness, and axial length were explored by the Pearson correlation. Statistical significance was determined by using generalized estimating equation models to account for possible correlation between fellow eyes. RESULTS: Mean IOP was 12.8±2.7 mm Hg. Mean wave speed in the cornea was 1.82±0.10 m/s. Young's modulus of elasticity was 696±113 kPa and was correlated with IOP (r=0.57; P=0.004), but none of the other variables (P>0.1). CONCLUSIONS: USWE is a novel noninvasive technique for measuring ocular biomechanical properties. Corneal Young's modulus in normal eyes is associated with IOP, consistent with measurements in cadaver eyes. Further work is needed to determine elasticity in other ocular tissues, particularly the sclera, and if elasticity is altered in glaucoma patients.

Comparison of Aqueous Outflow Facility Measurement by Pneumatonography and Digital Schiøtz Tonography.

Purpose: It is not known if outflow facilities measured by pneumatonography and Schiøtz tonography are interchangeable. In this study we compared outflow facility measured by pneumatonography to outflow facility measured by digital Schiøtz tonography. Methods: Fifty-six eyes from 28 healthy participants, ages 41 to 68 years, were included. Intraocular pressure (IOP) was measured in the sitting and supine positions with a pneumatonometer. With the subject in the supine position, IOP was recorded for 2 minutes by using a pneumatonometer with a 10-g weight and for 4 minutes by using a custom digital Schiøtz tonometer. Outflow facility was determined from the changes in pressure and intraocular volume and a standard assumed ocular rigidity coefficient for each instrument, respectively, and by using an ocular rigidity coefficient calculated by measuring pressure without and with a weight added to the pneumatonometer tip. Results: The outflow facility was 0.29 ± 0.09 µL/min/mm Hg by Schiøtz tonography and 0.24 ± 0.08 µL/min/mm Hg by pneumatonography (P < 0.001) when using the standard assumed constant ocular rigidity coefficient. Mean calculated ocular rigidity coefficient was 0.028 ± 0.01 µL-1, and outflow facility determined by using this coefficient was 0.23 ± 0.08 µL/min/mm Hg by Schiøtz tonography and 0.21 ± 0.07 µL/min/mm Hg by pneumatonography (P = 0.003). Outflow facilities measured by the two devices were correlated when the ocular rigidity was assumed (r = 0.60, P < 0.001) or calculated (r = 0.70, P < 0.001). Conclusions: Outflow facilities measured by pneumatonography were correlated with those measured by Schiøtz tonography, but Schiøtz tonography reported approximately 10% to 20% higher facilities when using the standard method. When ocular rigidity was determined for each eye, differences were smaller. Measurements from these devices cannot be compared directly.

Unconventional aqueous humor outflow: A review.

Aqueous humor flows out of the eye primarily through the conventional outflow pathway that includes the trabecular meshwork and Schlemm's canal. However, a fraction of aqueous humor passes through an alternative or 'unconventional' route that includes the ciliary muscle, supraciliary and suprachoroidal spaces. From there, unconventional outflow may drain through two pathways: a uveoscleral pathway where aqueous drains across the sclera to be resorbed by orbital vessels, and a uveovortex pathway where aqueous humor enters the choroid to drain through the vortex veins. We review the anatomy, physiology and pharmacology of these pathways. We also discuss methods to determine unconventional outflow rate, including direct techniques that use radioactive or fluorescent tracers recovered from tissues in the unconventional pathway and indirect methods that estimate unconventional outflow based on total outflow over a range of pressures. Indirect methods are subject to a number of assumptions and generally give poor agreement with tracer measurements. We review the variety of animal models that have been used to study conventional and unconventional outflow. The mouse appears to be a promising model because it captures several aspects of conventional and unconventional outflow dynamics common to humans, although questions remain regarding the magnitude of unconventional outflow in mice. Finally, we review future directions. There is a clear need to develop improved methods for measuring unconventional outflow in both animals and humans.

Corneal Hydration Control in Fuchs' Endothelial Corneal Dystrophy.

PURPOSE: To assess corneal hydration control across a range of severity of Fuchs' endothelial corneal dystrophy (FECD) by measuring the percent recovery per hour (PRPH) of central corneal thickness after swelling the cornea and to determine its association with corneal morphologic parameters. METHODS: Twenty-three corneas of 23 phakic FECD patients and 8 corneas of 8 healthy control participants devoid of guttae were graded (modified Krachmer scale). Effective endothelial cell density (ECDe) was determined from the area of guttae and local cell density in confocal microscopy images. Steady-state corneal thickness (CTss) and standardized central corneal backscatter were derived from Scheimpflug images. Corneal swelling was induced by wearing a low-oxygen transmissible contact lens for 2 hours in the morning. De-swelling was measured over 5 hours after lens removal or until corneal thickness returned to CTss. Percent recovery per hour was 100 × (1 - e-k), where k was determined from CT(t) = (de-kt) + CTss, and where d was the initial change from CTss. RESULTS: After contact lens wear, corneas swelled by 9% (95% CI 9-10). Percent recovery per hour was 49%/h (95% CI 41-57) in controls and 37%/h in advanced FECD (95% CI 29-43, P = 0.028). Low PRPH was associated with disease severity, low ECDe, and increased anterior and posterior corneal backscatter. Anterior backscatter was associated with PRPH in a multivariable model (R2 = 0.44). CONCLUSIONS: Corneal hydration control is impaired in advanced FECD and is inversely related to anterior corneal backscatter. Anterior corneal backscatter might serve as an indicator of impaired endothelium in FECD.

Measuring Corneal Haze by Using Scheimpflug Photography and Confocal Microscopy.

PURPOSE: We compared corneal backscatter estimated from a Scheimpflug camera with backscatter estimated from a clinical confocal microscope across a wide range of corneal haze. METHODS: A total of 59 corneas from 35 patients with a range of severity of Fuchs' endothelial corneal dystrophy and 15 corneas from 9 normal participants were examined using a Scheimpflug camera (Pentacam) and a confocal microscope (ConfoScan 4). The mean image brightness from the anterior 120 µm, midcornea, and posterior 60 µm of the cornea across the central 2 mm recorded by the Scheimpflug camera and analogous regions from the confocal microscope were measured and standardized. Differences between instruments and correlations between backscatter and disease severity were determined by using generalized estimating equation models. RESULTS: Backscatter measured by the two instruments in the anterior and midcornea were correlated (r = 0.67 and 0.43, respectively, P < 0.001), although in the posterior cornea they were not correlated (r = 0.13, P = 0.66). Measured with the Scheimpflug camera, mean backscatter from the anterior and midcornea were greater, whereas backscatter from the posterior cornea was lower (P < 0.001) than that measured by the confocal microscope. Backscatter from the anterior cornea was correlated with disease severity for both instruments (Scheimpflug, r = 0.55, P < 0.001; confocal, r = 0.49, P = 0.003). CONCLUSIONS: The Scheimpflug camera and confocal microscope should not be used interchangeably to measure corneal haze. The ability to detect changes in backscatter with disease severity is superior with the Scheimpflug camera. However, the confocal microscope provides higher resolution of corneal structure.

Intraocular Pressure After 2 Hours of Small-Diameter Scleral Lens Wear.

OBJECTIVES: Compression of episcleral veins or deformation of tissue in the Schlemm's canal beneath the landing zone of scleral lenses could elevate intraocular pressure (IOP). We examined the effect of 2 hr of small-diameter scleral lens wear on IOP. METHODS: Twenty-nine participants, 29 ± 6 years old (mean ± SD) who experienced no history of eye disease or scleral lens wear, were included in the study. Each participant was fitted with a 15-mm Jupiter scleral lens on one eye (study eye). Intraocular pressure was measured in both eyes by pneumatonometry centrally on the cornea and peripherally on the sclera. The lens was then placed on one eye and was worn for 2 hr. Intraocular pressure was remeasured immediately after lens placement, at 1 and 2 hr of lens wear, and immediately after lens removal. Intraocular pressure after removal of the scleral lens was compared with IOP before placing the lens and to IOP in the control eye using paired t tests. RESULTS: Immediately after removing the scleral lens, mean central IOP in the study eye (13.9 ± 3.1 mm Hg) was not different from mean central IOP in the control eye (13.5 ± 2.2 mm Hg, P = 0.4) or in the same eye before lens wear (13.6 ± 1.9 mm Hg, P = 0.6). There were also no differences in IOP measured peripherally at 2 hr of lens wear (P = 0.8). CONCLUSIONS: Neophyte scleral lens wear of a 15-mm scleral lens for 2 hr does not increase IOP in healthy eyes.

Descemet Stripping Endothelial Keratoplasty for Fuchs' Endothelial Corneal Dystrophy: Five-Year Results of a Prospective Study.

PURPOSE: To determine 5-year outcomes of Descemet stripping endothelial keratoplasty (DSEK) for Fuchs' endothelial corneal dystrophy (FECD). DESIGN: Prospective cohort study. PARTICIPANTS: Fifty-two eyes of 45 subjects with FECD undergoing primary DSEK. METHODS: Subjects were examined before and at fixed intervals through 60 months after DSEK. At each visit, graft survival was determined by slit-lamp examination; best spectacle-corrected visual acuity (BSCVA) was measured using the electronic Early Treatment Diabetic Retinopathy Study (ETDRS) protocol; total anterior corneal higher-order aberrations (HOAs) were derived from corneal topography; and corneal backscatter, corneal thickness, and endothelial cell density were measured from confocal microscopy images. Corneal thickness also was measured by ultrasonic pachymetry. Changes after DSEK were analyzed using generalized estimating equation models. MAIN OUTCOME MEASURES: Best-corrected visual acuity, HOAs, endothelial cell loss, corneal thickness, and corneal backscatter. RESULTS: Complete 60-month follow-up was possible in 34 eyes. Mean BSCVA±standard deviation improved from 0.45±0.19 logarithm of the minimum angle of resolution (logMAR) (Snellen equivalent, 20/56) before DSEK to 0.09±0.13 logMAR (Snellen equivalent, 20/25) at 5 years (P < 0.001). Between 1 and 5 years, BSCVA improved by 0.06 logMAR (or 3 ETDRS letters; 95% confidence interval, 0.05-0.07 logMAR) per year (P < 0.001), and 56% of eyes were 0.1 logMAR (20/25) or better at 5 years. Graft thickness (approximately 155 µm) and corneal thickness (approximately 700 µm) did not change after surgery. Anterior corneal HOAs and backscatter decreased between 1 and 5 years (P ≤ 0.002). Six grafts failed, of which 4 were primary (iatrogenic); mean endothelial cell loss±standard deviation was 55±15% at 5 years. CONCLUSIONS: Between 1 and 5 years after DSEK, BSCVA continues to improve such that at 5 years, more than half of eyes see better than 20/25 with a mean total corneal thickness of 700 µm. Improvement in vision is accompanied by continued reduction in corneal haze and aberrations, suggesting ongoing remodeling of the cornea after restoration of endothelial function.

Directional Posterior Corneal Profile Changes in Fuchs' Endothelial Corneal Dystrophy.

PURPOSE: To determine directional changes in peripheral corneal thickness and corneal astigmatism over a range of severity of Fuchs' endothelial corneal dystrophy (FECD). METHODS: Eyes with FECD were categorized as mild, moderate, or advanced according to the area and confluence of guttae and the presence of clinical edema. Normal corneas were devoid of guttae. Peripheral thickness centered on the corneal apex, and radii of posterior curvature were measured with Scheimpflug imaging. Variables were compared between groups by using generalized estimating equation models. RESULTS: Scheimpflug images were acquired in 101 normal corneas and 112 corneas with FECD. Normal corneas were 8.6 ± 4.8 µm thicker vertically than horizontally (P = 0.001); the steep posterior meridian was vertical in 91% of corneas. The difference between vertical and horizontal thicknesses decreased to 4.7 ± 7.3 µm in advanced FECD (P = 0.008); 46% had a steep vertical posterior meridian (P = 0.001). Vertical radius of curvature was flatter than normal in moderate (by 0.2 mm, P = 0.011) and advanced (by 0.4 mm, P < 0.001) FECD. Mean posterior corneal power was less negative in moderate (by 0.2 diopters [D], P = 0.009) and advanced (by 0.4 D, P < 0.001) FECD compared to normal. CONCLUSIONS: Posterior toricity is abnormal in advanced FECD because of relatively greater horizontal than vertical corneal thickening. Posterior corneal power decreases (i.e., is less negative) in moderate and advanced FECD, which can affect the choice of intraocular lens power during cataract surgery, and might explain the hyperopic shift after Descemet membrane endothelial keratoplasty.

Corneal High-Order Aberrations and Backscatter in Fuchs' Endothelial Corneal Dystrophy.

PURPOSE: Suboptimal visual acuity after endothelial keratoplasty has been attributed to increased anterior corneal high-order aberrations (HOAs). In this study, we determined anterior and posterior corneal HOAs over a range of severity of Fuchs' endothelial corneal dystrophy (FECD). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 108 eyes (62 subjects) with a range of severity of FECD and 71 normal eyes (38 subjects). METHODS: All corneas were examined by using slit-lamp biomicroscopy to determine the severity of FECD versus normality. Fuchs' endothelial corneal dystrophy corneas were categorized as mild, moderate, or advanced according to the area and confluence of guttae and the presence of clinically visible edema. Normal corneas were devoid of any guttae. Wavefront errors from the anterior and posterior corneal surfaces were derived from Scheimpflug images and expressed as Zernike polynomials through the sixth order over a 6-mm diameter optical zone. Backscatter from the anterior 120 µm and posterior 60 µm of the cornea also was measured from Scheimpflug images and was standardized to a fixed scatter source. Variables were compared between FECD and control eyes by using generalized estimating equation models to adjust for age and correlation between fellow eyes. MAIN OUTCOME MEASURES: High-order aberrations, expressed as root mean square of wavefront errors, and backscatter of the anterior and posterior cornea. RESULTS: Total anterior corneal HOAs were increased in moderate (0.61±0.27 µm, mean ± standard deviation; P = 0.01) and advanced (0.66±0.28 µm; P = 0.01) FECD compared with controls (0.47±0.16 µm). Total posterior corneal HOAs were increased in mild (0.22±0.09 µm; P = 0.017), moderate (0.22±0.08 µm; P < 0.001), and advanced (0.23±0.09 µm; P < 0.001) FECD compared with controls (0.16±0.03 µm). Anterior and posterior corneal backscatter were higher for all severities of FECD compared with controls (P ≤ 0.02, anterior; P ≤ 0.001, posterior). CONCLUSIONS: Anterior and posterior corneal HOAs and backscatter are higher than normal even in early stages of FECD. The early onset of HOAs in FECD might contribute to the persistence of HOAs and incomplete visual rehabilitation after endothelial keratoplasty.

Effect of topical anesthesia on episcleral venous pressure in normal human subjects.

PURPOSE: Topical anesthetics can reduce episcleral venous pressure (EVP) and IOP in rabbits. In this study, we investigated the effect of topical anesthesia on EVP in normal human subjects. METHODS: We included in this study 30 eyes of 15 healthy volunteers who were habitual soft contact lens wearers. The EVP was measured before and at 5 and 10 minutes after instillation of topical proparacaine 0.5% in one eye. The EVP was measured by using a custom objective venomanometer. We compared EVP at 5 and 10 minutes after proparacaine to EVP before instilling proparacaine. RESULTS: There was no significant difference between EVP in eyes receiving topical anesthetic at 5 or 10 minutes (7.2 ± 2.2 and 7.6 ± 2.7 mm Hg, respectively; mean ± SD) compared to contralateral eyes (6.9 ± 2.5 and 7.3 ± 2.6 mm Hg, respectively; P > 0.10). As well, EVP was not significantly different 5 or 10 minutes after topical anesthesia compared to baseline in either the eyes receiving anesthetic or the contralateral eyes (all P > 0.10; minimum detectable difference, 1.4-1.9 mm Hg, α = 0.05, ß = 0.20, n = 30 eyes). CONCLUSIONS: The EVP in human eyes is not affected significantly by topical anesthetics.

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.

Corneal abnormalities early in the course of Fuchs' endothelial dystrophy.

PURPOSE: Corneas with advanced Fuchs' endothelial dystrophy that require endothelial keratoplasty manifest anterior corneal structural and cellular abnormalities that have been associated with visual deficits before and after endothelial keratoplasty. In this study, we determined the onset of these abnormalities in the course of the disease. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty-three eyes (39 subjects) with a range of severity of Fuchs' dystrophy and 25 eyes (13 subjects) with normal corneas. METHODS: All corneas were examined using slit-lamp biomicroscopy, ultrasonic pachymetry, and confocal microscopy. The clinical grade of Fuchs' dystrophy was assessed according to the presence and extent of guttae and clinically evident edema and was categorized as mild (grades 1 and 2), moderate (grades 3 and 4), or advanced (grades 5 and 6). Normal corneas were devoid of any central guttae (grade 0). Corneal backscatter (haze) was measured from the confocal image light intensity profile. Stromal cell density and number and the presence of abnormal subepithelial cells were determined from confocal images. Comparisons between groups were made by using generalized estimating equation models. MAIN OUTCOME MEASURES: Anterior corneal backscatter, stromal cell density and number, presence of subepithelial cells, and central corneal thickness. RESULTS: Anterior corneal backscatter was 18% to 67% higher in eyes with moderate and advanced Fuchs' dystrophy compared with normal eyes (P ≤ 0.003); a similar trend was noted in mild Fuchs' dystrophy eyes compared with normal eyes (P = 0.08). Stromal cell density and the absolute number of stromal cells in the anterior 10% of the stroma were approximately 20% and 27% lower, respectively, in Fuchs' dystrophy (regardless of severity) compared with normal (P < 0.001). Abnormal subepithelial cells were visible in 9%, 19%, and 30% of corneas with mild, moderate, and advanced Fuchs' dystrophy, respectively. Only corneas with advanced Fuchs' dystrophy were thicker than normal (P < 0.001). CONCLUSIONS: Anterior corneal cellular and structural abnormalities begin early in the course of Fuchs' dystrophy, before the onset of clinically evident edema. The chronicity of these changes can explain their incomplete resolution after endothelial keratoplasty, and understanding the onset of these may help to determine the optimal time to intervene to achieve best outcomes.