Central corneal thickness measurements: using an ultrasonic instrument and 4 optical instruments.

PURPOSE: Both between-session and within-session repeatability were determined for measurement of corneal thickness with the following techniques: ultrasound pachymetry (UP), confocal microscopy (CS), Orbscan pachymetry (ORB), spectral oscillation interferometry (SOI), and optical coherence tomography (OCT). METHODS: The right eyes of 20 normal subjects were tested on 2 different days. For each session, 2 central corneal thickness measurements were determined using the ConfoScan 3 microscope, the Orbscan system, and the Stratus OCT system; 5 measurements were found with the Sonogage ultrasound pachymeter; and between 2 and 10 measurements were found with the SOI system. RESULTS: This study showed that SOI had the best repeatability, whereas CS had the worst repeatability for both within-session and between-session repeatability. Based on 95% limits of agreement (LoA), the within-session repeatability can be ranked as: (1) SOI; (2) UP; (3) OCT; (4) Orbscan pachymetry; and (5) CS. SOI had a bias of 0.13 and 95% LoA of -1.07 to 1.33, whereas UP had a bias of -0.98 and 95% LoA of -7.35 to 5.40. The between-session repeatability of the instruments can be ranked as: (1) SOI; (2) OCT; (3) UP; (4) Orbscan pachymetry; and (5) CS. Of the optical methods, SOI had the best repeatability with a bias of 1.26 and 95% LoA of -6.14 to 8.66, followed by OCT with a bias of 0.75 and 95% LoA of -16.22 to 17.27. CONCLUSIONS: Of the 4 instruments that are commercially available, the UP was the most repeatable for within sessions, and the OCT was the most repeatable for between sessions.

The influence of gender and hormone status on the severity and progression of keratoconus.

PURPOSE: To assess the effects of gender and hormone status on the severity and progression of keratoconus in patients enrolled in the Collaborative Longitudinal Evaluation of Keratoconus Study. METHODS: The severity and progression of keratoconus in both men (M) and women were evaluated over a 4-year period that encompassed menopausal transition for hormone-active women (HA) and hormone-inactive women (HI). Four outcome measures were selected as indicators of the severity of keratoconus: high-contrast best-corrected visual acuity, low-contrast best-corrected visual acuity, the steep keratometric measurement, and corneal scarring (yes/no). RESULTS: There were no statistically significant differences among the 3 groups (M, HA, and HI) in race, history of atopic disease, family history of keratoconus, or rigid contact lens wear in the right and left eyes. At baseline, there were no significant differences among the 3 groups in high-contrast best-corrected visual acuity, low-contrast best-corrected visual acuity, or steep keratometric reading. Progression of keratoconus, as assessed by changes in these 3 continuous variables, was equal for the 3 groups. M had more corneal scarring than did HA or HI; however, there was no progression of scarring for any of the groups. CONCLUSION: Keratoconus progressed in both men and women, aged 48-59 years; however, there were no differences among the groups in progression.

The contribution of lipid layer movement to tear film thinning and breakup.

PURPOSE: To investigate whether the tear film thinning between blinks is caused by evaporation or by tangential flow of the tear film along the surface of the cornea. Tangential flow was studied by measuring the movement of the lipid layer. METHODS: Four video recordings of the lipid layer of the tear film were made from 16 normal subjects, with the subjects keeping their eyes open for up to 30 seconds after a blink. To assess vertical and horizontal stretching of the lipid layer and underlying aqueous layer, lipid movement was analyzed at five positions, a middle position 1 mm below the corneal center, and four positions respectively 1 mm above, below, nasal, and temporal to this middle position. In addition, in 13 subjects, the thinning of the tear film after a blink was measured. RESULTS: The total upward movement could be fitted by the sum of an exponential decay plus a slow steady drift; this drift was upward in 14 of 16 subjects (P = 0.002). Areas of thick lipid were seen to expand causing upward or downward drift or horizontal movement. The velocity of the initial rapid upward movement and the time constant of upward movement were found to correlate significantly with tear film thickness but not with tear-thinning rate. CONCLUSIONS: Analysis indicated that the observed movement of the lipid layer was too slow to explain the observed thinning rate of the tear film. In the Appendix, it is shown that flow under a stationary lipid layer cannot explain the observed thinning rate. It is concluded that most of the observed tear thinning between blinks is due to evaporation.

Contributions of evaporation and other mechanisms to tear film thinning and break-up.

PURPOSE: To evaluate the contribution of three mechanisms-evaporation of the tear film, inward flow of water into the corneal epithelium or contact lens, and "tangential flow" along the surface of epithelium or contact lens-to the thinning of the tear film between blinks and to tear film break-up. In addition to a discussion of relevant studies, some previously unpublished images are presented illustrating aspects of tear film break-up. CONTRIBUTIONS OF THREE MECHANISMS TO TEAR FILM BREAK-UP: Inward flow of water into the epithelium or contact lens is probably unimportant, and a small flow in the opposite direction may actually occur. Tangential flow is probably important in certain special cases of tear film break-up-at the black line near the tear meniscus, over surface elevations, after partial blinks, and from small thick lipid spots in the tear film. In all these special cases it is argued that tangential flow is important initially, but evaporation may be needed for final thinning to break-up. It is argued that most of the observed tear film thinning between blinks is due to evaporation, rather than tangential flow, and that large "pool" break-up regions are the result of evaporation over an extended area. CONCLUSION: Evaporation in our "free-air" conditions may be four to five times faster than the average of the values reported in the literature when air currents are prevented by preocular chambers. However, recent evaporation measurements using "ventilated chambers" give higher values, which may correspond better to free-air conditions. Thus evaporation may be fast enough to explain many cases of tear film break-up, and to give rise to considerable increases in the local osmolarity of the tear film between blinks.

Sex- and gender-based differences in healthy and diseased eyes.

PURPOSE: The aim of this study was to identify sex- and gender-based differences in ocular anatomy, physiology, and disease susceptibility or manifestation. METHODS: Review of current indexed literature was conducted. RESULTS: Sex and sex hormones influence the lacrimal system, eyelids and blinking, corneal anatomy and disease, aqueous humor dynamics and glaucoma, crystalline lens and cataract, uveitis and retinal disease, ocular circulation, and optic nerve anatomy and disease. Systemic conditions, particularly autoimmune disease, and conditions that are unique to women, such as pregnancy and menopause, further illustrate the effects of sex hormones on the eye. Gender-based differences in ocular conditions and disease should be considered within the context of the underlying physical and social environment. CONCLUSIONS: Many sex- and gender-based differences exist in healthy and diseased eyes.

Oxygen demands with hybrid contact lenses.

PURPOSE: The purpose of this study was to assess the corneal response, as measured by corneal oxygen uptake, of keratoconic corneas to SoftPerm and SynergEyes hybrid contact lenses at the central cornea, 2.0 and 4.5 mm temporal to the central cornea, and 1 mm temporal to the limbus. METHODS: Corneal oxygen uptake rates were measured with a Clark-type polarographic electrode on the right eyes of 14 subjects and the left eye of 1 subject, all with keratoconus. Measurements were made at the central cornea, 2.0 and 4.5 mm temporal to the central cornea, and 1 mm temporal to the limbus. They were made for the open eye condition, as well as following 300 s of SoftPerm and SynergEyes hybrid contact lens wear. A one-way analysis of variance (ANOVA) was used to determine the effect of measurement location on oxygen uptake rates under uncovered eye conditions. To determine the difference among oxygen uptake rates relative to those of the uncovered eye at each measurement location for each hybrid lens, a two-way repeated measures ANOVA was used. Multiple comparisons with Tukey-Kramer adjustment were used post hoc to determine which locations were significantly different. RESULTS: For the uncovered keratoconic cornea, there was no significant difference among the oxygen uptake rates associated with the three corneal locations; however, the oxygen uptake rates measured 1 mm temporal to the limbus were significantly higher than those measured at the three corneal locations. Comparison of oxygen uptake rates measured with the SoftPerm and SynergEyes lenses relative to those of the uncovered eye at each location revealed significantly higher rates at the peripheral cornea than at the central cornea. At all locations, the relative oxygen uptake rates obtained with the SynergEyes lenses were lower than those obtained with the SoftPerm lenses. CONCLUSIONS: The SynergEyes lens allows significantly more oxygen to reach the cornea during wear than the SoftPerm lens at the central cornea, as well as 2.0 mm and 4.5 mm temporal to the central cornea.

Corneal oxygen uptake associated with piggyback contact lens systems.

PURPOSE: The purpose of this study was to determine the effects of static (without blinking) and dynamic (with blinking once every 5 seconds) wear of piggyback contact lens systems on corneal oxygen uptake. METHODS: Corneal oxygen uptake rates were measured on the right eyes of 11 human subjects by using a polarographic electrode. Measurements were made for the normal open eye and after 5 minutes of wear of 4 rigid lens materials (Dk/t 0-82.5), 4 soft lens materials (Dk/t 13-122), and 16 combinations of rigid and soft lens materials. The piggyback systems were worn under both static and dynamic conditions. Repeated-measures analysis of variance was used to compare oxygen uptake rates associated with the wear of the rigid lens components, soft lens components, piggyback systems, and static versus dynamic wearing conditions. Spearman correlation coefficients and regression analyses were used to examine relationships between corneal oxygen uptake rates. RESULTS: Measurable differences were found among oxygen uptake rates associated with the rigid lens components, soft lens components, and piggyback systems. Blinking resulted in no reduction in corneal oxygen uptake with the piggyback systems. Corneal oxygen uptake associated with the wear of the piggyback systems could not be predicted from those associated with the rigid and soft lens components of the systems. CONCLUSIONS: Piggyback combinations of rigid and soft lens components with the highest transmissibilities resulted in the least increase in corneal oxygen uptake beyond that of the normal open eye.

Factors influencing the measurement of oxygen shortfall of the human cornea: sequencing of test conditions.

PURPOSE: The effects of sequencing of test conditions, in this case contact lens thicknesses, on the measurement of the oxygen shortfall of human corneas were studied. METHODS: Corneal oxygen uptake rates were measured with a Clark-type polarographic electrode on the central, unanesthetized right corneas of 14 human subjects. Measurements were made under the following conditions: (1) the normal open eye; (2) after 5 min of static (without blinking) wear of each of seven rigid gas permeable lenses of seven center thicknesses (0.18, 0.12, 0.16, 0.20, 0.24, 0.28, and 0.32 mm); (3) after 5 min of static wear of a polymethylmethacrylate (PMMA) contact lens. Lens thicknesses were randomly assigned numbers, which were sequenced in seven cycles. Two subjects were assigned to each sequencing cycle, and each subject participated in two identical sessions. RESULTS: The interaction of order x thickness was determined to be insignificant (F=0.99; p=0.5101). The effect of lens order was also insignificant (F=0.76; p=0.6239), indicating that the order of lens placement did not affect the measured corneal oxygen shortfall. Not surprisingly, the analysis indicated a significant effect of lens thickness on corneal oxygen shortfall (F=3.94; p=0.0032). CONCLUSIONS: The sequencing of lenses of various thicknesses on the cornea does not affect the measurement of corneal oxygen shortfall.

Baseline factors predictive of incident penetrating keratoplasty in keratoconus.

PURPOSE: To identify baseline demographic and clinical factors associated with undergoing penetrating keratoplasty (PK) in a prospective cohort of 1,065 keratoconus patients followed for eight years in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. DESIGN: Multicenter, prospective, observational cohort study. METHODS: We report the rate of PK over eight years and baseline factors predictive of PK in 1,065 patients who, at the time of study enrollment, had not undergone PK in either eye. RESULTS: Eighty-two percent of patients completed the eight-year close-out visit. Twelve percent (126 of 1,065) had PK in one (9.3%) or both eyes (2.5%). Baseline factors associated with increased likelihood of PK included younger age, steeper keratometric values, worse visual acuity, corneal scarring, poorer contact lens comfort, and poorer vision-related quality of life. The percent of eyes undergoing PK was 15% for patients 40 years old and younger, 28% for eyes with a steep keratometric value greater than 52 diopters, 33% for visual acuity less than 20/40, and 24% for eyes with corneal scarring. CONCLUSIONS: The CLEK Study confirmed previous reports of the increased likelihood of PK associated with corneal scarring, steeper keratometry values, poorer visual acuity, and poorer contact lens comfort. The CLEK Study is among the first to report an increased risk of PK associated with younger age, worse vision-related quality of life, and flatter contact lens fits. Knowledge of these factors is beneficial to clinicians in patient education and may be useful in disease management.

Rigid gas-permeable contact lens base curve radius and transmissibility effects on corneal oxygen uptake.

PURPOSE: The purpose of this study is to determine the effects of rigid gas-permeable contact lens thickness, base curve radius, and material permeability on corneal hypoxic stress. METHODS: Corneal oxygen uptake rates were measured with a Clark-type polarographic electrode on the right eye of 10 human subjects for the normal open eye (air) and after 5 minutes of static wear of rigid contact lenses of four cornea-to-contact lens base curve fitting relationships: 0.2 mm steeper-than-K (STK), 0.1 mm STK, on K, and 0.1 mm flatter-than-K (FTK). There were also four materials (polymethylmethacrylate [Dk=0], lotifocon B [OP-2, Dk=15.9], lotifocon A [OP-3, Dk=30], lotifocon C [OP-6; Dk=60]) and three center thicknesses (0.14, 0.28, and 0.53 mm for the OP-6 lenses and 0.14 mm for all other materials) with all other parameters being constant. Each subject participated in two identical sessions. A repeated-measures analysis of variance was performed to compare the mean response across lens materials/thicknesses and the four curvature values. RESULTS: Significant differences were found only for lens material/thickness (p<0.0001). Although OP-2 and OP-6 (0.53 mm) were manufactured to have the same Dk/t, post hoc comparisons showed that the oxygen uptake rate with OP-6 (0.53 mm) was significantly lower. The same is also true for OP-3 and OP-6 (0.28 mm), with OP-6 (0.28 mm) having a significantly lower oxygen uptake rate. CONCLUSIONS: In contrast to past studies with PMMA, cornea-to-contact lens base curve fitting relationship, with the lens materials and designs studied here, did not affect corneal hypoxic stress, and thick, high Dk lenses resulted in less change in corneal response than did thin, lower Dk lenses of the same Dk/t. This is attributed to the lens reservoir effect that has been previously described.

Interferometric imaging of the full thickness of the precorneal tear film.

A method is described for recording interference images from the full thickness of the precorneal tear film (PCTF). Simultaneous images are recorded by two video cameras. One camera responds to broadband spectral illumination and records interference from the superficial lipid layer of the tear film. The other camera uses narrowband illumination and records interference from both the lipid layer and the full thickness of the PCTF. Thus the full-thickness interference fringes are derived from the difference between, or ratio of, narrowband broadband images. This method has the potential for evaluating the role of both tear film flow and evaporation in tear film thinning and breakup. It therefore may be applied to the analysis of dry eye disease.

Differences in keratoconus as a function of gender.

PURPOSE: To characterize gender differences in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. DESIGN: Observational, longitudinal study. METHODS: A total of 1209 subjects at 16 clinics. For eye-specific categorical variables, the number of eyes per subject with the characteristic was counted. For eye-specific continuous variables, the mean of both eyes was calculated. Multivariate linear (for continuous outcomes) and logistic (for categorical outcomes) regression models were created for each baseline characteristic with statistically significant (P < or = .05) differences between men and women. Age, race, education, and corneal curvature were covariates. RESULTS: The women were older, more likely to report a family history of keratoconus, more likely to be nonwhite, and less likely to complete college than men. Vogt's striae and monocular and binocular high-contrast entrance acuity were the only visual characteristics that varied between men and women in the multivariate model. Women were more likely than men to report ocular symptoms of dryness and complaints based upon a composite score of ocular symptoms. Women reported more hours per day of near work and were less likely to report the ability to wear contact lenses for enough hours to permit reading at home in the evening. Women reported more visits to their eye care practitioner during the previous 12 months. NEI-VFQ results revealed differences in self-reported difficulty with distance activities and driving. CONCLUSIONS: Gender differences exist in patient history, vision, and ocular symptoms in keratoconus patients.

The effects of high-Dk rigid contact lens center thickness, material permeability, and blinking on the oxygen uptake of the human cornea.

PURPOSE: The human corneal oxygen uptake responses associated with the static (nonblinking) and dynamic (blinking) wear of five rigid gas-permeable materials with high oxygen permeabilities were determined for three different center thicknesses and compared with the responses for the normal open eye and severe hypoxic stress (static wear of polymethylmethacrylate). METHODS: Corneal oxygen uptake rates were measured with a Clark-type polarographic electrode during two sessions with each of 10 human subjects. Measurements were made on the right eye for the normal open eye (air) and after 5 minutes of static and dynamic wear of polymethylmethacrylate and five rigid gas-permeable contact lens materials: Fluoroperm 92 (paflufocon A, Dk = 92), Fluoroperm 151 (paflufocon D, Dk = 151), 1992 Menicon SF-P (melafocon A, Dk = 102), 1995 Menicon SF-P (melafocon A, Dk = 159), and Menicon Z (tisilfocon A, Dk = 163-250). Lenses were manufactured in three different center thicknesses (0.12, 0.16, and 0.20 mm), with all other parameters remaining constant. Repeated-measures analysis of variance was used and included lens material (five levels), blinking condition (two levels), and lens thickness (three levels) as within-subject effects. RESULTS: Significant differences were found in corneal oxygen responses to lens material (p < 0.001) and lens thickness (p < 0.001), with lenses of lower oxygen permeability and thicker lenses being associated with higher oxygen uptake. No statistically significant differences were noted between static or dynamic wear of the lens materials (p = 0.59). CONCLUSIONS: For those very high Dk rigid lens materials studied here, moderate changes in lens thickness or material permeability may result in modest differences in corneal hypoxic relief, whereas blinking results in no significant improvement to corneal oxygenation.

The thickness of the tear film.

Measurements of the thickness of the pre-corneal tear film, pre-lens tear film, post-lens tear film, and the lipid layer on the surface of the tear film are summarized. Spatial and temporal variations in tear film thickness are described. Theoretical predictions of tear film thickness are discussed. Mechanisms involved in the upward drift of the tear film after a blink, and in the formation of dry spots, are considered.

Tear exchange and oxygen reservoir effects in silicone hydrogel systems.

PURPOSE: The effects of oxygen reservoir and tear exchange are known for conventional hydrogel contact lenses. This study attempted to (1) confirm their presence in lenses of a silicone hydrogel (SH) material and (2) evaluate their individual and combined contributions to hypoxic relief of the cornea. METHODS: Corneal oxygen uptake rates were measured polarographically for 10 OD corneas immediately after 300-sec periods (equivalent to 60+ blink cycles) of: (1) nonblink wear of a 0 Dk/L polymethylmethacrylate (PMMA) cap lens; (2) nonblink wear of that cap lens with a SH lens inserted between it and the cornea; (3) regular blinked wear of that same lens combination; (4) nonblinked wear of the SH lens alone; and (5) normal open-eye, non-lens wear. The rates for each eye had a ratio with its own baseline (no lens) rate, and the total sample mean was calculated for each condition from those individual eye means. RESULTS: (1) Under nonblink conditions, a 28% reduction in corneal oxygen demand was observed when a SH lens was inserted under the PMMA cap lens versus without. (2) When regular blinking was added to that lens combination, corneal oxygen demand decreased another 8%, for a total of 36%. The combination of SH insertion and blinking did achieve a statistically significant difference (P<0.05 by the Dunnett test) from the nonblink, 0 Dk/L, maximum deprivation condition. CONCLUSION: The statistically significant hypoxia reduction observed with the SH lens insertion and blinking indicates the additive presence of two factors: (1) a lens reservoir effect caused by the SH lens and (2) a bulk-flow tear exchange effect caused by blinking. Their respective contributions to the reduction of corneal oxygen demand over the period studied were found to be in the ratio of 3.4:1.

Enhancing RGP contact lens performance: comparing back surface options.

BACKGROUND: In some cases, rigid gas-permeable (RGP) contact lenses may be the best--or only--means of refractive correction. High Dk RGP materials have markedly reduced hypoxia under those lenses. With aspheric lens back surface designs, post-lens circulation may be enhanced as well by maximizing the provision of nutrients and the clearance of metabolic by-products, toxins, and debris, while minimizing the risk of lens binding. METHODS: Performances of four aspheric back surface RGP designs were compared with a spherical optic zone and peripheral curve back surface reference design. Oxygen uptake rates were measured for each of 40 wearing combinations (five lens designs fitted to each of eight eyes) under non-blink and blink conditions for their effectiveness in reduction of post-lens hypoxia. Hypoxic reductions with blinking were scaled in exchange efficiency (EE) units, and used as relative indicators of post-lens tear exchange. RESULTS: Combined exchange efficiency index (EE) scores (averaged responses across all eight eyes) for each of the five lens back surface designs ranged from a best overall performance of +13.9 EE units down to only +2.5 EE units, with the spherical reference design averaging +8.9 EE units. Tear pump efficiency of each of the eight eyes (averaged responses across all five lens designs) ranged from a high of +12.3 EE units down to -9.8 EE units (i.e., worse than the non-blink condition of 0 EE units). Among the 40 eye-lens back surface design combinations studied here, the highest exchange efficiency score registered was +28.4 EE units, the lowest being -13.8 EE units. CONCLUSIONS: Aspheric lens back surface and/or peripheral curve designs were found to vary significantly in their post-lens exchange efficiency performances, but no "universal problem-solver" design was found among the five we investigated.

Between-eye asymmetry in keratoconus.

PURPOSE: To report baseline differences between eyes on key variables in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study cohort compared with a retrospectively assembled group of myopic contact lens wearers without ocular disease. METHODS: A total of 1,079 keratoconus patients who had not undergone a penetrating keratoplasty in either eye before their baseline visit were enrolled and examined at baseline. Records from 330 contact lens-wearing myopes were reviewed. Corneal curvature (keratometry), visual acuity, refractive error (manifest refraction), and corneal scarring were measured. RESULTS: The mean differences between keratoconic eyes are as follows (better eye-worse eye for each variable, separately). Flat keratometry: -3.59 +/-4.46 D and steep keratometry: -4.35 +/-4.41 D; high-contrast best-corrected visual acuity: 7.30 +/-6.83 letters; low-contrast best-corrected visual acuity: 8.53 +/-7.51 letters; high-contrast entrance visual acuity: 9.03 +/-8.40 letters; low-contrast entrance visual acuity: 9.43 +/-7.88 letters; spherical equivalent refractive error: 3.15 +/-3.84 D; and refractive cylinder power 1.55 +/-1.42 D. Twenty-one percent of the keratoconus patients had corneal scarring in only one eye. There is an association between patient-reported unilateral eye rubbing and greater asymmetry in corneal curvature, and between a history of unilateral eye trauma and greater asymmetry in corneal curvature and refractive error, with the rubbed/traumatized eye being the steeper eye most of the time. CONCLUSIONS: Keratoconus is asymmetric in the CLEK Study sample.