Decreased visual performance in corneal ectasias such as keratoconus is predominantly optical in origin, typically resulting from bilaterally asymmetric elevated higher-order aberrations caused by the rotationally asymmetric irregular profiles of anterior and posterior corneal surfaces.1–3 Onset of most ectatic conditions is during adolescence, and these individuals usually experience normal visual stimulation throughout critical periods of development and undergo typical neural development. Hence, if the aberrated optics of these eyes can be appropriately corrected, normal levels of visual performance are expected to recover after habituation to the improved retinal image.
Current standards of care for corneal ectasias are rigid corneal or scleral lenses, which partially mask anterior cornea irregularities through approximate refractive index matching of the post-lens tear film and cornea and by providing a new optically well-formed first surface for the eye. Those refractive indices are, however, not perfectly matched, and residual anterior corneal surface aberrations remain, as do aberrations from the irregular posterior corneal surface,1–3 which cannot be masked by rigid contact lenses.
Wavefront-guided contact lens technology is designed to specifically target the unique aberrations of individual eyes, particularly the elevated levels of residual aberrations experienced by highly aberrated eyes wearing conventional contact lenses.2,4–6
Although customized wavefront-guided contact lenses have been manufactured and demonstrated with varying levels of efficacy in laboratory settings7–16 and studied using simulations and theoretical modeling,17–25 those studies that measured visual performance with these lenses7–16 did so immediately after manufacturing and fitting the lenses without allowing time for the visual systems of the wearers to habituate to the new percept.
Previous studies compared wavefront-guided lenses with habitual or conventional lenses that served as predicate stepping stones (for wavefront-guided lenses) and were not necessarily clinically optimized in terms of their fit and optics.10–12,14,16 In some studies, spherocylindrical components of the wavefront-guided lenses have been corrected using spectacle trial lenses before evaluating visual performance,11,14,15 and consequently, lenses were not dispensed.
Allowing the visual system time to adapt is common clinical practice when dispensing progressive addition lenses, large changes in prescriptions, and high cylinders, or after ocular surgery. Likewise, when highly aberrated eyes are acutely corrected (without providing time for adaptation) with adaptive optics, visual performance is improved but not to normal levels,26 and further gains are only achieved after habituation or training.27
Given that the visual system is adapted to its habitual aberration structure26,28 and given the considerable reduction in aberration magnitude imparted by wavefront-guided lenses (in this study and others14,16) along with the reversal2,3 in key aberrations (such as coma) associated with directional blur, patients should habituate to the corrections before visual performance is evaluated. Although visual performance reported with wavefront-guided lenses has been improved, we postulate that it has hitherto remained worse than normal (despite reduced levels of aberration12–14,16,29) because of insufficient habituation time and/or the interaction of residual aberrations being detrimental to visual image quality.
As wavefront-guided technology becomes more accessible, it is important to present controlled comparisons of state-of-the-art wavefront-guided scleral lenses with the best conventional scleral lenses prescribed in practice. In fact, first achieving clinically typical performance with best conventional scleral lenses is an essential prerequisite in appreciating any real gains in performance provided by wavefront-guided lenses and in identifying which eyes would benefit most from wavefront-guided lenses over conventional lenses.
Therefore, this article presents comparison of three corrections: (1) the subject's habitual correction, (2) a best conventional scleral lens, (3) and a best individualized wavefront-guided scleral lens, after lenses were dispensed and worn as part of daily life by eyes with corneal ectasias, which allowed approximately 8 weeks of habituation to each new correction in a crossover manner. This comparison is presented in terms of (1) residual higher-order root mean square wavefront error, (2) high-contrast visual acuity, (3) letter contrast sensitivity, and (4) the visual image quality metric logVSX (the logarithm of the visual Strehl ratio). Correlations between ocular biometric measures and the reduction in higher-order aberrations provided by the wavefront-guided lenses over conventional lenses are examined.
This research adhered to the tenets of the Declaration of Helsinki. Before data collection, the nature and potential consequences of the study were explained to each subject, and a University of Houston institutional review board–approved informed consent form was signed.
Ten subjects (nine male, one female) with corneal ectasia were recruited; nine were diagnosed as having bilateral keratoconus and one was diagnosed as having bilateral pellucid marginal degeneration. These conditions characteristically present with bilaterally asymmetric disease severities,4,30 and the ectasias of some fellow eyes were quite mild (these eyes stood to benefit less from wavefront-guided lenses than more severe ectasias). Nonetheless, both eyes of each subject (20 eyes) were included because each eye presented unique optical and fitting challenges. Appropriate statistical methods31,32 (see Results) were used to account for any dependency between the right and left eyes of each individual.
Table 1 classifies the severity of the subjects in terms of the ABCD keratoconus grading system,34 which incorporates anterior (“A”) and posterior (“B”) corneal radii of curvature and thinnest pachymetry (“C”), all determined by Topometric/KC Staging software on the Pentacam HR (Oculus Inc., Arlington, WA), as well as best-corrected distance visual acuity (“D”). Grading ranges from 0 (normal) to 4 (most severe).
Five subjects used spectacles for the habitual correction measurements; three used contact lenses on both eyes (two wore scleral lenses, one wore hybrid lenses); one used a toric soft lens on one eye and was unaided in the other; and one subject performed the habitual correction measurements unaided. Mean ± standard deviation age of the subjects was 34.4 ± 11.1 years (range, 24 to 55 years). Inclusion criteria were as follows: no corneal scarring over the central 7 mm of the pupil and unremarkable systemic and other ocular health.
Performance measures were recorded monocularly.
Higher-order Root Mean Square Wavefront Error
Three wavefront error measurements recorded using a COAS HD wavefront sensor (Johnson & Johnson Vision, Santa Ana, CA) and described by a 10th radial order normalized Zernike polynomial fit were averaged over a common dilated pupil size.
High-contrast Visual Acuity
High-contrast visual acuity was measured in a darkened room and calculated with per-letter scoring, terminating after five missed letters, as the mean of three unique Early Treatment Diabetic Retinopathy Study logMAR charts displayed with −100% Weber contrast (Display++ monitor; Cambridge Research Systems, Kent, United Kingdom) and a background luminance of 116 cd/m2 (Minolta LS-110; Konica Minolta, Ramsey, NJ).
Letter Contrast Sensitivity
Using the same monitor and darkened room, letter contrast sensitivity was measured using letter sizes having fundamental-spatial frequencies of 4, 8, and 16 cycles per degree (20/150, 20/75, and 20/37.5, respectively), and the area under the log contrast sensitivity function curve35 was calculated. For each letter size, contrast threshold was estimated to the nearest 0.2 log unit, after which three measures of contrast threshold were determined using rows of unique Sloan letters that began at a contrast level of 0.4 log unit greater than the initial estimate and reduced in steps of 0.1 log unit per line until five letters were missed.
The Logarithm of the Visual Strehl Ratio
Visual image quality was quantified using logVSX,36 a single value metric combining comprehensive description of the optics (here, wavefront error of an eye wearing a correction) with a measure of the neural processing of the visual system. logVSX has been shown predictive of subjective best focus36,37 and able to identify spectacle prescriptions equivalent to subjective refraction.38 Change in logVSX has been well correlated with change in logMAR visual acuity.39,40
VSX ranges from 0 (worst) to 1 (best). The (base 10) logarithm of 1 is 0; thus, the closer the value of logVSX to 0 (the less negative the value), the better the visual image quality. logVSX was calculated from mean wavefront error (of the corrected eyes) over 5-mm pupil diameters.
Study Format and Lens Designs
The study protocol began with measurement of the four outcomes using the habitual correction. Thereafter, fitting (but not necessarily dispensing) of conventional scleral lenses commenced, which involved adjusting the designs of the lenses to provide healthy, comfortable fits that were rotationally and translationally stable and to refine the sphere, cylinder, and axis.
The macro design of the conventional and wavefront-guided scleral lenses is described in detail elsewhere.16 Briefly, lenses were manufactured at the Visual Optics Institute, University of Houston, College of Optometry, using a DAC 2X-ALM OTT ophthalmic lens lathe (DAC International, Carpinteria, CA) and Boston XO material (Bausch + Lomb, Rochester, NY). Overall diameter ranged from 17 to 18.1 mm. The front surface was aspheric, designed to render the lens free of spherical aberration when on the eye and included a 10-mm central optic zone. The posterior surface contained six curves; the fifth curve was a toric annulus designed to impart rotational stability.41,42
After allowing for settling on the eye for 30 minutes, lens engravings were monitored to quantify lens rotation, and the orientation of the peripheral toric annulus was adjusted in subsequent lens designs to compensate for the observed rotation.16,42 When a stable and correctly oriented lens with a clinically acceptable fit was achieved, the location of the pupil center relative to the geometric center of the lens was measured such that the wavefront-guided prescription could be offset in opposite xy directions relative to the lens center to compensate. Most scleral lenses rested inferior and temporal relative to the center of the pupil,14 and consequently, most wavefront-guided prescriptions were offset superior and nasal relative to the lens center (Fig. 1). Thresholds for tolerable lens movements are inversely proportional to the magnitudes of wavefront-guided prescriptions17,18,22,24,25 and therefore varied across the range of ectasia severities included here.
Wavefront-guided lenses were designed using the macro parameters of the stable conventional lens. Residual wavefront error was measured through the stable lens after dilation (one drop of 1% tropicamide, one drop of 2.5% phenylephrine), and an offset wavefront-guided prescription targeting residual aberrations up to the fifth Zernike radial order33 was imparted into the anterior lens surface.
Median diameter of the wavefront-guided prescription was 8 mm (mean, 7.84 mm); this was limited on the low end by the maximal dilated pupil size, and the wavefront error measurements for the eyes with larger pupils were scaled43 down to 8 mm.
At this point, a crossover study design was initiated where each subject wore a best conventional scleral lens daily for approximately 8 weeks and a wavefront-guided scleral lens daily for an additional 8 weeks. This provided an opportunity for the visual system of each subject to habituate to the retinal image formed by each lens in his or her everyday environment, and follow-up visits provided opportunities (if needed) for refinement of the optics and the fit of each lens (which necessitated manufacture of new lenses). Subjects generally conformed to the 8-week period; some subjects wore a lens type for slightly longer, for example, because of travel or work obligations, illness, or natural disaster (hurricane Harvey). The order of lens wear was randomized; three subjects wore conventional lenses first, and seven wore wavefront-guided lenses first. Some subjects who wore the wavefront-guided lenses first expressed such substantial unhappiness during the conventional lens (second) part of the crossover that we will reevaluate this randomization during future studies. One subject did not complete the conventional lens part of the crossover but still wore the wavefront-guided lens for 8 weeks.
At the final visit with each lens, visual acuity and contrast sensitivity were measured with the lenses through natural pupils, and residual wavefront error was measured over dilated pupils.
Both statistical and clinical significance are considered. All standard deviations were calculated using analysis of variance and components of variance analyses to account for any dependence of the right and left eyes.31,32 Similarly, P values were calculated using split-plot analyses of variance.31,32 Plots for individual eyes use lines to track each eye across the three (categorical) corrections, and any given eye is consistently represented by the same color, symbol, and line across all four outcomes. The best conventional lens for 18 eyes was spherical, and that for two eyes was spherocylindrical.
Higher-order Root Mean Square Wavefront Error
Higher-order root mean square results were scaled43 to a 5-mm pupil diameter to better agree with habitual physiological pupil sizes and pupil sizes during visual acuity and contrast sensitivity measures, and they are presented up to the sixth radial order.
Mean ± standard deviation higher-order root mean square wavefront error decreased from the habitual correction (0.886 ± 0.589 μm, mean across modalities) to conventional lenses (0.458 ± 0.238 μm) and further decreased to within normal limits with wavefront-guided lenses (0.260 ± 0.077 μm; Fig. 2). These represent statistically significant reductions of 48% (P = .02) from habitual to conventional, 43% (P = .004) from conventional to wavefront guided, and 71% (P = .001) from habitual to wavefront guided. Note the reduction in variability with wavefront-guided lenses.
The unique reduction in higher-order root mean square wavefront error for each eye may be better appreciated as the percentage of the eyes within age-matched normal (normal eye)44 limits: 15% of the eyes were within normal limits wearing the habitual correction, 40% with best conventional scleral lenses, and 85% with wavefront-guided lenses. A representative example of higher-order wavefront error maps (across unaided and the three corrections) for one subject with moderate keratoconus is shown in Fig. 3.
Reduction in higher-order aberrations by wavefront-guided lenses over conventional lenses was best correlated (Fig. 4) with posterior corneal radius of curvature (dimension B34; R2 = 0.75) followed by the mean severity grading (averaging across dimensions ABC and D for the conventional lens [R2 = 0.62]).
Mean ± standard deviation logMAR visual acuity improved from the habitual correction (+0.09 ± 0.18, mean across modalities) to conventional lenses (−0.03 ± 0.09) and improved further with wavefront-guided lenses (−0.09 ± 0.10; Fig. 5). Disease severity dimension D (best-corrected distance visual acuity) thus varies depending on which correction (habitual, conventional, wavefront guided) is used; for example, subjects in each severity grade of D (0:1:2:3:4) were 8:10:2:0:0 with habitual, 12:8:0:0:0 with conventional, and 17:3:0:0:0 with wavefront-guided corrections.
Mean improvements from habitual to conventional and from habitual to wavefront guided were statistically significant (P = .05 and P = .007, respectively). Mean improvement from conventional to wavefront guided was not (P = .07); however, from an individual perspective, six eyes showed clinically significant improvements of greater than one line of logMAR visual acuity, and substantially more eyes reached normal45 levels: habitual correction, 25%; conventional lenses, 50%; and wavefront-guided lenses, 85%.
Letter Contrast Sensitivity
At each fundamental spatial frequency, most eyes improved in letter contrast sensitivity from the habitual correction to conventional scleral lenses and improved further with wavefront-guided lenses.
Mean ± standard deviation area under the log contrast sensitivity function35 (Fig. 6) improved from the habitual correction (11.07 ± 3.48, mean across modalities) to conventional lenses (13.91 ± 2.20) and improved further with wavefront-guided lenses (15.82 ± 2.34). These correspond to significant gains of 26% (P = .009) from habitual to conventional and 43% (P < .001) from habitual to wavefront guided. The 14% gain from conventional to wavefront guided was not significant (P = .09). The proportions of the eyes that were within normal limits were as follows: 30%, habitual correction; 60%, conventional lenses; and 90%, wavefront-guided lenses.
The Visual Image Quality Metric LogVSX (the Visual Strehl Ratio)
A similar pattern of gains was found for logVSX (Fig. 7): mean ± standard deviation metric value improved from the habitual correction (−1.55 ± 0.48, mean across modalities) to conventional lenses (−1.31 ± 0.51) and improved further with wavefront-guided lenses (−0.98 ± 0.27). Wavefront-guided lenses provided 37 and 25% statistically significant (P < .0001 and P = .02, respectively) better visual image quality than did the habitual and conventional corrections. The 16% improvement from habitual to conventional was not significant (P = .11). Although the pattern of results for logVSX agrees with the other outcomes and best visual image quality was provided by the wavefront-guided lenses, most eyes (18) did not reach the high logVSX levels theoretically obtained by objectively best-correcting normal eyes.47
This study sought to determine the benefit of transferring individuals with corneal ectasia from their habitual correction to best conventional scleral lenses and to personalized wavefront-guided lenses by dispensing each type of lens and allowing for approximately 8 weeks of habituation to the retinal image formed by each.
Best Conventional Scleral Lenses
Achieving equivalent or better than clinically representative performance with best conventional scleral lenses is an essential prerequisite in appreciating any gains in performance provided by wavefront-guided lenses.
Mean residual levels of higher-order root mean square wavefront error with best conventional lenses (0.30 μm over a 4-mm pupil, 0.46 μm over 5 mm, 0.58 μm over 6 mm) were equivalent to or better than reports of highly aberrated eyes wearing conventional scleral lenses6,14,16 or corneal rigid gas-permeable lenses.2,4,5 Similarly, best conventional scleral lenses provided mean visual acuity (−0.03) better than or equivalent to reports of highly aberrated eyes wearing conventional scleral lenses46 or corneal rigid gas-permeable lenses.48 Despite differences in methodology discussed hereinafter, letter contrast sensitivity with the best conventional scleral lenses was also equivalent to that of highly aberrated eyes wearing corneal rigid gas-permeable lenses.49 In this study, the magnitudes and distributions of residual higher-order aberrations through best conventional lenses interacted such that all eyes remained outside the objectively optimized logVSX levels of best-corrected normal eyes.47
Comparison of Wavefront-guided Lenses with Other Studies
Comparisons are made with (1) attempts to correct measured aberrations of real eyes and (2) benchmark modalities of clinical practice.
Higher-order Root Mean Square Wavefront Error
Mean higher-order root mean square levels with wavefront-guided lenses reported here (0.19 μm over a 4 mm diameter pupil, 0.26 μm over 5 mm, 0.33 μm over 6 mm) are statistically equivalent to previous reports of wavefront-guided scleral lenses,14,16 significantly better than reports of wavefront-guided soft lenses,10,11,13 better than that of conventional scleral lenses in this study and others,6,14,16 and better than reports of highly aberrated eyes wearing corneal rigid gas-permeable lenses.2,4,5
Visual acuity is a variable subjective quantity50 that can be relatively insensitive to visual blur,51 which could have contributed to lack of significance in gain between best conventional and wavefront-guided lenses. Nonetheless, mean logMAR visual acuity with wavefront-guided lenses in this study (−0.09) is clinically equivalent or better than other reports of scleral wavefront-guided lenses,14,16 better than wavefront-guided soft lenses,7,13,15 better than conventional scleral lenses in this study and elsewhere,46 and better than reports of highly aberrated eyes wearing corneal rigid gas-permeable lenses.48 These differences may be due to habituation.
Letter Contrast Sensitivity
Letter contrast sensitivity was compared with performance of well-corrected normal eyes on the same instrument system. First, common letter contrast sensitivity charts52 typically only test one low spatial frequency (1 to 2 cycles per degree). Second, contrast sensitivity with wavefront-guided lenses7,14 or corneal rigid gas-permeable lenses49 has been studied using sine-wave gratings. Although the fundamental frequencies of letter and sine-wave stimuli can be equivalent, sine-wave gratings are insensitive to phase errors present in normal53—and amplified in highly aberrated—eyes54 that can affect visual perception.55
Sabesan et al.14 presented change in contrast sensitivity with wavefront-guided lenses as a multiple of contrast sensitivity with conventional lenses. This can bias the performance of the wavefront-guided lenses because the conventional lenses were unrefined predicate lenses, as has been common practice.10–12,16 Overall, we found an opposite pattern of contrast sensitivity results in that performance with wavefront-guided lenses in this study gained more at higher spatial frequencies than at lower spatial frequencies. Comparing with their Fig. 5, mean log contrast sensitivity reported here was equivalent for 4 cycles per degree (1.64 ± 0.14) and significantly better for 8 cycles per degree (1.41 ± 0.19), and mean log contrast sensitivity reported here for 16 cycles per degree (1.01 ± 0.25) was significantly better than that at the highest spatial frequency (12 cycles per degree) they reported. These differences may be due to habituation.
The Visual Image Quality Metric (LogVSX)
Wavefront-guided lenses were designed to correct measured residual aberrations from the second through fifth radial orders. Although the total magnitude (root mean square) of higher-order aberrations was reduced to within normal levels for 85% of the eyes, the distribution and magnitude of individual aberration terms residual through the wavefront-guided lenses interacted visually such that logVSX for most eyes did not reach the objectively optimized levels of best-corrected normal eyes.47 Considering the realistic variability of subjective refraction, 14 eyes reached the logVSX limits (−0.580 ± 0.239; 5-mm pupil diameter) calculated from the typical subjective refraction of 200 young normal eyes.56
This indicates that further improvement in visual quality is possible as wavefront-guided corrections continue to be improved and might involve, for example, targeting particular aberrations such that the residual distributions of higher-order aberrations better resemble those of normal eyes.
Who Will Benefit Most from Wavefront-guided Lenses?
Health care is evolving toward personalized treatments tailored to the individual needs of each specific patient. Wavefront-guided contact lenses are serving as an ophthalmic application of such individualized medicine for corneal ectasias. However, the investments of time, technology, and cost involved in fitting wavefront-guided products are greater than conventional corrections, making them more comparable with prosthetic devices. Although the choice of corrections is influenced by the visual quality expectations of an individual in addition to the investments of time and money, it is desirable—perhaps even ethically necessary—to estimate the benefits that an individual could gain from wavefront-guided lenses over conventional scleral lenses. This is pertinent given that we are in the infancy of the clinical translation of wavefront-guided lenses, which will become more widely accessible, further improved, and an option for certain individuals with normal eyes wishing to reduce higher-order aberrations.
Residual higher-order root mean square wavefront error through best conventional scleral lenses best predicted (R2 = 0.94) the additional reduction in higher-order aberrations achieved by wavefront-guided lenses over conventional lenses. This is not surprising because wavefront-guided lenses were designed to specifically target residual higher-order root mean square wavefront error. Estimating a patient's potential gains using residual higher-order root mean square wavefront error through a conventional lens is reasonable because a best conventional lens is a prerequisite for a wavefront-guided lens. However, as visual processing is better understood and visual image quality metrics are better developed, it is likely that the field should strive to optimize these metrics as opposed to simplistically targeting a reduction in aberration terms.
Of the biometric measures, posterior corneal radius of curvature best correlated (R2 = 0.75) with the reduction in higher-order aberrations provided by wavefront-guided lenses, followed by mean disease severity (averaging grading dimensions A, B, C, and D for the conventional lens; R2 = 0.62), both of which can be evaluated with Pentacam software (Oculus Inc.).
Based on posterior corneal radius of curvature, the present sample of the eyes could be divided into (1) those of severity grades 0 and 1 (>5.7 mm) and (2) those of severity grades 2, 3, and 4 (<5.7 mm). Seventy-five percent of the eyes in the first group were within normal levels of higher-order root mean square wavefront error with a best conventional lens compared with 31% of the eyes in the second group. The eyes in the first group experienced a mean reduction of 0.057 μm in higher-order root mean square wavefront error (5-mm pupil) with the wavefront-guided lens over the conventional, whereas a mean reduction of 0.233 μm was experienced by the second group. A greater sample of eyes is needed before this threshold criterion could be confidently advocated.
If these insights were followed, some eyes fit with wavefront-guided lenses in this study would not be fit in practice; these eyes experienced smaller gains with the wavefront-guided lenses. Both eyes of each subject were fit here by experimental design to gain insights into who would benefit most. Given the bilateral asymmetry that characterizes corneal ectasias and the current state of wavefront-guided lenses, these individuals might currently be well served wearing a wavefront-guided lens on their more severe eye and a conventional lens on the less severe eye.
Predicting the individual benefit in this way only considers the unique optical challenges presented by each eye but neglects the many traditional challenges of scleral lens fitting; both sets of challenges need to be resolved for the successful fitting of wavefront-guided lenses. In this study, as is true of clinical practice, the challenges of fitting a stable scleral lens were sometimes significant. In contrast, the incorporation of the wavefront-guided correction was relatively easy (requiring additional two to three visits) once a stable well-fitting conventional scleral lens was achieved. Identifying individuals who stand to benefit from wavefront-guided lenses is important because the eyes in this study that experienced substantial gains, reported the investment of time to fit wavefront-guided lenses as worthwhile, and described the gains in visual performance and quality as life changing.
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