Abstract
Purpose:
The purpose of this study was to compare axial and peripheral eye elongation during myopia therapy with multifocal soft contact lenses.
Methods:
Participants were 294 children (177 [60.2%] girls) age 7 to 11 years old with between −0.75 diopters (D) and −5.00 D of myopia (spherical component) and less than 1.00 D astigmatism at baseline. Children were randomly assigned to Biofinity soft contact lenses for 3 years: D-designs with a +2.50 D addition, +1.50 D addition, or single vision. Five measurements of eye length were averaged at the fovea, ±20°, and ±30° in the horizontal and vertical meridians of the right eye using the Haag-Streit Lenstar LS 900.
Results:
Axial elongation over 3 years with single vision contact lenses was greater than peripheral elongation in the superior and temporal retinal qeuadrants by 0.07 mm (95% confidence interval [CI] = 0.05 to 0.09 mm) and 0.06 mm (95% CI = 0.03 to 0.09 mm) and similar in the inferior and nasal quadrants. Axial elongation with +2.50 D addition multifocal contact lenses was similar to peripheral elongation in the superior retinal quadrant and less than peripheral elongation in the inferior and nasal quadrants by −0.04 mm (95% CI = −0.06 to −0.01 mm) and −0.06 mm (95% CI = −0.09 to −0.02 mm).
Conclusions:
Wearing +2.50 D addition multifocal contact lenses neutralized or reversed the increase in retinal steepness with single vision lenses. The mismatch between greater inhibition of elongation at the fovea than peripherally despite greater peripheral myopic defocus suggests that optical myopia therapy may operate through extensive spatial integration or mechanisms other than local defocus.
A considerable amount of evidence shows that the growth of the eye and the development of refractive error can be modified by changes in visual experience. Lid occlusion and form deprivation in animal models, primarily chicks and monkeys, result in highly myopic refractive errors in a short amount of time.
1,2 These animal species are also responsive to the sign and magnitude of defocus created by lenses, compensating for the imposed refractive error by means of accelerated or inhibited ocular elongation.
3–5 Animal models have been useful in explaining some aspects of human refractive error development. Disruption of normal, high contrast vision in human infants results in myopic refractive errors.
6,7 Human infants are also responsive to their own native hyperopic refractive errors, with modulation of growth that results in near-emmetropia from an axial length well matched to ocular refractive power.
8–10
A key feature of the visual control of eye growth is local control, that ocular responses to changes in the visual environment are spatially specific. The portion of the visual field exposed to form deprivation or defocus in animal studies corresponds to the portion of the eye that exhibits the compensating change in growth.
11–13 Separating the eye from the central nervous system through optic nerve section does not prevent myopic responses to form deprivation or compensation for refractive errors imposed by minus lenses.
12,14 Whereas the central and peripheral retina are both sensitive to changes in the visual environment,
11 responses to peripheral manipulations are not always confined to the periphery. The ability of the retinal periphery to alter growth at the fovea has been well documented in foveal ablation experiments in the monkey.
15,16 Foveal elongation accelerates when the retinal periphery is preferentially exposed to form deprivation or blur using apertures,
15,17 but may not be affected if the exposure is too far into the periphery relative to the central retina.
18 Because these studies have only used animal models, the extent of spatial integration of a visual signal by the retinal periphery and its ability to influence foveal growth in children have yet to be determined.
There is good evidence that the peripheral visual environment in children may affect growth at the fovea. Children wearing progressive addition spectacle lenses experience less myopia progression.
19–21 These effects were assumed to be due to reduced hyperopic defocus at the fovea during near vision. However, a report from the Study of Theories about Myopia Progression project suggested that the beneficial effect of progressive addition lenses might be due to superior retinal myopic defocus from the inferiorly placed addition power.
21,22 Myopia control through center-distance multifocal contact lenses or overnight orthokeratology presents this additional plus power 360° around the periphery. The optical effect of these multifocal contact lenses is to reduce the peripheral hyperopia that is present when children wear a traditional single vision correction, such as glasses or contact lenses. Multifocal contact lens clinical trial results suggest that the influence of the periphery outweighs the local foveal visual signal; despite a clear foveal image and good visual acuity, altering the peripheral optical profile results in slower myopia progression and less axial elongation in children.
23,24 A theory of growth based on local control would predict that peripheral expansion might be inhibited more than axial elongation during optical myopia control. Different local effects might also be expected between ocular meridians. Baseline results without contact lenses showed that the Bifocal Lenses In Nearsighted Kids (BLINK) study participants had about +1.8 D of relative peripheral hyperopia at 40° in both the nasal and temporal visual fields. Interestingly, the superior and inferior visual fields at 30° showed the opposite sign of defocus, about −0.5 D of relative peripheral myopia.
25 Local control would predict that inhibition of peripheral ocular expansion would be greater in the vertical compared to the horizontal meridian due to greater peripheral myopia. The BLINK study cross-sectional results argue against this meridional local control. Both meridians showed steeper retinas at higher levels of myopia, but the difference between meridians remained similar throughout the range of refractive errors.
25
The purpose of the current report is to investigate whether the effect of wearing center-distance multifocal soft contact lenses on axial and peripheral elongation of the eye exhibits more local versus global effects compared to single-vision soft contact lenses. Baseline data have been reported previously.
25 The primary analyses in this report address the pattern of inhibition from +2.50 D addition contact lenses compared to +1.50 D addition and single vision contact lenses as a function of retinal meridian, quadrant, and eccentricity using longitudinal data collected over 3 years. Local control of ocular growth would predict that elongation in the vertical meridian would be less than in the horizontal meridian and that peripheral elongation would be inhibited more than axial elongation when wearing +2.50 D addition contact lenses. Similar levels of elongation in both meridians and similar (or greater) inhibition of elongation at the fovea than the periphery would indicate a more global response to wearing multifocal contact lenses.
Detailed methods used in the BLINK study, and those used for peripheral biometry and refractive error measurements, have been published previously.
25,26 To summarize, the BLINK study enrolled 294 children between the ages of 7 and 11 years old (inclusive) with between −0.75 D and −5.00 D of myopia in the most hyperopic meridian, less than 1.00 D of astigmatism, and 2.00 D or less of anisometropia into a 3-year randomized clinical trial to determine if center-distance multifocal contact lenses slowed the progression of myopia more than single vision contact lenses. Children were randomized in equal numbers (98 per group) to wear one of three Biofinity soft contact lens designs (CooperVision; Pleasanton, CA): single-vision, multifocal D with +1.50 D addition power, or multifocal D with +2.50 D addition power. The research adhered to the tenets of the Declaration of Helsinki, was reviewed and approved by independent ethical review boards at the University of Houston and The Ohio State University, conformed with the principles and applicable guidelines for the protection of human subjects in biomedical research, and was monitored by an independent data and safety monitoring committee. Assent from children and parental permission were obtained from each participant and participant's parent/guardian, respectively. The registration for this clinical trial can be found at ClinicalTrials.gov (Identifier: NCT02255474).
All central and peripheral measurements of eye length and refractive error for this report were made on the right eye only under cycloplegia. Subjects received one drop of either 0.5% tetracaine or 0.5% proparacaine followed by 2 single drops of 1% tropicamide 5 minutes apart in each eye. Central and peripheral eye length were the average of 5 valid measurements (unflagged by the instrument) at each retinal location using the Lenstar LS 900 optical biometer (Haag-Streit USA, Mason, OH). Axial length was measured along the line of sight, then peripheral eye length was measured by having the subject turn the eye to fixate small targets on the face of the instrument at eccentricities of 20° and 30°, both horizontally in nasal and temporal gaze and vertically in superior and inferior gaze. Central and peripheral refractive error were measured with and without contact lens correction using the open-view Grand Seiko WAM-5500 binocular autorefractor/keratometer (AIT Industries, Bensenville, IL). The central value was the average of 10 valid readings, whereas the peripheral values were the average of 5 valid readings (within ±1.0 D of the median value for sphere and cylinder). Central refractive error was measured along the line of sight, then horizontal peripheral refractive error was measured in nasal and temporal gaze at eccentricities of 20°, 30°, and 40°. Vertical peripheral refractive error was measured in superior and inferior gaze at 20° and 30°. Measurements of peripheral refractive error with the contact lenses in place were only made in the horizontal meridian because contact lens decentration could be avoided by having participants turn their head laterally during measurement instead of their eyes; this was not possible for vertical measurements. Peripheral refraction in the vertical meridian with contact lenses in place was estimated under an assumption of rotational symmetry. The differences in peripheral measurements between eye-only and the eye wearing a lens at each horizontal eccentricity were added to the corresponding eye-only values at each vertical eccentricity.
Statistical analyses were completed using SAS, version 9.4 for Windows (SAS Institute, Cary, NC). The modeled 3-year changes in elongation at 20° and 30° were analyzed by treatment group and within each of the 4 quadrants. The modeled 3-year change in axial elongation was compared to peripheral elongation, again by treatment group and within each of the 4 quadrants. In order to avoid the many comparisons generated by multiple eccentricities, and to create analyses similar to those for baseline data, individual participant peripheral eye length data were also fit by quadratic equations as a function of gaze angle, one horizontal and one vertical, for each study year.
25 This approach has been validated against magnetic resonance imaging (MRI) and schematic eye retinal contours.
27–29 Models for each of these analytic approaches included treatment group, study year (categorical variable), and their interactions adjusted for sex, age group, and study site. The
P values for eccentricity and quadrant comparisons were adjusted for multiple comparisons using the step-down Bonferroni method of Holm.
30
Supported by the National Institutes of Health (NIH) grants NIH U10 EY023204; NIH U10 EY023206; NIH U10 EY023208; NIH U10 EY023210; NIH P30 EY007551; and NIH UL1 TR002733.
Jeffrey J. Walline (Study Chair, The Ohio State University College of Optometry), David A. Berntsen (UH Clinic Principal Investigator, University of Houston College of Optometry), Donald O. Mutti (OSU Clinic Principal Investigator, The Ohio State University College of Optometry), Lisa A. Jones-Jordan (Data Coordinating Center Director, The Ohio State University College of Optometry), Donald F. Everett (NEI Program Official), Jimmy Le (NEI Program Official, 2019-present).
Kimberly J. Shaw (Study Coordinator, The Ohio State University College of Optometry), Juan Huang (Investigator, The Ohio State University College of Optometry), Bradley E. Dougherty (Survey Consultant, The Ohio State University College of Optometry).
Loraine T. Sinnott (Biostatistician, The Ohio State University College of Optometry).
University of Houston Clinic Site (University of Houston College of Optometry).
Laura Cardenas (Clinic Coordinator), Krystal L. Schulle (Unmasked Examiner, 2014–2019), Dashaini V. Retnasothie (Unmasked Examiner, 2014–2015), Amber Gaume Giannoni (Masked Examiner), Anita Tićak (Masked Examiner), Maria K. Walker (Masked Examiner), Moriah A. Chandler (Unmasked Examiner, 2016-present), Mylan Nguyen (Data Entry, 2016–2017), Lea Hair (Data Entry, 2017–2018), Augustine N. Nti (Data Entry, 2019–2020).
Ohio State University Clinic Site (The Ohio State University College of Optometry)
Jill A. Myers (Clinic Coordinator), Alex D. Nixon (Unmasked Examiner, 2014–2019), Katherine M. Bickle (Unmasked Examiner, 2014–2020), Gilbert E. Pierce (Unmasked Examiner, 2014–2019), Kathleen S. Reuter (Masked Examiner, 2014–2019), Dustin J. Gardner (Masked Examiner, 2014–2016), Andrew D. Pucker (Masked Examiner, 2015–2016), Matthew Kowalski (Masked Examiner, 2016–2017), Ann Morrison (Masked Examiner, 2017–2019), Danielle J. Orr (Unmasked Examiner, 2018-present).
Data Safety and Monitoring Committee
Janet T. Holbrook (Chair, Johns Hopkins Bloomberg School of Public Health), Jane Gwiazda (Member, New England College of Optometry), Timothy B. Edrington (Member, Southern California College of Optometry), John Mark Jackson (Member, Southern College of Optometry), Charlotte E. Joslin (Member, University of Illinois at Chicago).
Disclosure: D.O. Mutti, Bausch & Lomb (F), Vyluma (C); L.T. Sinnott, Bausch & Lomb (F); D.A. Berntsen, Bausch & Lomb (F), Visioneering Technologies (advisory board) (C, R); L.A. Jones-Jordan, Bausch & Lomb (F); D.J. Orr, None; J.J. Walline, Bausch & Lomb (F)