Three-Year Change in Subfoveal Choroidal Thickness and Area With Multifocal Contact Lens Wear in the Bifocal Lenses in Nearsighted Kids (BLINK) Study

Abstract

Purpose: To evaluate changes in subfoveal choroidal thickness and area in children wearing soft multifocal contact lenses (MFCLs) for myopia control.

Methods: Analyses included 281 myopic children aged 7 to 11 years in the Bifocal Lenses in Nearsighted Kids (BLINK) Study randomly assigned to wear single vision contact lenses (SVCLs), +1.50 D add, or +2.50 D add center-distance MFCL. Subfoveal choroidal thickness and choroidal area were measured using spectral-domain optical coherence tomography before and after 2 weeks of lens wear, and then annually for 3 years. Repeated measures linear regression was used to determine the effect of contact lens wear on the choroid and test the association between choroidal changes and axial elongation.

Results: After initiating contact lens wear, mean ± SE subfoveal choroidal thickness and choroidal area increased in the +2.50 D MFCL group compared with the SVCL group by 8 ± 3 µm (P = 0.003) and 0.07 ± 0.02 mm² (P = 0.002), a difference maintained throughout the 3-year study (P ≥ 0.55). Increased choroidal thickness and area after 2 weeks in the +2.50 D MFCL group vs. SVCL group were associated with less axial elongation over 3 years (β = −0.0058 mm/µm and −0.947 mm/mm²; P = 0.02 and P = 0.006; 20% and 29% of total treatment effect, respectively).

Conclusions: The choroid increased in subfoveal thickness and area after 2 weeks of +2.50 D MFCL wear, which was maintained for 3 years and was associated with slower axial elongation. However, only a portion of the treatment effect can be accounted for by the choroidal parameters.

The primary function of the choroid, the vascularized subretinal connective tissue in the posterior eye, is to provide oxygen and metabolic support to the retinal pigment epithelium and outer retina.¹ A number of factors can affect choroidal morphology, including water intake,^2,3 caffeine,⁴ blood pressure,^5,6 light levels,^7,8 diurnal rhythms,⁹ age,^10–16 and sex.¹⁷ The choroid also appears to be involved in modulating episcleral and scleral growth¹⁸ and can change in thickness in response to optical defocus.¹⁹ The association of refractive error and emmetropization with choroidal thickness has been shown in both animal^20–22 and human studies.^23,24 Specifically, work done in animal models decades ago established that myopia is associated with a thinner choroid and hyperopia with a thicker choroid.^19,21 In human ametropia, relatively thicker choroids are seen in hyperopic eyes and thinner choroids are observed in myopic eyes, most pronounced at extreme lengths.^17,25–29 Similarly, myopic and hyperopic children have been shown to have thinner and thicker choroids, respectively.²³ 

More recently, animal and human studies have demonstrated the ability to modulate choroidal thickness using optical and therapeutic treatments.^30–32 In animal models, choroidal thickness changes associated with the sign of imposed retinal defocus have been reported before compensating changes in the rate of axial eye growth.^19–21 Visual cues, including defocus, have been shown to cause local and regional changes in eye growth in animal models,^{19,20,22,33–35} with recent studies showing choroidal thickening after short-term soft multifocal contact lens (MFCL) wear,³⁰ orthokeratology,³⁶ and custom spectacle designs (e.g., DIMS lens).³⁷ Ocular therapeutics and low-level light therapy have also been shown to cause choroidal thickening.^7,8,38–40 However, there are some conflicting findings, and no studies have evaluated choroidal thickness longitudinally in a large population of children undergoing multifocal myopia control treatment. With the increasing prevalence of myopia and efforts to implement treatments that reduce axial elongation, there is a strong public health interest in understanding the natural course of choroidal thinning or thickening, as well as the effects of treatments to slow myopia progression. 

The Bifocal Lenses in Nearsighted Kids (BLINK) Study was a 3-year, double-masked, randomized clinical trial that compared the progression of myopia in children wearing +1.50 D and +2.50 D add center-distance MFCL with children wearing single vision contact lenses (SVCLs). The purpose of this analysis was to examine the effects of MFCL on subfoveal choroidal thickness and choroidal area over the 3-year period and to determine whether there is any association with axial elongation. 

Methods

This research adhered to the tenets of the Declaration of Helsinki, was reviewed by independent ethical review boards at the University of Houston and The Ohio State University, and conformed with the principles and applicable guidelines for the protection of human participants in biomedical research. Participants were enrolled in a double-masked, 3-year, randomized clinical trial between September 2014 and June 2016. The BLINK Study was funded by the National Eye Institute, registered with ClinicalTrials.gov (NCT02255474), and monitored by an independent data safety and monitoring committee. 

Eligibility Criteria

At the BLINK Study baseline visit, participants were 7 to 11 years and had myopia between −0.75 and −5.00 D (inclusive) spherical component (minus cylinder), 1.00 D astigmatism or less in each eye, and no more than 2.00 D of anisometropia measured by cycloplegic autorefraction. A full list of the eligibility criteria, as well as the baseline characteristics, methods, and primary study results were reported previously.^41,42 Masked examiners performed cycloplegic autorefraction and eye length measurements at annual visits. The methods relevant to the current analyses are described. 

Contact Lenses

All participants were assigned randomly in a 1:1:1 ratio to wear SVCLs (Biofinity sphere), a medium add center-distance multifocal contact lens (+1.50 D MFCL; Biofinity Multifocal D; CooperVision; Victor, NY, USA), or a high add MFCL (+2.50 D MFCL; Biofinity Multifocal D). The randomization assignment was stratified by clinical site and age group (7–9 years vs 10–11 years) using a random permuted block design with varying block sizes of three to six. All participants received contact lenses, contact lens solution, and contact lens cases throughout the study at no charge; participants also received updated spectacles at a reduced cost annually. Participants were encouraged to wear their contact lenses during the day as often as they could comfortably do so, but were restricted from overnight wear. Participants and parents were masked by removing all labels from the contact lens blister packs before receiving the lenses. 

Cycloplegic Autorefraction

Central refractive error (right eye) was measured on each eye with the Grand Seiko WAM-5500 Binocular Autorefractor/Keratometer (Visionix; Lombart, IL, USA).⁴³ Cycloplegia was achieved using one drop of either 0.5% proparacaine or tetracaine followed by two drops of 1.0% tropicamide, separated by 5 minutes. Measurements were taken 25 minutes after the second drop of tropicamide. Participants fixated 20/30 size letters on a near point test card viewed through a +5.50 D Badal lens. The letters were presented at the far point, then moved to a slightly blurred position to ensure relaxation of any residual accommodation.⁴⁴ The average M, J₀, and J₄₅ were calculated from the last 10 valid readings.⁴³ 

Axial Length

Axial length of the right eye was measured using the Lenstar LS 900 (Haag-Streit USA; Mason, OH, USA) after cycloplegic autorefraction, with the contralateral eye patched while fixating the internal red light. Five readings without a poor-quality warning indicator were obtained. 

Pupil Size

Pupil size (right eye) was measured at the baseline visit under photopic (approximately 500 lux) conditions to the nearest 0.1 mm using a NeurOptics VIP-200 Pupilometer (NeurOptics, Inc.; Irvine CA, USA), while the other eye fixated at distance. 

Choroidal Thickness and Area

Spectral-domain optical coherence tomography star scans composed of six 30° B-scans (1536 × 496 pixels; lateral resolution, 51.2 pixels/degree; axial resolution, 3.9 µm/pixel) measured using automatic retinal tracking and enhanced depth imaging were acquired from right eyes before and 2 weeks after starting study contact lens wear (images taken immediately after lens removal and before drop instillation), then yearly thereafter (Spectralis Optical Coherence Tomography; Heidelberg Engineering, Franklin, MA, USA) (Fig. 1). Each B-scan was an average of 30 scans. Follow-up mode was used for all scans after the initial baseline measurement, which ensures that the scanned area is the same region of retina relative to the baseline scan. Baseline choroid measurements were made immediately after removing the child's habitual correction, and all subsequent measurements were made immediately after removing the study contact lens from the right eye. A correction for lateral magnification was made using the Spectralis software, which uses corneal curvature and refractive error. Before segmentation of the B-scan images by a trained and certified examiner, each 30° B-scan was cropped by 2° per side to eliminate most edge and optic nerve artifacts, reducing each scan to 26°. Validated semiautomated routines were used to segment the retinal pigment epithelium–choroid boundary and choroid–sclera boundary.^45,46 Subfoveal choroidal thickness and cross-sectional area of each B-scan were calculated from the segmented images. 

Figure 1.

 

OCT segmentation. The star scan was acquired using OCT and the anterior (yellow line) and posterior (green) choroidal boundaries were detected using semiautomated routines. Subfoveal choroidal thickness and choroidal area were calculated from the boundaries in each of the six scans. Regional area was calculated using the appropriate part of each B-scan in each of the regions shown.

Statistical Analysis

Subfoveal choroidal thickness and overall choroidal area at each visit were calculated from the average of the six B-scans. Regional area was also calculated for the superior, inferior, nasal, and temporal retina using the appropriate portions of the B-scans as shown in Figure 1. Separate repeated-measures linear regression models were used to determine the effect of treatment group and visit on subfoveal choroidal thickness, overall choroidal area, and regional area over the 3-year study period and tested for an interaction between treatment group and visit. Separate models were used to determine the effect of the 2-week change in both subfoveal choroidal thickness and overall area, including interaction with treatment group, on the 3-year change in axial length. Models were also used to determine the effect of the 3-year change in axial length (i.e., axial elongation during the study) on both the final subfoveal choroidal thickness and overall area at the end of the 3-year study, including an interaction with treatment group. Models controlled for either baseline subfoveal choroidal thickness or area, clinic site, sex, age at randomization, baseline photopic pupil size, and baseline axial length. All statistical analyses were performed using SAS 9.4 (SAS; Cary, NC, USA), and P values of less than 0.05 were considered statistically significant. 

Results

A total of 281 of the 294 myopic children enrolled in BLINK contributed choroid data for this analysis. Baseline choroid data were not available for 13 children due to an instrument issue at one clinic site. The mean age of the children at the baseline visit was 10.3 ± 1.2 years (range, 7–11 years), spherical equivalent myopia was −2.41 ± 1.01 D (range, −0.82 to −5.48 D), photopic pupil size was 5.3 ± 0.7 mm (range, 3.1–7.0 mm), and 61% were female. Children reported wearing lenses 11.12 ± 2.95 (SVCL), 10.77 ± 3.30 (+1.50 D MFCL), and 10.77 ± 3.29 (+2.50 D MFCL) hours per day during the study period. Subjects wore spectacle correction when not in the treatment lenses. Baseline subfoveal choroidal thickness (mean, 303 ± 58 µm) and choroidal area (2.25 ± 0.39 mm²) did not differ between groups (both P ≥ 0.93). On average, the choroid was thickest inferior to the macula and thinnest nasal to the macula near the optic nerve head (Fig. 2A). The change in choroidal thickness by treatment group after 2 weeks of study contact lens wear are shown in Figure 2B. After 2 weeks of contact lens wear, a significant increase in both subfoveal choroidal thickness (mean ± SE, 8 ± 3 µm; P = 0.003) and choroidal area (0.07 ± 0.02 mm²; P = 0.002) were observed in the +2.50 D MFCL group compared with the SVCL group. There were no differences in subfoveal choroidal thickness or area between the +1.50 D MFCL group and the SVCL group (both P ≥ 0.25). Other than the initial thickening 2 weeks after initiating MFCL wear, there were no significant changes over the 3-year study period in either subfoveal thickness (P = 0.09) or area (P = 0.11). The initial increase in both subfoveal choroidal thickness and choroidal area in the +2.50 D MFCL group compared with the SVCL group was maintained through the 3-year visit by an average of 7 ± 3 µm (P = 0.01) and 0.06 ± 0.02 mm² (P = 0.003), respectively. There were no differences between the +1.50 D MFCL and the +2.50 D MFCL groups in subfoveal thickness (P = 0.13) or area (P = 0.07), or between the +1.50 D MFCL and SVCL groups (P = 0.29 and P = 0.25, respectively). 

Figure 2.

 

Choroidal thickness maps. Baseline choroidal thickness for all participants (A), and the change in choroidal thickness from baseline by treatment group after 2 weeks of study contact lens wear (B). MFCL, multifocal contact lens.

Figure 3 shows the subfoveal choroidal thickness and overall area at each visit, and Figures 4 and 5 show the change from baseline in subfoveal choroidal thickness and overall area and change in regional choroidal area at each visit, respectively. In the regional analysis, choroidal area was significantly greater after initiating study contact lenses in the +2.50 D MFCL group compared with the SVCL group in the superior, inferior, and temporal subareas (all P < 0.025), but not in the nasal region by the optic nerve where there was no difference between groups (P = 0.16). After the initial increase in choroidal area in the superior, inferior, and temporal regions 2 weeks after initiating MFCL wear, there were no significant changes over the 3-year study period (all P > 0.17). The mean variability of the subfoveal choroidal thickness values by visit and treatment group are shown in Supplementary Table S1. 

Figure 3.

 

Modelled choroidal thickness and overall area after study contact lens wear was initiated. Significant differences were observed between the +2.50 D MFCL and SVCL groups at all visits, with no differences seen between or within other groups at any visit. Models controlled for the initial thickness/area before initiating study contact lens wear, clinic site, sex, age, randomized treatment group, baseline photopic pupil size, and baseline axial length. The asterisk and bars connect groups within a visit that were significantly different from one another. SVCL, single vision contact lens. Error bars show the SEM.

Figure 4.

 

Modelled changes in choroidal thickness and overall area after study contact lens wear was initiated. Significant differences were observed between the +2.50 D MFCL and SVCL groups at all visits. Models controlled for the initial thickness before initiating study contact lens wear, clinic site, sex, age, randomized treatment group, baseline photopic pupil size, and baseline axial length. Error bars show the SEM.

Figure 5.

 

Modelled regional changes in choroidal area after study contact lens wear was initiated. Models controlled for the initial area before initiating study contact lens wear, clinic site, sex, age, randomized treatment group, baseline photopic pupil size, and baseline axial length. Error bars show the SEM.

Factors Influencing Choroidal Thickness and Area Over 3 Years

Models of both subfoveal choroidal thickness and choroidal area 2 weeks after initiating study contact lens wear through the 3-year visit are shown in the Table. Both subfoveal choroidal thickness (P = 0.04) and choroidal area (P = 0.01) after initiating study contact lens wear were greatest throughout the 3-year study in those assigned to wear +2.50 D MFCL. There were no differences in subfoveal choroidal thickness (P = 0.07) or choroidal area (P = 0.12) from the 3-week (2 weeks after initiating CL) through the 3-year visits (i.e., the initial increase observed 2 weeks after initiating +2.50 D MFCL wear was maintained for the remainder of the study). 

Table.

 

Modelled Subfoveal Choroidal Thickness and Choroidal Area by Treatment Group 2 Weeks After Initiating Study Contact Lens Wear Through the 3-Year Visit

 

Choroid Change After Initiating Study Contact Lenses and the 3-Year Change in Axial Length

The association between the 2-week change in both subfoveal choroidal thickness and area with the 3-year change in axial length are shown in Figures 6 and 7, respectively. Although the initial 2-week change in subfoveal thickness in the SVCL group was not associated with the 3-year change in axial length (P = 0.38), the association was significantly different in the +2.50 MFCL group with participants with more subfoveal thickening after initiating contact lens wear having less axial elongation over 3 years (β = −0.0058 mm less axial growth over 3 years per micron thickening after 2 weeks of lens wear compared with the SVCL group; P = 0.02). Based on the difference in slope of the association between the two groups of −0.0058 mm per micron and the average increase in subfoveal choroidal thickness of 8 microns in the +2.50 D MFCL group vs. the SVCL group, this model can explain 0.0464 mm (20%) of the 0.23-mm reduction in axial growth observed over 3 years when wearing +2.50 D MFCL. 

Figure 6.

 

Modelled change in subfoveal choroidal thickness (µm) 2 weeks after initiating study contact lenses vs. the 3-year change in axial length (mm) by the assigned treatment group, after adjusting for treatment group, visit, clinic site, sex, age group at randomization, baseline photopic pupil size, and axial length at baseline. Slope and 95% confidence intervals are shown for each group.

Figure 7.

 

Modelled change in choroidal area (mm²) 2 weeks after initiating study contact lenses vs. the 3-year change in axial length (mm) by the assigned treatment group, after adjusting for treatment group, visit, clinic site, sex, age group at randomization, baseline photopic pupil size, and axial length at baseline. Slope and 95% confidence intervals are shown for each group.

Similarly, although the 2-week change in choroidal area after initiating contact lens wear in the SVCL group was not associated with the 3-year change in axial length (P = 0.29), the association was significantly different in the +2.50 MFCL group with participants with more increases in choroidal area after initiating contact lens wear having less axial elongation over 3 years (β = −0.947 mm less axial growth over 3 years per square millimeter of thickening after 2 weeks of lens wear compared with the SVCL group; P = 0.006). Based on the difference in slope of the association between the two groups of −0.947 mm per square millimeter and the average 2-week increase in choroidal area of 0.07 mm² in the +2.50 D MFCL group vs. the SVCL group, this model can explain 0.066 mm (29%) of the 0.230-mm reduction in axial growth observed over 3 years when wearing +2.50 D MFCL. There were no statistically significant associations between the 3-year change in axial length and either the 2-week increase in subfoveal choroidal thickness or choroidal area in participants assigned to wear +1.50 D MFCL contact lenses (P = 0.07 and P = 0.054, respectively). 

Three-Year Change in Axial Length and Final Choroidal Subfoveal Thickness and Area

We determined whether the 3-year change in axial length influenced the final choroidal subfoveal thickness or area at the end of the 3-year study (Figs. 8 and 9, respectively). In the single vision group, there was a significant association between the 3-year increase in axial length and the final subfoveal choroidal thickness, although the relationship was clinically small (β = −0.7 µm thinner per mm of axial elongation; P = 0.002). The slope of the association was significantly more negative for the +2.50 D MFCL group than the SVCL group (β = −20.2 µm thinner per mm of axial growth over the 3-year study; P = 0.02). Similarly, although there was a significant association between the 3-year increase in axial length and the final choroidal area, the relationship was again clinically small (β = −0.021 mm² less choroidal area per millimeter of axial elongation; P = 0.0002). The slope of the association was again significantly more negative in the +2.50 D MFCL group than the SVCL group (β = −0.165 mm² less choroidal area per millimeter of axial elongation over 3 years; P = 0.006). In other words, while eye growth in the single vision group had a negligible effect on the final choroidal thickness and area, eyes in the +2.50 D MFCL group that grew less finished with slightly thicker choroids. There was no statistically significant difference in the slope of these associations between the +1.50 D MFCL and single vision groups for final choroidal subfoveal thickness (P = 0.10) or area (P = 0.20). 

Figure 8.

 

Modelled 3-year change in axial length (mm) vs. subfoveal choroidal thickness at the 3-year visit (µm) by the assigned treatment group, after adjusting for treatment group, visit, clinic site, sex, age group at randomization, baseline photopic pupil size, and axial length at baseline. Slope and 95% confidence intervals are shown for each group.

Figure 9.

 

Modelled 3-year change in axial length (mm) vs. choroidal area at the 3-year visit (mm²) by the assigned treatment group, after adjusting for treatment group, visit, clinic site, sex, age group at randomization, baseline photopic pupil size, and axial length at baseline. Slope and 95% confidence intervals are shown for each group.

Discussion

The BLINK study provides the longest longitudinal report of choroidal changes in myopic children wearing SVCL and MFCL. We found significant choroidal thickening 2 weeks after myopic children initiated +2.50 D MFCL wear that was maintained throughout the 3-year study period. These same children had, on average, 0.23 mm less axial eye growth over 3 years than children wearing SVCL.⁴¹ This study did not detect a significant increase in the thickness or area of the choroid in the +1.50 D MFCL group and similarly did not find that +1.50 D MFCL slowed axial elongation over 3 years. When examining regional changes in choroidal area, the superior, inferior, and temporal regions thickened in the +2.50 MFCL group, but we did not find significant thickening in the nasal region, likely owing to the choroid being thinner near the optic nerve. These findings could suggest a mechanistic role for the choroid in the +2.50 D MFCL treatment effect, and these results are consistent with numerous studies in both adults and children that have reported that myopia control interventions including myopic defocus (via spectacles, orthokeratology, or soft MFCL), atropine, and low-level red light thicken the choroid.^{8,30,32,38–40,47,48} Although Read et al.¹² reported that choroidal thickness was greater as age increased in a cross-sectional cohort of 4- to 12-year-old emmetropic children, our cohort was myopic and older (7–11 years at baseline). Shen et al.⁴⁹ assessed 2290 Chinese children and found a significant subfoveal choroidal thinning in the school aged progressive myopes, which is more consistent with our cohort and findings. Ultimately, it could be that, during active eye growth and myopia progression, the choroid tends to maintain thickness or become thinner, whereas nonmyopic eyes slowly thicken. 

The precise mechanism by which choroidal thickness affects axial elongation is not fully understood, but it is believed that the choroid modulates scleral biochemical properties by secreting various growth factors and matrix metalloproteinases.³⁵ The choroid also regulates blood flow to the outer eye, which has several implications for the delivery of nutrients and growth factors that could impact growth of the sclera and surrounding structures. More work is needed to continue furthering our understanding of the role the choroid plays in the regulation of eye growth. 

After the initial 2-week period of lens wear, there was no significant change in choroidal thickness or area over time; however, greater axial elongation over 3 years was associated with a thinner choroid at the end of the study. Likewise, especially among multifocal wearers, those with the least axial elongation had thicker choroids. In a previous study, Read et al.²⁴ reported slight subfoveal choroidal thickening over 18 months in normal children, but their cohort included both nonmyopic and myopic children and was older (10–15 years). In their study, myopic children had greater axial elongation and less choroidal thickening compared with nonmyopic children, and, in the case of the fastest progressors, some thinned over time.⁵⁰ Cross-sectional studies examining choroidal thickness in adults 20 to 90 years of age have found that older age and longer, more myopic eyes are associated with a thinner choroid.^25–28 In BLINK, aside from the treatment group-specific changes 2 weeks after initiating study contact lens wear, we did not find a statistically significant change in the choroid within each treatment group over the 3-year study period. 

This result of choroidal thickening with MFCL is consistent with shorter-term studies of optical interventions. In a study where the choroid was measured after 3 months of MFCL wear, Tarutta et al.⁵¹ found that subfoveal choroidal thickness increased in myopic children wearing a +4.00 D add power MFCL. As in our study, they found a negative correlation between choroidal thickness and the change in axial length in their MFCL group, but not in their control group. That said, not all studies have found such an association. Prieto-Garrido et al.³¹ examined the effect of MiSight contact lenses (a dual focus MFCL design) on choroidal thickness in myopic children, grouping participants as responders or nonresponders to treatment, and did not find a significant difference in choroidal thickness in either group compared with a single vision spectacle group. Studies evaluating choroidal thickness in orthokeratology have reported an increase in thickness after initiating orthokeratology lens wear that was significant initially,^52–54 but diminished over time.^53,54 Conflicting results may be due to smaller sample sizes, the type of myopia control treatment being evaluated, the conditions under which choroid measurements were made, and the protocol for imaging and analysis. High variability in choroid changes may also account for nonsignificance in smaller studies. 

On average, the increase in subfoveal choroidal thickness after 2 weeks of wearing +2.50 D MFCL in BLINK resulted in subfoveal choroidal thickening and an increase in choroidal area that were both associated with slower axial elongation. However, when considering the magnitude of the association, the average initial subfoveal choroidal thickening of 8 µm after wearing +2.50 D MFCL for 2 weeks only accounted for 20% of the 0.23-mm, 3-year decrease in axial growth. Similarly, the average initial increase in choroidal area in children wearing +2.50 D MFCL of 0.07 mm² accounted for 29% of the 3-year decrease in axial growth. Our findings are consistent with recently reported longitudinal data by Yam et al.³² that evaluated choroidal thickness and axial elongation in children receiving low concentrations of atropine during a 2-year randomized controlled trial. They reported dose-dependent thicker subfoveal choroidal thickness in groups receiving 0.050% or 0.025% atropine that was maintained over 2 years and was associated with decreased axial elongation. They estimated that subfoveal choroidal thickening accounted for 18.5% of the treatment effect of 0.05% atropine on slowing myopia progression.¹³ Together with our longitudinal results, these findings support the hypothesis that choroidal thickening plays a role in the myopia control effect. That said, despite sustained thickening in the treatment groups of both studies, choroidal thickening due to a myopia control intervention only accounted for a small portion (between 20% and 29%) of the observed treatment effect. 

Although we found an association between initial choroidal thickening and the 3-year slowing of eye growth, the high variability in choroid measurements questions their usefulness in predicting children who will respond best to treatment in a clinical setting. The mean changes in choroid were small and the standard deviations of the change within each group were many times greater, indicating that there is both thickening and thinning within each group. Although choroidal changes should not be used to predict individual treatment success, given a large enough sample size, short-term choroidal changes could help to determine which treatments have the greatest likelihood of success in a clinical trial. 

A limitation of the present study is that we were unable to precisely account for diurnal variations in the choroid. Choroidal thickness is reported to follow a diurnal pattern,⁵⁵ although myopes may have smaller amplitudes of diurnal variation.⁹ In this study, most visits were done at a consistent time of day (after school), so the impact of diurnal variation was at least somewhat minimized. There could also be seasonal variation, with smaller changes in winter months, which was not evaluated in this study but has been suggested in other studies.²⁴ Participants in our study returned for their annual visits at the same time each year. Another limitation is that the correction for lateral magnification in our study was calculated by the Spectralis software using refractive error and corneal curvature, and the accuracy of this correction could have been improved by incorporating axial length. Additionally, we did not attempt to control other factors that can influence choroidal thickness (e.g., prior near work, water intake, caffeine, and blood pressure).^56–60 Although some studies designed to look specifically at the choroid as the primary outcome have attempted to control various environmental factors for several minutes before measuring the choroid, our measurements were more consistent with what would be realistic in a standard clinical practice setting. 

In conclusion, there was an initial increase in subfoveal choroidal thickness and choroidal area 2 weeks after initiating +2.50 D MFCL wear that was maintained over the next 3 years. There was no significant initial change in the choroid in the +1.50 D MFCL group. In the +2.50 D MFCL group, eyes that had a smaller 3-year increase in axial length ended the study with a slightly thicker choroid. There was also an association in the +2.50 D MFCL group between greater initial choroidal thickening 2 weeks after initiating MFCL wear and less 3-year axial elongation, suggesting a potential mechanistic role for the choroid in the multifocal treatment effect. Whereas choroid changes at the group level could be used to identify myopia treatments with the best potential for future study, these changes had only low to moderate ability to predict future axial eye growth. The high within-group variability of choroidal changes (both thickening and thinning within treatment groups) limits the clinical utility of the choroid predicting whether a specific child is likely to respond to a treatment. 

Acknowledgments

Supported by the National Institutes of Health UG1-EY023204, UG1-EY023206, UG1-EY023208, UG1-EY023210, P30-EY007551, and UL1-TR002733. Bausch + Lomb (contact lens solution). 

BLINK Study Group 

Executive Committee: Jeffrey J. Walline, OD PhD FAAO (Study Chair); David A. Berntsen, OD PhD FAAO (UH Clinic Principal Investigator); Donald O. Mutti, OD PhD FAAO (OSU Clinic Principal Investigator); Lisa A. Jones-Jordan, PhD FAAO (Data Coordinating Center Director); Donald F. Everett, MA (NEI Program Official, 2014-2019); Jimmy Le, ScD (NEI Program Official, 2019-present). 

Chair's Center: Kimberly J. Shaw, CCRP (Study Coordinator); Jenny Huang Jones, OD PhD FAAO (Investigator, 2014-2019); Bradley E. Dougherty, OD PhD FAAO (Consultant, 2020-present); Mora E. Boatman, BS (Investigator, 2023-present). 

Data Coordinating Center: Loraine T. Sinnott, PhD (Biostatistician); Matthew L. Robich, MPH (Biostatistician, 2020-present); Pamela S. Wessel (Coordinator, 2014-2017, deceased); G. Lynn Mitchell, MAS (Biostatistician, 2024-present). 

University of Houston Clinic Site: Laura Cardenas (Clinic Coordinator, 2014-2024); Krystal L. Schulle, OD FAAO (Examiner, 2014-2019); Dashaini V. Retnasothie, OD MS FAAO (Examiner, 2014-2015); Amber Gaume Giannoni, OD FAAO (Examiner); Anita Tićak, OD MS FAAO (Examiner); Maria K. Walker, OD PhD FAAO (Examiner); Moriah A. Chandler, OD FAAO (Examiner, 2016-present); Mylan T. Nguyen, OD MS MSPH FAAO (Data Entry, 2016-2017); Lea A. Hair, OD MS (Data Entry, 2017-2019); Augustine N. Nti, OD PhD FAAO (Data Entry, 2019-2022); Justina R. Assaad, OD FAAO (Examiner, 2022-present); Erin S. Tomiyama, OD PhD FAAO (Examiner, 2019-2022). 

Ohio State University Clinic Site (The Ohio State University College of Optometry): Jill A. Myers (Clinic Coordinator); Alex D. Nixon, OD MS FAAO (Examiner, 2014-2019); Katherine M. Bickle, OD PhD FAAO (Examiner, 2014-2020); Gilbert E. Pierce, OD PhD FAAO (Examiner, 2014-2019, deceased); Kathleen S. Reuter, OD (Examiner, 2014-2019); Dustin J. Gardner, OD MS FAAO (Examiner, 2014-2016); Matthew Kowalski (Examiner, 2016-2017); Ann Morrison, OD PhD FAAO (Examiner, 2017-2019); Danielle J. Orr, OD MS FAAO (Examiner, 2018-present); Rachel L. Fenton, OD MS FAAO (Examiner, 2020-present). 

Data and Safety Monitoring Committee/Data Monitoring and Oversight Committee: Janet T. Holbrook, PhD (chair; Johns Hopkins Bloomberg School of Public Health); Jane Gwiazda, PhD (member; New England College of Optometry); Timothy B. Edrington, OD (member; Southern California College of Optometry); John Mark Jackson, OD, MS (member; Southern College of Optometry); Charlotte E. Joslin, OD, PhD (member; University of Illinois at Chicago). 

Disclosure: M.K. Walker, Bausch + Lomb (F); D.A. Berntsen, Bausch + Lomb (F); M.L. Robich, Bausch + Lomb (F); R.L. Fenton, Bausch + Lomb (F); A. Ticak, Bausch + Lomb (F); J.R. Assaad, Bausch + Lomb (F); H.M. Queener, None; S.J. Chiu, Patent 10,366,492 (P); S. Farsiu, Patent 8,811,745, Patent 9,299,155, Patent 9,589,346, Patent 10,366,492 (P); D.O. Mutti, Bausch + Lomb (F), Vyluma (C); L.A. Jones-Jordan, Bausch + Lomb (F); J.J. Walline, Bausch + Lomb (F), 24 Myoptechs Inc. (C)