To evaluate the effect of Prima BIO Bi-focal BFCLs on clinical refraction and axial length in patients with progressive mild to moderate myopia during a long- term follow-up period.

This study was conducted from September 2018 to December 2023 at the Ophthalmologic Clinic “Krugozor” in Moscow. Twenty-eight patients with mild to moderate myopia, ranging from -0.75 to -5.5 D spherical equivalent (SE), were included. Based on the degree of myopia, the patients were divided into two groups: the first group consisted of 13 patients with mild myopia (-0.75 to -3.00 D), and the second group included 15 patients with moderate myopia (-3.25 to -5.50 D). The baseline axial length inclusion criterion was set at 23.5 mm. The sex distribution across the groups was identical. Figure 1 presents the baseline axial length distribution for boys and girls, plotted against percentile curves for monitoring myopia progression, as compiled by Tideman J. et al. for European children. The majority of our patients fell along the 90th percentile curve, indicating a high risk of developing myopia, including high-grade myopia, in this cohort [20][21].

At baseline, all patients underwent comprehensive evaluation, including cycloplegic refraction, visual acuity, and general eye health. Objective refraction error were measured under cycloplegia using a TONOREF III Auto Ref/Keratometer (NIDEK, Japan). Cycloplegia was induced using double instillation of 1% cyclopentolate. Axial length measurements were obtained using the Aladdin optical biometer (Topcon, Japan). To correct and manage myopia, both groups were fitted with Hioxifilcon B hydrogel BFCLs for daily wear on a monthly replacement schedule. The BFCLs, developed by OKVision (Russia), featured two concentric zones, with a 2.5 mm central zone and +4.0 D add power in the periphery to create induced peripheral myopic defocus.

Contact lens wear was recommended for 10-12 hours per day, at least six days per week, with monofocal spectacles worn during the remaining time. Dynamic follow-up visits occurred every three months, during which the lens fit and corneal epithelium condition were assessed through biomicroscopy with fluorescein staining. Clinical refraction and axial eye length data were used to assess the effectiveness of the treatment.

The study was conducted in compliance with the ethical principles outlined in the Declaration of Helsinki. The study protocol was approved, and informed written consent from parents was obtained prior to the study’s commencement.

Statistical analysis and data visualization were conducted using R 4.4.1 (R Foundation for Statistical Computing, Vienna, Austria).

Descriptive statistics are presented as absolute and relative frequencies for qualitative variables and as medians (1st; 3rd quartiles) for quantitative variables.

The Mann-Whitney test was used to compare quantitative variables between the two groups, while Pearson's χ² test was applied for categorical variables. When comparing the groups in terms of the dynamics of quantitative indicators, we used robust linear regression models with mixed effects, implemented via the robustlmm 3.3-1 package [22]. Fixed effects included the degree of myopia, observation period, and their interactions, while nested random effects for patients and eyes were used to account for correlated observations. Contrast generation and pairwise post hoc comparisons were conducted using the emmeans 1.10.2 package, and the Hill procedure was applied to control for type I error inflation. Statistical significance was set at p<0.05.

During the follow-up period, 7% (2 out of 28) of patients with mild myopia and 11% (3 out of 28) of those with moderate myopia dropped out of the study for various reasons. The primary reason for withdrawal (4 out of 5 participants) was switching to orthokeratology lenses due involvement in active sports. One additional participant left the study due to relocation. Ultimately, 23 patients, aged 7 to 12 years, with mild to moderate myopia were included in the statistical analysis. Table 1 presents the demographic characteristics of the study groups. Comparative analysis revealed no statistically significant differences between the groups in terms of age (p=0.925, Figure 2) or sex composition (p=0.827, Figure 3), based on the degree of myopia.

Tables 2 and 3, along with Figures 4 and 5, present the results of the comparative analysis of axial eye length dynamics in the studied groups. We found a statistically significant association between the dynamics of axial eye length while wearing high add BFCLs and the degree of myopia (p<0.001). Throughout the observation period, patients with moderate myopia consistently exhibited significantly higher axial eye length, and in both groups, the change in this index over time was statistically significant (p<0.001). In the mild myopia group, axial eye length increased by 0.06 mm (-0.02; 0.19) after 36 months of lens wear (p=0.047), by 0.07 mm (-0.01; 0.21) after 48 months (p=0.008), and by 0.14 mm (0.03; 0.24) after 60 months (p<0.001) compared to baseline values. In the moderate myopia, the changes in the axial eye length were more pronounced. There was a statistically significant increase of 0.15 mm (0.04; 0.23) after 24 months (p<0.001), 0.1 mm (0.02; 0.19) after 36 months (p=0.002), and 0.12 mm (0.03; 0.15) after 48 months (p=0.002) compared to the previous stage of observation. When compared to baseline values, the median increases in axial length after 24, 36, 48, and 60 months were 0.13 mm (0.06; 0.28), 0.24 mm (0.13; 0.37), 0.4 mm (0.21; 0.55), and 0.48 mm (0.21; 0.55), respectively (p<0.001).

The results of the comparative analysis of refractive error dynamics are presented in Tables 3 and 4, and Figures 6 and 7. Statistically significant differences were observed between the groups regarding to the dynamics of this parameter during contact lens use. Throughout the entire observation period, patients with moderate myopia had statistically significantly higher refractive error values (p<0.001, Table 4). In both grouts, statistically significant changes in refractive error were noted over the follow-up period (p=0.011 for mild myopia and p<0.00 for moderate myopia). In the mild myopia group, there was a statistically significant increase in refractive error after 24 months (p=0.026), 36 months (p=0.028), 48 months (p=0.014), and 60 months (p=0.005) compared to pre-lens values. In the moderate myopia group, the changes in refractive error were more pronounced. After 12 months of lens use refractive error increased by 0.25 (0; 0.5) D compared to baseline values, with a further significant increase of 0.38 (0.06; 0.94) D after 24 months compared to the previous stage (p<0.001). After this period, the refractive error values tended to plateau (Figure 5).

No serious side effects were associated with BFCL use during follow-up period. In two cases within the mild myopia group, superficial small dot staining of the cornea, mainly at the limbus, and superficial circular staining of the conjunctiva corresponding to the lens edge were observed. These changes were asymptomatic, did not affect the functional state of the eye, and were managed with the local application of keratoprotectants.

In this study, the median axial length increase over five years was 0.14 mm in the mild myopia group and 0.48 mm in the moderate myopia group. According to the CLEERE study, these results are comparable to the growth rate of emmetropic eyes [23], suggesting that BFCLs effectively curb excessive axial elongation. The findings align with previous studies that have confirmed the slowing of myopia progression with BFCLs designed to induce peripheral myopic defocus [24-29].

We observed a statistically significant association between the axial length dynamics and the degree of myopia during BFCL wear (p<0.001). Over the entire observation period, patients with moderate myopia experienced a statistically significant greater increase in axial length. However, clinically, this difference can be interpreted as monor, since the eye growth in patients with mild myopia was lower than emmetropic elongation, while in the moderate myopia group, it was comparable to emmetropic growth [23]. According to Mutti et al., the difference in axial length gain between emmetropic and myopic children in an age-matched cohort was 0.14 mm/year, with emmetropic children showing an annual increase of about 0.1 mm, compared to 0.31 mm/year in myopic children. [30].

The pronounced antimyopic effect of BFCLs in our study may be attributed to the high add power of +4.00 D. Several studies have confirmed the relationship between higher add powers and increased efficacy of SCLs in inducing myopic defocus [17]. A three-year randomized clinical trial comparing different add powers of MFCLs found that lenses with +2.50 D add more effective in slowing myopia progression that those with +1.50 D add. [31].

Interestingly, in this study, the efficacy of BFCLs remained stable each year over the five-year period. This contrasts with meta-analysis of 30 studies (duration of one to three years), where Huang et al. concluded that the effectiveness of optical methods of myopia control peaked in the first year and tended to decline thereafter, particularly in terms of axial length changes [32]. Brennan and Cheng also reported a decrease in antimyopic efficacy over time [33]. Further research is needed to better understand how the efficacy of myopia control agents changes over longer periods.

Our study results indicate a slower rate of axial length growth and refractive error progression in the mild myopia group. In this group, the total chang in refractive error and axial length was 0.25 D and 0.14 mm, respectively, compared to 1.25 D and 0.48 mm in the  moderate myopia group. The greater antimyopic effect in the mild myopia group may be due to the later onset of myopia compared to the moderate myopia group, where earlier onset of myopia is likely. Although the two groups in our study were of similar age, it is well-established that earlier onset of myopia is associated with faster progression, the findings supported by several studies [34-36]. Hyman et al. found that the initial age of myopia onset was the most significant factor associated with faster progression [37], and Chua et al. similarly identified early onset as a predictor of rapid progression [38].

Another possible reason for the faster progression in moderate myopia patients, compared to mild myopia patients, may be their baseline refractive status. Tricard et al. observed that each additional diopter of baseline myopia was significant in predicting the risk of high myopia development during follow-up [39]. The authors noted that the risk of developing high myopia increased from 16% to 58% between the ranges of -3.00 to -4.00 and -4.00 to -6.00 D.

We were unable to find any studies that investigated the effect of high add MFCLs on axial length and refractive error changes in children over periods longer than three years. One of the strengths of our study is the inclusion criterion of an axial length of 23.5 mm or greater. The baseline axial eye length in our study, considering the average age of participants, corresponded to the 90th percentile for girls and the 75th percentile for boys, which is a risk factor for developing high-grade myopia [20][21].

A major limitation of this study is the lack of a control group. Additionally, the small sample size was due to the challenges of long-term follow-up, though patient retention in the study was high.

The findings indicate a clinically significant stabilizing effect of Prima BIO Bi-focal soft contact lenses on progressive myopia in children and adolescents with mild to moderate myopia. A greater antimyopic effect, in both refractive error dynamics and axial elongation, was observed in mild myopia group, suggesting that BFCLs may be recommended at the initial stages of myopia. BFCLs with high add power maintained their therapeutic efficacy over the five-year observation period, without diminishing after the first year of use. Further research is needed to explore the correlation between the myopia-slowing effects of BFCLs and the degree of myopia.

Authors contributions:

Research concept and design: A.V. Myagkov.

Data collection and processing: E.S. Zenkova.

Manuscript writing: E.S. Zenkova, A.V. Myagkov.

Final editing: A.V. Myagkov.