Abstract
Purpose
To explore the correlation between recombinant human growth hormone (rhGH) therapy and myopia progression, and to optimize the myopia control strategies in myopic children undergoing rhGH therapy.
Methods
This retrospective study included 27 myopic children receiving rhGH therapy and 57 myopic children in the control group, all of whom underwent myopia interventions. Axial length (AL) and refraction were measured by IOLMaster and an autorefractor after cycloplegia. AL changes were compared between the rhGH and control groups, before and after rhGH therapy, and among different myopia control strategies. Univariate and multivariate regression models analyzed factors associated with axial elongation.
Results
The rhGH group exhibited greater median AL change than the control group (0.29 mm/year; interquartile range [IQR], 0.19–0.40; n = 27 vs. 0.18 mm/year; IQR, 0.12–0.27; n = 57; P < 0.001). Median axial elongation increased after rhGH treatment (0.22 mm/year; IQR, 0.12–0.34 vs. 0.32 mm/year; IQR, 0.26–0.40; n = 14; P = 0.026), while it decreased after cessation (0.39 mm/year; IQR, 0.16–0.56 vs. 0.04 mm/year; IQR, –0.03–0.15; n = 6; P = 0.031). After adjusting for confounders, axial elongation was faster in the rhGH group (β = 0.13, P < 0.001). Longer rhGH therapy duration and shorter myopia control duration were associated with accelerated axial elongation (β = 0.13, P = 0.027). Dual-therapy myopia control appeared to mitigate excessive axial elongation in rhGH-treated children more effectively than monotherapy (0.27 mm/year; IQR, 0.18–0.31; n = 20 vs. 0.40 mm/year; IQR, 0.32–0.70; n = 7; P = 0.026).
Conclusions
Myopic children undergoing rhGH therapy would exhibit accelerated axial elongation despite myopia control. Close monitoring and dual-therapy myopia control strategies are recommended for these children.
1
Introduction
The prevalence of myopia has profoundly increased over the last three decades and has become a major global public health concern. Pathologic consequences of myopia, including myopic maculopathy and high myopia–associated optic neuropathy, can cause irreversible blindness. Useful clinical methods, including the application of low-dose atropine eye drops, defocus incorporated multiple segments (DIMS) spectacle lenses and orthokeratology (Ortho-K) lenses, have been proven to effectively reduce or slow the progression of myopia. The etiology of myopia involves a complex interaction between environmental and genetic factors. The association between height and axial length (AL) has been demonstrated in previous cross-sectional studies and longitudinal cohort studies. Furthermore, the increases in AL and height were demonstrated to be positively correlated. These results indicate that axial elongation should be intensively monitored for myopic control when children grow rapidly.
Growth hormone (GH) is considered essential for postnatal somatic growth, exerting its effect on growth through the production of insulin-like growth factor 1 (IGF-1). Parentin et al. reported that children with congenital GH deficiency (GHD) or insensitivity have a mean hyperopic defect related to a shorter AL and a greater corneal thickness representing delayed ocular growth. Furthermore, the refraction change of the GHD children could be related to somatic growth and partially induced by substitutive GH therapy.
Recombinant human GH (rhGH) has been approved to treat several conditions associated with poor growth and short stature. The efficacy of rhGH therapy has been demonstrated in various studies, and it has been shown to be largely safe in most population. However, whether it can influence the progression of myopia in young children remains unknown. Thus, to explore the correlation between rhGH therapy and myopia progression, as well as to optimize the myopia control strategies in myopic children undergoing rhGH therapy, we conducted this retrospective study to compare the change in ocular AL in two groups of myopic children undergoing myopia control with and without rhGH therapy.
2
Methods
2.1
Study design
Clinical records of myopic children referred to Hangzhou Chaoju Eye Hospital for myopia control from January 2019 to October 2023 were reviewed. All the subjects included in the study received myopia control treatment, and the initiation of myopia control was set as baseline. The inclusion criteria were as follows: 1) baseline age: 6–12 years old; 2) myopia control strategy, including Ortho-K, DIMS spectacle lens, low-dose atropine (LDA) and the dual treatment of LDA+Ortho-K/DIMS; 3) baseline cycloplegic spherical equivalent refraction (SER) between –0.50 and –5.00 diopters (D), astigmatism ≤ 2.50 D, anisometropia ≤ 1.50 D; 4) best-corrected visual acuity (BCVA) ≥ Snellen 20/20 in either eye; and 5) regular follow-up visit, that is, every 3–6 months routinely for myopia control. Children were excluded if they had strabismus and other ocular abnormalities, such as syndrome-associated myopia. A retrospective review of detailed medical records was conducted, identifying myopic patients who presented to our hospital for ophthalmologic examination during the study period and met the aforementioned inclusion criteria. Patients with a documented history of rhGH therapy were assigned to the study group. Concurrently, a control group was established by randomly selecting myopic patients without a history of rhGH use, matched to the study group for age and gender. Once all participants had been recruited, the baseline age, sex ratio, uncorrected visual acuity (UCVA), SER and AL were similar in both groups.
The study was approved by the Ethics Committee, Hangzhou Chaoju Eye Hospital and followed the tenets of the Declaration of Helsinki. Informed consent was obtained from all participants or their parents.
2.2
Axial length and cycloplegic refraction assessment
Ophthalmic examinations were performed and recorded at baseline and at all follow-up time points. UCVA and BCVA were assessed by a standard logMAR chart (Guangzhou Xieyi Weishikang). AL was measured by IOLMaster (Carl Zeiss 700, Meditec) before cycloplegia and averaged until the maximum error did not exceed 0.05 mm. Cycloplegia was induced using 3 drops of 1 % cyclopentolate (Alcon) 5 min apart. After an additional 30 min, full cycloplegia was present if the pupil diameter reached at least 6 mm and the pupillary reaction to light was absent. Refraction data were measured using an autorefractor (KR-800; Topcon) 3 times after cycloplegia and averaged until the desired precision (0.25 D) was achieved. SER was calculated as the spherical value plus the half-cylinder value.
2.3
Statistical analyses
GraphPad Prism 9.0 (GraphPad Software, Inc.) was used to analyze the data. Continuous data in the parametric data are expressed as mean and standard deviation (SD), and categorical data are expressed as number and percentage. In non-parametric data, continuous variable data are expressed as median and interquartile range (IQR). Only data from the left eyes were analyzed. The baseline characteristics were compared by χ 2 tests for sex and unpaired t tests for other characteristics. The changes in AL between control and rhGH group children were compared using the Mann-Whitney test. The Wilcoxon test was used for AL changes within groups (pre-rhGH treatment vs. post-rhGH treatment; on-rhGH treatment vs. off-rhGH treatment). Univariate and multivariate linear regression models were used to assess baseline factors associated with annual average AL change and factors related to the efficacy of controlling axial elongation in the rhGH group. A two-sided P value < 0.05 was considered statistically significant.
3
Results
3.1
Baseline characteristics
The rhGH group included 27 patients (8 boys, 19 girls; average baseline age 9.07 years, SD 1.44 years). rhGH therapy had been conducted in these patients for a mean period of 1.97 years. The control group included 57 children (26 boys, 31 girls; average baseline age 9.56 years, SD 1.51 years). The myopia control strategy included daily use of 0.01 % atropine eye drops (LDA), Ortho-K and the combined use of LDA and Ortho-K, as well as LDA and DIMS spectacle lenses. The baseline age, sex, UCVA, AL, SER, myopia control strategy and follow-up period between the rhGH group and the control group showed no significant difference ( P > 0.05). The demographic characteristics of the participants at baseline are summarized in Table 1 .
| Characteristics | rhGH group | Control group | P value* |
|---|---|---|---|
| No. subjects (eyes) | 27 (27) | 57 (57) | – |
| Age, years | 9.07 (1.44) | 9.56 (1.51) | 0.168 |
| Male, % | 8 (29.63) | 26 (45.61) | 0.234 |
| UCVA, logMAR | 0.44 (0.26) | 0.44 (0.23) | 0.993 |
| AL, mm | 24.07 (0.71) | 24.35 (0.74) | 0.102 |
| SER, diopter | −1.92 (0.91) | −1.98 (1.16) | 0.790 |
| No. myopia control strategy (LDA/Ortho-K/LDA+Ortho-K/LDA+DIMS) | 6/1/19/1 | 8/1/40/8 | 0.415 |
| Follow-up period, years | 2.12 (1.00) | 2.37 (1.09) | 0.336 |
3.2
Changes in AL between the rhGH and control groups
During the follow-up period, the median AL change was 0.29 mm/year (IQR: 0.19–0.40) and 0.18 mm/year (IQR: 0.12–0.27) in the rhGH (n = 27) and control groups (n = 57), respectively, with a significant difference between the groups ( P = 0.0009; Fig. 1 ).
3.3
Changes in AL between pre-rhGH and post-rhGH treatment
Among the 27 patients in the rhGH group, 14 children had initiated rhGH therapy during the follow-up period in this study. Therefore, the median AL changes between pre-rhGH and post-rhGH treatment were analyzed and compared. The results showed a significant increase in median AL change after rhGH treatment (0.22 mm/year; IQR, 0.12–0.34 vs. 0.32 mm/year; IQR, 0.26–0.40; n = 14; P = 0.026; Fig. 2 ).
3.4
Changes in AL between on-rhGH and off-rhGH treatment
Meanwhile, 6 children in the rhGH group discontinued rhGH treatment during the follow-up period. Thus, the AL changes before and after the cessation of rhGH application were also analyzed and compared. The results indicated a significant decrease in AL change after stopping the rhGH treatment (0.39 mm/year; IQR, 0.16–0.56 vs. 0.04 mm/year; IQR, –0.03–0.15; n = 6; P = 0.031; Fig. 3 ).
