Rachel Ka Man Chun

Purpose: Alpha-adrenergic receptors (ARs) may potentially play a critical role in controlling myopia, with subtype-specific signalling pathways mediating distinct effects. This study systematically investigated the efficacy of three subtype-specific pharmacological agents in myopia control and dose–response relationships in lens-induced myopia (LIM) chick models. Methods: White Leghorn chicks were randomised to a phosphate-buffered saline (PBS) control group or treated groups receiving metaraminol (α1-AR agonist), lofexidine (α2-AR agonist) or cirazoline (a dual α1‑AR agonist and α2‑AR antagonist) at low (3 nmol), medium (30 nmol) or high (300 nmol) doses. A −10 D single-vision lens was fitted to the right eye for 7 days to induce myopia, with intravitreal injections administered at baseline and on days 2, 4 and 6. Natural ocular recovery was allowed for another 7 days. Interocular differences (IOD) in spherical equivalent refraction (SER) and ocular biometrics were compared. Results: After 7 days of lens wear, all drug groups exhibited lower myopia progression than the control group. Lofexidine showed potent and consistent myopia-inhibiting effects. The IOD in SER, vitreous chamber depth (VCD) and axial length (AL) were significantly reduced at three doses compared with PBS control (all p < 0.05). Metaraminol and cirazoline exhibited significant efficacy mainly at medium and high doses. All three α-AR modulators alleviated choroidal thinning at both 30 and 300 nmol doses. During recovery, all treatment groups trended toward emmetropia, without significant differences from the PBS group. Conclusions: This first head-to-head in vivo comparison of three subtypes of α-AR modulators in the chick LIM model demonstrates the potent myopia-suppressive effects of α2-AR agonist lofexidine at low dose. α1-AR agonist metaraminol required a distinct threshold dose to achieve efficacy and blockade of α2-AR with cirazoline may counteract anti-myopic protection. These findings provide crucial subtype-specific preclinical insights for the rational development of future drugs for myopia.

Purpose: To compare radial and horizontal raster acquisition patterns using spectral-domain optical coherence tomography (OCT) for assessing choroidal vascularity index (CVI) in healthy eyes and to evaluate how variability in chorio-scleral interface (CSI) delineation influences CVI measurements. Methods: OCT images of 25 eyes from 25 healthy adults were acquired using 12-line radial and 31-line horizontal raster scans with enhanced depth imaging. CVI was measured manually using three different posterior boundaries—defined as the upper (vascular), middle (vascular–stromal) and lower (stromal) CSI boundaries. Agreement between CSI boundaries and scan patterns was assessed using Bland-Altman analysis. Topographical CVI variations across 6-mm Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields, quadrants and rings were evaluated using two-way repeated-measures ANOVA. Results: Participants were aged 21–31 years (72% female; mean spherical equivalent −2.97 ± 2.02 D). Mean CVI differences ranged from 1.43 to 2.38% between the upper and middle CSI boundaries and from 1.23 to 2.04% between the middle and lower CSI boundaries. Comparisons between the upper and lower CSI boundaries resulted in larger CVI differences, ranging from 2.90 to 4.42%. The coefficient of variation for CVI was low (p = 0.005) and outer ring (−0.77%, p = 0.02). No significant scan-pattern effect was found, but CVI varied significantly across the ETDRS grid, with the lowest values in the outer nasal subfield, nasal quadrant and outer ring. Conclusions: Radial scans provide CVI measurements comparable to raster scans, with faster acquisition, supporting practical use in children. Standardising CSI delineation is crucial for consistent CVI comparisons across studies.

Repeated low-level red light (RLRL) has been reported to control myopia progression clinically. Given safety concerns with laser sources, light-emitting diodes (LED)-sourced red light represents a promising alternative. This study investigated the effects of LED-sourced red light (RL) on cellular response in vitro and ocular growth in normal and lens-induced myopic chicks. In vitro, the mouse photoreceptor 661W cell line was exposed to 625 and 664 nm LED-sourced RL (3 min, twice daily) for 3 days, and cytochrome c oxidase (CCO) activity and cell viability were assessed. In vivo, chicks were randomly assigned to normal visual conditions or monocular −5D lens-induced myopia (LIM). Treatment groups received 664 nm LED-sourced RL (30 min, twice daily) at low, moderate, or high intensities for 10 days. In vitro, LED-sourced RL at 664 nm more effectively activated CCO and enhanced cell viability in 661W cells than RL at 625 nm and white light. In vivo, low-intensity RL exposure of 10 days significantly inhibited vitreous chamber depth (VCD) and axial length (AL) elongation compared to the normal light group (p < 0.05) in normally growing chicks but showed no significant effect in LIM eyes. By contrast, moderate- and high-intensity RL exposure for 10 days attenuated myopia progression in LIM eyes, as reflected by slower VCD and AL elongation and less myopic shift, compared to the normal light group (all p < 0.05). Notably, high-intensity RL also protected the untouched fellow eyes of the LIM chick models against myopic shift and excessive elongation. LED-sourced RL at 664 nm was effective in activating CCO, reducing apoptosis, and promoting cell viability. In chick models, it can also inhibit ocular growth in both normally growing and −5D lens-induced myopic chicks.

Background: Myopia is increasingly prevalent worldwide, with projections indicating that nearly 50% of the global population may have myopia by 2050. This surge poses significant concerns due to its impact on vision and quality of life and its link to a range of blinding diseases, including myopic macular degeneration, glaucoma, and retinal detachment. Current pharmacologic and optical interventions offer limited effectiveness in slowing myopia progression, highlighting the urgent need for more effective treatments. Objective: This study aims to examine the combined effect of bright light therapy and low-dose atropine on myopic progression. Methods: This is a single-site, 2-arm, single-masked (examiner-masked) randomized controlled trial to compare the effectiveness of low-dose atropine alone and its combination with bright light therapy in retarding myopia progression. The study protocol has been approved by the institutional review boards of Hong Kong Polytechnic University (HSEARS 20180829002-05) and the University of Hong Kong and Hospital Authority Hong Kong West Cluster (UW 20-362). Schoolchildren with myopia aged 7 to 12 years who have not undergone any previous myopic control intervention will be recruited and randomly allocated into 2 groups (n=67 per group) after baseline measurements. Both groups will receive 0.01% atropine twice daily for 24 months. The combination treatment group will also receive a high-intensity lamp for bright light therapy. The primary and secondary outcome measures will be the changes in cycloplegic autorefraction in spherical equivalent refraction and axial length, respectively, measured every 6 months over 2 years from baseline. Results: The project was funded in January 2019. The recruitment process started on March 21, 2023, and was completed on February 2, 2024. Data collection is expected to be completed in April 2026. Conclusions: This study will provide new information on whether the combination of bright light therapy and low-dose atropine is more effective than atropine alone in slowing down myopia progression. It will also assess the effectiveness of low-dose atropine used twice daily. Combining bright light therapy and atropine could become a new treatment option if shown to be effective. New data on the effectiveness of using atropine twice daily might also expand available treatment options.

Background: Spectacle-based interventions for myopia control are appealing to parents and children due to their non-invasive nature. However, long-term efficacy results remain modest and do not account for high-risk children with early-onset myopia and fast progression. This paper presents the protocol of a trial designed to evaluate the efficacy of the new-generation Defocus Incorporated Multiple Segments (DIMS) spectacle lenses in slowing the progression of myopia in children with early-onset and fast myopia progression. Methods and design: This is a prospective, double-masked, active-controlled, randomised trial (ClinicalTrials.gov identifiers: NCT05888792 and NCT05888805). Participants are Chinese schoolchildren aged 4–12 years with myopia of at least −0.75 diopter (D) in both eyes and with fast progression (≥ 0.50 D per year) or fast axial growth (≥ 0.27 mm per year) in either or both eyes. They are age-stratified and randomly assigned to an experimental arm, a control arm or an auxiliary arm in a 1:1:1 ratio. The experimental arm receives new-generation DIMS spectacle lenses, while the control arm receives single-vision spectacle lenses. The control subjects will crossover to experimental lenses at the end of the first year, and all subjects will continue wearing experimental lenses in the second year. The auxiliary arm receives marketed DIMS spectacle lenses for two years. The primary and secondary outcome measures are the changes in cycloplegic objective refraction and axial length at 12 months from baseline. Peripheral refraction and choroidal thickness will also be monitored, and their relationships with myopia control efficacy will be explored. Discussion: This study will provide insights into the efficacy of a new generation of DIMS technology for controlling myopia in children with early-onset and fast myopia progression, offering evidence-based practice for myopia management. Trial registration: ClinicalTrials.gov identifiers: NCT05888792 and NCT05888805

Aim To investigate the effect of the Defocus Incorporated Soft Contact (DISC) lenses on myopia progression and choroidal thickness (ChT) of Chinese mainland children over a period of 12 months. Methods This was a prospective double-blind randomised controlled trial involving 84 myopic children. Subjects were randomly assigned to use of either DISC or single vision contact lens (SVL). Cycloplegic spherical equivalent refraction (SER), axial length (AL) and ChT were measured at 6 and 12 months. Results For 12 months, the average changes in SER and AL in the DISC group were (−0.50±0.41) D and (0.22±0.13) mm. Corresponding values in the SVL group were (−1.23±0.50) D and (0.49±0.15) mm. Myopia control efficacy in SER was 59% and 55% in AL. For those aged under 10, myopia control efficacy in SER is higher at 95% in 6 months and 71.4% in 12 months. ChT increased by 0.16±24.46 µm in the DISC group, while in contrast, it thinned in the SVL group (−9.11±32.25 µm) after 12 months. ChT changes demonstrated a significant negative association with AL over 12 months in the DISC group but not in the SVL group. In contrast, ChT change over 12 months was significantly negatively associated with initial ChT in the SVL group, but not in the DISC group. Conclusions DISC lenses effectively slowed myopia progression and AL compared with SVL, especially for younger children. Myopia defocus treatment changes the original intrinsic relationship between ChT and myopia progression, providing strong evidence that myopia defocus design controls myopia progression by changing ChT.

Introduction: Myopia and its complications can lead to irreversible visual impairment and even blindness, making this a worldwide public health concern for the 21st century. While treatments to slow myopia progression exist, their average efficacy is moderate. Bright light exposure, either in controlled animal models or naturally under sunlight for children, has demonstrated a protective effect against myopia development. This study hypothesises that bright light therapy (BLT), delivered via a home-based device mimicking sunlight, could slow myopia progression in schoolchildren. Methods and analysis: We propose a 2-year, double-masked, randomised controlled trial to investigate the effectiveness of BLT and its combination with myopia control treatment in schoolchildren. Chinese schoolchildren aged 7–12 years will be recruited and randomly assigned to one of three arms in phase 1. Subjects will be instructed to perform a minimum of 45 mins of near tasks daily under either BLT (10 000 lux white Light Emitting Diode (LED) light) or placebo light therapy (500 lux white LED light). The control subjects will receive single-vision spectacles and placebo light therapy; the single treatment subjects will receive single-vision spectacles and BLT; and the combination treatment subjects will receive defocus-incorporated multiple segments spectacles and BLT. The primary and secondary outcome measures are changes in cycloplegic objective refraction and axial length over a 2-year period. Treatment dosage is indirectly measured using a monitoring sensor attached beneath the BLT lamp rather than a wearable light metre. Variations in dosage monitoring may influence the observed treatment efficacy. Ethics and dissemination: The study has been approved by the Institutional Review Boards of The Hong Kong Polytechnic University (HSEARS 20180829002–05) and The University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 20–362). The study results will be disseminated in scientific conferences and peer-reviewed indexed journals. Trial registration number: ClinicalTrials.gov identifier: NCT04923841

Purpose: Animal studies have suggested that visual degradation impacts eye growth due to the attenuation of high spatial frequencies. However, the influence of perceptual visibility remains unclear in humans. The aim of this study was to investigate the impact of visibility on visual attenuation-related eye changes during reading. Methods: Axial length (AxL) and choroidal thickness (ChT) changes associated with reading tasks were measured in two separate experiments. In the first experiment, the reading task was conducted under different forms of visual attenuation (contrast, resolution, defocus, noise, and crowding). For each form of visual attenuation, the text was set at a sub-threshold level of visibility, evaluated via prior measurement of reading performance, and kept constant via adaptive control of the intensity of the stimulation. Each sub-threshold reading condition was compared with a supra-threshold reading text, serving as control. In the second experiment, the effect of visibility on lens-induced defocus was further examined by comparing the effect of text stimulation with an equivalent dioptric of 5.5 D under sub- and supra-threshold levels of resolution. Results: Near distance reading with supra-threshold texts caused eye elongation (AxL: +12.942 μm ± 2.147 μm; ChT: − 3.192 μm ± 1.158 μm). Additional defocusing failed to exacerbate axial elongation under sub-threshold text visibility (mean difference: − 0.135 μm ± 2.783 μm), revealing a clear inhibitory effect of lowering visibility on eye changes. Other forms of visual degradation, including crowding (mean difference: 6.153 μm ± 2.127 μm) and noise (mean difference: 5.02 μm ± 2.812 μm) also showed an inhibitory effect on eye elongation. The significant effect of crowding indicated that post-retinal mechanisms, involving attentional processes related to crowded characters, may play a role in the influence of visibility. Conclusion: Although the featural composition of visual stimulation can drastically influence eye changes, this study revealed an important mediating role of visibility, previously underscored in chick studies, which warrants further explorations of the impact of post-retinal processes in eye growth.

Background: Myopia, characterized by excessive axial elongation of the eyeball, increases risks of having sight-threatening diseases and impose a financial burden to healthcare system. Although myopic control interventions showed their effectiveness in slowing progression, the efficacy varies between individuals and does not completely halt progression. The study aims to investigate the efficacy of combining 0.01% atropine administered twice daily with optical defocus for myopia control in schoolchildren. Methods and design: This is a prospective, parallel-group, single-blinded, randomized, active-control trial (ClinicalTrials.gov identifier: NCT06358755). Myopic schoolchildren with no previous myopic control interventions aged between 7 to 12 years will be recruited. They will be randomly allocated into two groups (n = 56 per group) after baseline measurement. Both groups will receive 0.01% atropine twice per day for 18 months (one drop in the morning and the other drop at night before bedtime). Defocus incorporated multiple segments (DIMS) spectacle lenses will be prescribed in atropine plus optical defocus (ATD) treatment group while single vision spectacle lenses will be given in atropine only (AT) group. Cycloplegic refraction and axial lengths will be monitored every 6 months over 18-month study period. The primary outcomes are changes in cycloplegic refraction and axial lengths relative to the baseline over the study period. Discussion: The result will examine the combination effect of low dose atropine and myopic defocus on myopia control in a randomized controlled study. The findings will also explore the potential benefits of applying 0.01% atropine twice per day on myopic control and its potential side effects.