Innovative wireless ocular modulation patch for controlled axial length shortening

In a recent paper published in Nature Communications, Zhong et al.1 described a wireless battery-free ocular modulation patch. This patch could be utilized in posterior scleral reinforcement (PSR) surgery, to correct high myopia by shortening the axial length (AXL) and reinforce the sclera to prevent myopia recurrence. Myopia is a state of refraction in which parallel rays of light coming from infinity are brought to focus in front of the retina. The mechanism of myopia involves various signals traveling from the retina through the choroid to the sclera, eventually resulting in scleral weakening and AXL elongation. The elongation of the AXL occurs, causing light to fail to converge on the retina. This also leads to various complications arising from changes in the posterior segment structures of the eye, including posterior staphyloma and myopic maculopathy, which in turn, contributes to the continual expansion of the globe in the posterior direction. There are many surgical options available for patients with high myopia. Myopic patients could avoid wearing glasses through corneal laser surgery and Implantable Collamer Lens surgery, which work by flattening the cornea or adding lenses to the anterior chamber to help converge light on the retina. However, these surgeries are purely optical corrections and do not address the pathological changes in the posterior segment structure in myopic eyeballs. Comparatively, traditional PSR surgery aims to strengthen the weakened posterior sclera by ocular patch. The technique was first reported by Shevelev in 1930 and was later modified by Snyder and Thompson. The primary goal of PSR surgery is to reinforce the weakened sclera, not to shorten the AXL to achieve perfect light convergence on the retina. Thus, PSR surgery is particularly essential for patients with high myopia and related complications. In light of the research background, Zhong et al. proposed the concept, that shortening AXL by a novel PSR surgery, is remarkably groundbreaking, potentially allowing for precise and personalized treatment of AXL shortening for patients with high myopia by PSR. Furthermore, traditional macular buckle is primarily used to treat macular schisis in high myopia, addressing the traction on the retina caused by posterior staphyloma in the macular area and promoting the reattachment of the macular schisis. Comparatively, this novel PSR surgery focused more specifically on the shrinkage of the sclera, further reinforcing the weakened sclera through scleral cross-linking (SCXL). For decades, ocular patch for PSR have consisted of homologous sclera, dura mater and pericardium patches.2 In recent years, nonbiological source materials have gained popularity. Researchers have proposed using various hydrogel materials were proposed for PSR, but these studies have remained limited to animal experiments.3, 4 Zhong et al. developed a novel wireless battery-free ocular modulation patch, powered and controlled by an external ultrasound source. The patch consisted of piezoelectric transducers, an electrochemical micro-actuator, a drug microneedle array, μ-LEDs, a flexible circuit and biocompatible encapsulation (Figure 1). The adoption of wireless energy transmission eliminated the inaccuracies associated with traditional PSR surgery in controlling the AXL and mitigates potential hazards posed by cumbersome batteries. The novel wirelessly powering micro-actuator could trigger electrolysis process, which involved the use of microfabricated copper/gold-forked electrodes to electrolyze the aqueous solution, producing hydrogen and oxygen gas. The generation of hydrogen and oxygen gas led to mechanical deformation of the polydimethylsiloxane/polystyrene-block-polybutadiene-block-polystyrene flexible membrane. When the ocular modulation patch was placed on the rabbit eye globe, the patch applied axial pressure to the macula, thus inducing scleral shortening through mechanical action. After the micro-actuator was activated, the rabbit AXL underwent a reduction of approximately 1217 μm. In human eyes, this 1217 μm change translated to a modification of refractive power by approximately 2.5D for myopic patients. In this study, Zhong et al. solely observed the impact of the patch on axial shortening in normal rabbits. We eagerly await the assessment of the efficacy of this ocular modulation patch in addressing myopic complications like posterior staphyloma and macular schisis. In addition, this wireless control of AXL shortening was coupled with another function: SCXL. The integration of axial shortening with SCXL theoretically stabilized the shortened AXL, prolonging the effectiveness of treatment and aiding in reducing the recurrence of high myopia. Previously, development of SCXL lagged far behind corneal cross-linking, with SCXL only being investigated in animal experiments. This was primarily due to the anatomical location of the posterior sclera, which made effective delivery of photosensitizers and illumination challenging. Most articles describe using 360-degree conjunctival peritomy and muscle traction to expose the equatorial-posterior sclera. Riboflavin is then applied to the exposed area,5 with some articles mentioning the use of iontophoresis technology to enhance absorption. Since it is difficult to expose the posterior sclera, most SCXL studies targeted the equatorial region of the sclera, which was not the most weakened position of the sclera in patients with high myopia. In this study, Zhong et al. combined SXL with PSR surgery to more directly target the posterior sclera. Notably, this ocular patch marked the first instance of delivering riboflavin to the posterior sclera through a microneedle array (polyvinylpyrrolidone and riboflavin), overcoming previous challenges in drug delivery for SCXL. Riboflavin is commonly combined with blue light in SCXL to avoid the potential side effects of ultraviolet light. The blue μ-LED (443 nm) has already been applied to the wireless ocular modulation patch and could be activated using ultrasound. Furthermore, the combination of PSR and SCXL surgery within a single procedure represented an exceptionally innovative surgical concept. The emergence of this combined surgery could significantly advance the application of composite and personalized scleral reinforcement in myopia control. Measurements of rigidity of the sclera revealed that, SCXL increased the scleral Young's modulus by approximately 151.25% at Day 7 and by 387% at Day 22. Collagen fibers exhibited a more tightly arranged structure after SCXL. Analysis of porosity from H&E-stained sections showed a 58.33% decrease in porosity in the SCXL group compared to the control group. A further comparison of the therapeutic efficacy of varying intensities of light exposure and different concentrations of riboflavin delivery might be a future research direction. As Zhang et al. noted, the study had limitations due to its small sample size and the relatively short 22-day postsurgery observation period. Potential postoperative complications, such as ocular hypertension, conjunctival tissue edema, and vitreous hemorrhage, should be considered in the future. Furthermore, it would be interesting to consider the changes in choroidal thickness and blood flow postsurgery, as choroidal blood flow is found to be closely related to the development of high myopia. In summary, Zhong et al. proposed a scleral reinforcement patch for treating high myopia, which combined the functions of axial shortening and SCXL in a wireless battery-free manner. While there were already various methods for treating myopia, achieving a balance between efficacy and safety is often crucial. This article primarily introduced an innovative concept for treating high myopia, but many issues remained unresolved. Further research is needed for long-term monitoring of axial shortening efficacy and safety. The size of rabbit eyes differs from human eyes, so it is uncertain whether the wireless ocular patch needs to be redesigned for human use. Additionally, we anticipate seeing the effectiveness of this new patch applied to myopic sclera, considering the significant differences between myopic sclera and normal sclera. Lin Ye: Conceptualization; investigation; visualization; writing—original draft. Jing Zheng: Conceptualization; project administration; supervision; visualization; writing—review & editing. All authors have read and approved the final manuscript. This study was supported by Grant 24NSFSC8140 from Sichuan Natural Science Foundation for Young Scholars. The authors declare no conflict of interest. Not applicable. Data sharing is not applicable to this article as no new data were created or analyzed in this study.