Short-Term Effect of Stimulating the Pterygopalatine Ganglion Via Electroacupuncture on Choroidal Structure in Human Subjects

Abstract

Purpose: Choroidal dysfunction is implicated in various ocular pathologies. The parasympathetic pterygopalatine ganglion (PPG) innervates orbital vessels supplying the choroid. While PPG stimulation has been shown to dilate cerebral blood flow, its effects on the choroid, particularly in human subjects, require further elucidation. This study aimed to investigate the short-term influence of PPG stimulation via electroacupuncture on choroidal structure.

Methods: In this crossover study, 22 healthy adults received PPG electrical stimulation and sham stimulation for one session each on two separate days in a randomized order. Measurements including choroidal thickness (ChT), choroidal vascularity index (ChVI), central subfield thickness, axial length, anterior chamber depth, and lens thickness were recorded before and at intervals (0, 15, 30, 45, and 60 minutes) postintervention.

Results: The ChT on the side receiving PPG stimulation demonstrated a sustained increase, peaking at 15 minutes poststimulation (17.2 µm, P < 0.001) and persisting for up to 60 minutes. Conversely, the ChVI exhibited a more immediate response, with a peak increase immediately poststimulation (3.8%, P = 0.003), followed by a gradual return to baseline. ChT and ChVI in the contralateral eye showed a nonsignificant trend to decrease. Additionally, a notable reduction in ipsilateral axial length was observed at specific time points poststimulation.

Conclusions: PPG activation via electroacupuncture elicited a short-term increase in ChT and ChVI in the ipsilateral eye compared to sham stimulation, with ChT increases trailing those of ChVI but displaying greater persistence.

Translational Relevance: Electrical stimulation of the PPG can produce a short-term increase in ipsilateral ChT and ChVI.

Introduction

The choroid, a complex network of vasculature embedded in the connective tissue of the stroma, is essential for ocular health as it primarily nourishes the retina. Preserving its structural and functional integrity is crucial. It is of note that the occlusion of one or more posterior ciliary arteries or a vortex vein can precipitate a rapid degeneration of the outer retina due to diminished choroidal blood flow.^1–3 Additionally, the choroid is instrumental in the process of emmetropization,⁴ a dynamic mechanism that depends on the choroid’s capacity to modulate its thickness in response to shifts in the image's focal plane.^5–8 This adaptation facilitates changes in scleral remodeling, thereby governing ocular growth.^9,10 An extensive body of systematic reviews has elucidated a correlation between variations in choroidal structure and a spectrum of ocular disorders.^11–15 Specifically, certain pathologies such as central serous chorioretinopathy¹⁴ are linked to an elevation in choroidal thickness (ChT), whereas conditions like myopia,^13,16 age-related macular degeneration (AMD),¹² and open-angle glaucoma¹¹ are associated with a reduction in ChT. Consequently, an in-depth understanding of the regulatory mechanisms of choroidal structure is essential for the development of efficacious therapeutic interventions for ocular diseases associated with these morphologic alterations. 

The choroid's extensive autonomic innervation suggests a role for the autonomic nervous system in its regulation.¹⁷ Three major types of nerve fibers innervate the choroid in mammals¹⁸: (1) parasympathetic fibers from the pterygopalatine ganglion (PPG), (2) sympathetic fibers from the superior cervical ganglion, and (3) sensory fibers from the trigeminal ganglion. A fluorescent retrograde labeling study revealed that PPG neurons projecting to the choroid contain nitric oxide synthase, vasoactive intestinal polypeptide, and choline acetyltransferase and are widely distributed within the PPG and its preganglionic root.¹⁹ Additionally, urocortin 1, a potent neuroregulatory peptide with vasodilatory effects in the cardiovascular system, was detected in the human choroid and PPG.²⁰ Parasympathetic fibers originating from the PPG that coexpress these neurotransmitters can form a dense perivascular plexus around the choroidal vessels, contributing to increased ChT via vasodilation. These fibers also extend to nonvascular smooth muscle cells and may independently control the size of choroidal lacunae to thicken the choroid, irrespective of blood flow. Lesions of the presynaptic autonomic facial nerve to the PPG inhibited the compensatory ChT increase in response to myopic defocus.²¹ Activation of the PPG via stimulation of the facial nerve^22,23 or through direct activation of preganglionic neurons within the superior salivatory nucleus (SSN)^24,25 has been demonstrated to enhance choroidal blood flow in mammals. Despite theoretical underpinnings linking PPG stimulation with choroidal structure, direct evidence in human studies is lacking, thus necessitating a well-designed study to address this knowledge gap. 

The PPG, also called the sphenopalatine ganglion, is located within the pterygopalatine fossa and is approximately 3 to 5 mm in diameter in humans. In addition to innervating the choroid, postganglionic fibers from the PPG project to various structures, including cerebral blood vessels, the lacrimal gland, blood vessels of the nasal mucosa and palate, and the meibomian glands.²⁶ The augmentation of cerebral blood flow via PPG activation by means of electrical stimulator implantation has been substantiated,²⁷ finding clinical application in the therapeutic paradigm for ischemic stroke.²⁸ Chinese otolaryngologist Xinwu Li²⁹ developed an acupuncture technique to stimulate PPG by employing a modified infra-zygomatic approach and a single acupuncture needle of specific length. This technique has been proposed as a minimally invasive and simple alternative to electrical stimulator implantation^30–33 and has likewise been reported to enhance cerebral blood flow.³⁰ Moreover, the intervention's commendable safety profile supports its viability for prolonged use. The unique anatomic location of the PPG and its role in mediating choroidal structure renders it a focal point of interest for acupuncturists seeking alternative treatment options for ocular diseases characterized by choroidal blood flow reduction. 

Given the species-specific differences in choroidal innervation, this study used a minimally invasive method to stimulate the human PPG and observe its effects on choroid structure, aiming to translate findings from animal models into human physiology and deepen our understanding of the autonomic control mechanisms of the choroid. We hypothesized that PPG electroacupuncture would activate parasympathetic nerve fibers innervating the choroid and mediate an increase in ChT and choroidal vascularity index (ChVI). The anticipated results could lay the groundwork for using this method to treat diseases associated with impaired choroidal circulation. 

Methods

Subjects

The study was approved by the Medical Ethics Committee of Fudan University Eye & ENT Hospital (No. 2023098) and registered with the Chinese Clinical Trial Registry (identifier: ChiCTR2300075160). Compliance with the 2013 version of the Declaration of Helsinki was ensured, and written informed consent was obtained from all participants and their guardians. The subjects were aged 18 to 30 years with spherical equivalent refraction between –4.00 D and +0.75 D (inclusive), with astigmatism of less than 1.00 D in both eyes, and with anisometropia of less than 1.00 D. All of them had best-corrected visual acuity of 0.00 logarithm of the minimum angle of resolution (logMAR) or better. No subjects had any severe systemic disease, ocular pathologies, or any history of ophthalmic surgery. Those who had any record of previous myopia control treatment or acupuncture intervention were excluded. 

Procedure

The study used a single-masked, randomized, two-period crossover design (Fig. 1). The active and sham PPG stimulation were tested on two separate days (with a 1-week washout period in between), in randomized order, for each subject. To limit the potential physiologic and pharmacologic influences on the results, the experiment for both sessions was conducted between 10 a.m. and 2 p.m. during weekends, and the subjects were instructed to avoid consumption of caffeine and alcohol prior to the sessions.³⁴ At each visit, subjects first watched a movie for 15 minutes at 4 m with full distance correction for both eyes. This resting period was implemented to minimize the possible influences of previous visual tasks on the choroid. After this distance viewing, baseline measurements of choroidal structure and other ocular biometrics were carried out. Subjects were then treated with either one session of active or sham stimulation on the right PPG. Measures were repeated immediately after and 15, 30, 45, and 60 minutes after the intervention. Several measuring instruments were placed in a small laboratory, allowing for immediate poststimulation assessments. During both experimental sessions, measurements focused exclusively on the right eye, where the ipsilateral PPG was stimulated. To explore potential crossover effects, choroidal assessments were additionally conducted on the left eye, where the contralateral PPG remained unstimulated. In addition, intraocular pressure (IOP) and corrected distance visual acuity (CDVA) were measured prior to and 60 minutes following the intervention to monitor any adverse effects arising from PPG stimulation via electroacupuncture. 

Figure 1.

 

Study design.

Randomization and Masking

Subjects were randomized 1:1 to undergo a single session of PPG stimulation followed by a single session of sham stimulation or vice versa. Randomization utilized a computer-based, permuted blocks-of-4 approach to allocate subjects to one of the two sequences. Participants were masked to the intervention administered during each test session. 

Intervention

First, the equidistant point between the infraorbital foramen and the center of the external auditory canal was marked with an X. This point serves as the superficial indication of the position of the PPG.²⁹ The insertion site for the needle is strategically positioned at the inferior border of the zygomatic arch, slightly rearward to the protrusion of the temporozygomatic suture, identified as the “pterygopalatine” point (Fig. 2A). The linear distance from this insertion point to the PPG approximates 50 to 55 mm. Prior to the insertion procedure, subjects were instructed to sustain a neutral head posture and gaze directly forward, and they were informed that “you may feel a mild numbness sensation, if so, please raise your hand.” 

Figure 2.

 

Anatomy relevant to the PPG stimulation via electroacupuncture (A) and details of the unipolar acupuncture needle (B). The needle was jointly developed by the University of Science and Technology Beijing and Xiyuan Hospital of CACMS. The figure was created in BioRender.

Electroacupuncture stimulation of the PPG was conducted with a pair of body-insulated stainless-steel acupuncture needles (size: 0.30 × 60 mm, Fig. 2B). The micron coating precludes electrical contact of the needle body with the subject except at the very tip of the needle. For the active stimulation, the acupuncturist sterilized the skin overlying the “pterygopalatine” point and inserted the first acupuncture needle toward the pterygopalatine fossa at a depth of 50 to 55 mm, guided by the marked point X. Contact of the PPG by the needle's tip elicited a report of mild numbness from the subject, occasionally accompanied by ipsilateral lacrimation. Subsequent to this response, the needle was retracted by 1 to 2 mm. The depth of needle entry (around 50–55 mm) was previously verified by high-resolution sinus computed tomography to ensure that the tip of the needle could (only) be placed in the pterygopalatine fossa (Supplementary Fig. S1). Misdirection of the needle insertion could result in obstruction by the maxillary sinus or the lateral pterygoid plate before achieving the intended depth, necessitating minor adjustments in angle. The second needle was also inserted into the pterygopalatine fossa, positioned at a proximity of 1 to 2 mm parallel to the first needle. Both needles were connected to the CMNS6-3 electroacupuncture apparatus (Wuxi Jiajian Medical Instrument Co., Ltd., Wuxi, China), administering a 5-minute stimulation at a 1-mA current with a 5-Hz frequency in an intermittent wave pattern. 

For the sham stimulation, superficial needle insertion (depth: 10 mm, size: 0.25 × 25 mm) was performed at the same site as used in the active stimulation. These needles were similarly attached to the electroacupuncture apparatus to emulate the active stimulation protocol. However, the current was switched on only for 15 seconds at the beginning and 15 seconds before the end. The display interface of the device still provided real-time visualization of the applied current, frequency parameters, and time throughout each session, thus manifesting an operational “active” status. 

Data Collection

Choroidal imaging in the macular region was conducted using a high-definition optical coherence tomography (OCT) (Cirrus HD-OCT 5000; Carl Zeiss Meditec, Jena, Germany). Structural OCT of the macular region was performed with EDI foveal scanning. Choroidal segmentation in the OCT images was automated using a U-shaped convolutional network (U-Net), in alignment with methodologies previously described by our group.³⁵ The inner boundary of the choroid was defined by the basal margin of the retinal pigment epithelium, and the choroidal–scleral interface was delineated as the outer boundary. Prior to segmentation, attenuation compensation was conducted to mitigate the impact of retinal vessel projection shadows, thereby improving the visibility of the choroidal–scleral interface. The U-Net model, developed and executed in Pytorch, demonstrated a mean unsigned surface detection error of 2.52 pixels in choroidal segmentation. Following automated segmentation, the data were manually inspected to ensure accuracy. These validated measurements were then used to compute the subfoveal ChT. 

The ChVI was quantified using a methodology analogous to that described by Agrawal et al.,³⁶ employing the publicly available ImageJ software (version 1.53t; National Institutes of Health, Bethesda, MD, USA). This process involved the application of Niblack's auto local thresholding technique, which computes the mean pixel value and its corresponding standard deviation across all points. Following the outcomes of automatic choroidal segmentation, a subfoveal choroidal area extending 1.5 mm from the foveal center was designated as the region of interest (ROI). The image was subsequently converted to the RGB color format, facilitating the use of the color threshold tool to identify dark pixels, which were defined as the luminal area (LA). The regions within the ROI manager were then amalgamated using the “AND” operator in the software to delineate the LA within the specified polygon. Both the total subfoveal circumscribed choroidal area (TCA) and the circumscribed LA were quantified, and the ChVI was calculated as the ratio of the circumscribed LA to the TCA. 

Central subfield thickness (CST) was evaluated using a macular cube scan with a resolution of 512 × 128 µm, specifically measuring the thickness between the internal limiting membrane and the retinal pigment epithelium at the fovea. Axial length (AL), anterior chamber depth (ACD), and lens thickness (LT) were assessed using swept-source OCT with the IOL-Master 700 system (Carl Zeiss Meditec). IOP was measured via a noncontact tonometer (NT-510; NIDEK Co. Ltd., Gamagori, Japan). CDVA was determined using a 6-m logMAR chart. All adverse events were meticulously documented throughout the duration of the study. 

Statistical Analysis

This investigation was conceived as an exploratory study, targeting the completion of both active and sham PPG stimulation tests by a minimum of 20 subjects, alongside the acquisition of short-term choroidal data for each subject. Given the absence of precedent studies on this subject matter, a formal power calculation was not conducted. The chosen sample size was aligned with that of preceding randomized trials that explored short-term changes in choroidal parameters.³⁷ The anticipated population size was 24, accounting for a potential 15% attrition rate. 

Complete case analysis was applied. Change from baseline to each time point in ocular parameters was compared between groups. The analysis of normally distributed variables was conducted using a paired t-test, while the Mann–Whitney–Wilcoxon rank-sum test was used for variables not conforming to normal distribution. Separate analyses were carried out for the right and left eyes. Adjustment for carryover and period effects was deemed unnecessary due to the study's design, which included a sufficiently extended washout period, standardized testing timings, and balanced sequence allocation, thus minimizing potential biases.³⁸ Statistical analyses were conducted using a two-sided alpha level of 0.05, utilizing SAS software version 9.4 (SAS Institute, Cary, NC, USA). 

Results

Demographics

From December 30, 2023, to April 13, 2024, a total of 24 people were recruited, and 22 subjects completed the study. The subject flow within the trial is illustrated in Supplementary Figure S2. Two subjects withdrew before starting their second test session because of work (both were randomized to sham stimulation first). Baseline characteristics of the subjects are presented in Table 1. 

Table 1.

 

Baseline Characteristics

 

Table 2.

 

Change in Ocular Measures From Baseline

 

ChT, ChVI, and CST

The mean change in ChT across two distinct stimulation conditions is presented in Table 2 and Figure 3. Relative to sham stimulation, ChT in the ipsilateral eye exhibited a continuous increase following PPG stimulation, with the increment peaking at 15 minutes poststimulation (mean difference, 17.2 µm; 95% confidence interval, 10.4–24.0; P < 0.001) and remaining significant at 30 (mean difference, 16.5 µm; P < 0.001), 45 (mean difference, 13.1 µm; P < 0.001), and 60 (mean difference, 11.9 µm; P < 0.001) minutes poststimulation. Contrary to the trends observed in ChT, ChVI in the ipsilateral eye experienced an immediate elevation post-PPG stimulation in comparison to sham stimulation (mean difference, 3.8%; P = 0.003), thereafter exhibiting a gradual decline from its apex and reverting to baseline levels 30 minutes subsequent to stimulation (mean difference, –0.7 µm; P = 0.48). Both ChT and ChVI in the eyes contralateral to the site of PPG stimulation demonstrated a trend toward diminution, yet these alterations did not achieve statistical significance when compared to sham stimulation. No significant intragroup disparities were observed in CST. 

Figure 3.

 

Change in choroidal structure in ipsilateral (A) and contralateral eyes (B) after stimulation. Error bars represent standard error of the mean. *Significant difference between two types of stimulation.

AL, ACD, and LT

Figure 4 and Table 1 present the mean changes in AL, ACD, and LT metrics obtained from IOL-Master 700. In comparison with the sham stimulation, PPG stimulation resulted in a reduction of the ipsilateral AL, with pronounced significant effects observed at 15 minutes (19.1 µm vs. –2.3 µm; P < 0.001) and 30 minutes (19.6 µm vs. 3.2 µm; P = 0.006) poststimulation. The trend of change in AL paralleled that observed in ChT, albeit with a greater magnitude and in the opposite direction. Throughout the 60-minute observation period, neither ACD nor LT demonstrated significant alterations attributable to PPG stimulation (all P > 0.05). 

Figure 4.

 

Change in other ocular biometrics after ipsilateral stimulation. (A) CST, (B) AL, (C) ACD, and (D) LT. Error bars represent standard error of the mean. *Significant difference between two types of stimulation.

Safety

The IOP and CDVA demonstrated stability over time across both stimulation conditions (Supplementary Table S1). One subject developed localized subcutaneous bruising the day after receiving PPG stimulation, but the symptoms disappeared 3 days later. 

Discussion

The main finding is that stimulation of ipsilateral PPG via electroacupuncture evoked a short-term increase in ChT and ChVI in the human eye. Specifically, ChT in the eyes ipsilateral to PPG stimulation exhibited a steady increase, with the magnitude of increase reaching its peak 15 minutes poststimulation and preserving its significance for the subsequent 45 minutes. In contrast, ChVI displayed a more rapid increase, peaking immediately after the stimulation and then gradually declining toward baseline levels. Overall, there was no evidence of safety concerns. The current study highlights the role of PPG activation via electroacupuncture in mediating choroidal structure in humans and suggests the potential therapeutic value of this intervention for ocular diseases characterized by choroidal blood flow reduction. 

Choroidal Structure Changes With Ipsilateral PPG Stimulation

In young adults, the extent of short-term variations in ChT observed following PPG stimulation, which ranges between 5 and 19 µm, exhibits a general equivalence to the changes recorded (6–25 µm) in response to an assortment of physiologic, pharmacologic, optical, and environmental stimuli.³⁴ The finding of altered choroidal structure accords with the known physiologic importance of PPG to choroidal vasodilation and with preclinical animal studies showing choroidal blood flow responses with stimulation of preganglionic input to the PPG. Notably, research conducted by Nickla and Schroedl²¹ on avian models revealed that transection of the parasympathetic input to the eye from the PPG did not significantly alter choroidal thickness. Unlike in birds, where the choroidal parasympathetic innervation predominantly originates from the ciliary ganglia with minimal contribution from the PPG, the parasympathetic innervation of the mammalian choroid is primarily derived from the PPG.²⁶ This distinction may elucidate the observed variability in physiologic responses across different taxa. 

The principal morphologic feature associated with increased ChT is primarily attributed to the expansion of the fluid-filled lacunae within the stroma, which are connected to arterioles and can exhibit dramatic volume changes.³⁹ Academics have conjectured that changes in choroidal blood flow, lymphatics, osmotic macromolecules, and nonvascular smooth muscle play roles in the expansion of the lacunae. Notably, the current study reports that ChVI peaked immediately after PPG stimulation, followed by a decline, whereas the marked augmentation in ChT was not prominent until 15 minutes following the stimulation. The temporal divergence observed between these two metrics, coupled with the transient nature of the ChVI elevation (increase in number and/or diameter of vascular channels), aligns with the hypothesis that choroidal blood flow acts as a trigger for ChT. The PPG-evoked choroidal blood flow may exert a driving force to facilitate the translocation of fluid from the vasculature into the stromal lacunae. Previous studies have established that nonvascular smooth muscle receives both sympathetic and parasympathetic inputs. The nitric oxide (NO) released by PPG is speculated to relax the muscle and thereby thicken the choroid.¹⁷ Nevertheless, should the modification in choroidal architecture induced by PPG stimulation be contingent upon alterations in the tone of nonvascular smooth muscle, it would be logical to anticipate that the zenith in ChT would materialize immediately after stimulation, presumably preceding the acme in ChVI. Such an expectation stands in contradiction to the observed inverted U-shaped trajectory of ChT delineated in the extant findings. 

Choroidal Structure Changes With Contralateral PPG Stimulation

The potential for a crossover effect is suggested by the simultaneous reduction in ChVI and ChT observed in the contralateral eye following PPG stimulation via electroacupuncture, despite the presence of only a borderline statistical difference. The PPG receives its preganglionic input from the SSN in the hindbrain. Using pseudorabies virus tracing, researchers have identified that the SSN receives input from several higher-order brain regions, including the paraventricular nucleus and the nucleus of the solitary tract.⁴⁰ These regions are involved in systemic blood pressure regulation and sympathetic control, indicating that the SSN-PPG circuit integrates signals related to systemic vascular homeostasis and adapts choroidal blood flow accordingly. While PPG electroacupuncture primarily affects the parasympathetic nerves on the stimulated side, systemic blood pressure and sympathetic input may result in an asynchronous response in the contralateral choroid. Prior research has also demonstrated the effect of unilateral electrical stimulation of the PPG on lateral cerebral blood flow.²⁷ Similarly, monocular optical interventions have been documented to cause alterations in the ChT of the contralateral eye.⁴¹ These observations, along with our results, underscore the central regulation of ocular hemodynamics, highlighting the need for future in-depth studies to reveal its complexity. 

Effect of PPG Stimulation on Other Ocular Parameters

The lack of observable alterations in the anterior segment of the eye (AL and LT), subsequent to PPG stimulation, intimates that PPG does not participate in the neural regulation of ocular accommodation. This inference aligns with established anatomic perspectives.²⁶ AL, as assessed via the IOL Master, is delineated as the distance spanning from the anterior corneal surface to the retinal pigment epithelium.⁴² The observation of a shortened AL in the eye ipsilateral to the stimulation can be attributed to an increase in ChT. It is noteworthy that the magnitude of the change in ChT was slightly smaller than that of AL. The quantification of ChT benefited from a high level of precision and objectivity, afforded by an automated choroidal segmentation approach underpinned by advanced machine learning techniques. Consequently, the slight discrepancy observed between ChT and AL measurements cannot be solely ascribed to inaccuracies in measurement. This raises the prospect of modifications within the posterior sclera as a potential area for further investigation.⁴³ Previous research has demonstrated that PPG stimulation results in elevated IOP in primates,²² whereas blockade of PPG does not induce significant IOP alterations in humans.⁴⁴ In the current study, no significant variations in IOP were detected following PPG stimulation, thereby ruling out the possibility that PPG-induced modulation of IOP was a contributory factor to the current changes in ChT.³⁹ 

Potential of PPG Electroacupuncture for Studying Choroidal Neural Control Mechanisms

Electroacupuncture stimulation to the PPG offers significant potential for studying choroidal neural control mechanisms due to its minimally invasive nature, allowing for safe and repeatable human studies. PPG electroacupuncture can be used to assess neural control differences across various ocular diseases, helping to identify and quantify abnormalities by comparing responses in patients and healthy individuals. Due to a frequency-dependent variability of response in PPG activation and vascular diameter,^45–48 it may be possible to manipulate PPG activation (≤10 Hz) and inhibition (>10 Hz) by adjusting the parameters of electroacupuncture stimulation to gain more insight into the control of choroidal blood flow. Additionally, this method also facilitates the study of systemic feedback mechanisms, as autonomic stimulation may influence not only local choroidal blood flow but also systemic blood pressure and cardiovascular function. By monitoring these systemic changes, researchers can better understand the complex interactions between the autonomic nervous system and choroidal regulation. Thus, combining PPG electroacupuncture with today's increasingly intelligent and accurate choroidal measurements^49,50 can advance our understanding of choroidal neural control mechanisms. 

Potential Applications of PPG Electroacupuncture in Ocular Diseases

The promising aspect of this potential treatment for inadequate choroidal perfusion lies in its direct approach to a major physiologic obstacle. Unlike the retinal circulation, the choroid lacks autoregulation to increase blood flow when needed, placing it at a disadvantage.⁵¹ As reviewed by Reiner et al.,¹⁸ impairments in the neural regulation of choroidal blood flow become evident with aging and in the presence of various ocular (such as AMD and glaucoma) or systemic disorders (such as hypertension and diabetes). Recent discoveries indicate that the subretinal drusenoid deposit (SDD) form of AMD, as opposed to the drusen form, is strongly associated with high-risk vascular diseases (HRVDs) that can directly impair ocular and choroidal perfusion.⁵² The three major classes of HRVDs identified are myocardial damage, cardiac valve disease, and ischemic stroke with internal carotid artery (ICA) stenosis. The hypothesis posited that inadequate choroidal blood flow due to HRVDs is the cause of SDDs.^52–54 Supporting data show direct associations of SDDs with reduced cardiac index, severity of valvular disease, and percentage of ICA stenosis in patients with these systemic diseases.^55,56 PPG electroacupuncture could potentially benefit patients with SDD-AMD and merits a controlled study to evaluate its efficacy. Additionally, ophthalmic artery angioplasty has been shown to successfully restore ocular perfusion in patients with AMD, leading to positive visual outcomes.⁵⁷ 

Substantial evidence has corroborated the intricate linkage between the choroid and the regulatory mechanisms that influence ocular growth. Interventions that directly alter choroidal blood flow through surgical or pharmacologic means have been documented to impact the development of the eyeball.^58,59 Changes in ChT are strongly correlated with the degree of long-term axial elongation.^60,61 Additionally, Lin et al.⁶² observed that elevated sympathetic nervous system activity, as inferred from urinary catecholamine concentrations, is associated with a reduction in ChT and accelerated elongation of the AL. The pressurized conditions prevalent in educational environments, particularly in East Asia, may perturb the homeostasis between the sympathetic and parasympathetic nervous systems, culminating in choroidal thinning and the progression of myopia. Therapeutic restoration of this disrupted homeostasis may be attainable through targeted enhancement of parasympathetic activity within the choroid, facilitated by stimulation of the PPG. 

Limitations

One of the limitations of the study is the exclusive inclusion of young, healthy adults. For a comprehensive exploration of the implications of PPG stimulation, further studies are imperative across diverse cohorts experiencing choroidal dysfunctions, including individuals with AMD, those with glaucoma, or children with rapid myopia progression. Additionally, the relatively brief observation window of 60 minutes may not sufficiently capture the effects of acupuncture-induced PPG stimulation on the choroidal structure. However, conducting assessments over longer durations, such as 24 hours, poses challenges due to the necessity for constant management of visual tasks. 

Conclusions

Electrical activation of the PPG through electroacupuncture produced a short-term increase in ChT and ChVI in the ipsilateral eye compared to sham stimulation, with changes in ChT lagging behind ChVI but being more sustained. 

Acknowledgments

Supported by the Sailing Program of Science and Technology Commission of Shanghai Municipality (22YF144400) and the Chinese and Western Medicine Collaborative Guidance Programme for General Hospitals (ZXXT-202307). 

Disclosure: X. Kong, None; G. Yang, None; Y. Cao, None; R. Han, None; X. Wang, None; Y. Yang, None; J. Hong, None; X. Zhou, None; X. Ma, None