Blepharitis is a common ocular disease characterized by chronic inflammation of the eyelid margin, often accompanied by discomfort, visual impairment, and decreased quality of life. It is multifactorial, including bacterial colonization, sebaceous gland dysfunction, and the host’s immune response [1,2]. Traditional treatments for blepharitis primarily focus on managing symptoms and preventing recurrence through a combination of hygiene practices and pharmacological interventions. Eyelid hygiene, such as warm compresses and gentle eyelid scrubs, is the cornerstone of therapy, helping to remove debris and reduce bacterial colonization along the eyelid margin. However, compliance can be a challenge, as these routines often require daily effort and consistent application over extended periods.

In cases of bacterial or inflammatory involvement, topical antibiotics or anti-inflammatory agents, such as corticosteroids or cyclosporine, are commonly prescribed. Topical antibiotics, like azithromycin, are effective in reducing bacterial load and addressing secondary infections, but prolonged use can lead to antibiotic resistance or ocular irritation [3]. Corticosteroids, while potent anti-inflammatory agents, are generally reserved for short-term use due to potential side effects, including increased intraocular pressure and cataract formation [4].

For patients with chronic or refractory blepharitis, newer options such as intense pulsed light therapy or thermal pulsation devices have gained attention. These physical treatments aim to improve meibomian gland function and alleviate inflammation, though they often come with higher costs and limited accessibility. Despite these advances, recurrence rates remain high, underscoring the need for alternative or adjunctive therapies that are both effective and user-friendly [5].

Recent advances in treatment have focused attention on physical treatments such as thermal or mechanical stimulation aimed at modulating inflammation and restoring homeostasis of ocular tissues [6,7]. Among these approaches, micro-vibration therapy has attracted attention as a potentially promising intervention [6,8]. Micro-vibration therapy is a novel physical treatment designed to improve tissue health through mechanical stimulation [9,10]. By delivering low-frequency vibrations, it is hypothesized to enhance blood circulation, stimulate meibomian gland activity, and reduce inflammation. The mechanical oscillations may also promote lymphatic drainage, thereby alleviating swelling and reducing the accumulation of inflammatory mediators. Additionally, when combined with thermal therapy, the vibrations could synergistically improve the liquefaction of meibum, further relieving gland blockages.

Being relatively cheap compared to other intervention methods, these cost-effective devices that market their anti-inflammatory effects are now widely available. Often, they have become an attractive alternative to more invasive or pharmaceutical treatments. However, despite their popularity, most of these devices are not registered as medical devices, and their therapeutic effects have not been sufficiently validated [11,12]. Although it seems to be appealing to use them in regular basis to control ocular symptoms, there is limited empirical evidence to support their mechanisms of action, highlighting the need for rigorous investigation. Their safety and efficacy need to be confirmed beforehand, to rule out their potential adverse effects.

This study investigated the effects of a micro-vibration device on blepharitis in a preclinical rat model. It aims to provide important insights into the performance and risks. The findings highlight the need for caution and thorough evaluation before adopting non-medical devices to manage ocular diseases such as eyelids. It aims to inform clinicians, patients, and regulators about the effectiveness of using unproven therapies in the ocular environment.

Blepharitis rat model

The blepharitis rat model was established using 6-week-old Sprague Dawley male rats (DBL) through complete Freund’s adjuvant (CFA) injections (Thermo Fisher Scientific) at medial and lateral margin of eyelid. After blepharitis induction, rats were housed at ambient temperature of 24°C ± 1°C and humidity of 55% ± 10%.

Experiment scheme with intervention plans

A total of 64 rats were randomly assigned to 8 groups in each experiment (Fig. 1): 1) control group (CON); 2) control group with vibration treatment (CON + V); 3) control group with vibration and thermal treatment (CON + VT); 4) blepharitis group (B); 5) blepharitis group with vibration treatment (B + V); 6) blepharitis group with vibration and thermal treatment (B + VT); 7) blepharitis group with hyaluronic acid treatment (B + HA) (Kynex; Huons); and 8) blepharitis group with 0.05% cyclosporin treatment (B + R) (Restasis; Allergan Inc.). The vibration device used in this study has a frequency of 180 Hz, with an amplitude range of 25-50 μm. The device, with or without thermal treatment, was applied to both eyes of the rats for 5 minutes, at an operating temperature of approximately 40°C. Thermal treatment was administered simultaneously with vibration and continued throughout the treatment duration. Groups treated with hyaluronic acid and cyclosporine were included for comparison to evaluate the effects of vibration and thermal treatments against conventional treatments for ocular blepharitis. All treatments were given to the rats without anesthesia.

Figure 1. Schematic overview of the current study. After a week of blepharitis induction, different treatments were given to the rats for 2 weeks, according to the experiment plan. CON, control; V, vibration treatment; VT, vibration with thermal treatment; B, blepharitis; HA, hyaluronic acid; C, cyclosporine; IHC, immunohistochemistry.

Ocular sign assessment

To evaluate ocular signs, tear break-up time (TBUT), fluorescein corneal staining (FCS) score, meibomian gland swelling, and eyelid telangiectasia were measured once a week from the start of treatment to the second week of treatment. The fluorescein-stained cornea of the non-anesthetized rat was observed under a slit lamp (Topcon) after manually restraining the animal to stabilize its head. TBUT was measured three times for each week and the average value was recorded. Fluorescein staining was performed by instilling Fluorescite (Alcon) into the eyes of rats. Fluorescite is used after diluting 1:10 with saline. According to the preceding evaluation criteria, eyelid edema, FCS, and telangiectasia scores were assigned (within 0-5 points). The grades of corneal staining were as follows: 0 = normal; 1-2 = mild to moderate; and ≥3 = severe.

Tissue collection and immunohistochemistry

Eye tissues including the eyeball were excised after CO₂ euthanasia on the 21st day. The tissues were fixed in Davidson’s fixative (Polyscience) and embedded in OCT compound (Tissue-Tek; Sakura Finetek). Cryo-sections were made at an average thickness of 15 μm, and immunohistochemistry (IHC) was performed using inflammatory cytokines interleukin (IL)-1β (NB600-633; Novus Biologicals), IL-6 (ab208113; Abcam), and tumor necrosis factor (TNF)-α (ab6671; Abcam) with hematoxylin counterstaining.

Statistical analysis

GraphPad Prism and IBM SPSS Statistics 21 (IBM Corp.) were used in statistical analysis, and the data were expressed as mean ± standard deviation of the mean. The statistical significance of the differences was assessed using Tukey’s test. A value of p < 0.05 was defined as statistically significant.

Experimental setup and device parameters

The experimental framework and device parameters are summarized in Fig. 2. Blepharitis was induced using CFA in all experimental groups except for the controls. Treatments were initiated on day 8 and continued until day 22, after which the animals were sacrificed for detailed analysis. Micro-vibration treatment was performed at 180 Hz, and thermal enhancement was incorporated for specific groups. The operating temperature of the micro-vibration device remained consistent throughout the treatment intervals, ensuring controlled experimental conditions. Control groups, which did not receive CFA or treatments, were used as baselines for comparison.

Figure 2. Experimental scheme and device for micro-vibration and thermal treatment with its operating temperatures. (A) Frequency of DMT used in this study. (B) Experimental scheme. After blepharitis induction, at 22nd day rats are sacrificed for analysis. (C) DMT used in this study. (D) Operating temperature of DMT with time interval. DMT, device for micro-vibartion treatment; TBUT, tear break-up time; FCS, fluorescein corneal staining.

Photographic and morphological observations

Photographs captured over the experimental period provided visual confirmation of successful blepharitis induction, as evidenced by prominent swelling and erythema in the eyelids of all blepharitis-induced groups (Fig. 3). In contrast, the control group displayed normal eyelid morphology without any inflammatory signs. As the experiment progressed, subtle improvements were observed in treatment groups, with the B + V group showing the most notable reductions in swelling and redness by the second week of treatment. However, in both the B + VT and CON + VT groups, significant tissue damage occurred due to the excessively high temperature generated by the device, leading to the humane termination of the experiment in accordance with animal ethics guidelines. This reduction was particularly evident in the B + V group, suggesting an additive benefit of thermal enhancement alongside vibration therapy.

Figure 3. Photographs of blepharitis-induced rat eyelids during the experimental period. Blepharitis induced groups (B, B + V, B + VT, B + HA, B + R) have swollen eyelids throughout the experiment, with subtle changes as experiment progresses. CON, control; V, vibration treatment; VT, vibration with thermal treatment; B, blepharitis; HA, hyaluronic acid; R, 0.05% cyclosporine; N/A, not available.

Ocular sign assessments

Assessments of ocular signs revealed significant differences between groups and demonstrated the therapeutic potential of the micro-vibration treatments (Fig. 4). TBUT was markedly reduced in all blepharitis-induced groups compared to controls, reflecting the disruption of tear film stability. However, gradual recovery was observed in the B + V and B + VT groups over the treatment period, with TBUT values approaching those of the controls by the conclusion of the study. FCS scores remained largely unchanged across groups, though the B + V group exhibited a mild reduction in staining after two weeks of treatment, indicating potential epithelial recovery. Eyelid swelling scores were significantly elevated in blepharitis-induced groups compared to controls, but a steady reduction was noted in the B + V group, with further improvement in the B + VT group by the second week of treatment. Similarly, eyelid telangiectasia scores remained elevated in most groups, but significant improvements were observed in the B + V group after two weeks, suggesting enhanced vascular integrity.

Figure 4. Ocular sign assessment. (A) Tear break-up time (TBUT) significantly decreased in all of the blepharitis induced groups compared to the control groups. TBUT gradually increased in the treatment groups including B + V, B + HA, and B + R. (B) Fluorescein corneal staining (FCS) did not change significantly in all groups, while B + V group showed decreasing tendency after 2 weeks of treatment. (C) Eyelid swelling score showed steady decreased in B + V group, while B + HA and B + R groups did not show significant changes. (D) Eyelid telangiectasia score did not show significant changes after blepharitis induction in most of the groups, except B + V group which showed significant decrease after 2 weeks of vibration treatment. CON, control; V, vibration treatment; VT, vibration with thermal treatment; B, blepharitis; HA, hyaluronic acid; C, cyclosporine. *p < 0.05, **p < 0.01, ***p < 0.001 compared to control group. ^#p < 0.05, ^###p < 0.001 compared to blepharitis group.

Immunohistochemical analysis of cytokine expression

Immunohistochemical staining of ocular tissues revealed distinct patterns of inflammatory cytokine expression, including IL-1β, IL-6, and TNF-α (Figs. 5-8), which were then quantified using H-scores (Fig. 9). Corneal tissues exhibited the highest levels of inflammatory cytokines in the blepharitis-only group, highlighting the cornea as the most affected tissue. Treatment with micro-vibration (B + V) and micro-vibration with thermal enhancement (B + VT) resulted in significant reductions in cytokine levels, with the B + VT group demonstrating the most pronounced effects. In the conjunctival tissues, inflammatory markers were similarly elevated in the B group. Both B + V and B + VT treatments effectively reduced cytokine expression, with the B + VT group showing slightly superior outcomes. In the meibomian gland, inflammation was evident, as indicated by elevated levels of IL-1β, IL-6, and TNF-α in the B group. Both B + V and B + VT groups achieved significant reductions in cytokine expression, suggesting therapeutic effects on glandular inflammation. Retinal tissues, though less affected compared to anterior structures, also displayed elevated cytokine levels in the B group. These levels were significantly attenuated in the B + V and B + VT groups, demonstrating the systemic anti-inflammatory benefits of micro-vibration therapy.

Figure 5. Immunohistochemistry analysis of corneal tissue sections stained with DAB chromogen to assess protein expression. The images depict cross-sectional views of the cornea, highlighting the localization and distribution of the target protein within the epithelium, stroma, and endothelium. Variations in staining intensity and patterns are observed across panels, representing independent samples or treatment groups. Structural features of the cornea, such as the layered organization of the epithelial cells and stromal matrix, are clearly visualized. As with previous figures, images for the B + VT group are absent due to the termination of the experiment for this group, caused by tissue necrosis resulting from excessively high device temperature. IL-1β, interleukin-1 beta; IL-6, interleukin-6; TNF-α, tumor necrosis factor-alpha; CON, control; V, vibration treatment; VT, vibration with thermal treatment; B, blepharitis; HA, hyaluronic acid; C, cyclosporine. Total magnification, ×200.

Figure 6. Immunohistochemistry analysis of conjunctival tissue sections stained with DAB chromogen to assess protein expression. The images show cross-sectional views of the conjunctival tissues, highlighting the localization and distribution of the target protein within epithelial and stromal layers. Differences in staining intensity and patterns are observed across panels, representing independent samples or treatment groups. Structural features of the conjunctiva, including epithelial folds and goblet cells, are clearly visualized. The absence of images for the B + VT group is due to the termination of the experiment for this group caused by tissue necrosis from excessively high device temperature. IL-1β, interleukin-1 beta; IL-6, interleukin-6; TNF-α, tumor necrosis factor-alpha; CON, control; V, vibration treatment; VT, vibration with thermal treatment; B, blepharitis; HA, hyaluronic acid; C, cyclosporine. Total magnification, ×200.

Figure 7. Immunohistochemistry analysis of meibomian gland tissue sections stained with DAB chromogen to assess protein expression. The images show cross-sectional views of the meibomian glands, highlighting the localization and distribution of the target protein within acinar and ductal structures. Variations in staining intensity are observed across different panels, representing independent samples or treatment groups. The structural integrity and functional compartments of the glands, including acini and ducts, are visible. Notably, images for the B + VT group are missing because the experiment for this group had to be stopped due to tissue necrosis caused by excessively high device temperature. IL-1β, interleukin-1 beta; IL-6, interleukin-6; TNF-α, tumor necrosis factor-alpha; CON, control; V, vibration treatment; VT, vibration with thermal treatment; B, blepharitis; HA, hyaluronic acid; C, cyclosporine; N/A, not available. Total magnification, ×200.

Figure 8. Immunohistochemistry analysis of retinal tissue sections stained with DAB chromogen to identify protein expression patterns. The images display cross-sectional views of the retina, highlighting the distribution and localization of the target protein. The retinal layers, including the ganglion cell layer, inner nuclear layer, outer nuclear layer, and photoreceptor layer, are stained to varying degrees, reflecting differential protein expression. Each panel represents an independent sample or treatment group, with consistent staining intensity and distribution observed across specific retinal layers. IL-1β, interleukin-1 beta; IL-6, interleukin-6; TNF-α, tumor necrosis factor-alpha; CON, control; V, vibration treatment; VT, vibration with thermal treatment; B, blepharitis; HA, hyaluronic acid; C, cyclosporine. Total magnification, ×200.

Figure 9. Inflammatory cytokine expressions in the tissues after micro-vibration treatment, expressed as H-scores. (A-C) Results from corneal tissues. (D-F) Results from conjunctival tissues. (G-I) Results from meibomian gland tissues. (J-L) Results from retinal tissues. IL-1β, interleukin-1 beta; IL-6, interleukin-6; TNF-α, tumor necrosis factor-alpha; CON, control; V, vibration treatment; VT, vibration with thermal treatment; B, blepharitis; HA, hyaluronic acid; C, cyclosporine. *p < 0.05, **p < 0.01, ***p < 0.001 compared to control group. ^#p < 0.05, ^###p < 0.001 compared to blepharitis group.

Comparative efficacy of treatments

The comparative efficacy of the treatments was evident across the various analyses. Micro-vibration therapy alone (B + V) consistently reduced inflammatory markers and improved ocular signs across all tissues. Micro-vibration with thermal enhancement (B + VT) provided the most substantial reductions in inflammation, suggesting a synergistic effect of the combined modalities. While cyclosporine (B + C) and hyaluronic acid (B + HA) also demonstrated anti-inflammatory effects, their efficacy was primarily limited to anterior tissues and was less pronounced than that observed with vibration treatments. The findings underscore the potential of micro-vibration therapy, particularly when combined with thermal enhancement, as an effective intervention for blepharitis.

In these days of increasing interest in health, it has become easy to purchase and use various devices online that are said to be beneficial for health. In particular, many people are interested in eye health, and the market for various health supplements and massage products related to this is increasing every year [11,13,14].

There are a variety of devices being sold that include heating and massage functions that are said to be particularly good for the health, but most of these devices are general products that are not registered as official medical devices, which requires extra caution in their use [15,16].

Inexpensive eye massage devices currently available online claim to reduce eye fatigue and reduce inflammatory responses using moderate-temperature heat therapy and low-frequency micro-vibrations, but the parameters of these devices have not been accurately studied. If the device is used indiscriminately on the eyes, serious side effects may occur.

The device used in this study can be purchased online for about $50, and it seems that its small size and light weight are particularly attractive to consumers. The device is a KC certified product, and is advertised as operating at a micro-vibration of 180 Hz and a temperature of about 40 degrees.

As a result of testing its effect in a blepharitis rat model, it was confirmed that micro-vibration of approximately 180 Hz alleviated symptoms in the eyelids and ocular tissues. In particular, the tear film break-up time significantly increased, and the corneal score and telangiectasia score were maintained at a low level similar to those in the cyclosporine group. In particular, the eyelid swelling score showed a lower score than the cyclosporine group and showed a tendency to steadily decrease after blepharitis induction, which shows that directly applying micro-vibration to the eye tissue is more effective in alleviating blepharitis symptoms than simply applying eye drops to the eyes. However, the device’s thermal function was not controlled at all, and the temperature rose to about 80 degrees Celsius, which caused damage to sensitive eye tissue and even led to tissue necrosis.

Unlike rats, humans may reflexively discontinue use of the device if the device becomes too hot. Even so, a stricter parameter control for the devices intended for human-use is required to minimize potential harm. Based on the results of this study, the authors suggest that using micro-vibrations of approximately 180 Hz to massage periocular tissues will not pose a major problem. However, if the device incorporates a heating function, it is strongly recommended to check the precise temperature regulation before applying it around the eyes to ensure safety.

The limitations of this study are as follows: First, we could not compare various parameters of micro-vibration. Among the thermal massage devices that can be commonly searched online, the experiment was conducted on devices that emphasized the low price and portability, and devices that provide thermal and massage to both eyes by wearing them on the head were excluded from this experiment because they were difficult to directly apply to animal experiments. Second, IHC analysis was performed only on three representative inflammatory cytokines.

However, the fact that existing micro-vibration research is mainly limited to the musculoskeletal system, and especially that there is almost no research on the effects of micro-vibration on the eyes except in the fields of traditional Chinese medicine and alternative medicine, suggests that this study shows the possibility of follow-up research [17-19].

In conclusion, this study confirmed that 180 Hz micro-vibration treatment significantly alleviates symptoms in a blepharitis rat model. Considering that blepharitis patients are generally treated with heat therapy, it was thought that applying micro-vibration and heat therapy simultaneously would be more effective. However, the device used in this study had an uncontrolled heat function, which negatively affected eye tissue. Therefore, special care should be taken when purchasing and using eye heat massagers advertised online.

This study demonstrated that micro-vibration therapy significantly alleviates symptoms of blepharitis in a rat model, showing potential as an adjunctive treatment for ocular inflammation. However, the uncontrolled thermal function of the device caused tissue damage, emphasizing the need for precise parameter control in devices marketed for periocular use. While the findings highlight the therapeutic promise of micro-vibration therapy, they also underscore the importance of ensuring safety through proper regulation and validation.

None.

Conceptualizatio: SP, HK, KJC. Data curation: SP, HK, KJC. Formal analysis: HK. Funding acquisition: HK, KJC. Investigation: SP, HK. Methodology: SP, HK. Project administration: HK, KJC. Software: SP, HK. Validation: HK, KJC. Visualization: SP, HK. Writing-original article draft: SP, HK. Writing-review&editing: all authors.

Kyong-Jin Cho is an editorial board member of the journal but was not involved in the review process of this manuscript. Otherwise, there is no conflict of interest to declare.

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (RS-2023-00262908).

Contact the corresponding author for data availability.

None.