Effectiveness of ozonized oil-based ear drops in patients with external ear canal dermatitis: a prospective observational study

Dermatitis of the external ear canal is an inflammatory condition characterized by itching, desquamation, erythema, and discomfort. Although topical corticosteroids are commonly used as first-line therapy, prolonged administration may lead to adverse effects, including skin atrophy and irritation. Therefore, alternative treatments with a safer profile are being explored. Ozonized oil has gained attention due to its antimicrobial, anti-inflammatory, and tissue-repairing properties. This study aimed to evaluate the effectiveness and safety of ozonized oil-based ear drops in reducing symptoms and improving clinical signs in patients with non-infectious dermatitis of the external ear canal. In this prospective observational study, adult patients diagnosed with non-infectious dermatitis of the external ear canal were enrolled. Participants were treated with ozonized oil-based ear drops twice daily for 2 weeks. Clinical effectiveness was assessed before and after treatment using the Modified Itch Severity Scale (MISS), the Visual Analog Scale (VAS) for pain, and otoscopic evaluation of hyperemia, edema, and desquamation. Statistical analysis was performed using the Wilcoxon signed-rank test. Thirty-five patients were enrolled, and 33 completed the study. Treatment resulted in a significant reduction in itching frequency and intensity (p < 0.001), as well as improvement in otoscopic signs (p < 0.001). Sleep onset improved significantly, while nighttime awakenings did not. Mild otalgia occurred in three patients and resolved. No adverse effects were reported. Ozonized oil-based ear drops were associated with an improvement in symptoms and otoscopic findings in this prospective observational study. However, controlled studies are required to confirm these findings.

Dermatitis of the external ear canal is an inflammatory condition characterized by itching, desquamation, and erythema of the canal skin. It represents a heterogeneous clinical entity with multiple possible etiologies. In many cases, it is associated with underlying dermatologic conditions such as atopic dermatitis, seborrheic dermatitis, or psoriasis. In other cases, it may result from contact-related factors, including exposure to external agents such as earrings, headphones, hearing aids, cosmetics, or chemical products.

Clinically, external ear canal dermatitis frequently presents with an eczematous pattern, which reflects a nonspecific inflammatory response rather than a distinct disease entity (Kantor et al., 2016). Among the underlying conditions associated with this presentation, atopic dermatitis (AD) is one of the most common. AD is a chronic, relapsing, inflammatory skin disease characterized by pruritic eczematous lesions and immune dysregulation (Weidinger and Novak, 2016; Langan et al., 2020). Elevated allergen-specific serum IgE levels are observed in many patients (Nutten, 2015). Currently, AD affects approximately 10%–20% of children and 1%–3% of adults, with an increasing prevalence in developed countries (Kreuter et al., 2004).

The treatment of dermatitis of the external ear canal remains challenging due to its chronic and relapsing nature. Scratching can make the condition worse, increase the risk of acute bacterial or fungal infections, and make the illness last longer (Eichenfield and Beck, 2003). Topical corticosteroids are currently considered the first-line treatment for eczematous dermatitis of the external auditory canal due to their anti-inflammatory effects. However, prolonged or inappropriate use may be associated with adverse effects, including thinning of the epidermis, decreased microvascularization, and reduced keratinocyte size (Nemeth et al., 2022; Kolbe et al., 2001).

Recently, ozonized oil-based ear drops have gained increasing attention among otolaryngologists. Ozone gas (O 3) has well-documented antibacterial and antifungal properties, primarily due to its ability to oxidize and damage microbial cell membranes (Valacchi et al., 2005; Guinesi et al., 2011; Sechi et al., 2001). Furthermore, by inducing controlled oxidative stress at the skin surface, it promotes the release of growth factors and may stimulate tissue repair processes (Valacchi et al., 2005; Ugazio et al., 2020). Due to its intrinsic instability, ozone can be stabilized through its reaction with unsaturated fatty acids in vegetable oils, allowing its use in topical formulations such as ear drops and other medical applications (Ugazio et al., 2020).

A specific formulation has been recently developed for ear use, based on liposomal ozonized sunflower oil. Ozonized oils have been widely described in the literature for their antimicrobial and tissue-repairing properties, mainly related to the release of reactive oxygen species and lipid peroxides (Guinesi et al., 2011). In addition to ozonized oil, the formulation contains phospholipids, hydroxypropyl methylcellulose, boric acid, sodium tetraborate, polyhexamethylene biguanide (PHMB), and purified water, which may contribute to its emollient, buffering, and antimicrobial properties.

The aim of this study was to evaluate the effectiveness of ozonized oil-based ear drops in the treatment of external ear canal dermatitis, with particular focus on alleviating symptoms, especially itching, and improving clinical signs.

This prospective observational single-arm study was conducted to evaluate the effects of ozonized oil-based ear drops in adult patients with non-infectious dermatitis of the external ear canal. The diagnosis was established based on clinical symptoms and otoscopic findings, including inflammation, edema, and hyperemia of the external ear canal.

Patients under 18 years of age, as well as those with tympanic membrane perforation, chronic otitis media, acute otitis externa, a history of ear surgery, anatomical abnormalities of the external ear canal, or clinical evidence of infectious disease, were excluded.

The study was conducted in accordance with the ethical standards of the institutional research committee and the 1964 Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from all participants. Ethical approval was granted on 26 September 2024.

Patients were consecutively enrolled at the Department of Integrated Therapies in Otolaryngology (Campus Bio-Medico University Foundation, Rome, Italy) between October 2024 and January 2025.

During the first consultation, a detailed medical history was obtained, and each patient was evaluated by: Patient discomfort, assessed using the Modified Itch Severity Scale (MISS) questionnaire (Acar et al., 2010);

Otoscopic examination;

Pain intensity, assessed using the Visual Analog Scale (VAS).

The Modified Itch Severity Scale (MISS) is a questionnaire designed to assess the severity of itching experienced by a patient. It consists of 5 questions aimed at evaluating the intensity, frequency, and impact of itching on the patient’s daily life. For statistical analysis, each response in the first four sections of the questionnaire was assigned a numerical value to allow for quantitative evaluation. Specifically, responses were scored on a scale from 0 to 3 or 0 to 4, depending on the number of answer options available for each question. This scoring system enabled the calculation of mean values and facilitated comparisons between pre- and post-treatment phases.

In contrast to the original scoring method, which provides a composite score ranging from 0 to 15, we analyzed each item separately to better capture changes in specific domains of itching (e.g., frequency, intensity, and impact on daily life). This approach allowed a more detailed evaluation of treatment effects across different aspects of the symptom.

Three parameters were evaluated by otoscopy: hyperemia, edema, and desquamation. Each parameter was assigned a score from 1 to 4.

After the diagnosis, informed consent was obtained. Each patient received a vial of a liposomal ozonized oil-based formulation (Otizon). Each patient was instructed to use Otizon as follows: 3–4 drops in the external ear canal, twice a day, for 2 weeks.

After 2 weeks of treatment, the patient returned for a follow-up visit. During this consultation, we re-assessed the patient’s condition using the same three parameters that were evaluated during the initial consultation.

A total of 35 patients were initially enrolled in the study, including 14 males and 21 females, with a mean age of 53.9 years (±27.2). Two female patients (aged 44 and 68 years) were excluded due to discontinuation of therapy. After exclusion, the final sample consisted of 33 patients, including 14 males and 19 females, with a mean age of 53.8 years.

The study results demonstrated improvements across various clinical parameters following the treatment. However, not all outcomes reached statistical significance: nighttime awakenings and VAS scores did not show statistically significant changes. All other analyzed parameters showed statistically significant improvements (p < 0.05).

In addition to the reduction in mean scores, a shift in the distribution of responses was observed, with fewer patients reporting higher severity categories after treatment. Itching Frequency: Pre-treatment assessments indicated that pruritus was reported with the following frequencies: morning (mean score 1.39), afternoon (1.42), evening (1.61), and night (1.18). Post-treatment, these values decreased notably to 0.36 (p < 0.001) in the morning, 0.55 (p < 0.001) in the afternoon, 0.52 (p < 0.001) in the evening, and 0.39 (p < 0.001) at night, showing a marked reduction in the occurrence of symptoms across all times of day (Figure 1).

Itching Characteristics: A clear reduction was observed in all assessed characteristics of itching following the intervention. Stinging: The mean score decreased from 0.33 in the PRE phase to 0.16 (p = 0.030) in the POST phase, indicating a notable reduction in discomfort. Burning: A significant improvement was noted, with the score dropping from 0.33 to 0.03 (p = 0.009). Irritating: This characteristic showed a marked decline, with a PRE score of 2.12 decreasing to 1.06 post-intervention (p < 0.001). Worrisome: The score decreased substantially, from 0.30 to 0.03 (p = 0.016) suggesting a considerable alleviation of concern (Figure 2).

Itch Intensity: The intensity of pruritus improved across all phases.

In the best phase, the mean score dropped from 0.88 (PRE) to 0.30 (POST) (p = 0.002). In the moderate phase, scores improved from 1.67 to 0.76 (p < 0.001). In the worst phase, the intensity decreased significantly from 2.67 to 1.30 (p < 0.001) (Figure 3). Itch-related situations: In the study, only a few patients reported mood changes. A significant improvement was observed in sleep-related disturbances. Pre-treatment, patients reported difficulty falling asleep, with a mean score of 0.33, which decreased to 0.12 post-treatment (p = 0.042). Nighttime awakenings were also reduced, from 0.24 to 0.09; however, this difference did not reach statistical significance (p = 0.083). In the analyzed sample, no patients reported the use of sleep medication either before or after treatment (score = 0.00 in both cases), indicating that this parameter remained unchanged (Figure 4).

Otoscopy: A general improvement in otoscopic signs of inflammation and irritation was observed following the intervention. Hyperemia showed a noticeable decrease, with the mean score dropping from 1.73 in the PRE phase to 1.06 (p < 0.001) in the POST phase. Desquamation, initially marked with a mean score of 3.00, was significantly reduced to 1.88 (p < 0.001) after treatment. Similarly, edema improved considerably, with scores declining from 1.39 to 0.97 (p < 0.001), indicating a clear reduction in tissue swelling and inflammatory response (Figure 5).

Pain Assessment (VAS Scale): Out of the 33 patients included in the study, only 3 reported mild otalgia, with scores ranging from 4 to 5 on the Visual Analog Scale (VAS). After treatment, these patients experienced a reduction in pain intensity, with post-treatment scores decreasing to a range of 2–3, indicating a general improvement in auditory discomfort.

Mood Changes: Mood alterations related to pruritus were rare among participants. Only 2 out of 33 individuals reported increased agitation as a result of persistent itching. Notably, this emotional response continued even after treatment, suggesting that in isolated cases, the psychological impact of chronic pruritus may persist despite physical symptom relief.

In this prospective study, treatment with ozonized oil-based ear drops was associated with a reduction in itching frequency and intensity in patients with external ear canal dermatitis. Improvements were also observed in clinical signs, including hyperemia, desquamation, and edema, with most parameters showing statistically significant changes after treatment. Overall, these findings suggest a potential clinical benefit in the symptomatic management of external ear canal dermatitis.

In this context, several therapeutic alternatives to corticosteroids and antibiotics have been explored. Among these, topical pimecrolimus has shown promising results. Beriat et al. (2012) reported outcomes comparable to 1% hydrocortisone, while Acar et al. (2010) demonstrated a significant reduction in itching severity in patients with pruritic external auditory canal. Similarly, Nemeth et al. (2022) observed sustained symptom control with pimecrolimus compared to clobetasone butyrate, and Lee et al. (2021) reported significant improvement in itching compared with moisturizing therapy.

Furthermore, real-world evidence highlights the heterogeneity of treatment approaches in external ear inflammatory disorders. In particular, Gelardi et al. (2023) emphasized the variability of therapeutic strategies adopted in clinical practice and the need for effective and well-tolerated topical therapies tailored to patient characteristics and symptom severity.

In this context, ozonized oil-based formulations have been proposed as a potential therapeutic option. This approach is supported by their antimicrobial and anti-inflammatory properties, which may contribute to symptom improvement and restoration of the skin barrier. Although the present study was not designed as a comparative trial, the observed clinical improvements support further investigation of this approach in controlled settings.

From a mechanistic perspective, ozone is highly unstable and rapidly degrades when used in its gaseous or aqueous form, limiting its direct application in topical treatments. However, stabilization can be achieved through its reaction with the double bonds of unsaturated fatty acids, such as those present in sunflower or olive oil, leading to the formation of ozonized oils containing active compounds known as ozonides. These ozonides act as reservoirs of reactive oxygen species (ROS) and oxygenated molecules, including hydroperoxides and lipid peroxides, which are released upon contact with biological tissues. This process is thought to underlie the antimicrobial activity, through oxidative damage to microbial cell membranes and mitochondrial structures, as well as the stimulation of tissue repair mechanisms (Guinesi et al., 2011; Sechi et al., 2001).

In addition, pure ozonized oil may be irritating to sensitive tissues; therefore, encapsulation technologies have been developed to improve tolerability. In particular, liposomal formulations allow the incorporation of ozonized oil into phospholipid vesicles, enhancing its delivery and potentially increasing the selectivity of its antimicrobial action (Ugazio et al., 2020).

To our knowledge, this is one of the first studies to evaluate the effectiveness of an ozonized oil-based formulation in the treatment of external ear canal dermatitis. Several studies in the literature have already demonstrated the effectiveness of ozonized oil in other medical contexts. For instance, multiple studies on ozonized oil-based eye drops have assessed their effectiveness both in vivo and in vitro, highlighting their antimicrobial and reparative activities. Paduch et al. (2021) demonstrated that the formulation has antioxidant activity within specific concentration ranges and can stimulate nitric oxide release, particularly in corneal epithelial cells. Spadea et al. (2018) reported reparative and regenerative effects of liposomal ozonized oil combined with hypromellose (Ozodrop®), with significant clinical improvements observed in spontaneous external ocular pathologies in both animal and human studies. Additionally, Celenza et al. (2020) investigated the antifungal properties of liposomal ozonized oil eye drops, showed effectiveness against several Candida species, including C. albicans, C. glabrata, C. krusei, and C. orthopsilosis, with a dose-dependent effect mediated by increased reactive oxygen species production, lipid peroxidation, and mitochondrial membrane depolarization. Other studies (Mukherjee et al., 2024) have also highlighted the beneficial role of ozonized oil in the treatment of chronic periodontitis, further supporting its potential therapeutic applications across different inflammatory and infectious conditions.

Limitations

This study presents several limitations. First, the sample size was relatively small, and therefore the results should be interpreted as preliminary and hypothesis-generating. Second, the follow-up period was limited, and it remains unclear whether symptoms may recur after discontinuation of the treatment. Third, the absence of a control group restricts the ability to assess potential placebo effects and prevents direct comparison with other therapeutic options. In addition, the study design was non-blinded, which may have introduced performance or reporting bias.

Additionally, the multi-component nature of the formulation should be considered. Although ozonized oil is regarded as the main active ingredient, the contribution of the other components cannot be completely excluded, and potential synergistic effects may have influenced the overall clinical outcomes.

This prospective study showed improvements in symptoms and otoscopic findings following treatment with ozonized oil-based ear drops, suggesting that these ear drops may represent a promising therapeutic option for the symptomatic management of external ear canal dermatitis. However, given the limitations of the study design, further randomized controlled trials are required to confirm these findings. In addition, due to the multi-component nature of the formulation, the observed clinical effects may reflect the combined action of ozonized oil and other ingredients present in the formulation.