Oxymetazoline Successful Therapy To Improve Droopy Eye Appearance
Overview
Oxymetazoline hydrochloride has demonstrated effectiveness in several studies for treating acquired blepharoptosis and improving the aesthetic appearance of the upper eyelid. This study systematically reviewed existing literature on the topical use of oxymetazoline for the treatment of acquired blepharoptosis. A comprehensive review was performed on studies published between 2013 and 2024, adhering to PRISMA guidelines, using the PubMed, Scopus, and Cochrane databases. The primary outcomes measured included changes in marginal reflex distance (MRD1) from pre- to post-treatment with topical oxymetazoline and the mean difference in MRD1 compared to control groups.
Introduction
Blepharoptosis, or ptosis, refers to the abnormal drooping of one or both upper eyelids, which not only affects the appearance of the eyes but may also impair the superior visual field, leading to functional difficulties. This condition can create an uneven or fatigued appearance, and it is often associated with psychological impacts such as anxiety, depression, and concerns over appearance. Additionally, ptosis can diminish patients’ independence in performing daily activities, further affecting their quality of life. Prevalence estimates suggest that ptosis affects between 4.7% and 13.5% of the adult population, underscoring its significant burden.
Ptosis may be congenital, meaning present from birth, or acquired later in life. Acquired blepharoptosis can result from various causes, classified into neurogenic (related to nerve dysfunction), myogenic (related to muscle weakness), traumatic (due to injury), mechanical (from external forces like tumors), or iatrogenic (resulting from medical interventions). The severity of ptosis is commonly evaluated using Marginal Reflex Distance 1 (MRD1), which measures the distance from the corneal light reflex to the upper eyelid margin. In individuals without ptosis, MRD1 measures 4-5 mm, while in patients with ptosis, it is less than this normal range.
Botulinum toxin A, used in some cases to slightly lift the lateral brow by targeting the orbicularis oculi muscle, has been shown to provide minimal improvement in acquired blepharoptosis. Surgical correction remains the gold standard treatment for ptosis, but it comes with several risks, including infection, asymmetry, overcorrection, recurrence of the ptosis, corneal injury, and lagophthalmos (difficulty closing the eyelid). Given these potential complications, there is a growing demand for a non-invasive and pharmacological treatment option for blepharoptosis that could avoid the risks associated with surgery while effectively managing the condition.
Müller’s muscle, which plays a key role in maintaining upper eyelid elevation, has been a common target in surgical approaches for ptosis correction. This muscle is closely associated with the levator palpebrae superioris muscle and contains adrenergic receptors, making it an attractive pharmacologic target for non-surgical treatments. Oxymetazoline hydrochloride, a 0.1% ophthalmic solution, was developed as a pharmacologic option and approved in 2020 for the treatment of acquired blepharoptosis. Oxymetazoline is a sympathomimetic agent that stimulates the adrenergic receptors in Müller’s muscle, leading to an elevation of the upper eyelid. Its approval marked a significant step forward in non-surgical treatments for this condition, offering an alternative to patients who may not want or cannot undergo surgery.
Previous studies have shown that oxymetazoline can be an effective treatment for acquired blepharoptosis, leading to improved MRD1 measurements and a more elevated eyelid appearance. However, most studies conducted to date have been single-center trials with small sample sizes, limiting the generalizability of the findings. No comprehensive study has compiled the existing evidence on oxymetazoline’s efficacy to provide a broader understanding of its role in treating acquired blepharoptosis.
This systematic review aims to gather and evaluate the current literature on the effectiveness of oxymetazoline for treating acquired blepharoptosis. By analyzing the data from various studies, the review seeks to determine how significantly oxymetazoline can improve MRD1 in patients and assess its overall clinical utility in managing the condition. The hypothesis is that oxymetazoline will substantially increase MRD1 in individuals with acquired blepharoptosis, offering an effective non-surgical alternative for those affected by this condition. Through this review, clinicians may gain a clearer understanding of how to incorporate oxymetazoline into treatment plans for blepharoptosis, potentially offering patients a safer and less invasive treatment option.
Also read Dry Eye Disease and Dehydration
Methods
Inclusion Criteria:
- Study Design:
– Double- or single-blinded randomized controlled trials (RCTs)
– Double- or single-blinded randomized comparison trials
– Non-randomized controlled trials
– Prospective or retrospective observational studies
- Population:
– Adult patients (18 years or older) diagnosed with acquired blepharoptosis or blepharospasm.
– Patients with blepharoptosis secondary to conditions such as botulinum toxin injections or myasthenia gravis.
- Intervention:
– Use of oxymetazoline ophthalmic drops to treat acquired blepharoptosis.
- Comparator:
– Control group treated with non-pharmacologically active lubricating drops or placebo.
- Outcomes:
– Measured improvement in Marginal Reflex Distance 1 (MRD1) pre- and post-treatment.
- Language:
– Studies published in English.
- Timeframe:
– Studies published from 2013 to 2024.
Exclusion Criteria:
- Population:
– Pediatric patients (under 18 years of age).
– Patients with otologic disease.
- Study Type:
– Review articles, case reports, or editorials.
– Non-human studies.
– Studies with incomplete or missing statistical data.
– Studies involving intravenous or cutaneous use of oxymetazoline instead of ophthalmic application.
- Language:
– Non-English language studies.
- Duplicates:
– Duplicate studies or publications.
- Accessibility:
– Studies that were inaccessible or unavailable in full-text format after two attempts to contact the primary author for additional data.
This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to ensure a systematic approach to reviewing the literature. To identify relevant studies, comprehensive search strategies were developed for three databases: PubMed, Scopus, and Cochrane, covering the period from inception to May 2024. The search used both subject headings (such as MeSH terms in PubMed) and keywords, focusing on the terms “Oxymetazoline” and “blepharoptosis.” For each database, the search strategy was adapted, with subject headings replaced or modified as needed. References were then imported into the Rayyan software to aid in study selection.
The study followed a PICO(S) framework, selecting studies that evaluated patients with ptosis treated with oxymetazoline ophthalmic drops, compared to those receiving a placebo or non-active lubricating drops. The primary outcome measured was the improvement in Marginal Reflex Distance 1 (MRD1). Included studies involved various designs, such as double- or single-blinded randomized controlled trials, non-randomized controlled trials, and prospective or retrospective observational studies. Eligible studies focused on adult patients with acquired blepharoptosis or blepharospasm, including cases secondary to botulinum toxin or myasthenia gravis. Studies were excluded if they involved pediatric populations, non-English languages, non-human subjects, review articles, case reports, or incomplete statistical data. Other exclusions included the use of intravenous or cutaneous oxymetazoline and the presence of otologic disease.
Two reviewers independently screened abstracts (M.N. and H.E.) to determine which studies met the inclusion criteria, with a third reviewer (C.M.) resolving any conflicts. The included articles were critically evaluated for their level of evidence using the Oxford Center for Evidence-Based Medicine criteria. The risk of bias was assessed using the Cochrane Handbook for Systematic Reviews of Interventions (version 6.0), with the ROBINS-I tool applied to non-randomized studies. Two reviewers conducted pilot assessments on three studies for consistency, after which they independently assessed the remaining studies. Any disagreements were resolved by a blinded third reviewer.
The risk of bias was graded across various dimensions, including bias due to confounding, participant selection, intervention classification, deviations from intended interventions, missing data, outcome measurement, and selection of reported results. Each aspect was rated as low, moderate, or high risk.
Data extraction was performed independently by two reviewers (M.N. and H.E.). Extracted data included patient demographics (age, sex), type of intervention (oxymetazoline, Botox, control), and pre- and post-treatment MRD1 values. In cases where data was incomplete, the primary authors were contacted via email for clarification or additional information. Two attempts were made to retrieve missing data.
Analysis
Meta-analyses comparing means and standard deviations between pretreatment and post-treatment groups, as well as evaluating differences between pre-/posttreatment and control groups, were conducted using Cochrane Review Manager (RevMan) version 5.4 (The Cochrane Collaboration, 2020). The random-effects model was employed, which assumes that true effects vary across studies. This model provides a weighted average of the effects and yields more conservative estimates with broader confidence intervals. When heterogeneity was detected, the random-effects model was preferred. A p-value of <0.05 was deemed statistically significant for all tests. Due to the inclusion of fewer than 10 studies, neither a funnel plot nor Egger’s test for publication bias was performed, as there was insufficient power for these assessments.
Results
The systematic review identified 157 unique articles from the literature search. After screening the titles and abstracts, 143 articles were excluded due to irrelevance. A thorough full-text review led to the exclusion of nine additional articles, ultimately leaving five studies that met the inclusion criteria for the final analysis. The risk of bias was assessed using the Cochrane Risk of Bias tools, and the majority of the studies were rated as having a low overall risk, with the exception of the study by Bernardini et al., which had some moderate concerns.
The five included articles were published between 2020 and 2023, comprising two case reports/series, one randomized controlled trial, one prospective cohort study, and one clinical trial. All studies directly measured Marginal Reflex Distance 1 (MRD1), which is a standard clinical measurement used to assess the severity of blepharoptosis by calculating the vertical distance between the corneal light reflex and the upper eyelid margin. The included studies provided a range of evidence levels, between 2 and 4, based on the Oxford Levels of Evidence. This reflects a moderate-to-high level of reliability, with randomized controlled trials being considered the gold standard of clinical evidence.
Patient characteristics across the five studies included a total of 458 participants, with a reported mean age ranging from 31 to 65 years, resulting in an overall mean age of 45.5 years. Of these, 130 (28.4%) were male and 328 (71.6%) were female, reflecting the higher prevalence of blepharoptosis in women. The studies consistently used oxymetazoline hydrochloride ophthalmic solution, 0.1%, to treat acquired blepharoptosis.
A meta-analysis of the five studies showed a significant improvement in MRD1 following treatment with oxymetazoline. The pooled data revealed an increase of 1.40 mm in MRD1 (95% CI [0.41 mm, 2.40 mm]), indicating that oxymetazoline effectively elevates the upper eyelid in patients with blepharoptosis. When compared to control groups that received non-active treatment, the increase in MRD1 from the baseline was 0.83 mm (95% CI [0.10 mm, 1.55 mm]), further supporting the efficacy of oxymetazoline in improving eyelid drooping.
In addition to quantitative improvements, the studies also examined patient-reported outcomes to assess the qualitative effects of oxymetazoline. Bernardini et al. reported high levels of patient satisfaction with the treatment. In another study by Shoji et al., patients in the treatment group reported significant improvements in eye appearance, including increased eye size and reduced eye redness compared to the control group. Eye redness was objectively measured using the Validated Bulbar Scale, where patients in the oxymetazoline group reported an eye redness score of 10.5 out of 100, compared to 11.6 in the control group, which was statistically significant (p = 0.0002). This reduction in redness contributed to improved cosmetic outcomes and patient satisfaction.
Shoji et al. also measured patient satisfaction using the FACE-Q, a validated questionnaire commonly used in cosmetic and facial surgery assessments. This tool assesses patient satisfaction with appearance, health-related quality of life, and adverse events. The oxymetazoline group reported a significant increase in satisfaction scores, from a baseline of 21.1 to 24.4 after treatment, whereas the control group saw a smaller increase, from 22.7 to 23.5 (p = 0.0002). This indicated that patients were more satisfied with their eye appearance after using oxymetazoline.
Furthermore, Slonim et al. examined the effects of oxymetazoline on peripheral vision using the Leicester Peripheral Field test, a validated visual field assessment that measures superior visual field loss due to ptosis. The results showed a significant improvement in the number of points detected in the visual field test among patients treated with oxymetazoline compared to those who received placebo drops. This suggests that oxymetazoline not only improves eyelid appearance but also enhances functional visual outcomes, particularly in individuals experiencing visual obstruction from ptosis.
Conclusion
In conclusion, oxymetazoline hydrochloride 0.1% ophthalmic solution is an effective non-surgical treatment for acquired blepharoptosis. It significantly improves eyelid elevation (MRD1), enhances eye appearance, reduces redness, and increases patient satisfaction. Additionally, it can improve peripheral vision affected by ptosis, making it a safe and effective alternative to surgical interventions.
Oncology Related Tools
Other
Latest Research
