Corticosteroids are extensively used in ophthalmology, particularly for treating various inflammatory conditions such as uveitis, optic neuritis, thyroid-associated ophthalmopathy, and other ophthalmic inflammatory diseases (Raizman, 1996; McGhee et al., 2002). They possess powerful anti-inflammatory and immunosuppressive properties, enabling them to rapidly control inflammation, relieve symptoms, and help preserve vision (Cutolo et al., 2019). Corticosteroids are available in various dosage forms and administration methods in ophthalmology, with a specific choice depending on the type and severity of the condition (Kiernan and Mieler, 2012; Puglia et al., 2021; Romano et al., 2023). Common forms include topical eye drops, eye ointments, intraocular injections, and systemic medications such as oral or intravenous injections (Figure 1). Topical eye drops and ointments are commonly used for anterior eye diseases like keratitis and anterior uveitis, delivering medication directly to the affected area. Intraocular injections are preferred for treating posterior eye conditions such as posterior uveitis and diabetic retinopathy, providing efficient local drug concentrations. Additionally, low-solubility Corticosteroid polymer sustained-release systems are employed for long-term intraocular treatments, such as in cases of diabetic macular edema, to ensure prolonged therapeutic effects (Busch et al., 2018). Systemic Corticosteroids are reserved for severe or widespread inflammatory diseases, including optic neuritis (Fung et al., 2020; Gaballa et al., 2021).

Although Corticosteroids are crucial in treating ophthalmic diseases, long-term or high-dose use can lead to side effects such as increased intraocular pressure, cataract formation, corneal ulcers, and secondary infections (Huscher et al., 2009; Roberti et al., 2020). Therefore, ophthalmologists must carefully balance the benefits and risks, tailoring individualized treatment plans based on the specific disease, its severity, and patient conditions (Bucolo et al., 2018). The choice of Corticosteroid dosage form and application can also vary depending on the disease’s severity and location and the individual patient’s circumstances (Caplan et al., 2017; Boscia et al., 2024). However, no current studies provide sufficient data to compare the safety profiles of different glucocorticoid drugs, highlighting the need for further research in this area.

The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) is a public, accessible, and free database containing millions of voluntarily submitted adverse drug reactions (ADRs) reports from healthcare professionals, consumers, and manufacturers (Hoffman et al., 2014). It is an important tool for post-marketing drug safety surveillance and signal detection and is widely used in pharmacovigilance research, including ocular ADRs (Fang et al., 2019; Ma et al., 2022; Zhao et al., 2023). Signal detection from FAERS data has become a recognized and effective method to identify potential safety risks associated with medications in real-world settings. By utilizing FAERS data, researchers can identify disproportionate reporting of ADRs, helping to establish hypotheses about causal relationships between drugs and adverse events, particularly for rare or severe outcomes (Fukazawa et al., 2018; Subeesh et al., 2018).

Despite the widespread use of glucocorticoids in ophthalmology, there is limited real-world data on their associated ADRs. Therefore, this study aims to utilize the FAERS database to conduct a pharmacovigilance analysis of glucocorticoids used in ophthalmology, identifying potential ADR signals and evaluating their severity and clinical impact. The findings from this research will contribute to a better understanding of the safety profile of glucocorticoids in ophthalmic settings, offering valuable insights for clinicians in minimizing the risk of adverse outcomes while optimizing therapeutic benefits.

Corticosteroids are steroid hormones known for their anti-inflammatory, anti-allergic, anti-shock, and immunosuppressive properties (Barnes, 2006; Kapugi and Cunningham, 2019). Their mechanism of action primarily involves a genomic pathway mediated by glucocorticoid receptors, which bind to specific DNA sites, initiating gene transcription and the synthesis of various proteins (Claman, 1975). These drugs are widely used in ophthalmology, with different molecular structures and dosage forms developed to cater to the specific needs of ocular treatments (McGhee et al., 2002; Gaballa et al., 2021). However, glucocorticoids are also associated with numerous adverse reactions, including increased risk of infections, elevated intraocular pressure, cataract formation, delayed wound healing, and systemic effects such as weight gain, osteoporosis, and hyperglycemia, especially with prolonged use. Clinical practice must carefully manage These potential side effects to balance therapeutic benefits with risks (Carnahan and Goldstein, 2000; Vetro et al., 2022). Pharmacovigilance analysis is an effective tool for monitoring drug safety and identifying potential risks, ensuring that adverse effects are detected and addressed promptly (Ventrice et al., 2013; Gozzo et al., 2021; Vetro et al., 2022). To our knowledge, this study is the first to identify and describe adverse reactions significantly associated with commonly used glucocorticoids in ophthalmology, offering valuable insights into their safety profiles and highlighting the importance of monitoring potential risks in treatment.

In this study, we conducted basic demographic statistics on patients primarily suspected of experiencing adverse reactions related to ophthalmic glucocorticoids, as shown in Table 3. The results showed that the number of women was significantly higher than that of men, which may be due to the higher incidence of most autoimmune diseases in women. Women are generally more frequently affected by these conditions than men (Ngo et al., 2014). Consequently, when using glucocorticoids for treatment, women may require longer treatment durations or higher doses, potentially increasing their risk of side effects. The Weibull distribution test results indicate that seven ophthalmic glucocorticoids follow an early failure distribution pattern, suggesting that ADRs tend to occur in the early stages of drug use, highlighting the need for careful monitoring for adverse reactions soon after initiating treatment.

Maxidex has been linked to endocrine disorders (ROR = 2.16). The associated PT adrenal insufficiency has a count of 13 and a notably high ROR of 19.44, indicating a strong association with the condition studied. Additionally, Cushing’s syndrome has a count of 5 and a high ROR of 18.64, further suggesting a significant association. Similar reports have also been found in many studies, particularly concerning children (Bangsgaard et al., 2018; De Vleeschhauwer et al., 2024). Reports of adrenal suppression with local ocular steroids have also been documented in adults (Sandhu et al., 2012). Given the lack of precise data on the systemic and local concentrations of pediatric eye drops, the use of topical ocular steroids in children requires special attention to avoid potential risks such as adrenal suppression. Durezol was found to be associated with an increased risk of renal and urinary disorders (ROR = 1.77). Through searching related PTs, Chronic kidney disease (CKD) has the highest count (85) and a relatively high ROR of 7.33, indicating a strong association with the condition being studied. End-stage renal disease (ESRD) has a high ROR of 8.62, suggesting that it is also significantly associated, despite having a lower count (24). Renal failure and acute kidney injury have relatively lower RORs (2.84 and 2.09, respectively). Currently, there is no research documenting the relationship between Durezol and renal/urinary diseases. However, corticosteroids are known to directly cause vasoconstriction of arterioles and increase salt and water retention in the kidneys, which may contribute to their impact on renal health (Gibbison et al., 2020). Ozurdex, Iluvien, and Triesence have a high signal regarding product issues, which may be attributed to the invasive procedures involved in administering these medications. Furthermore, Ozurdex and Iluvien, being intravitreal implants with relatively recent marketing authorization, also carry the risk of device dislocation and device malfunction.

A total of seven PTs appeared in these drugs: eye inflammation, cataract, visual impairment, uveitis, eye pain, vision blurred, visual acuity reduced, and retinal detachment. Apart from the clinical manifestations of indications, cataract is the common ADR of these drugs. The increased risk of cataracts is widely acknowledged as a significant side effect of long-term corticosteroid use, although its pathogenesis remains incompletely understood (Smeeth et al., 2003; Wang et al., 2009). Several mechanisms have been proposed to explain this association, including alterations in protein structure and function mediated by glucocorticoid receptors, abnormal cell differentiation influenced by growth factors, modifications in the structure and function of lens proteins, and the role of oxidative stress (Jobling and Augusteyn, 2002; James, 2007). These factors may contribute to lens opacification, ultimately leading to the development of cataracts in individuals undergoing prolonged corticosteroid therapy.

The FAERS database offers significant advantages for studying ADRs. It provides extensive real-world data, enabling the identification of rare or previously unrecognized ADRs, making it an essential tool for post-market drug safety surveillance. By using signal detection methods such as ROR, FAERS data can help screen for potential ADRs and is widely employed in pharmacovigilance efforts. However, the database has its limitations. As a spontaneous reporting system, FAERS data may be influenced by underreporting, misreporting, and duplicate reports, potentially compromising data completeness. Furthermore, FAERS does not support the calculation of ADR incidence rates and lacks detailed patient characteristics and clinical information, which hinders the ability to establish causal relationships. Reporting bias is another concern, as most reports come from Western countries, limiting the generalizability of the findings to other regions. While signal detection can reveal statistical associations, it does not confirm causality between drugs and ADRs. Therefore, FAERS data should be combined with large-scale, well-designed epidemiological studies to investigate further ocular adverse events associated with glucocorticoids in future studies (Gozzo et al., 2023).

In summary, this study utilized data mining methods to explore the systemic and, particularly, ocular safety concerns associated with currently marketed corticosteroid drugs used in ophthalmology. The findings provide valuable data to support the rational use of corticosteroids in eye treatments and serve as a reference for future safety research. Physicians should remain vigilant for potential adverse reactions, especially in the early stages of glucocorticoid therapy. Early diagnosis and timely intervention can help prevent or mitigate serious consequences stemming from these adverse reactions.