Corresponding Author: Jin Sook Yoon, MD, PhD. Institute of Vision Research, Department of Ophthalmology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea. Thyroid eye disease (TED), also known as Graves orbitopathy, is the most common extrathyroidal manifestation of Graves disease and reflects a localized expression of a systemic autoimmune process [1]. It is characterized by inflammation and expansion of the extraocular muscles and orbital connective tissue, leading to functional and aesthetic complications, including proptosis, diplopia, and, in severe cases, vision loss. Active TED is marked by ongoing inflammatory changes, and timely initiation of immunosuppressive therapy during this phase is critical for achieving optimal outcomes [2]. Delayed or inadequate treatment may result in irreversible fibrotic changes and reduced therapeutic response. Therefore, early recognition and appropriate referral by local physicians, particularly endocrinologists and general practitioners, are essential for effective management of TED.
Over the past decade, significant advances have been made in the diagnosis and treatment of TED, supported by evolving international consensus guidelines. The European Group on Graves’ Orbitopathy (EUGOGO) published evidence-based guidelines in 2016 and updated them in 2021, providing structured recommendations on assessing disease activity, severity, and treatment strategies [3,4]. Similarly, the 2022 consensus from the American Thyroid Association (ATA) and the European Thyroid Association (ETA) further emphasized a multidisciplinary, severity-based approach in managing TED [5]. These guidelines have contributed to greater standardization in clinical decision-making across regions. Furthermore, the introduction of targeted therapies such as teprotumumab, a monoclonal antibody against insulin-like growth factor 1 receptor, has transformed the treatment paradigm, offering new options for patients with moderate-to-severe or treatment-refractory TED [6]. Consequently, the therapeutic landscape is rapidly evolving, with increasing interest in biologics and personalized treatment approaches.
Despite global advancements, no nationwide survey or established clinical consensus on TED management currently exists in South Korea. Given the distinct characteristics of the South Korean healthcare system, referral patterns, and accessibility to novel therapies, understanding current real-world practices and clinician perspectives is essential. In particular, with the potential introduction of new biologics such as teprotumumab into the South Korean market, foundational data are needed to guide future guidelines and policy decisions. Therefore, this study aimed to investigate the current state of TED diagnosis and treatment in South Korea, focusing on physician awareness of international guidelines, preferred treatment strategies, and perspectives on emerging therapies.
Materials and Methods
Ethics statement
The study protocol was approved by the Institutional Review Board of Yonsei University Severance Hospital, with a waiver of informed consent (No. 4-2025-0440).
Study population
A survey was conducted in May 2025 among members of the Korean Society of Ophthalmic Plastic and Reconstructive Surgery (KSOPRS), comprising oculoplastic surgeons specializing in TED treatment. The survey link was emailed to all 226 physicians registered with KSOPRS since its inception in 1988. Among them, 60 ophthalmologists were active members who had completed oculoplastic fellowship training. A total of 32 oculoplastic specialists (53.3 %) responded to the survey.
Survey instrument development and data collection
The survey was developed by three oculoplastic specialists and reviewed by the KSOPRS board. The questionnaire was designed to evaluate clinicians’ awareness of the EUGOGO consensus and current clinical practices in TED management. It included items on physician demographics, hospital characteristics, diagnostic methods, and treatment approaches, including intravenous (IV) glucocorticoid (GC) therapy, orbital radiotherapy, immunosuppressive agents, serologic evaluation, and selenium supplementation for mild TED. The survey also addressed off-label use of tocilizumab, rituximab, and local triamcinolone injections, as well as management strategies for dysthyroid optic neuropathy (DON). Clinical scenarios were incorporated to assess perspectives on the potential use of teprotumumab in South Korea. The questionnaire also comprised singleand multiple-response items, along with questions evaluating relative treatment priorities. The original survey instrument is detailed in Supplementary Material 1.
The survey was administered electronically using a secure online platform (Google Forms, Google). Data were collected over 1 month, with reminders sent to optimize response rates. All responses were anonymized and compiled for analysis after survey closure.
Statistical analysis
During data analysis, categorical variables were presented as frequencies and percentages, whereas priority ranking data were summarized as mean priority ranks with standard deviations. Differences in rankings were assessed using Friedman test, and Kendall coefficient of concordance (W) was calculated to evaluate the degree of agreement among respondents. All statistical analyses were performed using R ver. 4.1.0 (R Foundation for Statistical Computing). A p-value of less than 0.05 was considered statistically significant.
Results
Physician characteristics
A total of 32 physicians participated in the survey. The largest age group was 40-49 years (n = 13, 40.6%), followed by those aged ≤39 years (n = 7, 21.9%), 50-59 years (n = 7, 21.9%), and 60-69 years (n = 5, 15.6%). Female physicians accounted for 17 respondents (53.1%). Regarding clinical experience, 13 respondents (40.6%) had been in practice for ≥20 years, 7 respondents (21.9%) for <5 years, and the remaining 12 (37.5%) for 5-19 years. Most respondents were affiliated with tertiary hospitals (n = 22, 68.8%), and 21 (65.6%) were based in Seoul, Gyeonggi-do, or Incheon regions (Table 1).
Diagnostic and monitoring approaches in clinical practice
The most commonly utilized tools for evaluating TED were the Clinical Activity Score (CAS) and the EUGOGO severity classification, each employed by 28 respondents (87.5%). In contrast, the VISA (vision, inflammation, strabismus, and appearance) classification and the Graves’ Ophthalmopathy Quality of Life (GO-QOL) assessment were less frequently used (15.6% and 6.2%, respectively). Monitoring of thyroid-stimulating hormone receptor (TSH-R) antibodies was performed by 30 physicians (93.8%), and 29 (90.6%) considered thyrotropin-binding inhibitory immunoglobulin (TBII) or thyroid-stimulating immunoglobulin (TSI) levels when determining surgical timing. Specifically, 18 (56.2%) evaluated both TBII and TSI, whereas 5 (15.6%) assessed only TBII and 6 (18.8%) assessed only TSI. Furthermore, 14 (43.8%) recommended total thyroidectomy for patients with persistently elevated TSH-R antibody levels. Regarding imaging, contrast-enhanced computed tomography (CT; n = 14, 43.8%) and noncontrast CT (n = 13, 40.6%) were most commonly preferred, followed by magnetic resonance imaging (n = 4, 12.5%). Various diplopia assessment tools were employed, with the Hess test (n = 19, 59.4%), Lancaster test (n = 15, 46.9%), and binocular single vision test (n = 13, 40.6%) being the most frequently used (Table 2).
Medical treatment patterns
For mild, active TED, 29 physicians (90.6%) recommended selenium supplementation, and 26 (81.2%) utilized subconjunctival or eyelid triamcinolone injections, with most (18 of 26, 69.2%) limiting the number of injections to 3. Retrobulbar triamcinolone injections were used by two respondents (6.2%). For moderate-to-severe active TED, 31 respondents (96.9%) administered IV GC pulse therapy following EUGOGO guidelines (total dose of 4.5 g), whereas 6 (18.8%) escalated the dose to 7.5 g in more severe cases. IV GC was predominantly administered by ophthalmologists (n = 30, 93.8%). Oral GCs were prescribed by 16 respondents (50.0%). Among them, 14 (87.5%) used GCs for tapering after IV GC therapy; 9 (56.3%) used them as a first-line treatment for mild, active TED; and 8 (50.0%) used them for patients with CAS <3 but with significant soft tissue inflammation. Immunosuppressants were prescribed by 13 (40.6%), with mycophenolate mofetil (7 of 13, 53.8%) and methotrexate (6 of 13, 46.2%) being the most commonly selected agents. Off-label use of tocilizumab (n = 2, 6.2%) and rituximab (n = 1, 3.1%) was infrequent. Orbital radiotherapy was recommended by 29 (90.6%), most commonly when IV GC was ineffective or not feasible (n = 28, 96.6%) or as a first-line treatment in cases with extraocular muscle enlargement (n = 18, 62.1%) (Table 3).
Surgical treatment patterns
Regarding surgical management, 23 respondents (71.9%) performed orbital decompression, 27 (84.4%) performed eyelid retraction surgery, and 10 (31.3%) performed strabismus surgery. Blepharoplasty was also frequently conducted (n = 28, 87.5%) (Supplementary Table 1).
Management of DON
In managing DON, 13 physicians (40.6%) administered IV GC therapy alone following the EUGOGO guidelines, whereas 19 (59.4%) combined IV GC therapy with orbital radiotherapy as part of first-line management. If no improvement was observed 2 weeks after a 3-day IV GC course, 29 (90.6%) proceeded with orbital decompression (Table 4). In assessing treatment response, visual acuity (mean rank, 1.88 ± 1.14) and relative afferent pupillary defect (mean rank, 2.63 ± 1.43) were ranked as the highest priorities, followed by color vision (mean rank, 3.38 ± 1.56) and visual field testing (mean rank, 3.47 ± 1.41). Structural indicators, such as apex crowding on CT (mean rank, 4.34 ± 1.53) and optic disc swelling (mean rank, 4.81 ± 1.51), were given lower priority. Friedman test revealed a statistically significant difference among the rankings of the six clinical indicators (χ2 = 133.15, p < 0.001), and Kendall W was 0.332 (p < 0.001), indicating a moderate level of agreement among respondents (Table 5).
Therapeutic considerations for teprotumumab
Physicians assigned generally similar priority levels to various clinical scenarios for teprotumumab use. The mean priority ranks were 2.09 ± 0.73 for active TED with poor response to IV GC therapy, 2.13 ± 0.89 for active TED as first-line therapy, 2.28 ± 0.91 for active TED with poor response to both IV GC and radiotherapy, and 3.31 ± 0.97 for inactive TED with mild proptosis (21-22 mm). Friedman test revealed a statistically significant difference among the rankings of the four clinical scenarios (χ2 = 49.31, p < 0.001). Kendall coefficient of concordance indicated a fair level of interrater agreement (W = 0.201, p < 0.001) (Table 6).
Discussion
This nationwide survey revealed a high degree of adherence to international guidelines among South Korean oculoplastic specialists in the diagnosis and treatment of TED. Most respondents routinely employed CAS and the EUGOGO severity classification, with IV GC pulse therapy being the predominant first-line treatment for moderate-to-severe, active TED. Additionally, local triamcinolone injections and selenium were widely used for mild cases. Although immunosuppressants and biologics such as tocilizumab and rituximab were used less frequently, orbital radiotherapy and surgical interventions were commonly integrated into treatment strategies. These findings provide a comprehensive overview of current clinical practice patterns and therapeutic preferences in South Korea.
The widespread adoption of CAS and EUGOGO severity classification (both reported by 28 respondents, 87.5%) reflects a strong consensus on the value of standardized assessment tools in clinical practice [7]. However, the limited use of the VISA classification and GO-QOL assessment suggests an opportunity to more broadly incorporate patient- centered outcome measures, including quality-of-life measures and functional assessments, in routine care [8,9].
Serological testing for TSH-R antibodies was performed by nearly all respondents (93.8%), with 29 (90.6%) incorporating TBII or TSI levels into surgical decision-making. This underscores the growing recognition of these markers not only for diagnosis but also for determining the timing of orbital decompression surgery [10]. Additionally, 14 physicians (43.8%) considered total thyroidectomy in cases with persistently elevated antibody levels, suggesting a trend toward more proactive thyroid ablation strategies in refractory cases. Regarding imaging, both contrast-enhanced and noncontrast CT were commonly preferred, consistent with their diagnostic utility in assessing extraocular muscle involvement and orbital apex crowding [11].
The medical treatment patterns observed in this study largely adhere to international guidelines. For moderate- to-severe active TED, 31 respondents (96.9%) administered IV GC pulse therapy following the EUGOGO regimen (4.5 g cumulative dose). Notably, nearly one-fifth (n = 6) escalated the dose to 7.5 g in severe cases, consistent with recent EUGOGO recommendations [4]. Oral GCs were frequently used as either adjunctive therapy or as first-line treatment in milder cases, demonstrating flexibility in real-world clinical practice.
The widespread use of local triamcinolone (n = 26, 81.2%) for mild TED aligns with existing evidence supporting its efficacy and safety [12,13]. However, the relatively low uptake of immunosuppressants (n = 13, 40.6%) and the limited use of off-label agents such as tocilizumab (n = 2, 6.2%) and rituximab (n = 1, 3.1%) likely reflects limited access, reimbursement challenges, and the absence of clear consensus on their use in South Korea, despite increasing evidence supporting their benefit in steroid-refractory TED [14-18].
In managing DON, 19 respondents (59.4%) used a combination of IV GC and orbital radiotherapy as first-line therapy. This dual-modality approach is supported by evidence indicating improved outcomes with combination therapy in compressive optic neuropathy [19]. Most physicians (n = 29, 90.6%) proceeded to orbital decompression within 2 weeks for nonresponders, indicating timely escalation of care in accordance with EUGOGO guidelines [20,21].
Functional indicators such as visual acuity (mean rank, 1.88 ± 1.14) and relative afferent pupillary defect (mean rank, 2.63 ± 1.43) were prioritized over structural markers such as CT-detected apex crowding (mean rank, 4.34 ± 1.53) and optic disc swelling (mean rank, 4.81 ± 1.51) for evaluating treatment response. The statistically significant difference in rankings (χ2 = 133.15, p < 0.001) and moderate agreement among respondents (Kendall W = 0.332) suggest that while functional indicators are generally prioritized in assessing treatment response in DON, clinical variability persists. These results highlight the need for standardized assessment criteria that integrate both functional and structural measures.
Several South Korea-specific practice patterns were notable. First, serologic evaluations were actively utilized. Thirty respondents (93.8%) monitored TSH-R antibodies and 29 (90.6%) considered TBII or TSI levels when determining surgical timing. Eighteen respondents (56.3%) performed both TBII and TSI testing, which is substantially higher than the 21% reported in the recent international survey [22]. Second, imaging modalities were actively utilized. Thirty-one respondents (96.9%) employed at least one imaging modality for evaluation of TED. Third, dual-modality therapy with IV GC and orbital radiotherapy was frequently adopted as first-line treatment for DON (n = 19, 59.4%), whereas international guidelines indicate that radiotherapy is generally regarded as an adjunctive option [5].
Regarding teprotumumab, physicians predominantly prioritized its use for patients with active TED, particularly when conventional medical therapies such as IV GC had failed to yield sufficient clinical improvement. Notably, its preference as a first-line therapy in active TED was comparable to its use as a second-line option, indicating growing confidence in its efficacy even in early stages of intervention. In contrast, teprotumumab was deprioritized for inactive TED with mild proptosis, reflecting a more cautious stance when the expected benefits may not outweigh the potential risks.
The statistically significant difference in the prioritization of teprotumumab use across clinical scenarios (χ2 = 49.31, p < 0.001) indicates that physicians’ preferences are influenced by clinical context, particularly in relation to disease activity and prior treatment response. However, the relatively lower Kendall coefficient of concordance (W = 0.201) indicates only fair interrater agreement, highlighting variability in clinical decision-making regarding the optimal use of teprotumumab. This variation may be attributed to limited clinical experience with the drug in South Korea, uncertainty regarding cost-effectiveness, and the absence of local guidelines incorporating biologic therapies. As access to teprotumumab increases, establishing clearer consensus criteria may help promote consistent and evidence-based use in clinical practice.
Although teprotumumab has demonstrated clinical efficacy in randomized trials, potential adverse effects such as hearing loss (approximately 10%), hyperglycemia (approximately 10%), and other systemic symptoms raise concerns regarding its safety profile [23-26]. Additionally, its high cost, approximately US $360,000 per treatment course in the United States, poses a major barrier [5]. In South Korea, where teprotumumab is not yet reimbursed, the exact cost remains unknown but is expected to be similarly high given its international valuation.
In contrast, IV GC therapy is widely accessible and inexpensive in South Korea, costing approximately US $10 to $50 per infusion. Decompression surgery also costs approximately US $1,500 to $2,000 per eye, rendering both options more viable in current clinical settings. However, conventional treatments such as IV GC or radiotherapy have limited effect on proptosis, and many patients ultimately require orbital decompression to address disfiguring or functionally significant proptosis. Although decompression is relatively affordable in Korea, it remains a technically demanding and invasive procedure, associated with postoperative pain and potential complications. Notably, the 2022 ATA/ETA consensus guidelines recognize teprotumumab as the only medical therapy with proven efficacy in reducing proptosis [5]. Recent reports have also demonstrated a significant decrease in decompression surgeries following teprotumumab treatment [27,28]. Given its demonstrated ability to significantly reduce proptosis and potentially eliminate the need for surgery, teprotumumab may see broader indications in the future as clinicians increasingly weigh its high cost against its capacity to provide noninvasive, transformative outcomes.
Recent international surveys have revealed regional variations in TED management. Brito et al. [29] reported more frequent use of selenium in Europe and a preference for teprotumumab in North America. In China, Chen et al. [30] observed a strong reliance on corticosteroids, with limited access to biologics and multidisciplinary care. Similarly, a recent global survey by Villagelin et al. [22] revealed concentrated teprotumumab use in North America, whereas GCs remained the mainstay elsewhere. Our national survey revealed similar clinical trends, particularly the prioritization of IV GC and limited use of biologics, likely reflecting comparable barriers related to access, cost, and insurance coverage. Collectively, these findings emphasize the need to develop standardized, region-specific treatment algorithms that integrate both evidence-based guidelines and real-world constraints.
This study has certain limitations. First, the sample size was relatively small (n = 32), although it represented a significant portion of actively practicing oculoplastic surgeons in South Korea. Second, given that the survey relied on self-reported data, it may be subject to recall or response bias. Third, the findings reflect the perspectives of oculoplastic surgeons and may not be generalizable to endocrinologists or general ophthalmologists who also treat TED.
In conclusion, this nationwide survey demonstrates substantial adherence to international guidelines among Korean oculoplastic specialists in managing TED. Furthermore, although CAS scoring, EUGOGO classification, and IV GC therapy are widely utilized, variability exists in the use of immunosuppressants, radiotherapy, and biologics. These insights underscore the need for South Korea-specific clinical guidelines that reflect both global standards and local realities. Future research should explore long-term outcomes, cost-effectiveness, and broader multidisciplinary perspectives to guide optimal, patient-centered care.
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