The study, published in Frontiers in Ophthalmology by oculoplastic surgeons at Kahana Oculoplastic and Orbital Surgery and Corewell Health William Beaumont University Hospital Eye Institute, included 36 patients with active thyroid eye disease, defined by a Clinical Activity Score of at least 3, who underwent single or staged orbital decompression between February 2023 and September 2025. Fourteen of them had preoperative dysthyroid optic neuropathy, the vision-threatening complication that has traditionally justified urgent surgery regardless of disease phase. The remaining 22 underwent decompression for indications that conventional practice would have deferred: retrobulbar pain, disfiguring proptosis with exposure keratopathy, or restrictive strabismus.

The results were striking. Mean Clinical Activity Score fell from 4.7 to 1.6, a reduction of 3.1 points with a 95 percent confidence interval of -3.92 to -2.36, well clear of zero. Mean proptosis, measured by Hertel exophthalmometry, dropped from 22.7 millimeters to 19.7 millimeters, a 3.0-millimeter reduction with a confidence interval of -3.28 to -2.23. Only one patient, a 2.8 percent rate, met the study’s definition of postoperative worsening, a two-point or greater increase in Clinical Activity Score at least eight weeks after surgery. No patients developed new-onset diplopia, a feared complication of orbital surgery, and many patients with preexisting double vision actually improved.

The technical innovation at the heart of the study is the combination of apical orbital decompression with a standardized intraorbital corticosteroid injection. During every lateral wall decompression, the surgeons contoured the deep sphenoid bone using ultrasonic aspiration and stereotactic navigation, excised intraconal fat with a median volume of 1.25 milliliters, and injected 1 milliliter of a 1:1 mixture of triamcinolone 40 milligrams per milliliter and dexamethasone 4 milligrams per milliliter into the lacrimal gland and surrounding orbital fat. The injection is considered an integral component of the operative technique rather than an optional adjunct, designed to deliver anti-inflammatory and anti-congestive effects directly at the surgical site alongside the mechanical decompression.

The rationale for targeting the orbital apex reflects a contemporary understanding of thyroid eye disease physiology. The condition is an autoimmune orbitopathy in which immune cells and cytokines stimulate orbital fibroblasts and adipocytes through thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor signaling, driving glycosaminoglycan deposition, fat expansion, and fibrosis. Active disease involves not just inflammation but significant orbital congestion from expanded fat and muscle, and congestion can cause tissue hypoxia that contributes to fibrotic remodeling. The authors argue that decompression at the apex, the primary site of venous outflow, restores drainage, reduces orbital pressure, and may even hasten resolution of inflammation, making surgery beneficial during the active phase rather than harmful.

The authors postulate that the traditional caution against operating during active disease originated in an era of anterior decompression techniques that failed to adequately address venous outflow at the orbital apex. In that context, postoperative edema and inflammation could compound preexisting congestion and produce poor outcomes. Modern techniques that contour the deep sphenoid diploe, open the posterior ethmoid, and remove the orbital process of the palatine bone all target the apex, and the study found that active inflammation did not meaningfully contribute to operative blood loss or technical difficulty. Intraoperative bleeding arose predominantly from perforating diploic venous channels within the greater wing of the sphenoid rather than from inflamed orbital soft tissue.

Because contemporary thyroid eye disease management frequently includes systemic corticosteroids and insulin-like growth factor-1 receptor inhibitors such as teprotumumab, the researchers prespecified strict endpoint rules to prevent medical therapy from artificially lowering postoperative scores. Endpoint Clinical Activity Score was defined as the last recorded value at least eight weeks after decompression, or the final score immediately before initiation of any postoperative disease-modifying therapy, with a steroid washout period of at least twelve weeks when applicable. Under these rules, outcomes were consistent regardless of perioperative medical treatment: patients without preoperative disease-modifying therapy showed a mean Clinical Activity Score reduction of 2.8 and proptosis reduction of 3.2 millimeters, while those with prior therapy showed reductions of 2.7 and 2.2 millimeters respectively, differences that were not clinically meaningful.

A post hoc analysis focused on the 12 patients whose primary surgical indication was retrobulbar pain or pain with eye movement, the subgroup most directly challenging the traditional timing doctrine. In these patients, mean Clinical Activity Score decreased from 4.9 to 1.7, a reduction of 3.3 points, and mean proptosis fell from 22.4 to 19.6 millimeters. None of the 12 met criteria for postoperative worsening, developed new-onset diplopia, or experienced a major surgical complication. Five patients, 41.7 percent, received postoperative disease-modifying therapy, but the authors note that in both early and late escalation groups, Clinical Activity Score had already improved before any adjunctive treatment, supporting that the combined decompression-injection approach delivered genuine clinical benefit.

The single patient who met postoperative worsening criteria illustrates the complexity of interpreting flares in a relapsing-remitting condition. She was a 73-year-old woman with severe, recurrent thyroid eye disease dating back to her hyperthyroid diagnosis in the 1960s, with persistently elevated thyroid-stimulating immunoglobulin levels. Her score had fallen to 1 by postoperative month five, but at month eight she developed a third flare-up with a score of 7, coinciding with thyroid hormone instability and rising antibody titers. Given the delayed timing and concurrent thyroid dysfunction, the authors attribute the episode to persistent autoimmunity rather than a response to the surgery itself.

The study has limitations inherent to its retrospective, single-center design. The sample was modest, and the absence of an untreated, injection-only, or inactive-phase control group means the observed improvements cannot be definitively attributed to decompression, the corticosteroid injection, patient selection, or the natural course of the disease. The universal administration of the intraorbital injection also means the individual contributions of mechanical decompression and corticosteroid cannot be disentangled within this dataset. The Clinical Activity Score captures both inflammatory and congestive signs, so some patients may have had predominantly congestive rather than immunologically active disease, which could have favorably influenced the response. Still, the authors argue that randomized prospective surgical trials are not feasible in this context, and that the evidence base for orbital surgery must rely on well-characterized retrospective cohorts. Their findings suggest that active disease alone should not automatically preclude surgery in carefully selected patients with disabling symptoms, though larger cohorts stratified by surgical indication are needed before broader adoption can be recommended.

Subject of Research: Ophthalmology

Article Title: Orbital decompression with intraorbital corticosteroid injection during the active phase of thyroid eye disease: outcomes in a real-world cohort

Article References: Neuhouser, A. J., Skender, S., Spadaro, J. Z., & Kahana, A. (2026). Orbital decompression with intraorbital corticosteroid injection during the active phase of thyroid eye disease: outcomes in a real-world cohort. Frontiers in Ophthalmology, 6, Article 1935053. https://doi.org/10.3389/fopht.2026.1935053

Image Credits: AI Generated

DOI: 10.3389/fopht.2026.1935053

Keywords: thyroid eye disease, orbital decompression, Graves orbitopathy, intraorbital corticosteroid injection, Clinical Activity Score, dysthyroid optic neuropathy, proptosis, orbital apex, teprotumumab, IGF-1R inhibitor, oculoplastic surgery, Frontiers in Ophthalmology