Teprotumumab for Dysthyroid Optic Neuropathy: A Systematic Review and Single-Arm Meta-Analysis of Visual and Orbital...

Dysthyroid optic neuropathy (DON) is a sight-threatening complication of thyroid eye disease (TED). The pivotal teprotumumab trials excluded patients with DON, and the only prior treatment meta-analysis addressed intravenous glucocorticoids and orbital decompression, leaving the role of teprotumumab in DON unsynthesised.

To systematically review and, where possible, meta-analyse visual and orbital outcomes following teprotumumab treatment for DON.

PubMed, Ovid (MEDLINE/Embase) and Web of Science were searched from inception to 7 June 2026, following PRISMA 2020 guidelines. Eligible studies enrolled adults with DON treated with teprotumumab. Single-arm random-effects meta-analysis (inverse-variance, REML) pooled the proportion with DON resolution and mean changes in proptosis and best-corrected visual acuity (BCVA); risk of bias was assessed with the ROBINS-I tool.

Of 310 unique records, 4 reports met eligibility. Four multi-patient series/cohorts (40 patients) were meta-analyzed. The pooled proportion with DON resolution was 0.77 (95% CI 0.58-0.89; k = 4, I² = 0%). Proptosis fell by a pooled -4.80 mm (95% CI - 6.69 to -2.90; k = 3) but with substantial heterogeneity (I² = 87%), with a two-study BCVA estimate of -0.56 logMAR. Visual fields, color vision and relative afferent pupillary defects improved in the large majority of eyes, often within one to two infusions; DON recurred in approximately 15% at long-term follow-up.

The available data on teprotumumab for DON come from only a few small retrospective series without comparator groups, leaving certainty low to very low; even so, treated eyes showed reproducible and frequently early recovery of vision, reversal of optic neuropathy, and reversal of proptosis, and this lack of definitive trial evidence should not be seen as absence of benefit. Because the antibody acts directly on the orbital tissue expansion that compresses the optic nerve, it is a plausible first-line medical option for DON where it is accessible and patients can be monitored closely, provided that eyes failing to improve promptly are escalated without delay to orbital decompression and that emergency surgery remains the response to rapidly worsening sight loss. Adequately designed prospective comparative studies, with longer follow-up of recurrence, safety, and cost, are needed to establish teprotumumab's place in the DON treatment pathway.