Eyelid surgery in thyroid eye disease

What it treats

• Thyroid eye disease (TED, also called Graves' orbitopathy) is the most frequent extrathyroidal manifestation of Graves' disease; it is mild in 77% of patients, moderate-to-severe in 22%, and sight-threatening in 1% (PMID 40324443).
• Moderate-to-severe forms needing aggressive treatment are no more than 5-6% of all TED cases (PMID 33329408, PMID 38054980).
• Mechanism: swollen extraocular muscles and orbital fat drive eyelid retraction, lid and conjunctival edema, proptosis, diplopia and, in severe cases, optic neuropathy (PMID 40324443).
• Risk factors: male sex, older age, smoking, diabetes, hypercholesterolemia, longer duration of hyperthyroidism, radioactive iodine therapy, and thyrotropin receptor (TSHR) antibodies, detectable in more than 95% of patients (PMID 40324443).
• Natural history: an active (inflammatory) phase, a plateau, then an inactive or "burnt-out" phase after roughly 18-24 months; minimal-to-mild disease often remits on its own, more severe disease rarely returns to normal without treatment (PMID 38054980).
• Background review of Graves' disease and its eye involvement (PMID 27797318).

How it is done

Medical treatment before surgery

• 2021 EUGOGO guidelines: intravenous methylprednisolone combined with mycophenolate is first-line for active moderate-to-severe disease in Europe; teprotumumab is listed as a second-line option (PMID 34297684).
• 2022 ATA/ETA consensus, by contrast, recommends teprotumumab as first-line for most phenotypes of active moderate-to-severe disease, particularly when proptosis predominates; the two guidelines otherwise agree on classification and on mild or sight-threatening disease (PMID 41283777).
• Teprotumumab is a fully human IGF-1R-inhibiting monoclonal antibody, given as 8 infusions every 3 weeks; it was FDA-approved in January 2020 on the basis of two randomized trials (PMID 31971679).
• More than 5,800 patients had been treated with teprotumumab since approval, per a 2024 review (PMID 38838219).

The surgical sequence

• The classic Shorr-and-Seiff sequence is 4 stages: (1) orbital decompression, (2) eye muscle (strabismus) surgery, (3) eyelid retraction repair, (4) blepharoplasty for excess skin and fat (PMID 29373659).
• Orbital decompression removes orbital bone, fat, or both to expand orbital volume; approaches include lateral wall, medial wall, two- or three-wall, and endoscopic transnasal, coded separately from external decompression in claims data (PMID 40079573, PMID 29243735).
• Lower eyelid retraction repair combines retractor release with a posterior lamellar graft (hard palate mucosa, free tarsoconjunctiva, or free sclera) and lateral eyelid tightening (PMID 18520836).
• Upper eyelid retraction repair commonly uses anterior levator disinsertion/reinsertion with Müllerectomy (ALDM) (PMID 32930505).
• A single-incision technique harvests a tarsoconjunctival graft from the upper lid to use as a lower-lid spacer while recessing the upper lid through the same conjunctival opening (PMID 29742012).
• A novel inert spacer, filamentous knitted polyester fabric, has been used for both upper and lower lid retraction in a 30-patient series (PMID 42671099).
• Aesthetic rehabilitation can be combined into one stage: decompression with upper and lower blepharoplasty, retraction repair, and lateral canthopexy performed together (PMID 29373659).

Results and evidence

Teprotumumab (medical treatment, not surgery, but it changes what surgery is needed)

• Pivotal phase 3 trial, 41 teprotumumab vs 42 placebo: proptosis response 83% vs 10% (P<0.001), mean proptosis change -2.82 mm vs -0.54 mm (PMID 31971679).
• Pooled analysis of both pivotal trials, 84 vs 87 patients: proptosis response 77% vs 15% (number needed to treat 1.6); responses were sustained in 67-92% of patients at 51 weeks after the last dose (PMID 33865501).
• OPTIC-X re-treatment study: 33 of 37 prior placebo patients (89.2%) became proptosis responders once switched to teprotumumab; 5 of 8 patients who had flared after an initial response (62.5%) responded again on re-treatment (PMID 34688699).
• Indirect comparison with intravenous methylprednisolone: the proptosis treatment difference favored teprotumumab by 2.31 mm; diplopia response favored teprotumumab 2.3-fold over methylprednisolone (PMID 35175308).
• Long-term follow-up across 3 trials (112 patients): at week 72, 66.1% remained Overall responders and mean proptosis reduction was 2.68 mm; 82% of patients needed no additional TED therapy, including surgery, through 99 weeks after the final dose (PMID 38824618).
• Reactivation in a 21-patient single-center series: 8 of 17 initial responders (47%) reactivated, at a median 12.25 months; only 7 of 21 patients (33%) responded throughout follow-up, and diplopia improvement was not statistically significant (PMID 38142982).
• 2025 meta-analysis, 4 randomized trials (210 vs 193 controls): proptosis response relative risk 4.18, diplopia regression relative risk 2.29; a pooled observational cohort of 211 patients showed an 82% proptosis response rate (PMID 39952471).

Orbital decompression

• 93 orbits, 55 patients: mean exophthalmos reduction 4.2 mm for lateral (single) wall decompression and 7.6 mm for two-and-a-half wall decompression; new postoperative diplopia occurred in 9% of lateral-wall cases versus 39% of other bony decompressions (PMID 29243735).
• 130 orbits, 80 patients: preoperative Hertel exophthalmometry was the strongest predictor of proptosis reduction (P<0.0001); combined endoscopic medial and open lateral wall decompression reduced proptosis 3.13-3.85 mm depending on preoperative severity (PMID 40207636).
• Customized decompression with zygomatic basin removal (105 orbits, 57 patients) improved lower lid position (MRD2, P<0.05) without reducing the proptosis benefit, and the authors suggest it can reduce the need for separate lower lid retraction surgery (PMID 27997462).

Eyelid retraction repair

• Largest published series, 659 eyelids in 400 patients over 15 years: scleral show fell about 1.3 mm and lagophthalmos about 0.5 mm, with 90% of patients reporting fewer symptoms (PMID 18520836).
• ALDM for upper lid retraction, 305 patients (471 eyelids): a good result in 71.6% of eyelids and 64.3% of patients; 16% of eyelids needed reoperation, after which cumulative success rose to 78.6% of eyelids and 79% of patients (PMID 32930505).
• Combined single-incision upper and lower repair, 22 eyes: MRD1 changed by a mean 1.86 mm and inferior scleral show by 1.3 mm; 17 of 19 patients reported improved surface exposure symptoms (PMID 29742012).
• Müllerectomy for upper lid retraction, 32 eyes: MRD1 fell from 7.2 to 4.3 mm as intended, while MRD2 (lower lid) rose slightly from 5.6 to 6.1 mm, a change the authors called statistically significant but clinically negligible (PMID 41942639).
• Novel polyester-fabric spacer, 30 patients: MRD1 fell from 9.73 to 3.85 mm and scleral show resolved in both lids, with no reported complications (PMID 42671099).
• One-stage decompression plus aesthetic eyelid surgery, 40 patients: 65% had bilateral upper blepharoplasty and 80% had transconjunctival lower blepharoplasty at the same setting as decompression; 58% also had upper lid retraction repair and 30% lateral canthopexy; 17% needed later strabismus surgery for new diplopia and none needed revision eyelid surgery (PMID 29373659).
• Adjunctive lid surgery after decompression, 65 patients (120 orbits): ocular surface area fell from 2.98 to 2.52 cm² after decompression alone, then to 2.31 cm² after adjunctive lid procedures; canthoplasty was the most common adjunct (13 of 65 patients) (PMID 34526052).

Risks and complications

• Teprotumumab hearing loss: cited at roughly 30% of patients in a 2025 review, against roughly 10% in the pivotal pooled trial analysis (PMID 40324443, PMID 33865501).
• FDA adverse-event database analysis: teprotumumab use carried a nearly 24-fold higher reporting rate of any hearing disorder (proportional reporting ratio 23.6) than a comparison group with the same underlying diagnosis, with bilateral deafness reported at a 41.9-fold rate (PMID 38771914).
• Early case series, 4 of 28 patients across 3 clinicians developed audiologically confirmed hearing loss, ranging from mild to severe and sometimes irreversible, prompting a proposed monitoring protocol (PMID 34085994); an earlier commentary first flagged the signal (PMID 33622158).
• Multicenter adverse-event study, 131 patients: 81.7% had at least one adverse event (median 4 per patient), 8.4% were severe, and 12.2% discontinued therapy, most often for hearing loss (4 of 16 discontinuations) (PMID 37852417).
• Hyperglycemia in 42 patients: 52% developed hyperglycemia on teprotumumab, graded life-threatening in 1 case; age, pre-existing diabetes, and Hispanic or Asian ethnicity were risk factors (PMID 36300333).
• Orbital decompression: new diplopia is more frequent with two-and-a-half wall and medial-wall decompression (up to 39-45% across the reviewed literature) than with lateral-wall-only decompression (0-38%); postoperative numbness reaches up to 52% with other bony approaches (PMID 29243735).
• Cochrane review found only 2 randomized trials of decompression technique; the transantral approach had more complications than endoscopic transnasal decompression in the one trial that compared them (PMID 22161415).

Recovery

• Reactivation after teprotumumab can occur a median 12.25 months after the last infusion, in 47% of initial responders in one series, and is not reliably predicted by baseline factors (PMID 38142982).
• Long-term follow-up across 3 trials: 82% of patients needed no further TED treatment, including surgery, in the 99 weeks after the final teprotumumab dose (PMID 38824618).
• After ALDM upper lid retraction repair, 16% of eyelids needed a second procedure to reach the final success rate (PMID 32930505).
• A secondary-effects review found orbital decompression lowers intraocular pressure and eyelid pressure and improves eyelid retraction and lateral flare, but can reduce Bell's phenomenon and worsen nasal function or refraction in some patients (PMID 36631972).

Combined procedures

• The 4-stage Shorr-and-Seiff sequence separates decompression, strabismus surgery, retraction repair and blepharoplasty; the one-stage alternative combines decompression with blepharoplasty, retraction repair and canthopexy in a single operation, reporting high satisfaction and lower direct and indirect costs in 40 patients (PMID 29373659).
• Case report of a staged approach in a 59-year-old woman with both TED and age-related lid laxity: decompression first, then (strabismus surgery not needed), then levator advancement for ptosis and a skin-muscle-flap lower blepharoplasty (PMID 34306906).
• Canthoplasty was the single most frequent adjunctive procedure after decompression in a 65-patient series, more often performed on the lower lid than the upper (PMID 34526052).

Current questions

• Teprotumumab has changed how much decompression surgery is performed: US Medicare claims data show a 37% drop in orbital decompression volume from 2016-2019 to 2020-2023, with the specialty mix shifting away from oculofacial plastic surgeons (-10%) toward otolaryngologists (+18%), and more cases done endoscopically (+13%) (PMID 40079573).
• A single-center comparison found decompression fell from 25.0% to 4.1% of eyes in the teprotumumab era, but eyelid surgery rates were unchanged (22.7% vs 21.6%) and strabismus surgery rates were unchanged, so teprotumumab has not reduced the demand for eyelid surgery the way it reduced decompression (PMID 40699109).
• Decompression is still needed in a minority of patients after teprotumumab: 25% of patients and 18% of orbits at one center, a mean 12.6 months after stopping the drug (PMID 39059786).
• Optimal surgical timing relative to the last teprotumumab dose is unsettled: a 53-patient multicenter study found no significant difference in postoperative regression rates between surgery under 180 days versus 180 days or more after the last infusion, but patients operated on later needed more additional procedures when they did regress (PMID 39656059).
• A second IGF-1R inhibitor, IBI311, chemically identical to teprotumumab but in a different formulation, produced an 85.8% proptosis response versus 3.8% with placebo in a 2025 Chinese phase 3 trial, with no new safety signal reported (PMID 41066129).
• The 2021 EUGOGO guideline and the 2022 ATA/ETA consensus still disagree on first-line drug therapy for active moderate-to-severe disease; both groups flag future revisions on biologics for optic neuropathy and on using teprotumumab for longstanding inactive disease (PMID 41283777).

Terms

• Thyroid eye disease (TED) / Graves' orbitopathy: autoimmune orbital disease causing lid retraction, proptosis and diplopia, usually with Graves' hyperthyroidism (PMID 40324443).
• Proptosis (exophthalmos): forward displacement of the eyeball from orbital tissue expansion (PMID 40324443).
• Clinical Activity Score (CAS): a scored measure of orbital inflammation used to judge disease activity and treatment response (PMID 31971679).
• Teprotumumab: an IGF-1R-inhibiting monoclonal antibody, FDA-approved in January 2020 for active TED (PMID 31971679).
• Orbital decompression: surgical removal of orbital bone, fat, or both, to expand orbital volume and reduce proptosis (PMID 22161415).
• MRD1 / MRD2: margin reflex distance from the corneal light reflex to the upper (MRD1) or lower (MRD2) lid margin, used to measure lid retraction (PMID 32930505).
• Müllerectomy: excision of Müller's muscle, often combined with levator recession to correct upper lid retraction (PMID 32930505).
• Posterior lamellar graft: tissue (hard palate mucosa, tarsoconjunctiva, or sclera) placed to lengthen a retracted lower eyelid (PMID 18520836).
• EUGOGO: the European Group on Graves' Orbitopathy, which publishes consensus management guidelines (PMID 34297684).
• Scleral show: visible white sclera between the eyelid margin and the iris caused by lid retraction (PMID 34526052).

Papers