Endocrine Abstracts

Dysthyroid Optic Neuropathy (DON) is a rare but sight threatening complication of Graves orbitopathy (GO), secondary to optic nerve compression or optic nerve stretching. A previous study from our group showed that medical and surgical treatment of DON according to EUGOGO guidelines resulted in a significant recovery in 70% of DON. However 30% had only partial or no recovery. Teprotumumab is an Insulin Growth Factor -1Receptor inhibitor (IGF-1R) showing impressive results in the remission of inflammation and orbit remodeling, but little is known about its effect on DON.

Objective: To investigate Teprotumumab efficacy on severe and steroid and surgical resistant DON.

Patients and methods: 6 patients (1 M and 5 F), for a total of 8 eyes, with steroid and surgical resistant GO and DON, were treated between July 2021 and February 2023 with intravenous teprotumumab infusion (10 mg/kg for first infusion, and 20 mg/kg for the subsequent) every three weeks at our referral center for GO. Clinical and ophtalmological parameters were collected retrospectively. Recovery was defined as significant, partial or none, based on evolution of BCVA and VF mean deviation (MD). Treatment was authorized by French health authorities according to the severity and sight threatening conditions.

Results: Median age was 54.5 years, median follow-up duration from the first teprotumumab infusion was 53 weeks (36-69). All patients had previously received intravenous glucocorticoids infusion and surgical orbital decompression, with only partial or absent recovery of DON. At inclusion median CAS was 4 [4-6.23] and median protrusion was 24 mm [20.7-25.5]. Median BCVA was 0.41 LogMAR [0.17-0.62] and median MD visual field defect 3.3dB [2.8-3.9]. 4/6 patients received the complete 8 infusions regimen, while the remaining two were respectively treated with 6 full-dose, and 4 half-dose infusions because of side effects. At the end of teprotumumab treatment (post-tepro) median CAS was 0 [0-0.25], median proptosis was 17 mm [16.2-19.2] with a median gain of 6.5 mm [4.2-7.2]. At last Follow-up (FU) median CAS was 1 [0-2.25], and proptosis 20.5 mm [16.5-21]. At the end of treatment significant visual improvement was found in 5/8 eyes, while it was absent in 1/8 and partial in 2/8. At the end of follow-up,7/8 (87.5%) eyes had significant recovery, median BCVA was 0.02 logMAR [-0.00-0.11] and median visual field defect MD 1.2 [0.2-2.4], with a median visual field MD improvement of 74% [35-92]. Main side effects were: alopecia (50%), hearing impairment (33,3%) with hearing loss registered in one patient at the end of treatment, and diarrhea (33.3%) which led to a discontinuation of treatment after 4 half-dose infusions

Conclusion: This preliminary study on a small patient group shows very promising data about teprotumumab efficacy on resistant DON, with significant improvement of this sight threatening condition.