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Background Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of active Thyroid eye disease (TED). The current study reviews its efficacy in chronic TED. Methods In this retrospective review, consecutive patients with chronic stable TED (>2 years), who had received ≥3 infusions of teprotumumab were included. All patients had measurements of proptosis, and calculation of the CAS and diplopia scores before and after therapy. Five-point strabismus scores were also calculated. Patients who had imaging within 4 months prior to therapy and 6 weeks post therapy underwent orbital 3D volumetric analysis. Results Thirty-one patients met the inclusion criteria. The mean (SD) duration of TED was 81 months (56) and the mean (SD) number of infusions received by each patient was 7 (2). Mean (SD) reduction in proptosis for each study orbit was 3.5 mm (0.4) and 3 mm (0.3) for the fellow orbit. The CAS response was 90% for the study orbit and 87% for the fellow orbit. Of the 15 patients who had diplopia at baseline, 67% had a clinically significant response, while 47% had complete resolution following treatment. Following teprotumumab, mean (SD) reduction of muscle tissue was 2011 mm3 (1847) in the study orbit and 1620 mm3 (1759) in the fellow orbit. The mean (SD) reduction of fat volume was 2101 mm3 (1681) in the study orbit and 1370 mm3 (1181) in the fellow orbit. Conclusion Teprotumumab significantly reduces proptosis, inflammation, diplopia, strabismus and orbital soft tissue volume in patients with chronic TED.

PurposeThyroid eye disease (TED) is a progressive, debilitating and potentially vision-threatening autoimmune disease. Teprotumumab, a novel human monoclonal antibody, has been shown to reverse the clinical manifestations of TED. Patients receiving teprotumumab have been shown in two multicenter, randomized placebo-controlled trials to have decreased proptosis, diplopia and inflammation after 24 weeks of treatment. This study aims to analyse volumetric and inflammatory changes on orbital imaging prior to and after teprotumumab treatment from one of these trials.DesignRetrospective review.SubjectsSix patients enrolled in the phase III teprotumumab clinical trial (OPTIC, NCT03298867) with active TED who received 24 weeks of teprotumumab and had pre- and post-treatment orbital imaging (CT or MRI). Additionally, 12 non-TED patients (24 orbits) were analysed as a comparative control group.Methods3D volumetric calculations of the extraocular muscles (EOMs), orbital fat, and bony orbit were measured using previously validated image processing software. 3D volumetric results and changes in EOM inflammation were compared with clinical measurements of TED.ResultsTotal EOM volume within each orbit was markedly reduced post-teprotumumab in all patients (n=six patients, 12/12 orbits, p<0.02). There was no statistical difference in post-treatment EOM volume when compared to non-TED controls. Total orbital fat volume was also reduced in 11 of 12 studied orbits (n=six patients, p=0.04). Overall EOM inflammation based on MRI signal intensity ratio was reduced in 8/8 orbits (n=four patients, p<0.01).ConclusionOrbital imaging demonstrated decreased EOM volumes and orbital fat tissue volumes after teprotumumab treatment.

Purpose Teprotumumab, a blocking antibody to the insulin like growth factor 1 receptor (IGF-1R) has been shown to significantly reduce proptosis in recent phase 2 and 3 trials in patients with inflammatory thyroid eye disease (TED). Herein, we investigate the impact of teprotumumab on patients with non-inflammatory TED. We also investigate the expression of the IGF-1R on orbital tissues from patients with inflammatory and non-inflammatory TED compared to controls. Methods Consecutive patients with non-inflammatory TED (clinical activity score, CAS ≤ 1, for at least 4 months, were treated with teprotumumab. They received a complete course (total eight infusions) of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for subsequent infusions every 3 weeks). The primary outcome was a proptosis response at week 24. Further, IGF-1R α and β expression was evaluated on orbital tissue from patients with inflammatory and non-inflammatory TED, as well as healthy controls. Non-biased histological analysis of IGF-1R expression was performed using ImageJ. Results Four patients met eligibility criteria for the clinical study, with a mean (SD) CAS of 0 (0). Following teprotumumab treatment, there was a mean (SD) reduction in proptosis of 2.6 mm (1.2). Five patients were included for each group of the histological study; inflammatory TED, non-inflammatory TED and controls. IGF-1Rα and IGF-1Rβ expression was significantly greater in the orbital tissues of patients with inflammatory TED and non-inflammatory TED, when compared to controls. Conclusion Our findings demonstrate for the first time, that teprotumumab, a blocking antibody to the IGF-1R reduces proptosis in a series of patients with non-inflammatory TED. Overexpression of the IGF-1R in orbital tissue from patients with non-inflammatory disease compared to controls may be an important consideration for effect.

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Background: Retrobulbar injection of hyaluronidase is a proposed but unproven treatment for blindness induced by hyaluronic acid gel fillers. This study examines the viability of this treatment by determining whether hyaluronidase can diffuse through the dural sheath of the optic nerve to clear a filler-mediated occlusion of the central retinal artery. Methods: Six human cadaveric optic nerves were studied in vitro. One optic nerve was selected as a control and maintained at physiologic temperature, without any exposure to hyaluronic acid gel or hyaluronidase. Another optic nerve was randomly selected to simulate the filler-induced central retinal artery occlusion with subsequent retrobulbar hyaluronidase injection. To simulate a central retinal artery occlusion, this experimental nerve and additional controls were injected with hyaluronic acid gel. These hyaluronic acid gel–injected nerves were then either injected directly with hyaluronidase to establish a control for intraneural hyaluronidase exposure, or immersed in undiluted hyaluronidase to simulate retrobulbar hyaluronidase injection. To control for passive diffusion of hyaluronic acid gel from neural parenchyma, one nerve was immersed in saline. Following fixation, the nerves were grossly and microscopically assessed for the quantity and distribution of hyaluronic acid. Results: Intact hyaluronic acid gel was observed grossly and microscopically in the control optic nerves injected directly with filler and not with hyaluronidase. The control optic nerve injected with intraneural hyaluronidase exhibited partial digestion of the filler. Immersion in undiluted hyaluronidase led to no apparent gross or microscopic digestion of injected intraneural hyaluronic acid gel. Conclusion: Hyaluronidase does not demonstrate the ability to cross the dural sheath of the optic nerve, suggesting that retrobulbar hyaluronidase injection is unlikely to alleviate hyaluronic acid gel–mediated central retinal artery occlusion and blindness.

This subgroup of TED patients do not conform to the typical inflammatory natural history of TED. We propose that the heterogeneity of the orbital fibroblast pool and their function may be different in this subgroup. Further work will be required to reveal the pathophysiology of this atypical TED process, potentially revealing links between aging and the inflammatory mediators in TED.

Purpose To determine whether the incidence of chalazion increased significantly in the San Francisco Bay Area and Los Angeles County following the widespread adoption of face mask wear in response to the COVID-19 pandemic. Methods This is a retrospective multicenter study of two ophthalmology institutions: a private Oculoplastics practice in San Francisco and the Oculoplastics division of the Stein Eye Institute at the University of California, Los Angeles. All patients seen during the studied time periods with a diagnosis of chalazion or hordeolum were identified through review of electronic medical records and included in the study. Incidence was determined for each month between January and August 2020, and compared to data from prior years via ANOVA to evaluate for changes after the onset of the pandemic. Results In San Francisco, the incidence of chalazion rose significantly in June through August of 2020 when compared to the same interval in 2016, 2017, 2018, and 2019. In Los Angeles, the rise in chalazion incidence in 2020 was also statistically significant when compared to data from the years 2018 and 2019. Conclusion /Importance: Widespread mask wear does appear to correspond to an increased incidence of chalazion. This risk may be minimized, while still maintaining the protective benefits of mask wear, by taking the proactive measures discussed to decrease mask induced eye dryness and changes in the eyelid microbiome.