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Abstract Disclosure: A. Patel Jain: Viridian Therapeutics, Inc., Amgen Inc. K. Cockerham: Viridian Therapeutics, Inc., Amgen Inc, Lassen Therapeutics LLC, Roche Pharmaceuticals, Immunovant, Tourmaline. J. Abrams: Viridian Therapeutics, Inc., Amgen Inc. J. Mandeville: Viridian Therapeutics, Inc. M. Al Khudari: Viridian Therapeutics, Inc. S. Leibowitz: Viridian Therapeutics, Inc., Amgen Inc, Lassen Therapeutics LLC. D. Lemor: Viridian Therapeutics, Inc. R.E. Turbin: Viridian Therapeutics, Inc., Amgen Inc, Medtronic. R.E. Turbin: Viridian Therapeutics, Inc., Amgen Inc, Medtronic. A. Kossler: Viridian Therapeutics, Inc., Amgen Inc, Sling Therapeutics, Lassen Therapeutics LLC, Immunovant, Genentech, Inc., Argenx, Acelyrin. W. Conroy: Viridian Therapeutics, Inc. A. Narvekar: Viridian Therapeutics, Inc. T.A. Ciulla: Viridian Therapeutics, Inc. R. Tang: Viridian Therapeutics, Inc., Amgen Inc, Alexion Pharmaceuticals, Inc., EMD Serono. Introduction: TED remains a condition with significant unmet needs, particularly in the chronic phase, where treatment options are limited. IGF-1R antagonism has emerged as a key therapeutic approach, addressing inflammation and proptosis. Veligrotug (veli), a full antagonist humanized monoclonal antibody targeting IGF-1R, previously demonstrated positive results in the ongoing phase 3 THRIVE trial for active TED. Here, we present efficacy and safety data from the ongoing phase 3 THRIVE-2 trial (NCT06021054) of veli in chronic TED at the primary timepoint of 15 weeks. Methods: Adults with moderate-to-severe chronic TED (onset >15 months, proptosis ≥3 mm, with any clinical activity score [CAS]) were randomized (2:1) to 5 IV infusions 3 weeks apart of either 10 mg/kg veli or placebo. The following were assessed through 15 weeks: proptosis responder rate (PRR), defined as ≥2-mm reduction vs baseline by Hertel exophthalmometry; overall responder rate (ORR; PRR and no worsening in CAS); PRR by MRI/CT; mean change from baseline in proptosis; Gorman diplopia responder rate (DRR) and complete resolution; and treatment-emergent adverse events (TEAEs). Results: 188 patients were randomized to veli (n=125) or placebo (n=63) and included in the intent-to-treat population. Baseline values for veli vs placebo were balanced including mean proptosis, 24.3 mm vs 23.8 mm; presence of diplopia, 52% vs 59%; CAS ≥3, 57% vs 52%. 15-week results for veli vs placebo were as follows: Hertel PRR, 56% vs 8% (p<0.0001), with a mean reduction of 2.34 mm vs 0.46 mm (p<0.0001); MRI/CT PRR, 48% vs 3% (p<0.0001); ORR, 56% vs 7% (p<0.0001). In patients with diplopia at baseline, DRR was 56% vs 25% (p=0.0006); complete resolution occurred in 32% vs 14% (p=0.0152). In patients with CAS ≥3 at baseline, CAS 0/1 (exploratory endpoint) was achieved in 54% vs 24% (nominal p=0.0060). Most TEAEs were mild, with most common being muscle spasms (36% vs 6%) and menstrual disorders (33% vs 10% for menstruating women). Hearing impairment was 13% vs 3%. Serious TEAEs were 2% vs 3% (1 related to treatment in each group). Conclusions: THRIVE-2, which assessed 5 IV infusions of veli vs placebo, is the first RCT in chronic TED to show statistically significant improvement not only in proptosis, but also in subjective diplopia, with a generally well-tolerated safety profile. Results suggest the promising potential of veli in chronic TED. Follow-up through 52 weeks is ongoing. Presentation: Monday, July 14, 2025

In a good example of translational research, investigators who had initially demonstrated a role for insulin-like growth factor I in the pathogenesis of thyroid eye disease showed that an antibody to the receptor (teprotumumab) produced a meaningful improvement in 83% of patients.

Modified Harada-Ito surgery is traditionally used to treat excyclotorsion due to superior oblique weakness. However, it may also be utilised for restrictive torsional diplopia. We present a large case series of outcomes following Harada-Ito surgery.73 modified Harada-Ito operations were identified at a tertiary hospital; 56 for IV nerve palsy, 8 for restrictive and 9 for other non-restrictive causes. 11 Consultants performed the operations (range 1–21), which were classified as full or partial, depending on whether the tendon was fully advanced to the superior lateral rectus border. Unilateral full surgery provided a mean improvement of 6° incyclotorsion in primary position, and 7.75° in worst gaze position. This represents improvements of 0.46° and 0.54° per mm of advancement. Partial surgery provided 5.68° and 6.53° of total improvement respectively. These were similar among the different groups, however restrictive causes appeared to regress more rapidly. 35 patients (47.9%) had resolution of diplopia in at least primary position, although most had persistent diplopia in extreme gaze. No patients with restrictive strabismus had resolution of diplopia after Harada-Ito alone. 7 patients (9.6%) developed iatrogenic Brown syndrome, while 1 developed scarring requiring surgical release. 24 patients (32.9%) had subsequent surgery for ongoing diplopia.Modified Harada-Ito surgery is an effective treatment for torsional diplopia. This is the largest outcome study to date and suggests more modest improvements than some previous studies. The surgical effect may be more transient in restrictive cases. Serious complications are rare, but further surgery is common, particularly where horizontal or vertical diplopia co-exists.

Diplopia is a reason for emergency department (ED) visits with both ophthalmological and neurological causes, some of which may require urgent therapeutic intervention. Epidemiological data on this symptom, particularly in the context of general EDs, remain scarce. This study aims to investigate the epidemiology, clinical characteristics, management strategies, and etiologies of diplopia in general EDs. We conducted a bicentric retrospective study of patients admitted for diplopia between January 2022 and December 2023 in the general EDs of two French university hospitals. We included 788 patients admitted for diplopia, representing 0.2 % of all ED admissions. Binocular diplopia was predominant, accounting for 751 cases (95 %), with the most common etiologies being microangiopathies (250 cases, 33 %), strokes (140 cases, 19 %), and myasthenia gravis (36 cases, 5 %). Cardiovascular risk factor prevalence did not differ between monocular and binocular diplopia. Imaging was performed in 712 cases (90 %), including 694 cases (92 %) of binocular diplopia and 18 cases (48 %) of monocular diplopia. The imaging primarily consisted of magnetic resonance imaging in 550 cases (70 %), computed tomography in 283 cases (36 %), and both modalities in 121 cases (15 %). Urgent etiological treatment was needed in 332 (42 %) cases, and 248 (31 %) patients required hospitalization. Diplopia accounted for 0.2 % of all ED admissions. Binocular diplopia predominated, with microangiopathies and strokes as leading causes. The use of imaging was high, even for monocular diplopia. The high rate of urgent treatments highlights the need for clearer imaging guidelines in emergency settings.

A 23-year-old female was admitted to ED two weeks after delivery with severe migrainous headaches and a painful pupil-sparing partial right third nerve palsy presenting as diplopia on upward and lateral gaze and a partial ptosis. This was the third such presentation for her as she was diagnosed with oph- thalmoplegic migraine (OM) since 8 years old. A second episode at the 18 years of age required steroid treatment due to a delayed recovery for few months.Repeat orbit MRI confirmed slightly grown lesion on the right oculomotor nerve compared scans 4 years apart appearing as a thickened nodular enhancement between the P1 segment and superior cerebel- lar artery. Multiple neuro-oncology and neuro-radiology MDTs confirmed this lesion to be an oculomotor nerve schwannoma. She had to be treated with steroids due to deficits and 2 months later while migrain- ous headache was fully resolved, she was still left with subtle upward and lateral gaze diplopia. She will have surveillance imaging and follow up.Recurrent Painful Ophthalmoplegic Neuropathy (RPON) is replacing OM and expected to be associated with a resolution of the enhancement. Schwannomas on the other hand are known to be growing during pregnancy and affected by hormonal changes. Transient or recurrent oculomotor nerve deficits may be the primary manifestations of cranial nerve schwannoma and we hypothesise this tumour being the cause of her RPON which must be considered in OM.

To analyze epidemiology, clinical features, and surgical outcomes of type III acute acquired concomitant esotropia (Bielschowsky esotropia (BE)). The medical charts of patients diagnosed with acquired concomitant esotropia between 2013 and 2021 were reviewed. Assessed data were age, gender, age at diplopia onset, age at the diagnosis, refraction, visual acuity, neuroimaging, diplopia onset, angle of deviation, stereopsis, surgical procedure, amount of surgery, and relapse of diplopia after surgery. Moreover, we investigated the correlation between the use of electronic devices and the onset of diplopia. One hundred seventeen patients (mean age 35.07 ± 15.81 years) were included in the study. The mean delay to the diagnosis was 3.29 ± 3.62 years. Myopia range was 0 to 17 diopters spherical equivalent. 66,3% spent more than 4 hours a day using laptops, tablets, or smartphones at the onset of diplopia, and 90,6% presented a subacute onset. None showed neurologic signs or symptoms. Patients who underwent surgery were ninety-three, with a rate of surgical success of 93.6%, and a relapse rate of 17.2%. A negative correlation resulted between pre-operative deviation and age at diagnosis (ρ = -0.261; p<0.05), whereas factors associated with surgical failure were older age at diplopia onset (p = 0.042) and longer delay between onset and diagnosis (p = 0.002). We registered an outstanding increase in prevalence of BE, which could be related to the exponential increase in the use of electronic devices for professional, educational, and recreational purposes. A prompt diagnosis and an augmented dose of surgery allows good motor and sensory results.

Background/AimsTo ascertain factors associated with persistent diplopia after orbital fracture reconstruction.MethodsIn this retrospective study, we reviewed 798 cases with depressed fragment fracture at the Department of Kyoto Prefectural University of Medicine Hospital between January 2009 and November 2023. The restriction of extraocular movements and diplopia was assessed using the Hess area ratio (HAR). The factors for HAR% ≥85% before surgery and 6 months after surgery were assessed.ResultsOf the 798 cases in this study, 437 cases (54.8%) had an HAR% of ≥85%, and 361 cases (45.2%) had an HAR% of <85% before surgery. Age ≤18 years old (p=0.017), orbital tissue herniation volume

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