Improvement In Proptosis Research Articles

Effects of Teprotumumab and Role of Human Leukocyte Antigens Markers in Patients With Thyroid Eye Disease

ObjectiveTo evaluate the effects of teprotumumab on ophthalmologic and biochemical findings and assess potential genetic markers for response to treatment. MethodsThis is a retrospective study. Participants were 18-76 year old. All subjects were treated with teprotumumab. The primary outcome was the change in proptosis before and after teprotumumab treatment. Secondary outcomes include change in other ophthalmic measures and thyroid laboratory tests. Human leukocyte antigens (HLA) markers were analyzed for response to teprotumumab. ResultsTwenty-six patients were included in the final analysis. There was a significant decrease in thyroid stimulating immunoglobulin and thyrotropin receptor antibody levels and significant increases in glycated hemoglobin A1c, fasting glucose, and total T3 levels. There was also significant reduction in proptosis, clinical activity score, retinal nerve fiber layer thickness, ganglion cell analysis, and intraocular pressure. HLA haplotypes were distinct between responders and nonresponders, with HLA-DRB3 02:02:01G, HLA-DRB4 neg, and HLA-DQB1 02:01:01G demonstrating better response to teprotumumab and HLA-A 23:01:01G strongly correlating to nonresponse. ConclusionsPatients with both acute and chronic thyroid eye disease treated with teprotumumab had a significant reduction in thyroid stimulating immunoglobulin and thyrotropin receptor antibody levels and improvement in proptosis, clinical activity score, retinal nerve fiber layer and ganglion cell analysis thickness, and intraocular pressure. HLA may predict responders vs nonresponders. Further studies with longer duration and larger population comparing teprotumumab with steroids or other immunomodulatory agents (tocilizumab, rituximab, etc) may be helpful.

Long-Term Efficacy of Teprotumumab in Thyroid Eye Disease: Follow-Up Outcomes in Three Clinical Trials.

Introduction: Thyroid eye disease (TED) is an autoimmune process characterized by extraocular muscle and orbital fat remodeling/expansion resulting in swelling, pain, redness, proptosis, and diplopia. Teprotumumab, an insulin-like growth factor-I receptor inhibitor, demonstrated improvements in TED signs and symptoms in three adequately powered clinical trials of 24 weeks duration. Here we analyze the long-term maintenance of responses with teprotumumab from these trials. Methods: A total of 112 patients who received 7 or 8 infusions of teprotumumab in the Phase 2, Phase 3 (OPTIC study), and OPTIC Extension (OPTIC-X) studies were included in this analysis. Responses, including clinical activity score (CAS ≥2-point improvement), the European Group of Graves' Orbitopathy ophthalmic composite outcome, diplopia (≥1 Gorman grade improvement), proptosis (≥2 mm improvement), Overall (improvement in proptosis + CAS), and disease inactivation (CAS ≤1), were assessed and pooled from study baseline to week 24 (formal study) and up to week 72 (formal follow-up). Graves' Ophthalmopathy quality-of-life (GO-QoL) scores were also assessed. Outcomes included the percentages of observed patient responsesfrom the study baseline. Additional alternative treatments for TED were assessed as a surrogate of persistent benefit from week 24 through week 120 (extended follow-up). Studies differed in the timing of follow-up visits, and data from some visits were unavailable. Results: At week 72, 52/57 (91.2%), 51/57 (89.5%), 35/48 (72.9%), 38/56 (67.9%), and 37/56 (66.1%) of patients were responders for CAS, composite outcome, diplopia, proptosis, and Overall response, respectively. The mean reduction in proptosis was 2.68 mm (SD 1.92, n = 56), mean GO-QoL improvement was 15.22 (SE 2.82, n = 56), and disease inactivation (CAS ≤1) was detected in 40/57 (70.2%). Over 99 weeks following teprotumumab therapy, 19/106 (17.9%) patients reported additional TED therapy during formal and extended follow-up. Conclusion: The long-term response to teprotumumab as observed 51 weeks after therapy was similar to week 24 results in the controlled clinical trials. Inflammatory and ophthalmic composite outcome improvements were seen in 90% of patients with nearly 70% reporting improvement in diplopia and proptosis. Further, 82% of patients in this analysis did not report additional TED treatment (including surgery) over 99 weeks following the final teprotumumab dose.

Graves’ ophthalmopathy: the clinical and psychosocial outcomes of different medical interventions – a systematic review

BackgroundGraves’ ophthalmopathy is a complex autoimmune disorder that can significantly affect quality of life (QoL), vision and physical appearance. Recently, a deeper understanding of the underlying pathogenesis has led to...

Erdheim-Chester Disease With Eyelid and Orbital Involvement: A Review of Treatment Modalities at One Institution From 2014 to 2022.

To review all cases of Erdheim-Chester disease (ECD) with orbital involvement treated at Bascom Palmer Eye Institute in Miami, Florida from 2014 to 2022 and compare presentations, treatment modalities, and outcomes. A retrospective chart review of all patients diagnosed with ECD who presented to Bascom Palmer Eye Institute from 2014 to 2022 was performed. Data collected included demographics, pretreatment history and ophthalmic examination, pathology report, treatment, subsequent examination, and relevant laboratory results. Histopathology, treatments, and outcomes were reviewed and compared between patients. Four cases were included. Primary treatments included vemurafenib (n = 2), cobimetinib (n = 1), and prednisone (n = 1). All patients demonstrated improvement of ophthalmic symptoms. Vemurafenib was the only medical treatment that was tolerated well and resulted in significant improvement in proptosis despite some reported dry eye; all other medications were discontinued due to intolerable side effects. BRAF inhibitors such as vemurafenib have been used as novel therapy in the treatment of ECD. Vemurafenib demonstrated its utility in reducing proptosis in ECD patients at one ophthalmic institution. Vemurafenib may be a favorable treatment option for BRAF -positive ECD patients presenting with orbital disease.

Reactivation After Teprotumumab Treatment for Active Thyroid Eye Disease

PurposeTo determine the recurrence and reactivation rates after teprotumumab therapy for active thyroid eye disease. DesignRetrospective consecutive case series. MethodsSetting: Institutional, Study Population: All patients followed for active thyroid eye disease at the Cole Eye Institute treated with teprotumumab between May 2020 and May 2021. Patients with under 6-months follow-up after completion of infusions were excluded., Outcome Measures: Primary outcome measure was reactivation, defined as a regression in proptosis (increase of ≥2mm in either eye and to within ≤ 2mm of pre-treatment level) and CAS (worsening of 2 points or greater). Secondary outcome was diplopia response. ResultsTwenty-one patients were included in the study. The average long-term improvement in proptosis in the eye with more proptosis after teprotumumab was 1.57mm (range, -3-4 mm). Of the 17/21 of initial responders, there were 8 reactivations (47%) and 2 isolated proptosis regressions (12%); Overall, 7/21 patients (33%) responded throughout the study period. Average time to regression was 12.25 months (range, 2-22.5 months). There was no statistically significant change in diplopia at final visit in any subgroup (p=0.68->0.99). ConclusionsAt most, 33% of patients demonstrate continued response two years after teprotumumab treatment. The proptosis and CAS regression occurs in the setting of disease reactivation in 80% of regressions. Teprotumumab treatment appears to offer minimal long term improvement in diplopia.

Volumetric Analysis of Spheno-Orbital Meningiomas: Prognostic Correlation and a Compartmentalized Approach.

Spheno-orbital meningiomas arise from the arachnoid villi cap cells at the sphenoid ridge and have the ability to spread through soft tissue extension and cranial bone invasion. Owing to their orbital hyperostosis and intraorbital soft tissue extension, they commonly present with ophthalmologic manifestations. This study aims to investigate the correlation between tumor volume with the presenting symptoms and postoperative outcomes. This retrospective study analyzed patients who underwent surgical resection of spheno-orbital meningiomas. Tumor volumes in different compartments were measured using preoperative and postoperative imaging. Linear and logistic regression analyses were used to identify correlations between tumor volumes and presenting symptoms preoperatively and postoperative outcomes. Sixty-six patients were included in this study, of whom 86.4% had proptosis, 80.3% had decreased visual acuity (VA), 30.3% had visual field defects, and 13.6% had periorbital edema. Preoperatively, proptosis linearly correlated with intraosseous tumor volume (coefficient = 0.6, P < .001), while the decrease in baseline VA correlated with the intraorbital tumor volume (coefficient = 0.3, P = .01). The odds of periorbital edema were found to increase with an increase in intraosseous tumor volume with an adjusted odds ratio of 1.4 (95% CI, 1.1-1.7, P = .003), while the odds of visual field defects were found to increase with an increase in intraorbital tumor volume with an adjusted odds ratio of 2.7 (95% CI, 1.3-5.6, P = .01). Postoperatively, the volume of intraosseous tumor resected linearly correlated with the improvement in proptosis (coefficient = 0.7, P < .001), while the volume of intraorbital tumor resected linearly correlated with improvement in VA (coefficient = 0.5, P < .001) and with a larger effect size in patients presenting with moderate-to-severe decrease in VA preoperatively (coefficient = 0.8). Underscoring the importance of each tumor compartment relative to the patient's symptomatology serves as a valuable guide in implementing a compartmentalized resection approach tailored to the surgical objectives.

SAT455 A Randomized, Quadruple-masked, Placebo-controlled, Multicenter Trial To Evaluate The Efficacy And Safety Of Teprotumumab In Patients With Chronic (Inactive/Low CAS) Thyroid Eye Disease

Abstract Disclosure: R.S. Douglas: Consulting Fee; Self; Horizon Therapeutics plc, Immunovant, Viridian. S. Couch: None. S.T. Wester: Advisory Board Member; Self; Horizon Therapeutics plc. Consulting Fee; Self; Immunovant, Sling. B. Fowler: Consulting Fee; Self; Horizon Therapeutics plc. C. Liu: Other; Self; Walter Kluwer Health. P. Subramanian: Consulting Fee; Self; Gensight, Horizon Therapeutics plc, Viridian. R. Tang: Consulting Fee; Self; Viridian, Alexion, Valenza. Research Investigator; Self; Viridian, Horizon Therapeutics plc, Novartis, Immunovant, Vasaragen. Speaker; Self; Serono Speaker Journal Club. Q.T. Nguyen: None. K. Hsu: Employee; Self; Horizon Therapeutics plc. Stock Owner; Self; Horizon Therapeutics plc. M. Karon: Employee; Self; Horizon Therapeutics plc. Stock Owner; Self; Horizon Therapeutics plc. M.N. Stan: Consulting Fee; Self; Immunovant, Horizon Therapeutics plc, Sling, Genentech, ArgenX. Background: Thyroid eye disease (TED) is characterized by expansion of peri- and retro-orbital fat and muscle, often resulting in disfiguring proptosis (eye-bulging) and diplopia (double vision) which may persist chronically. Teprotumumab, an inhibitor of the insulin-like growth factor-1 receptor, demonstrated improvements in proptosis, diplopia, inflammation and quality of life in clinical trials in patients with TED history of short duration (6-13 months), and active disease (clinical activity score [CAS] ≥4). In a published study of 31 patients with CAS≤3 and TED duration &amp;gt;2 years, teprotumumab reduced proptosis, diplopia and inflammation.1 We have undertaken the first randomized, placebo (PBO)-controlled trial to evaluate teprotumumab in patients with chronic/inactive/low CAS TED. The trial has completed randomization with results available in May 2023. Here we report characteristics of the randomized patients. Methods: The trial (NCT04583735) is being conducted in 11 centers in the United States. Key inclusion criteria were age≥18 years, TED duration ≥2 years but &amp;lt;10 years and CAS≤1 in both eyes, ≥3mm proptosis from baseline and/normal for sex and race, or no progression in proptosis or diplopia or new inflammatory symptoms in the preceding year. Patients must have been euthyroid or mildly hypo/hyperthyroid, and not require surgical intervention through the trial. Patients could not have received teprotumumab previously, or steroids within 3 weeks before screening. Patients were randomized 2:1 to receive 8 infusions of teprotumumab (10 mg/kg for the first infusion and 20 mg/kg for the remaining 7 infusions) or PBO once every 3 weeks. The primary endpoint is improvement in proptosis (mm) as compared with PBO from baseline at Week 24. Other endpoints include percentage of proptosis responders (improvement of ≥2mm), diplopia responders (improvement of ≥1 grade in diplopia on the Bahn-Gorman scale, 0-3), and improvement in Graves’ Ophthalmopathy- Quality of Life (GO-QoL), all at Week 24. Adverse events (AE) and AE of special interest will be reported. Results: 62 patients were randomized. 80.6% are female, mean (SD) age was 48.7 (14.94) years. 54.8% are White, 24.2 %, Black or African American, and 12.9%, Asian. Mean (SD) TED duration was 5.2 (1.77) years. 87.1% are never/former smokers. At baseline, mean (SD) proptosis in the study eye was 24.4 (2.94) mm, and mean (SD) CAS was 0.4 (0.49). 27.4% had binocular diplopia with a mean diplopia score of 2. The mean overall GO-QoL score was 63.9 indicating similar disutility as observed in the acute trial population (previously published). Results from this 24-week trial will be presented. Conclusions: Despite a long duration of TED and low “activity”, patients enrolled in this trial have high levels of proptosis and impaired quality of life at baseline. Presentation: Saturday, June 17, 2023

OR27-04 Efficacy And Safety Results From The Randomized, Placebo-controlled Multicenter Trial With Teprotumumab In Chronic-Low Clinical Activity Score Thyroid Eye Disease Patients

Abstract Disclosure: R.S. Douglas: Consulting Fee; Self; Horizon, Immunovant, Viridian. Research Investigator; Self; Horizon. S. Couch: Research Investigator; Self; Horizon. S.T. Wester: Advisory Board Member; Self; Horizon. Consulting Fee; Self; Immunovant, Sling. Research Investigator; Self; Horizon. B.T. Fowler: Consulting Fee; Self; Horizon. Research Investigator; Self; Horizon. C. Liu: Research Investigator; Self; Horizon. Other; Self; Royalties from Wolters-Kluwer. P. Subramanian: Consulting Fee; Self; Horizon, Gensight, Viridian. Research Investigator; Self; Horizon. R. Tang: Consulting Fee; Self; Viridian, Alexion, Valenza. Research Investigator; Self; Horizon, Viridian, Novartis, Immunovant, Vasaragen. Speaker; Self; Serono Journal Club. Q.T. Nguyen: Research Investigator; Self; Horizon. R.N. Maamari: Research Investigator; Self; Horizon. K. Hsu: Employee; Self; Horizon. Stock Owner; Self; Horizon. M. Karon: Employee; Self; Horizon. Stock Owner; Self; Horizon. M. Stan: Consulting Fee; Self; Septerna Inc, Third Rock Ventures LLC, Genentech, MedicXi Ventures, ArgenX US Inc, Tourmaline Bio, Lassen Therapeutics, Ortho Clinical Diagnostics, Siemens Healthcare, Tolmar Inc, OSE, Immunotherapeutics, Roivant Sciences. Research Investigator; Self; Horizon, Immunovant, ValenzaBio, Sling Therapeutics. Background: Early inflammatory thyroid eye disease (TED) gives way to chronic disease which may lead to long-term disfiguring proptosis (eye-bulging). Teprotumumab, an IGF-1 receptor inhibitor, significantly improved signs and symptoms of newly diagnosed TED (6-13 months) with active disease (clinical activity score [CAS] ≥4) in prior studies. We present data from the first randomized, placebo (PBO)-controlled trial (NCT04583735) with teprotumumab in chronic/low CAS TED, where disease has not regressed. Methods: Pts met all following criteria: ≥18 yrs, TED 2-10 yrs, inactive disease or &amp;gt;1 yr without progression in proptosis/diplopia/new symptoms, baseline (BL) CAS≤1, increased proptosis ≥3mm before TED or from normal, euthyroid/mildly hypo/hyperthyroid, no prior teprotumumab and no steroids within 3 wks of screen. Pts received teprotumumab or PBO once every 3 wks for 21 wks. Primary endpoint was improvement in proptosis(mm) from BL at Wk 24 vs PBO. Secondarily proptosis responders (≥2mm improvement), diplopia responders (≥1 grade improvement on Gorman scale 0-3) with resolved diplopia (grade 0) and improvement in Graves’ Ophthalmopathy-QoL (GO-QoL) visual function (VF) and appearance (AP) subscales were assessed. Treatment-emergent adverse events (TEAE) and AEs of special interest are reported. Study was solely sized/powered for proptosis. Results: 62 pts were randomized 2:1 (ITT, teprotumumab:42; PBO:20), 80.6% were female, mean(SD) age was 48.7(14.94) yrs. Mean(SD) TED duration was 5.2(1.8) yrs. 87.1% were never/former smokers. At BL, mean(SD) proptosis was 24.4(2.94) mm, mean CAS was 0.4, and 29% (teprotumumab, n=14, PBO, n=4) had diplopia with a mean score ∼2. 93%(39) of teprotumumab pts completed the study. At Wk 24, proptosis improvements from BL were significantly greater in the teprotumumab group [2.41 (0.228) mm] vs PBO [0.92(0.323) mm], P&amp;lt;.001. Proptosis response was observed in 26/42 (62%) of teprotumumab pts vs 5/20 (25%) of PBO, P=.01. Diplopia improvement was observed in 6/14 (43%) teprotumumab pts with resolved diplopia in 4(29%) vs 2/4(50%) in PBO and 1(25%) resolved. Significantly greater improvement from BL was observed on GO-QoL-VF for teprotumumab (8.73) vs PBO (2.41), P=.03. Change from BL on AP was 10.03 vs 7.19, P= .65. TEAEs proportions were similar: 33/41(80.5%) of teprotumumab, and 16/20(80%) of PBO pts. Hyperglycemia was reported in 6(15%) vs 2(10%) and hearing impairment in 9(22%) vs 2(10%), respectively. There were two AE discontinuations: teprotumumab (left ear conductive hearing loss with congenital anomaly) and PBO (infusion related). Conclusions: For the first time in pts with longstanding TED and low CAS/inflammation, a medical therapy, teprotumumab, produced significant improvement in proptosis as compared with PBO supporting its use regardless of TED duration or activity. The safety profile was comparable to that previously reported. Presentation: Saturday, June 17, 2023

Real-World Experience With Teprotumumab in Patients With Dysthyroid Optic Neuropathy.

Teprotumumab, an insulin-like growth factor I receptor inhibitory antibody, improved proptosis, diplopia, inflammatory signs/symptoms, and quality of life in patients with active thyroid eye disease (TED) in clinical trials. The trials excluded patients with dysthyroid optic neuropathy (DON). Recently, many case reports and case series have reported the successful use of teprotumumab to treat DON. Here, we review the data from published cases and our clinical experience in treating patients having DON with teprotumumab. A literature search was conducted of patients with DON treated with teprotumumab from January 2020 through September 2022. Data from DON patients from the authors' (M.A.T. and C.A.B.) clinical practice were included. Primary outcome measure was mean (SD) improvements for visual acuity, color vision, and visual fields. Improvements in proptosis and clinical activity score (CAS) and diplopia were compared before and after teprotumumab administration. Ten observational studies/case reports were identified along with 2 patients in our practice. In all, there were 24 active TED patients with DON (37 eyes) who were treated with teprotumumab. Mean (SD) age was 66.5 (13.6) years and 13 (54%) were females, disease duration ranged from 2 months to >15 years. 22/24 patients had none, minimal improvement or progression of visual loss with intravenous/oral corticosteroids, orbital decompression (n = 9), and orbital radiation (n = 2). There were 2 patients who received teprotumumab as the only therapy. Overall, 88% (21/24) reported improvement in visual acuity after teprotumumab and in 75% (18/24), improvement in vision was observed after just 2 infusions of teprotumumab. Three eyes had decompression surgery in close proximity to teprotumumab infusions and were excluded from analyses. Mean (SD) improvement in visual acuity was 3.73 lines (SD 3.74), range 2-15 lines in 33 eyes. The mean (SD) improvement in the mean deviation on visual field testing in 15 eyes was 5.6 db (3.0 db). Mean (SD) improvement in proptosis was 4.37 mm (SD: 2.11) (20 patients, 32 eyes); and clinical activity score: mean reduction of 5.1 (1.3) for 18 patients. Teprotumumab was well tolerated in all but one patient. Adverse events reported included fatigue, dysgeusia, hearing loss, nausea, hyperglycemia, and muscle spasms. Teprotumumab is an effective treatment for DON in our experience and in published cases in whom treatment with steroids, surgery, or orbital radiation was unsuccessful.

Medical Therapy in Patients with Moderate to Severe, Steroid-Resistant, Thyroid Eye Disease.

Background: Corticosteroid therapy is often employed in thyroid eye disease (TED), but its efficacy is variable. Teprotumumab and tocilizumab have been considered as effective alternatives. This study aims to evaluate their clinical outcomes and safety in patients with steroid-resistant TED. Methods: A retrospective case-control study was conducted between 2018 and 2022 within a national multicenter health system. Thirty-seven patients with moderate to severe steroid-resistant TED treated with teprotumumab or tocilizumab (cases) were compared with steroid-naïve patients treated with similar therapy (controls). Due to lack of steroid-naïve patients treated with tocilizumab, a control subgroup for tocilizumab was not included in the analysis. Demographic and clinical characteristics were described. Proptosis, diplopia, clinical activity score (CAS), and disease severity (European Group on Graves' orbitopathy classification) were evaluated at weeks 0, 12, 24, and 52 after therapy initiation. Results: Thirty-one patients received teprotumumab (13 cases and 18 controls) and 6 received tocilizumab (cases). The mean age was 57 years (standard deviation ±14.3), median duration of TED was 11.5 months (interquartile range [IQR]: 7.2-17.7), and median excess proptosis was 4 mm (IQR: 2-8) above the upper limit of normal for sex and race. At week 24, in the teprotumumab cases, 81% had proptosis response (reduction of ≥2 mm), 45.5% resolution of diplopia, 85.7% disease inactivation (CAS <3), and 58.3% reverted to mild disease severity. There were comparable results in teprotumumab controls, with no significant differences between subgroups. In the tocilizumab cases, 50% had a proptosis response, 16.7% resolution of diplopia, 100% disease inactivation, and 75% returned to mild disease. In the teprotumumab cases, there was a trend toward worsening proptosis and diplopia between weeks 24 and 52. In the same time frame, the tocilizumab cases had a trend toward worsening diplopia, disease activity, and severity. In the teprotumumab subgroup, 46.2% experienced otic changes and 23.1% hyperglycemia. In the tocilizumab subgroup, there were no reported adverse events. Conclusions: Teprotumumab and tocilizumab improved inflammation in patients with moderate to severe TED who had failed previous steroid therapy. Additionally, the teprotumumab cases demonstrated similar improvement in proptosis and diplopia to the teprotumumab controls. Further evaluation, particularly regarding the long-term response and side effect profile, of these medications in steroid-resistant TED is needed.

Invasive Sinusitis Presenting with Orbital Complications in COVID Patients: Is Mucor the Only Cause?

The second wave of COVID pandemic was associated with an outbreak of Mucormycosis. The mortality rate of Mucormycosis reaches 50-80% in cases with orbital and intracranial extension (Fadda in Acta Otorhinolaryngol Ital 41:43-50, 2021). In this outbreak we found that few of these patients had bacterial invasive sinusitis mimicking fungal sinusitis. Amphotericin the only effective drug against Mucormycosis is highly toxic and expensive and not indicated in bacterial sinusitis. Our aim was to determine the exact etiologic agent, predisposing factors and outcome of treatment of COVID associated invasive sinusitis presenting with orbital complications. It is a retrospective observational study done in 33 patients with orbital complications in COVID associated invasive sinusitis. Demographic details of the patients and clinical presentation were documented. Rhinological examination was done and a nasal swab was taken for KOH mount along with Gram`s stain and Culture and Sensitivity. All Patients underwent radiological evaluation by contrast enhanced computed tomography (CECT) or MRI. Liposomal Amphotericin B was started. Surgical debridement done. Amphotericin-B was stopped in cases reported negative for fungal elements and antibiotics administered for two weeks. Outcome of treatmentwas documented. A total of 33 patients were included in the study. 48.5% patients were found to have bacterial infection and 27.3% patient's fungal infections and 24.2% mixed infections.Eschar formation, necrotic tissue, erosion of the lamina papyracea was seen in both Klebsiella (33.3%) and Staphylococcal infections (16.6%) similar to Mucor and mixed infections. Persistent opthalmoplegia and deterioration of vision was associated with Mucor and mixed infections. However improvement in proptosis, ptosis, ophthalmoplegia, and vision was observed in cases associated with bacterial invasive sinusitis. Invasive bacterial sinusitis was under diagnosed during second wave of COVID. Identification of invasive bacterial sinusitis can help in de-escalation of treatment.

Efficacy and Safety of intravenous monoclonal antibodies in patients with moderate-to-severe active Graves'ophthalmopathy: a systematic review and meta-analysis.

The effects of various treatments on Graves' ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to severe GO, direct comparisons between different mAbs are lacking.We therefore conducted this meta-analysis to objectively compare the efficacy and safety of intravenous mAbs. To identify eligible trials, references published before September 2022 were electronically searched in PubMed, Web of Science, Pubmed, Embase,Cochrane Library, CBM, CNKI,Wan-Fang and ICTRP databases.The Newcastle-Ottawa scale (NOS) and the Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias of the original studies.The primary and secondary outcomes were the response and inactivation rates, with the secondary outcomes being the clinical activity score (CAS),the improvement of proptosis and diplopia improvement,and the adverse event rate. Publication bias was evaluated, along with subgroup and sensitivity analyses. A total of 12 trials with 448 patients were included. The meta-analysis showed that TCZ (tocilizumab) was most likely to be the best treatment in terms of response according to indirect contrast, followed by TMB (teprotumumab) and RTX (rituximab).TCZ, followed by TMB and RTX, was also most likely to be the best treatment in terms of reducing proptosis. In terms of improving diplopia, TMB was most likely to be the best treatment, followed by TCZ and RTX.TCZ was the highest probability of safety, followed by RTX and TMB. Based on the best available evidence,TCZ should be the preferred treatment for moderate to severe GO.In the absence of head-to-head trials,indirect comparisons of treatments are routinely used to estimate the effectiveness of the treatments of interest. In addition,the optimal dose and potential mechanism of action of monoclonal antibodies remain to be established,and it is encouraging that the treatment paradigm for GO may change in the future.This study was designed in accordance with the Preferred Reporting Items for conducting Systematic Reviews and Meta-Analyses (PRISMA)(27). http://www.crd.york.ac.uk/prospero, identifier CRD42023398170.

Functional and clinical outcomes after superior eyelid transorbital endoscopic approach for spheno-orbital meningiomas: illustrative case and literature review.

The pattern of growth of spheno-orbital meningiomas accounts for the main presenting symptoms, such as proptosis, eye motility deficit, visual impairment, diplopia. As these are benign tumors, the postoperative patient's quality of life is an important factor to consider during the preoperative planning.A detailed literature review of superior eyelid transorbital endoscopic approach for spheno-orbital meningiomas, including our own case, was made. A Medline search up to March 2022 in PubMed online electronic database was made using the following key phrases: "superior eyelid endoscopic transorbital approach spheno-orbital meningiomas," "superior eyelid endoscopic transorbital approach," "spheno-orbital meningiomas endoscopic approach." The inclusion criteria were surgical series, reviews, and case reports in English language, as well as papers written in other languages, but including the abstract in English. Cadaveric studies, multiportal combined approaches for SOM, were excluded. The literature review has disclosed five studies for a total of 65 patients, whose demographic, clinical, pathological, surgical, complications, and outcome data were analyzed.Functional and esthetic outcome data after superior eyelid transorbital approach are the following: improvement of proptosis (100%), of visual deficits (66.66%) and of ocular paresis (75%), with only 11 complications (4 trigeminal dysesthesia, 2 CSF leak, 2 wound complications, 1 upper eyelid necrosis, 1 hemorrhage of surgical field, 1 keratitis) reported, but at the expense of extent of resection (gross total resection 33.39%).Based on the outcome data, the superior eyelid transorbital endoscopic approach results in a suitable operative technique for selected spheno-orbital meningiomas.

RF35 | PSAT299 Thyroid Eye Disease Activation After mRNA SARS-CoV-2 Vaccination in Patients With Autoimmune Thyroid Disease

Abstract Background Occurrence of Graves’ disease (GD) has been reported following SARS-CoV-2 vaccine administration, but little is known about thyroid eye disease (TED) after SARS-CoV-2 vaccination. Case 1 A 50-year-old non-smoker male was diagnosed with GD in March 2019 and treated with methimazole. In April 2020, he developed TED with bilateral proptosis, pain, erythema and diplopia and clinical activity score (CAS) 6/7. Following poor response to 3-month oral steroids, he underwent total thyroidectomy in November 2020. In six weeks, his TED improved (CAS 4/7) and thyroid stimulated immunoglobulin (TSI) levels normalized from 4.13 IU/l (preoperatively) to 0.70 IU/l (reference&amp;lt; 1.75 IU/l). In January 2021, he received 2 doses of the mRNA BNT162b2-SARS-CoV-2 vaccine (Pfizer-BioNTech). Three weeks after the second dose, TED deteriorated significantly with severe eye pain, lid swelling, conjunctival erythema, and worsening proptosis and diplopia (CAS 6/7). TSI levels rose to 4.45 IU/l, while patient was euthyroid on levothyroxine (TSH 2.3 mIU/l). He received 12 weekly methylprednisolone infusions (cumulative dose of 4.5 g) with limited response. He was then treated with three monthly cycles of intravenous tocilizumab with partial response (CAS 5/7). Case 2 A 71-year-old non-smoker female had a 40-year history of hypothyroidism, controlled on levothyroxine. In March 2021, three days after her second dose of the mRNA-1273 SARS-CoV-2 vaccine (Moderna), she developed bilateral eye swelling and burning. She initially received anti-histamines and steroid eye drops without improvement. By August 2021, her eyes further deteriorated with eye pain, redness, lid edema and erythema, diplopia, and worsening proptosis (CAS 4/7). She also experienced 20 Ib weight loss, palpitations, tremors, and heat intolerance. TSI index was 5.5 (reference ≤1.3), TSH was undetectable, and FT4 1.4 ng/dl (reference 0.93-1.70 ng/dl). Levothyroxine was discontinued. Two weeks later she was admitted to the hospital with loss of color vision and decreased visual acuity in the right eye. She received 2 daily doses of 1 g intravenous methylprednisolone and intravenous teprotumumab on hospital day 3. She responded well to teprotumumab infusions every 3 weeks, with return of color vision and improvement of proptosis and periorbital edema (CAS 1/7). Discussion Activation of TED has so far only been described in four patients following SARS-CoV-2 vaccination. Here we report two more cases: one of TED deterioration in a GD patient with prior TED, and one of de novo TED progressing to dysthyroid optic neuropathy in a patient with a long history of Hashimoto's hypothyroidism. Possible etiologies include a maladaptive autoimmune/inflammatory syndrome from polyclonal B cell stimulation by adjuvants or activation of preexisting autoimmune disease. The possibility of new onset or deterioration of TED after SARS-CoV-2 vaccination in patients with underlying autoimmune thyroid disease and its mechanism should be further studied. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:18 p.m. - 1:23 p.m.

Outcomes of Transcutaneous Retrobulbar Amphotericin B in Rhino-Orbital-Cerebral Mucormycosis Among Patients Recovering From COVID-19: A Preliminary Experience.

BackgroundIn this study, we aimed to assess the outcomes of transcutaneous retrobulbar injection of amphotericin B (TRAMB) in rhino-orbital-cerebral mucormycosis (ROCM) among patients recovering from coronavirus disease 2019 (COVID-19).MethodologyThis retrospective study was conducted at a tertiary care center in eastern India from May 29th to July 31st, 2021, and included post-COVID-19 patients admitted with stage 3 and 4a ROCM who underwent TRAMB. The details of the ophthalmic examination, laboratory investigations, and radiological examination were retrieved from patients records. Patients were given TRAMB (3.5 mg/mL) on alternate days till they underwent debulking surgery and resumed from the second postoperative day alternatively till the patients showed clinical stabilization or improvement.ResultsIn total, 45 eyes of 41 patients were included in the study. The median number of injections given was six (minimum = 3; maximum = 10). Following was the distribution of number of injection needed in each eye: eight eyes (three injections), six eyes (four injections), seven eyes (five injections), three eyes (six injections), eight eyes (seven injections), 11 eyes (eight injections), and one eye had received nine and ten injections each. Overall, 21/32 (65.62%) eyes had improvement in proptosis whereas 9/32 (28.12%) had improvement in ptosis. Six patients had improvement in extraocular movement. In total, 25 eyes had no improvement whereas seven eyes had improvement in vision. Four eyes underwent exenteration. All nine patients with limited orbital disease had good improvement with fewer injections (median = 4). None of the patients undergoing TRAMB had an intracranial extension of disease. Moreover, 8.88% (4/45) of the eyes had post-TRAMB transient inflammation which resolved without any intervention. Finally, 3/41 of the patients died.ConclusionsTRAMB can be considered as an useful therapeutic adjunct in managing ROCM. Further, it can halt the progression of the disease while awaiting definitive surgical intervention.

Spheno-orbital meningiomas: Is orbit reconstruction mandatory? Long-term outcomes and exophthalmos improvement.

Background: Meningiomas correspond to one-third of all primary central nervous system tumors. Approximately 9% of them are spheno-orbital meningiomas (SOMs), presenting significant clinical symptoms as visual impairment and orbital esthetics. This article aims to evaluate exophthalmos’ improvement in a surgical series without orbital reconstruction.Methods: We consecutively included all patients diagnosed with SOM, admitted to a single institution for 10 years. Surgical resection was the standard of care, associated or not with adjuvant radiation therapy. The radiological investigation included preoperative and postoperative head CT or MRI. We quantified proptosis through imaging.Results: Forty patients composed this series, 87.5% were female. Proptosis was the most common presentation (90%), followed by decreased visual acuity (65%), motility deficit (20%), and headache (20%). Gross total resection was achieved in 65% of the procedures. In late outcomes, 78% of the patients maintained or improved visual acuity and 85% maintained or improved headache. Proptosis significantly improved after surgery and along with the follow-up (P < 0.001). Ten patients were submitted to adjuvant RT, six of them after a subtotal resection. All patients of this subgroup had proptosis. It was observed a higher frequency of worse in visual acuity in patients submitted to RT (71% vs. 28%, P = 0.038).Conclusion: Resection of SOM was sufficient to stop the evolution of visual deficit and allowed the improvement of proptosis. Orbital reconstruction does not seem to be an essential step in reducing enophthalmos.

Echographic Assessment of Extraocular Muscle Response to Teprotumumab.

To evaluate extraocular muscle response to teprotumumab using orbital echography in thyroid eye disease. This retrospective study included adult thyroid eye disease patients with pre- and post-teprotumumab orbital echography. Data collected included: age, Hertel measurements, clinical activity score, Gorman diplopia scores, ocular motility, and recti muscle diameters measured by echography. The patient's more proptotic eye before treatment initiation was designated as the study orbit. Ocular motility was assessed by totaling the ductions in all 4 cardinal directions. Orbital echography was obtained pre- and post-treatment to assess response of extraocular muscle diameters. Six patients with a mean age of 67 years were included. There was a mean improvement in proptosis of 4.3 mm in the study eye with 11/12 orbits showing improvement in globe position ( p < 0.05). All patients had a decrease in clinical activity score with a mean reduction of 2.5. Four patients had an improvement in Gorman diplopia score. Ocular motility in the study orbits improved by a total mean of 26.9° ( p < 0.05). Mean total extraocular muscle diameter was reduced from 27.4 to 23.4 mm ( p < 0.001). On average, superior recti were largest pre- and post-treatment, followed by inferior, medial, then lateral recti. However, inferior recti showed the greatest reduction of 23% ( p < 0.02). Orbital echography demonstrated extraocular muscle reduction in all patients after teprotumumab, correlating with improved clinical activity score, ocular motility, and proptosis. Orbital echography is a safe and cost-effective imaging alternative to monitor therapeutic response to teprotumumab.

Therapy With Different Dose Regimens of Rituximab in Patients With Active Moderate-To-Severe Graves' Orbitopathy.

BackgroundImmunosuppressive therapy of Graves’ orbitopathy (GO) is indicated during the active phase of disease. Intravenous steroids (IVGC) are effective in about 70% of patients, although unresponsiveness or relapse are observed. In previous studies, rituximab (RTX) has been shown to be effective in inactivating moderate-to-severe GO when used early in the disease, but its optimal dosage has never been studied in randomized clinical trials. Aim of this study was to compare the efficacy and safety of different doses of RTX, based on a post-hoc analysis of two open label studies and one prospective trial randomized to IVGC.Methodsof 40 patients (35 women, 5 men), with active moderate-to-severe GO treated with RTX, 14 received a single dose of 100 mg (Group 1), 15 a single dose of 500 mg (Group 2) and 11 two 1000 mg doses, administered one week apart (Group 3). Thyroid function, TSH-receptor antibodies (TRAb) and peripheral CD19+ cells were measured. Primary endpoint was disease inactivation, measured as a decrease of the Clinical Activity Score (CAS) of at least two points. Secondary endpoints were improvement of proptosis, diplopia, quality of life and safety.ResultsBaseline CAS decreased significantly in all groups (P<0.0001), independently of GO duration or whether patients had newly occurring or relapsing GO after IVGC. Proptosis did not significantly change. There was an inverse correlation between the Gorman score for diplopia and RTX dose (P<0.01). The appearance score of the GO-QoL improved in Group 1 (P=0.015), and the visual function score, in Group 2 (P=0.04). A reduction of serum TRAb was observed in Group 1 (P=0.002) and Group 2 (P<0.0002), but not in Group 3. CD19+ cell decreased in all groups (P<0.01), independently of the dose.ConclusionsWe studied the optimal dosage of RTX in the treatment of active moderate-to-severe GO. In this analysis, we considered the efficacy of RTX in inactivating GO, in changing its natural course, its effect on disease severity and on the patients’ quality of life. Based on our clinical findings, and balancing the cost of therapy, a single 500 mg dose regimen is suggested in the majority of patients.

To study the clinical course of rhino orbital mucormycosis in post COVID-19 patients: A case series

Rhino orbital cerebral mucormycosis is an opportunistic fungal infection with high morbidity and mortality which has seen the rise during the second wave of covid 19 in our country. Aim of our study was to study the clinical course, diagnosis and management of patient of rhino orbital mucormycosis in post covid phase presenting at our tertiary care centre. 4 cases of rhino-orbital mucormycosis who presented to us in post covid phase was followed and details recorded and analyzed to study its clinical course, diagnosis and management. 4 patients presented to us in post covid phase with signs of orbital cellulitis like periorbital swelling with pain, drooping of eyelids, proptosis, restriction of extraocular movements, decrease and loss of vision and sluggish reacting pupil. MRI/CT of the patients showed intraconal and extraconal involvement suggestive of orbital cellulitis. Diagnostic Nasal Endoscopy (DNE) was done and tissue sent for KOH mounting, culture and histopathology. After KOH mount showed fungal hyphae, patients were started on IV liposomal amphotericin B and retrobulbar amphotericin B. Patients were then taken up for endoscopic debridement and significant improvement in proptosis, ptosis, peribulbar swelling and pain was seen in immediate post op period. significant improvement was seen in patients with IV amphotericin B, retrobulbar amphotericin B and endoscopic debridement. Patients with rhino orbital mucormycosis can be managed with amphotericin and endoscopic debridement when exenteration is not possible.

Revision orbital decompression for thyroid eye disease

ObjectiveTo compare the indications, surgical techniques and outcomes for revision orbital decompression surgery for thyroid eye disease in open, endoscopic, and combined open and endoscopic approaches. MethodsA retrospective review of all revision orbital decompression procedures for thyroid eye disease from a single large academic institution over a 17-year period (01/01/2004–01/01/2021) was performed. Patient demographics, as well as indications and types of surgery were reviewed. Outcome measures included changes in proptosis, intraocular pressure, visual acuity and diplopia. ResultsThirty procedures were performed on 21 patients. There was a median of 9.4 months between primary orbital decompression and revision decompression surgery. There were 6 bilateral procedures, and 2 of these patients underwent additional revision surgeries due to decreased visual acuity with concern for persistent orbital apex compression or sight-threatening ocular surface exposure in the setting of proptosis. Twenty-five procedures were performed as open surgeries with 5 endoscopic/combined cases. Combined Ophthalmology/Otolaryngology surgery via combined open/endoscopic approaches was favoured for persistent orbital apex disease. Visual acuity remained preserved in all patients. The overall median reduction in proptosis was 2 mm and intraocular pressure change was 1 mmHg regardless of surgical approach. The overall rate of new onset diplopia after surgery was 15%. These patients had open approaches. All endoscopic/combined approach patients had pre-existing diplopia. There were no statistically significant differences between the open and endoscopic/combined groups in regard to change in visual acuity, reduction in proptosis or intraocular pressure. ConclusionRevision orbital decompression is an uncommon procedure indicated for those patients with progressive symptoms despite previous surgery and intensive medical management. Both endoscopic and non-endoscopic techniques offer favourable outcomes with respect to visual acuity, decrease in intraocular pressure, and improvement in proptosis and overall lead to a low incidence of new onset diplopia. Level of evidenceLevel IV.