Intoxication of antibiotic persisters by host RNS inactivates their efflux machinery during infection.

The host environment is of critical importance for antibiotic efficacy. By impacting bacterial machineries, stresses encountered by pathogens during infection promote the formation of phenotypic variants that are transiently insensitive to the action of antibiotics. It is assumed that these recalcitrant bacteria-termed persisters-contribute to antibiotic treatment failure and relapsing infections. Recently, we demonstrated that host reactive nitrogen species (RNS) transiently protect persisters against the action of ß-lactam antibiotics by delaying their regrowth within host cells. Here, we discovered that RNS intoxication of persisters also collaterally sensitizing them to fluoroquinolones during infection, explaining the higher efficiency of fluoroquinolones against intramacrophage Salmonella. By reducing bacterial respiration and the proton-motive force, RNS inactivate the AcrAB efflux machinery of persisters, facilitating the accumulation of fluoroquinolones intracellularly. Our work shows that target inactivity is not the sole reason for Salmonella persisters to withstand antibiotics during infection, with active efflux being a major contributor to survival. Thus, understanding how the host environment impacts persister physiology is critical to optimize antibiotics efficacy during infection.

Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multicenter Study.

PURPOSE: To assess the duration, incidence, reversibility, and severity of adverse events (AEs) in patients with thyroid eye disease (TED) treated with teprotumumab. DESIGN: Multicenter, retrospective, observational cohort study. PARTICIPANTS: Patients with TED of all stages and activity levels treated with at least 4 infusions of teprotumumab. METHODS: Patients were treated with teprotumumab between February 2020 and October 2022 at 6 tertiary centers. Adverse event metrics were recorded at each visit. MAIN OUTCOME MEASURES: The primary outcomes measure was AE incidence and onset. Secondary outcome measures included AE severity, AE reversibility, AE duration, proptosis response, clinical activity score (CAS) reduction, and Gorman diplopia score improvement. RESULTS: The study evaluated 131 patients. Proptosis improved by 2 mm or more in 77% of patients (101/131), with average proptosis improvement of 3.0 ± 2.1 mm and average CAS reduction of 3.2 points. Gorman diplopia score improved by at least 1 point for 50% of patients (36/72) with baseline diplopia. Adverse events occurred in 81.7% of patients (107/131). Patients experienced a median of 4 AEs. Most AEs were mild (74.0% [97/131]), 28.2% (37/131) were moderate, and 8.4% (11/131) were severe. Mean interval AE onset was 7.9 weeks after the first infusion. Mean resolved AE duration was 17.6 weeks. Forty-six percent of patients (60/131) demonstrated at least 1 persistent AE at last follow-up. Mean follow-up was 70.2 ± 38.5 weeks after the first infusion. The most common type of AEs was musculoskeletal (58.0% [76/131]), followed by gastrointestinal (38.2% [50/131]), skin (38.2% [50/131]), ear and labyrinth (30.5% [40/131]), nervous system (20.6% [27/131]), metabolic (15.3% [20/131]), and reproductive system (12.2% [16/131]). Sixteen patients (12.2%) discontinued therapy because of AEs, including hearing loss (n = 4), inflammatory bowel disease flare (n = 2), hyperglycemia (n = 1), muscle spasms (n = 1), and multiple AEs (n = 8). CONCLUSIONS: Adverse events are commonly reported while receiving teprotumumab treatment. Most are mild and reversible; however, serious AEs can occur and may warrant treatment cessation. Treating physicians should inform patients about AE risk, properly screen patients before treatment, monitor patients closely throughout therapy, and understand how to manage AEs should they develop. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Raine syndrome: Prenatally identified severe craniofacial phenotype with multisuture synostosis and brain abnormalities associated with variants in FAM20C.

Raine syndrome (MIM 259775) is a rare autosomal recessive disorder, first described by Raine et al. in 1989, with an estimated prevalence of <1/1,000,000. This is due to pathogenic variants in FAM20C characterized by osteosclerosis, typical craniofacial features, and brain calcifications. Here, we report a novel variant in FAM20C, describe a uniquely severe craniofacial and CNS phenotype of Raine syndrome, and correlate it with prenatal findings. Fetal phenotyping was based on ultrasound and MRI. Solo exome sequencing was performed from DNA extracted from postmortem skin biopsy. Targeted parental variant testing was subsequently performed. A homozygous missense variant NM_020223.4 (c.1445 G > A (p.Gly482Glu)) was identified in FAM20C associated with Raine syndrome. The infant had the characteristic dysmorphic features seen in Raine syndrome. He had particularly significant CNS manifestations consisting of multisuture craniosynostosis with protrusion of the brain parenchyma through fontanelles and cranial lacunae. Histological sections of the brain showed marked periventricular gliosis with regions of infarction, hemorrhage, and cavitation with global periventricular leukomalacia. Numerous dystrophic calcifications were diffusely present. Here, we demonstrate the identification of a novel variant in FAM20C in an infant with the characteristic features seen in Raine syndrome. The patient expands the characteristic phenotype of Raine syndrome to include a uniquely severe CNS phenotype, first identified on prenatal imaging.

Bridging and Validation of the Specific Graves Ophthalmopathy Quality of Life Questionnaire With Health State Utility Values.

OBJECTIVE: In thyroid eye disease (TED), inflammation and expansion of orbital muscle and periorbital fat result in diplopia and proptosis, severely impacting patient quality of life (QOL). The reported health state utility (HSU) scores, which are QOL measures, allow quantification of TED impact and improvement with therapies; however, no current QOL instrument has been validated with HSU scores for TED. Here, we used the disease-specific Graves Ophthalmopathy Quality of Life (GO-QOL) questionnaire and HSU scores to validate QOL impact. METHODS: The GO-QOL scores from patients in 2 randomized, masked, placebo-controlled teprotumumab trials (N=171) were compared with 6 HSU values based on severity of proptosis/diplopia in those studies. Patient GO-QOL and HSU scores were compared at baseline and after 6-month treatment via regression analyses. GO-QOL and HSU scores were correlated for validation and quantification of QOL impact by severity state and to estimate quality-adjusted life year improvement. RESULTS: GO-QOL scores were correlated with TED severity, indicating that worse severity was associated with lower (worse) GO-QOL scores. Less severe health states were represented by higher (better) GO-QOL scores. Importantly, GO-QOL scores were positively correlated with utility scores of the 6 health states, allowing for conversion of the GO-QOL scores to utility scores. A positive (improved) 0.013 utility change was found for each 1-point (positive) improvement in GO-QOL score produced by teprotumumab versus placebo. CONCLUSION: Patients with moderate-to-severe active TED health states demonstrate increasing TED severity associated with declining utility values and worsening GO-QOL scores. These results indicate that the GO-QOL scores can be used to bridge to the HSU scores for benefit quantification.

Comparison of surgical effect in active and inactive Dysthyroid Optic Neuropathy after Endoscopic Transnasal Medial Orbital Decompression.

PURPOSE: To evaluate and compare the changes in orbital soft tissue volume and visual function after endoscopic transnasal medial orbital decompression in patients with active and inactive dysthyroid optic neuropathy (DON). METHODS: This prospective, cohort study recruited 112 patients (112 eyes) with DON who were divided into an active and inactive DON group (56 eyes each) by clinical activity scores. All patients underwent endoscopic transnasal medial orbital decompression. The pre- and post-operative orbital soft tissue volumes were measured with high-resolution computed tomography (CT) using Mimics software. Visual function, including best-corrected visual acuity (BCVA), visual field (VF), and visual evoked potential (VEP), was recorded before and after surgery. RESULTS: Preoperatively, compared with the inactive DON group, the active DON group had greater extraocular muscle volume (EMV) and EMV/orbital volume (OV) ratio, but worse BCVA, VF, and exophthalmos. Postoperatively, although the EMV slightly increased, with the enlarged medial rectus muscle contributing dramatically, the EMV/OV ratio decreased in patients with DON. Besides, visual function including BCVA, VF, VEP and exophthalmos was also improved in both groups after surgery. There were no significant differences in postoperative OV; EMV; EMV/OV ratio; and the BCVA, VF, and VEP parameters between both groups (all P > 0.05). CONCLUSION: Patients with DON who did not respond well to steroids, regardless of disease activity, may benefit from orbital decompression via the decrease in the proportion of EMV in OV, especially patients with active DON, who showed more improved visual function than patients with inactive DON.

A case of bilateral amyloidosis localized to extraocular muscles mimicking thyroid eye disease.

BACKGROUND: Amyloidosis is a rare condition characterized by the abnormal deposition of amyloid proteins in various tissues and organs. While systemic amyloidosis has been well-documented, amyloid deposition in extraocular muscles is an exceptionally rare occurrence, with only 35 reported cases. This case report sheds light on the importance of considering amyloidosis in the differential diagnosis of patients presenting with proptosis and diplopia, which are often associated with thyroid eye disease. CASE PRESENTATION: A woman in her twenties sought medical attention due to a complaint of diplopia. Her ocular examination revealed almost normal findings except for exotropia and proptosis. Orbital magnetic resonance imaging displayed fusiform enlargement of nearly all eye muscles, a presentation typically observed in thyroid eye disease. However, despite corticosteroid therapy, her symptoms showed no improvement. Given the unusual lack of response to conventional treatment, and inhomogeneous enhancement of the muscle, an extraocular muscle biopsy was conducted. This biopsy yielded a unique finding-amyloid deposition within the muscle tissue. This discovery was particularly intriguing due to the extreme rarity of amyloidosis affecting extraocular muscles, with fewer than three dozen documented cases worldwide. CONCLUSION: This unique case underscores the critical need for a comprehensive approach to diagnosing patients with proptosis and diplopia. While these symptoms are commonly attributed to thyroid eye disease, it is essential to consider alternative diagnoses such as amyloidosis, especially when standard treatments fail to yield results. The discovery of amyloid deposition in the extraocular muscles, although exceedingly rare, emphasizes the significance of a thorough differential diagnosis. In conclusion, this case report highlights the importance of vigilance in clinical practice, encouraging ophthalmologists to explore less common diagnostic possibilities when faced with challenging cases. Further research and clinical investigation are warranted to better understand the mechanisms and potential treatments for amyloidosis affecting the extraocular muscles.

Objective Diplopia Outcomes for Patients Treated With Teprotumumab for Thyroid Eye Disease.

BACKGROUND: Thyroid eye disease (TED) is a condition caused by inflammatory damage to the periocular tissue that often leads to double vision. Teprotumumab is an insulin-like growth factor 1 receptor antibody that was FDA approved for the management of TED in 2020, although much is yet to be elucidated regarding its effects on diplopia outcomes among patients with TED. Diplopia is a significant and life-altering effect of TED. Previous studies have reported the effect of teprotumumab on double vision subjectively using the Gorman diplopia score. However, there is a gap in the literature addressing the effect of teprotumumab treatment on objective ocular alignment measures. The purpose of our study was to address this gap. METHODS: We performed a retrospective review of patients who were diagnosed with TED, presented with diplopia, and treated with teprotumumab in a single-center academic ophthalmology practice. The primary outcome was change in ocular alignment in primary gaze position at 6 months (completion of teprotumumab treatment). Secondary outcomes included change in ocular alignment in other gaze positions, proptosis, eyelid position, and clinical activity score (CAS) at 6 months compared with baseline. To determine what factors may predict ocular alignment response to teprotumumab, we analyzed baseline characteristics among 3 groups, divided based on whether ocular alignment was worsened, stable, or improved at 6 months. RESULTS: Seventeen patients met inclusion criteria, 3 (18%) worsened, 10 (59%) were stable, and 4 (24%) improved. CAS ( P = 0.02) was significantly different among the groups and was higher in those who worsened and those who improved compared with those who remained stable. Right gaze horizontal prism deviation ( P = 0.01) and left gaze horizontal prism deviation ( P = 0.03) were significantly different among the groups, with a greater degree of left gaze horizontal prism deviation in the worse group than the stable group ( P = 0.04). CONCLUSIONS: Our study demonstrated that most patients remained stable after teprotumumab treatment regarding ocular alignment in primary gaze and the number of patients who improved was slightly higher than the number of patients who worsened after teprotumumab treatment. There are some baseline measures, such as CAS and right and left gaze horizontal prism deviation that can help better predict how a patient will respond to teprotumumab treatment. Our results can better inform physicians of how to counsel patients with TED when considering teprotumumab therapy.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Predictive factors of the postoperative proptosis recovery in surgery of spheno-orbital meningiomas.

OBJECTIVE: This study aimed to identify factors affecting proptosis recovery in spheno-orbital meningioma (SOM) surgery and assess functional and oncological outcomes. METHODS: Data from 32 consecutive SOM surgery cases (2002-2021) were analyzed. Clinical, radiological, operative, and oncological parameters were examined. Proptosis was assessed using the exophthalmos index (EI) on MRI or CT scans. Statistical analyses were performed to identify predictive factors for proptosis recovery. RESULTS: Proptosis improved in 75% of patients post-surgery (EI decreased from 1.28 ± 0.16 to 1.20 ± 0.13, p = 0.048). Patients with stable or worsened EI had higher body mass index (28.5 ± 7.9 vs. 24.1 ± 4.7, p = 0.18), Simpson grade (IV 75% vs. 65%, p = 0.24), and middle sphenoid wing epicenter involvement (63% vs. 38%, p = 0.12), but no significant factors were associated with unfavorable exophthalmos outcomes. The improvement group had higher en plaque morphology, infratemporal fossa invasion, and radiation treatment for cavernous sinus residual tumor (88% vs. 75%, p = 0.25; 51% vs. 25%, p = 0.42; 41% vs. 25%, p = 0.42, respectively), but without statistical significance. Visual acuity remained stable in 78%, improved in 13%, and worsened in 9% during follow-up. Surgery had a positive impact on preoperative oculomotor nerve dysfunction in 3 of 4 patients (75%). Postoperative oculomotor nerve dysfunction was observed in 25%, of which 75% fully recovered. This occurrence was significantly associated with irradiation of an orbital tumor residue (p = 0.04). New postoperative trigeminal hypoesthesia was observed in 47%, of which 73% recovered. All SOMs were classified as WHO grade 1, and complementary treatments achieved oncological control, requiring gamma-knife radiosurgery in 53% and standard radiotherapy in 6%. CONCLUSIONS: Surgery effectively improves proptosis in SOM, though complete resolution is rare. The absence of predictive factors suggests multifactorial causes, including body mass index and tumor resection grade. Postoperative oculomotor nerve dysfunction and trigeminal hypoesthesia are common but often recover. Gamma-knife radiosurgery maintains long-term oncological control for evolving tumor residue.

Proptosis Regression After Teprotumumab Treatment for Thyroid Eye Disease.

PURPOSE: This study analyzed the degree and timing of proptosis regression after teprotumumab therapy. METHODS: A retrospective study of all patients who completed 8 teprotumumab infusions at 1 institution from January 1, 2020 to December 31, 2022. Change in proptosis was assessed in millimeters and percentages compared with immediate post-treatment and pretreatment proptosis. RESULTS: Of 119 patients with post-treatment data (mean follow-up 10.56 months, range: 3.05-25.08), 208 (87.39%) eyes of 110 patients had initial proptosis improvement. Of the 78 patients with multiple follow-up visits, 102 (65.38%) eyes of 59 patients had proptosis regression averaging 12.78% (range: 1.85-58.82%) compared with immediately post-treatment or 2.43 mm (0.5-10.0 mm). Eight (7.84%) eyes had initial documentation of regression more than 1 year after treatment, 40 (39.22%) between 6 months and 1 year, and 54 (52.94%) eyes within 6 months with 25 (46.30%) of these continuing to worsen at subsequent follow-up. Forty (25.64%) eyes of 24 patients had more proptosis at most recent follow-up than before teprotumumab, with an average regression of 1.53 mm (0.5-4.0 mm) or 7.74% (1.85-20.69%) of pretreatment proptosis. In comparison, 99 (63.46%) eyes of 54 patients maintained improvement, with reduction averaging 3.13 mm (0.5-11.0 mm) or 13.19% (1.92-41.67%) of pretreatment proptosis ( p < 0.001). CONCLUSIONS: Two-thirds of eyes had regression despite initial teprotumumab response, typically within 1 year of treatment, with ongoing worsening over time. Most patients maintained some proptosis reduction compared with before treatment despite regression, although 25% were worse than pretreatment. The occurrence of regression was independent of the pretreatment duration of clinical thyroid eye disease. Overall, compared with preteprotumumab, there was a greater amount of improvement than regression at most recent follow-up.

A Rapidly Expanding Hemorrhagic BRAF-Mutant Orbital Atypical Glomus Tumor.

A healthy 32-year-old woman presented with the acute onset of left sided eye pain, upper eyelid fullness, and binocular diplopia during light weightlifting. Examination elevated intraocular pressure, proptosis, upper eyelid ptosis, and motility deficits. CT demonstrated a well-circumscribed, homogeneous-appearing extraconal mass in the superior left orbit. The patient underwent an urgent orbitotomy with the excision of a hemorrhagic mass. Histopathology showed a glomus tumor with atypical features and hemorrhagic infarction, best classified as having uncertain malignant potential. A B-Raf proto-oncogene V600E mutation was detected with immunohistochemistry, which suggests a more aggressive tumor behavior yet presents an opportunity for targeted primary or adjunctive therapy. This is the first reported case of a B-Raf proto-oncogene-mutant atypical glomus tumor arising in the orbit.

Orbital Liposarcoma Progression From a Well-Differentiated to a Dedifferentiated Type in a Young Patient.

A young male patient presented with unilateral proptosis of the left eye. Laboratory tests and an initial computed tomography scan of the orbit were compatible with euthyroid orbitopathy. He subsequently underwent decompression surgery for unfavorable cosmesis and corneal exposure symptoms with good results, but returned 1 year later for recurrence of proptosis. There was a superomedial fatty density extraconal mass on computed tomography scan. A biopsy done a year later confirmed the diagnosis of well-differentiated liposarcoma from the previously noted mass and a dedifferentiated component in the newly appeared mass in the intraconal space. Orbital exenteration with radial forearm free flap was performed followed by orbital radiotherapy. No disease recurrence or metastasis was seen on follow-ups for 7 years since undergoing treatment.

Superior Ophthalmic Vein Thrombosis Associated With Asymptomatic COVID-19 Infection.

Superior ophthalmic vein thrombosis is a rare condition scarcely described in clinical literature with potentially severe consequences including permanent vision loss. This report details the case of a 70-year-old woman who presented with acute binocular horizontal diplopia, relative proptosis of the OD by 4 mm, and pain OD. On exam, visual acuity was 20/20 OD and 20/30 OS with full extraocular movements. CT revealed proptosis OD with a thrombosed superior ophthalmic varix. Evaluation for etiology of hypercoagulability was unremarkable, although the patient did have an asymptomatic COVID-19 infection 1 month prior. To the authors' knowledge, this is the first reported case of superior ophthalmic vein thrombosis secondary to an asymptomatic COVID-19 infection.

Hybrid Schwannoma-Perineurioma of the Orbit.

A 52-year-old woman presented with a 6-month history of progressive right proptosis associated with intermittent right retrobulbar and facial pain. MRI revealed a heterogeneously enhancing, well-circumscribed, ovoid, soft tissue mass in the intraconal space near the right orbital apex displacing the optic nerve medially. Excisional biopsy established the diagnosis of a schwannoma-perineurioma hybrid peripheral nerve sheath tumor (HPNST). This case represents only the second reported occurrence, to our knowledge, of an orbital schwannoma-perineurioma HPNST.

Successful Case of Teprotumumab Treatment in an Adolescent Patient With Thyroid Eye Disease.

A 16-year-old black female presented with a 4-month history of significant proptosis and diplopia in the setting of diagnosed Graves disease. The patient underwent 8 infusions of teprotumumab. She had migraines and diplopia that were resolved with treatment. There was also a dramatic improvement in her proptosis. The authors present the first reported case of successful teprotumumab treatment in an adolescent patient, describing outcomes and proposing a mechanism for her transient side effects.

Current Therapeutic Approaches for Graves' Orbitopathy - are Targeted Therapies the Future? / Aktuelle Therapieansätze der endokrinen Orbitopathie ­ sind die zielgerichteten Therapien die Zukunft?

Graves' orbitopathy is an autoimmune disease of the orbit that most frequently occurs with Graves' hyperthyroidism. The occurrence of autoantibodies directed against the TSH receptor (TRAb) is of central importance for the diagnosis and pathogenesis. These autoantibodies are mostly stimulating, and induce uncontrolled hyperthyroidism and tissue remodelling in the orbit and more or less pronounced inflammation. Consequently, patients suffer to a variable extent from periocular swelling, exophthalmos, and fibrosis of the eye muscles and thus restrictive motility impairment with double vision. In recent decades, therapeutic approaches have mainly comprised immunosuppressive treatments and antithyroid drug therapy for hyperthyroidism to inhibit thyroid hormone production. With the recognition that TRAb also activates an important growth factor receptor, IGF1R (insulin-like growth factor 1 receptor), biological agents have been developed. Teprotumumab (an inhibitory IGF1R antibody) has already been approved in the USA and the therapeutic effects are enormous, especially with regard to the reduction of exophthalmos. Side effects are to be considered, especially hyperglycaemia and hearing loss. It is not yet clear whether the autoimmune reaction (development of the TRAb/attraction of immunocompetent cells) is also influenced by anti-IGF1R inhibiting agents. Recurrences after therapy show that the inhibition of antibody development must be included in the therapeutic concept, especially in severe cases.

Extraocular muscle enlargement and proptosis in carotid cavernous fistulas.

PURPOSE: To evaluate the prevalence and pattern of extraocular muscle enlargement and proptosis in patients with carotid cavernous fistulas (CCF). METHODS: We conducted a retrospective study on patients with digital subtraction angiography (DSA) confirmed CCFs with neuroimaging (computed tomography or magnetic resonance imaging) performed prior to the DSA. The maximum extraocular muscle diameters were recorded. Extraocular muscles were considered enlarged if they were greater than two standard deviations above the normal muscle diameters. Proptosis was defined as the distance between the interzygomatic line to the anterior globe of ≥2 mm compared to the contralateral orbit or ≥21 mm. RESULTS: Forty orbits from 20 patients were included. The mean age of participants was 65 ± 15 years and 13 (65%) were female. Thirteen (65%) fistulas were indirect and seven (35%) were direct. There was enlargement of at least one muscle in 11 (27.5%) orbits, and this was not correlated with the type of fistula (direct/indirect). The inferior rectus was most commonly enlarged in seven orbits (17.5%), followed by the medial rectus in five orbits (12.5%). Proptosis was found in 17 (43%) orbits and was more common ipsilateral to the fistula (58% ipsilateral group vs 19% contralateral group, p < .01). CONCLUSION: Extraocular muscle enlargement was observed in over one-fourth of CCFs. When enlarged, the inferior and medial rectus muscles are most commonly involved. These findings may help clinicians and radiologists when evaluating the CT or MRI scans of patients with suspected CCFs.

A comparison of proptosis reduction with teprotumumab versus surgical decompression based on fat-to-muscle ratio in thyroid eye disease.

PURPOSE: To explore if orbital fat-to-muscle ratio (FMR) is predictive of whether surgical decompression or teprotumumab leads to greater proptosis reduction in thyroid eye disease (TED). METHODS: A single-center retrospective cohort study comparing surgical decompression with teprotumumab according to FMR. All TED patients completing an 8-dose course of teprotumumab between January 2020 and September 2022 and all patients undergoing bony orbital decompression from January 2017 to December 2019 were included. Subjects were excluded if they were <18 years, received both surgical decompression and teprotumumab, or lacked orbital imaging. The primary exposure variable was teprotumumab or surgical decompression. The secondary exposure variable was baseline FMR. The primary outcome measure was change in proptosis (mm). RESULTS: Thirty-eight patients, mean age 53.5 years (±11.4), were included in the teprotumumab group and 160 patients, mean age 48 years (±11.1), in the surgical group. Average proptosis reduction after teprotumumab and surgical decompression was 3 mm (±1.44) and 5 mm (±1.75), respectively. The FMR was stratified at the median of 1.80. In subjects with FMR < 1.80, teprotumumab showed equivalent proptosis reduction compared to surgical decompression, -0.33 mm (SE 1.32) p = .802. In subjects with FMR ≥ 1.80, surgical decompression led to significantly more proptosis reduction than teprotumumab, 3.01 mm (SE 0.54), p < .001. CONCLUSIONS: Baseline FMR can be used to counsel patients as to proptosis reduction with teprotumumab versus surgery. Subjects with low FMR obtain comparable proptosis reduction with teprotumumab or surgery, whereas high FMR is associated with more significant proptosis reduction following surgery over teprotumumab.

Orbital abscess with white eye in patients treated with oral antibiotics for orbital cellulitis.

PURPOSE: To report a case series of seven patients with late presentation of orbital/subperiosteal abscess following oral treatment of orbital cellulitis. METHODS: A retrospective case series of all patients presented with orbital abscess following oral treatment of orbital cellulitis from two tertiary-care eye centres in Riyadh, Saudi Arabia, was conducted. Demographic profiles, risk factors, initial clinical presentation, management regimens, and final outcome were analysed. RESULTS: Patients presented mainly with proptosis and limitation of extraocular motility without external ophthalmic inflammatory signs. Most patients needed surgical evacuation despite the appropriate initiation of intravenous antibiotics following presentation to our hospitals. CONCLUSION: Treating orbital cellulitis with oral antibiotics may lead to delayed presentation of orbital abscess without external ophthalmic inflammatory signs.

A meta-analysis of the efficacy of two-wall orbital decompression operations for thyroid-associated ophthalmopathy.

BACKGROUND: The main treatment for the symptoms of proptosis and optic nerve compression caused by thyroid-associated ophthalmopathy is orbital decompression surgery. Medial inferior wall decompression and balanced decompression are two frequently used surgical procedures. However, there is no unified consensus on how to choose different surgical options for orbital decompression in clinical practice. AIMS: To compare the effects of medial inferior wall decompression and balanced decompression surgery through meta-analysis and to provide reference for clinical optimal decision making. METHODS: Databases, including PubMed, Web of Science, Ovid, Cochrane Library, and ClinicalTrials.gov, were searched for randomized controlled trials and cohort studies on decompression surgery for thyroid-associated ophthalmopathy published from inception to March 21, 2023. Using RevMan 5.3 software, a meta-analysis was conducted based on the following outcome indicators: proptosis, diplopia rate, intraocular pressure, visual acuity, and complication rate. RESULTS: Two randomized controlled trials and five cohort studies with a total of 377 patients were included in this analysis. After balanced decompression surgery, patients with thyroid-associated ophthalmopathy experienced a significant decrease in proptosis [MD = 4.92, 95% CI (4.26, 5.58), P < 0.0001]. Balanced decompression can improve postoperative visual acuity [MD = - 0.35, 95% CI (- 0.56, - 0.13), P = 0.001] and intraocular pressure [MD = 5.33, 95% CI (3.34, 7.32), P < 0.0001]. The rates of proptosis [MD = 0.33, 95% CI (- 1.80, 2.46), P = 0.76] and diplopia [OR = 1.20, 95% CI (0.38, 3.76), P = 0.76] did not differ between patients who underwent medial inferior wall decompression and those who underwent balanced decompression. CONCLUSION: Balanced decompression and medial inferior wall decompression are both effective options for surgical treatment of thyroid-associated ophthalmopathy in clinical practice.