Orbital Inflammation Research Articles

Ophthalmic immune-related adverse events associated with immune checkpoint inhibitors.

To investigate the incidence of immune-related adverse events (irAEs) of immune checkpoint inhibitor (ICI) therapy and to report the clinical features, management, and outcomes of ophthalmic irAEs. We retrospectively reviewed the medical records of patients who received ICI therapy from January 2016 to September 2022 at Peking Union Medical College Hospital and analyzed the incidence of systemic and ophthalmic adverse effects of this therapy. Of 962 patients, 248 (25.8%) experienced irAEs. The first-year incidences of total irAEs and ophthalmic irAEs were 23.5% and 1.1%. The most common ICI received by the patients was pembrolizumab (373; 38.8%). Nearly half of the patients (477; 49.6%) had lung cancer. Combination therapy was associated with an increased incidence of irAEs without statistical significance. Patients with lung cancer presented with an increased incidence of total irAEs (p = 0.003) and ophthalmic irAEs (p = 0.032). Eleven patients had ophthalmic manifestations, including ophthalmoplegia (6/11), conjunctivitis (3/11), reactive cutaneous capillary endothelial proliferation (RCCEP) (1/11), and orbital inflammation (1/11). Eight patients had concomitant extra-ophthalmic irAEs. Furthermore, ICIs were discontinued in nine patients, and most ophthalmic manifestations were well controlled with topical and systemic steroids. Ten patients were treated with intravenous or oral steroids. However, cancer progression occurred in five out of eleven patients after the interruption of ICIs. IrAEs are correlated with ICI regimens and underlying neoplasia. In our Chinese cohort, patients have a higher risk of ophthalmoplegia than uveitis. Early recognition and multidisciplinary consultation are crucial for optimal treatment of ophthalmic irAEs.

MEDICAL MANAGEMENT OF OCULAR SARCOIDOSIS

Sarcoidosis is one of the leading causes of inflammatory eye disease. Ocular sarcoidosis can involve any part of the eye and its adnexal tissues, and may cause uveitis, episcleritis/scleritis, eyelid abnormalities, conjunctival granuloma, optic neuropathy, lacrimal gland enlargement and orbital inflammation. Glaucoma and cataract can be complications from inflammation itself or adverse effects from therapy. Ophthalmic manifestations can be isolated, or associated with other organ involvement. Patients with ocular sarcoidosis can present with a wide range of clinical presentations and severity. Multi-disciplinary approaches are required to achieve the best treatment outcomes for both ocular and systemic manifestations.

Rapamycin improves Graves' orbitopathy by suppressing CD4+ cytotoxic T lymphocytes.

CD4+ cytotoxic T lymphocytes (CTLs) were recently implicated in immune-mediated inflammation and fibrosis progression of Graves' orbitopathy (GO). However, little is known about therapeutic targeting CD4+ CTLs. Herein, we studied the effect of rapamycin, an approved mTORC1 inhibitor, in GO mouse model, in vitro and in refractory GO patients. In the adenovirus-induced model, rapamycin significantly decreased the incidence of orbitopathy. This was accompanied by reduction of CD4+ CTLs, and improvement of inflammation, adipogenesis and fibrosis in orbits. CD4+CTLs from active GO patients showed upregulation of mTOR pathway, while rapamycin decreased their proportions and cytotoxic function. Low-dose rapamycin treatment substantially improved diplopia and clinical activity score in steroid-refractory GO patients. Single-cell RNA sequencing revealed that eye motility improvement was closely related to suppression of inflammation and chemotaxis in CD4+ CTLs. In conclusion, rapamycin is a promising treatment for CD4+ CTL-mediated inflammation and fibrosis in GO.

Weak acid-initiated slow release of Dexamethasone from hydrogel to treat orbital inflammation.

Rationale: Orbital inflammation is a prevalent and prolonged ocular disease that poses a significant challenge to clinicians. Glucocorticoid Dexamethasone sodium phosphate (Dex) has demonstrated efficacy in the clinical treatment of nonspecific orbital inflammation. However, frequent administration is required due to the short half-life of Dex, which may lead to drug waste and adverse side effects. Methods: In this study, we co-assembled Dex with a weak acid responsive hydrogelator Py-Phe-Phe-Lys-Lys-OH (K) to obtain a novel supramolecular hydrogel Dex/K that could release Dex in a slow manner to treat orbital inflammation. The therapeutic effect of Gel Dex/K on orbital inflammation was verified by in vitro and in vivo experiments. Results: In vitro experiments indicated that co-assembly of Dex with K significantly increased mechanic strength of the hydrogel, enabling a continuous release of 40% of total Dex within 7 days. In vivo experiments further demonstrated that sustained release of Dex from Gel Dex/K could effectively alleviate the infiltration of inflammatory cells and the release of inflammatory factors in the orbit of mice, improving symptoms such as increased intraocular pressure and proptosis. Additionally, Gel Dex/K mitigated the degree of tissue fibrosis and fatty infiltration by reducing the development of local inflammation in the orbit. Conclusions: Our research results indicate that Gel Dex/K could more efficiently achieve responsive drug release in orbit, providing an innovative method for treating orbital inflammation.

Not all orbital inflammations in the COVID-19 era are due to mucormycosis – A case of orbital pseudotumour leading to vision loss

A 57-year-old male patient with type 2 diabetes mellitus who had survived severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19) presented with loss of vision in the right eye (RE) of 20-day duration. The patient had been diagnosed elsewhere with orbital mucormycosis and had been treated for it. The patient developed vision loss in RE 1 week after the initiation of treatment. At the time of presentation in our institute, vision in RE had reduced to no perception of light. Examination showed a relative afferent pupillary defect and pale optic disc in RE. Gadolinium-enhanced contrast magnetic resonance imaging of the brain, orbit and paranasal sinuses suggested perineuritic type of idiopathic orbital inflammation. In the present COVID-19 scenario, diagnosis other than mucormycosis should be kept in mind when dealing with cases of orbital inflammation.

Changes in retinal nerve fiber layer, ganglion cell complex, and ganglion cell layer thickness in thyroid eye disease: A systematic review.

Thyroid eye disease (TED) is characterized by progressive orbital inflammation. In severe cases, it can lead to dysthyroid optic neuropathy (DON), involving death of retinal ganglion cells and permanent vision loss. Imaging with optical coherence tomography (OCT) has enabled noninvasive examination of the structural impact of the disease, including of the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), and the inner plexiform layer (IPL). In this study, we systematically review 20 studies (897 patients, 1430 eyes) to evaluate changes in retinal thickness in patients with TED, stratified by severity. Most studies found a decrease in thickness in peripapillary RNFL (pRNFL), non-pRNFL, combined RNFL/GCL/IPL, or combined GCL/IPL when comparing patients with DON to healthy controls or to patients without DON. However, results were equivocal regarding differences between non-DON TED patients and controls. In addition, several studies reported a postoperative decrease in pRNFL thickness after orbital decompression surgery. Future studies examining OCT changes of retinal thickness along with disease progression are needed to assess the potential of OCT in diagnosis and management of patients with TED.

Orbital sarcoidosis. Case report

AbstractPurpose: Sarcoidosis is an autoimmune granulomatous disease that can affect any organ system in the body. Orbital manifestations are relatively uncommon. We present the clinical features and management in a case report with orbital sarcoidosis.Methods: This case report study a 51 year‐old female patient being investigated for headache, blurred vision and diplopia of 7 days onset. She had proptosis of the left eye, diplopia and complete ophthalmoparesis on supraversion and abduction and partial on adduction. The magnetic resonance showed probable orbital inflammation (inflammatory pseudotumor)/Tolosa Hunt syndrome with predominant involvement of the left superior rectus muscle, cavernous sinus, and pachymeninges. Chest X‐ray showed no pathological findings and laboratory tests, thyroid profile, serology, IgG subclasses, angiotensin converting enzyme and autoantibodies were negative. The computed tomography (CT) showed pulmonary lesions compatible with stage III sarcoidosis. After the results of the imaging tests, it was decided to start treatment with a bolus of methylprednisolone for 5 days and then oral prednisone was started with clear clinical and radiological improvement. The mediastinal lymph node biopsy could not be performed due to the decrease in its size.Results: The patient was treated with decreasing doses of corticosteroids until the disappearance of the orbital and pulmonary radiological symptoms. It has been followed for 2 years without recurrence.Conclusions: The presentation of sarcoidosis simulating a pseudotumor is uncommon. Despite this, we must take it into account in the differential diagnosis. In our case, the presentation of CT showing a pulmonary lesion compatible with sarcoidosis and the improvement with corticoid treatment made us reinforce the suspicion of a diagnosis of sarcoidosis. In any case, the definitive diagnosis of this pathology is biopsy and pathological analysis.

Acute Orbital Apex Syndrome Caused by Idiopathic Sclerosing Orbital Inflammation.

Idiopathic sclerosing orbital inflammation (ISOI) is a distinct entity among other orbital diseases. It is characterized by marked fibrosis and inflammatory cell infiltration that can damage orbital structures. Clinical manifestations were variable, including ocular and periocular redness, proptosis, and pain. Ocular motor restrictions and optic nerve dysfunction might occur in severe cases. We herein report a patient of ISOI who presented with total ophthalmoplegia and acute vision loss. His symptoms were relieved mainly as his vision improved to 20/25 after receiving corticosteroid and immunosuppressant therapies. Therefore, ISOI should be one of the deferential diagnoses when we encounter cases with acute orbital apex syndrome. With prompt evaluation and in-time treatment, a favorable outcome is possible.

Commentary: Dysthyroid optic neuropathy: A lurking danger in thyroid eye disease.

Poonam et al., in their retrospective study, highlighted male gender, hyperthyroidism, and smoking as risk factors of developing dysthyroid optic neuropathy (DON) over four years. They highlighted the potential of recurrence of DON in patients with diabetes.[1] DON is the most dreaded complication of thyroid eye disease (TED), warranting an urgent intervention. Fortunately, the occurrence of DON is noted only in 5%–7% of TED cases.[2] The diagnosis of established DON is majorly clinical, but the diagnosis of subclinical DON may need detailed ophthalmic examination and imaging. Patients with subclinical DON may not experience a sudden diminution of vision, abnormal pupillary reflexes, and features of orbital inflammation—classical of severe TED.[2] The risk factors for clinical and subclinical DON include older age, male gender, smoking, diabetes (controlled or uncontrolled), radioisotope therapy, hyperthyroidism or Grave’s ophthalmopathy, and high level of thyroid autoantibodies.[12] The pathogenesis of DON involves mechanical, inflammatory, and vascular factors causing damage to the nerve cells and axons of the optic nerve.[2] TED patients can be classified as type I (predominantly fat enlargement) or type II disease (predominantly extraocular muscle enlargement). In type II TED, the mechanical compression of optic nerve blood supply and axonal flow at the crowded orbital apex occurs due to enlarged extraocular muscles. The reduced arterial supply to the optic nerve and sluggish outflow of the blood from the superior ophthalmic vein comprises of major vascular insults contributing to the DON.[2] Moreover, these phenomena occurring at the orbital apex do not contribute much to clinical proptosis; hence many remain underdiagnosed. In ophthalmic examination, relative afferent pupillary defect (RAPD), blue-yellow (Tritan) color deficiency, and reduced contrast sensitivity in patients of TED are sensitive parameters for detecting DON. Clinical examination of the optic disc and optic disc imaging are important for the monitoring of DON.[2] Orbital magnetic resonance imaging with or without contrast may provide sufficient details about the extraocular muscles, orbital fat, optic nerve, orbital apex, superior ophthalmic vein, and other essential orbital structures. Apparent diffusion coefficient readings from magnetic resonance imaging (MRI) may provide the activity details in the extraocular muscles. Barrett’s muscle index of >60% is considered highly sensitive and specific for DON.[3] It is calculated on coronal computed tomography (CT) or MRI at a mid-point between the posterior globe and the orbital apex. Barrett’s index includes two indices, horizontal and vertical, and the larger of the two is taken as significant. Other parameters are extraocular muscle volume/orbital volume (MV/OV) and crowding index (CI) are considered reliable indicators of DON. The 3D MRI-based volumetric analysis showed the larger extraocular muscle volume as the most relevant factor in DON.[4] Optical coherence tomography angiography (OCTA) has been used to measure retinal nerve fiber layer thickness and peripapillary capillary vessel density (whole image and radial vessel density) as DON parameters. The patients with subclinical DON have shown significantly lower vessel densities as compared to normal individuals.[25] Intravenous steroids and orbital decompression surgery remain the mainstay of treatment in DON patients. The best outcomes for DON patients are provided by combined intravenous methylprednisolone and 3-wall orbital decompression, as vision is successfully preserved in most cases with a reduction in proptosis.[6] The advent of teprotumumab, a targeted insulin-like growth factor 1 (IGF-1) receptor-based therapy, is slowly establishing itself as “medical orbital decompression” therapy. It reduces the levels of thyroid stimulating hormone (TSH) receptors and IGF-1 receptors on fibroblasts and reduces the release of pro-inflammatory cytokines like interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-α) responsible for severe TED.[26] Hence, an ophthalmologist should be aware of the clinical features of subclinical DON and maintain a low threshold for aggressive treatment. For the holistic management of DON, a multidisciplinary team involving an ophthalmologist, endocrinologist, and otolaryngologist should be working in coordination to avoid blindness.

Ocular Side Effects of Bisphosphonates: A Review of Literature.

In rare cases, bisphosphonates are well established to cause ocular inflammation, presenting as uveitis, episcleritis, scleritis, orbital inflammation, and/or conjunctivitis. Some reports of bisphosphonate-associated neuro-ophthalmic complications also exist. We identified 101 reports in the literature relating to bisphosphonate-associated ocular complications. In a great majority of cases, symptoms resolve after discontinuation of the drug and anti-inflammatory treatment. Many cases recur if rechallenged with the same bisphosphonate. First-generation nonamino bisphosphonates, including clodronate and etidronate, are not associated with ocular inflammation. Only 2nd- and 3rd-generation amino bisphosphonates, including pamidronate, alendronate, risedronate, ibandronate, and zoledronate are associated with these complications. The mechanism of bisphosphonate-induced ocular inflammation may be related to activation of γ/δ T cells or M1 macrophages. Intravenous forms, such as pamidronate and zoledronate, tend to have higher rates and faster onset of ocular inflammation, generally presenting within days of infusion. In oral bisphosphonates, such as alendronate and risedronate, these complications present with more sporadic timing. Rates of complications are also higher when bisphosphonates are used for malignancy, as doses tend to be higher compared with doses for osteoporosis.

Novel Insights into Pathophysiology of Orbital Inflammatory Diseases and Progression to Orbital Lymphoma by Pathway Enrichment Analysis.

Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are currently treated with non-specific immunosuppressive agents based on non-randomized, uncontrolled studies. Therefore, relapses and prolongated courses are common and remain challenging. For a more specific therapy, a better understanding of the underlying pathophysiology is crucial. Therefore, we aimed to analyze signaling pathways to expand the knowledge on the pathophysiology and possibly identify specific targets in the future, as occurred recently in Graves’ orbitopathy with the IGF-1 receptor. Furthermore, we analyzed potential mechanisms for the described potential progression to orbital MALT (mucosa-associated lymphoid tissue) lymphoma. The investigation cohort for this screening study comprised of 12 patients with either typical NSOI (n = 6), IgG4-ROD or MALT lymphoma (n = 3 each). Mean age was 56.4 ± 17 years. MALT samples, in contrast with IgG4-ROD and NSOI, showed overall upregulation for extracellular matrix receptor interaction (ECM) and adipocytokine signaling. Investigating signaling compounds for MALT samples, differentially expressed genes were re-identified as targets with relevant expression. Even though pathway analysis showed differentially altered products when comparing IgG4-ROD with MALT, main conductors of differentiation in B- and T-cell signaling were commonly altered when observing the microenvironment of examined tissues. Our data reveal the characteristic differences and similarities in genetic-expression-based pathway profiles between MALT lymphoma, IgG4-ROD and NSOI, which may be useful for elucidating the associated pathogenic mechanisms and developing specific treatments for these orbital diseases.

MRI-Based Radiomics Nomogram for Preoperative Differentiation Between Ocular Adnexal Lymphoma and Idiopathic Orbital Inflammation.

Ocular adnexal lymphoma (OAL) and idiopathic orbital inflammation (IOI) are malignant and benign lesions for which radiotherapy and corticosteroids are indicated, but similar clinical manifestations make their differentiation difficult. To develop and validate an MRI-based radiomics nomogram for individual diagnosis of OAL vs. IOI. Retrospective. A total of 103 patients (46.6% female) with mean age of 56.4 ± 16.3 years having OAL (n=58) or IOI (n=45) were divided into an independent training (n=82) and a testing dataset (n=21). A 3-T, precontrast T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and postcontrast T1WI (T1 + C). Radiomics features were extracted and selected from segmented tumors and peritumoral regions in MRI before-and-after filtering. These features, alone or combined with clinical characteristics, were used to construct a radiomics or joint signature to differentiate OAL from IOI, respectively. A joint nomogram was built to show the impact of the radiomics signature and clinical characteristics on individual risk of developing OAL. Area under the curve (AUC) and accuracy (ACC) were used for performance evaluation. Mann-Whitney U and Chi-square tests were used to analyze continuous and categorical variables. Decision curve analysis, kappa statistics, DeLong and Hosmer-Lemeshow tests were also conducted. P < 0.05 was considered statistically significant. The joint signature achieved an AUC of 0.833 (95% confidence interval [CI]: 0.806-0.870), slightly better than the radiomics signature with an AUC of 0.806 (95% CI: 0.767-0.838) (P=0.778). The joint and radiomics signatures were comparable to experienced radiologists referencing to clinical characteristics (ACC=0.810 vs. 0.796-0.806, P > 0.05) or not (AUC=0.806 vs. 0.753-0.791, P > 0.05), respectively. The joint nomogram gained more net benefits than the radiomics nomogram, despite both showing good calibration and discriminatory efficiency (P > 0.05). The developed radiomics-based analysis might help to improve the diagnostic performance and reveal the association between radiomics features and individual risk of developing OAL. 3 TECHNICAL EFFICACY: 3.

Retrobulbar Injection of Amphotericin B in Patients With COVID-19 Associated Orbital Mucormycosis: A Systematic Review.

Purpose:Following COVID-19 infection a rising count of rhino-orbito-cerebral mucormycosis is observed, requiring orbital exenteration, a disabling lifetime affecting surgery. One of the potential interventions for globe salvage in these patients is retrobulbar injections of amphotericin B. This study was conducted to review protocols, outcomes, and side effects of retrobulbar injection of amphotericin B in patients with COVID-19 associated rhino-orbito-cerebral mucormycosis (CAM).Methods:The PubMed, Scopus, Web of Science, and Embase databases were searched using a comprehensive string of relevant keywords. All English studies with the confirmed diagnosis of CAM infection were included. We excluded all studies in which retrobulbar injection of amphotericin B was not implemented in any of the patients or there was a lack of clarified and detailed data about this procedure among participants.Results:A total of 647 cases had a history of retrobulbar injection(s) of amphotericin B in 13 reviewed studies with 3,132 subjects of CAM. The most common protocol was the retrobulbar injection of 1 ml of 3.5 mg/ml liposomal amphotericin B for 3 doses daily or on alternate days. We discerned that the globe salvage rate was 95.0% in eyes with a history of retrobulbar injection(s). The total rate of orbital exenteration was 14.9%, regardless of the history of retrobulbar injection of the drug. Other outcomes of this intervention were vision salvage and reduced major ophthalmic complaints, including pain, swelling, chemosis, ptosis, and ophthalmoplegia. The side effects of this intervention were not serious, and most of them were transient. They included swelling at the injection site, restriction of ocular motilities, exacerbation of orbital inflammation, and even intensification of visual impairment in a few cases.Conclusions:Retrobulbar injection of amphotericin B should be considered a nearly safe and protective intervention against orbital exenteration in patients with CAM. It may also be effective in saving vision. Since the effectiveness of orbital exenteration in the survival of patients is not ascertained, retrobulbar injections can be considered an alternative intervention.

Evaluation of Orbital Lymphoproliferative and Inflammatory Disorders by Gene Expression Analysis.

Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are often challenging to differentiate. Furthermore, it is still uncertain how chronic inflammation, such as IgG4-ROD, can lead to mucosa-associated lymphoid tissue (MALT) lymphoma. Therefore, we aimed to evaluate the diagnostic value of gene expression analysis to differentiate orbital autoimmune diseases and elucidate genetic overlaps. First, we established a database of NSOI, relapsing NSOI, IgG4-ROD and MALT lymphoma patients of our orbital center (2000–2019). In a consensus process, three typical patients of the above mentioned three groups (mean age 56.4 ± 17 years) at similar locations were selected. Afterwards, RNA was isolated using the RNeasy FFPE kit (Qiagen) from archived paraffin-embedded tissues. The RNA of these 12 patients were then subjected to gene expression analysis (NanoString nCounter®), including a total of 1364 target genes. The most significantly upregulated and downregulated genes were used for a machine learning algorithm to distinguish entities. This was possible with a high probability (p < 0.0001). Interestingly, gene expression patterns showed a characteristic overlap of lymphoma with IgG4-ROD and NSOI. In contrast, IgG4-ROD shared only altered expression of one gene regarding NSOI. To validate our potential biomarker genes, we isolated the RNA of a further 48 patients (24 NSOI, 11 IgG4-ROD, 13 lymphoma patients). Then, gene expression pattern analysis of the 35 identified target genes was performed using a custom-designed CodeSet to assess the prediction accuracy of the multi-parameter scoring algorithms. They showed high accuracy and good performance (AUC ROC: IgG4-ROD 0.81, MALT 0.82, NSOI 0.67). To conclude, genetic expression analysis has the potential for faster and more secure differentiation between NSOI and IgG4-ROD. MALT-lymphoma and IgG4-ROD showed more genetic similarities, which points towards progression to lymphoma.

Proteotranscriptomics of ocular adnexal B-cell lymphoma reveals an oncogenic role of alternative splicing and identifies a diagnostic marker

BackgroundOcular adnexal B-cell lymphoma (OABL) is a rare subtype of non-Hodgkin lymphoma. The molecular characteristics of OABL remain poorly understood. We performed an integrated study to investigate the proteotranscriptome landscape and identify novel molecular characteristics and biomarkers of OABL.MethodsIntegrated quantitative proteome and transcriptome were performed on 40 OABL 12 idiopathic orbital inflammation, 6 reactive lymphoid hyperplasia, and 13 aesthetic orbital plastic surgery specimens. Complete clinicopathologic and prognostic data of the patients were recorded.ResultsWe identified high global protein-mRNA concordance as a novel characteristic of OABL. High concordance was related to OABL recurrence. By integrated expression profile, motif enrichment and trend analysis, we found that alternative splicing is inflammation-independently dysregulated in OABL. After portraying the aberrant alternative splicing event landscape, we demonstrated the oncogenic role of ADAR, a core splicing regulator that regulates the splicing of Rho GTPase and cell cycle members. We found that ADAR regulates cell proliferation and Rho GTPase inhibitor sensitivity of lymphoma. We identified DNAJC9 as a potential biomarker for OABL in proteomic analyses. Immunohistochemistry and immunofluorescent staining showed the nuclear staining of DNAJC9 was significantly higher in extranodal marginal zone lymphomas compared with inflammation specimens.ConclusionsThese results provide an integrated gene expression profiling and demonstrate that high global protein-mRNA concordance is a prognosis-related molecular characteristic of OABL. We portray the alternative splicing events landscape of OABL, and reveal the oncogenic role of ADAR. We identified strong nuclear staining of DNAJC9 as a promising pathology diagnostic biomarker for extranodal marginal zone lymphomas.

Bilateral Orbital Inflammation Associated with COVID-19 Infection: A Case Report and Brief Review of the Literature

A 31-year-old woman with no history of systemic autoimmune disease developed bilateral pain, redness, periorbital edema, and proptosis while being hospitalized for mild coronavirus disease 2019 (COVID-19) pneumonia. The onset of ocular symptoms occurred six days after systemic COVID-19 symptoms. Computed tomography examination of the orbit revealed diffuse inflammation involving multiple orbital structures. A complete systemic workup was performed to exclude other systemic inflammatory diseases. She was initially diagnosed with probable orbital cellulitis secondary to sinusitis. However, she did not improve with antibiotic therapy. Empirical administration of systemic corticosteroids led to a dramatic clinical response. The patient has been maintained on a gradual steroid taper without inflammation relapse. This article describes a potential causal association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and orbital inflammation. Ophthalmologists should be aware of this presentation when assessing patients with COVID-19 who present with orbital inflammatory symptoms.

Orbital inflammatory syndrome after mechanical thrombectomy of acute carotid occlusion

Introduction: Orbital ischemic syndrome (OIS) is a rare disorder that presents with acute loss of visual acuity, chemosis, proptosis, ptosis and ophtalmoparesis. We present a case with acute onset of orbital inflammation following mechanical thrombectomy that mimicked an OIS, except for the absence of vision loss. Case report: A 65-year-old woman presented to our emergency department after an episode of transient dysarthria and left-sided hemiparesis and paresthesia that lasted about forty minutes. Head computed tomography showed no signs of intracranial bleeding or acute ischemia. CT angiogram showed occlusion of the right ICA terminus. Mechanical thrombectomy was then performed and the clot was removed with combined technique. Eight hours later, she developed orbital pain, ptosis, chemosis and complete ophthalmoplegia of the right eye. She had no diplopia, visual acuity and funduscopic examination were normal and there was no audible bruit in the orbit. Brain MRI performed showed hyperintensity of orbital fat along with hyperintensity and enlargement of all the extraocular There were no signs of orbital infarction and the optic nerve was structurally normal. Time of flight magnetic resonance angiography revealed reduced calibre of the distal portion of ICA, with associated contrast enhancement on vessel wall imaging. She was started on intravenous dexamethasone with full recovery two days later. Discussion: We present the case of an orbital inflammatory syndrome after mechanical thrombectomy. The mechanical stress exerted by endovascular devices has been associated with endothelial damage that correlates with vessel wall thickening and contrast enhancement in high resolution MRI studies. The temporal correlation with mechanical thrombectomy, the absence of vision loss or orbital infarction and the good clinical response to steroids support the hypothesis of an internal carotid artery wall inflammation due to endovascular manipulation of the stent retriever to be responsible for this acute orbital syndrome. This case highlights the need for close postprocedural monitoring after MT and the consideration of orbital inflammation secondary to endovascular devices in the differential diagnosis of an acute orbital syndrome. Further studies are needed to understand the long-term consequences of arterial wall lesions associated with these devices.

Influence of Clinically Active Graves' Ophthalmopathy on Spherical Equivalent and Visual Acuity.

PurposeClinical experience regarding the fluctuations of the refractive error of the eye during the different stages of Graves’ ophthalmopathy observed through outpatient clinic frequent check-ups points towards an underestimated and often overlooked problem. Published data about it are sparse. The clinical manifestations of Graves’ ophthalmopathy can be understood from the perspective of “compartment syndrome” and literature implies how such changes can affect the refractive error and consequently, the visual acuity. The purpose of the study was to explore how the clinical activity score of Graves’ ophthalmopathy affects refractive error and visual acuity.Patients and MethodsThe study was prospective and observational, including 60 eyes of 30 patients with clinically active Graves’ ophthalmopathy. All the patients were monitored and evaluated over a period of 36 months by the clinical activity score, spherical equivalent and visual acuity. All the observed parameters were statistically analyzed.ResultsThe mean values of spherical equivalent and visual acuity throughout the observed period showed continuous fluctuation. Repeated measure analysis of variance showed statistically significant differences in visual acuity and spherical equivalent over the observed period. There was a statistically significant positive correlation between visual acuity and clinical activity score. The correlation between spherical equivalent and clinical activity score was also positive but not statistically significant.ConclusionA decrease in the clinical activity score is either the result of a spontaneously resolving course of Graves’ ophthalmopathy or a consequence of treatment, so lowering in fluctuation of refractive error and improved visual acuity may be associated with a reduction in orbital inflammation.

Overview of Orbital Inflammation/Unmet Needs

Diseases of the orbit and periorbital eye tissues manifest in a wide variety of clinical presentations. Space occupying lesions in the orbit include infections, inflammations, vascular malformations, and malignancies. The significant variation in presentations is due to the complex anatomy of the orbit and the heterogeneous nature of the multiple disease processes that present themselves as orbital inflammatory processes. Additionally, although specific disease entities often show similar patterns of orbital tissue involvement, there is still a spectrum of clinical presentations within disease processes, which furthermore overlap with other inflammatory etiologies. This heterogeneity creates a significant challenge in determining specific diagnoses and subsequently instituting timely medical and surgical management of patients with orbital inflammation. Despite advances in imaging, physical examination, and laboratory tests, a biopsy is often needed for diagnosis and to guide treatment. Unfortunately, the biopsy is too often read as non-specific or idiopathic inflammation, a term that gives minimal guidance to the patient or to the clinician. There is clearly a need for developing more specific and sensitive clinical diagnostic testing.

Systemic inflammatory markers differentiate between orbital cellulitis and non-specific orbital inflammation

ABSTRACT Purpose Bacterial orbital cellulitis (OC) and diffuse non-specific orbital inflammation (DNSOI) may be challenging to differentiate clinically. This study investigates the utility of systemic inflammatory markers, namely white cell count (WCC) and C-reactive protein (CRP), in differentiating between OC and DNSOI. Methods A single-centre retrospective study of patients diagnosed with OC or DNSOI, between 2003 to 2021, who had WCC and/or CRP obtained at presentation. The mean levels of these factors and the proportion of positivity were compared between OC and DNSOI. A receiver operating characteristic (ROC) analysis was conducted to calculate the specificity and sensitivity of WCC or CRP in each group. Results 49 patients were included in this study. The mean age was 56 ± 20 years, and 21 patients were females. 26 (53.1%) patients had OC, and 23 (46.9%) patients had DNSOI. Mean WCC for OC and DNSOI were 14.5 × 103/μL and 9.27 × 103/μL, respectively (P = 0.001). Mean CRP for OC and DNSOI were 104.4 mg/L and 10.0 mg/L, respectively (P < 0.001). The optimal CRP cut-off value of 20.2 mg/L demonstrated 90.9% sensitivity and 90.5% specificity (AUC = 0.946, P < 0.001) for differentiating between OC and DNSOI. CRP was more predictive of OC than WCC (P = 0.017). 7/26 (26.9%) OC patients with fever also had an elevated CRP, while 1/23 (4.3%) of DNSOI with fever had a normal CRP. Conclusions An elevated WCC is suggestive of OC. However, a normal WCC can neither exclude nor differentiate between OC and DNSOI. CRP may be a more accurate predictor of OC compared to WCC.