Cellular pattern and orbital fat involvement are possible risk factors for the failure of corticosteroids in patients with pure idiopathic orbital inflammation syndrome: lessons from the French prospective SIOI cohort study (part II).

PURPOSE: To better characterise the effects of corticosteroids on the course of pure idiopathic orbital inflammation syndrome (pIOIS). METHODS: This was a national, multicentre, prospective, non-interventional cohort study (SIOI). Among the 35 patients with histologically proven orbital inflammation who had previously been studied for their IgG4 immunostaining status, we selected those with a negative IgG4 status (ie, pIOIS) who received corticosteroids as single first-line treatment. Clinical, morphological and pathological findings at diagnosis and during follow-up from treatment initiation to study completion were analysed. Patients were assessed for their response to prednisone after the 24-month prospective phase in terms of remission (≤10 mg/d) or failure (>10 mg/d). Daily standard doses of prednisone (DSDP) were calculated at different time-points and compared between response groups. RESULTS: Of the 17 patients with pIOIS included in the final analysis, two-thirds received corticosteroids only. DSDP (mg/kg-day) were significantly higher at the time of failure in eight patients (47%) than in nine (53%) remitting at M24 (0.16 vs 0.045; p: 0.03). Notably, patients with pIOIS with a cellular pattern or orbital fat involvement tended to receive higher daily corticosteroid doses in the event of failure than remission (0.16 vs 0.045 and 0.12 vs 0.042, respectively). During treatment, maximal DSDP was 0.52 in failed patients. CONCLUSION: The highest corticosteroid doses were insufficient to prevent failure in patients with pIOIS, particularly in those with a cellular pattern or orbital fat involvement. Large-scale interventional studies are now necessary to clarify prognostic factors and optimise corticosteroid management in patients with pIOIS.

BOB-ACG study: Pulse methylprednisolone to prevent bilateral ophthalmologic damage in giant cell arteritis. A multicentre retrospective study with propensity score analysis.

INTRODUCTION: Giant cell arteritis (GCA) is complicated in 10 to 20% of cases by permanent visual ischemia (PVI). International guidelines advocate the use of intravenous pulse of methylprednisolone from 250 to 1000mg per day, for three days, followed by oral prednisone at 1mg/kg per day. The aim of this study is to assess whether this strategy significantly reduces the risk of early PVI of the second eye, compared with direct prednisone at 1mg/kg per day. METHODS: We conducted a multicentre retrospective observational study over the past 15 years in 13 French hospital centres. Inclusion criteria included: new case of GCA; strictly unilateral PVI, prednisone at dose greater than or equal to 0.9mg/kg per day; for the intravenous methylprednisolone (IV-MP) group, total dose between 900 and 5000mg, close follow-up and knowledge of visual status at 1 month of treatment, or earlier, in case of contralateral PVI. The groups were compared on demographic, clinical, biological, iconographic, and therapeutic parameters. Statistical analysis was optimised using propensity scores. RESULTS: One hundred and sixteen patients were included, 86 in the IV-MP group and 30 in the direct prednisone group. One patient in the direct prednisone group and 13 in the IV-MP group bilateralised, without significant difference between the two strategies (3.3% vs 15.1%). Investigation of the association between IV-MP patients and contralateral PVI through classical logistic regression, matching or stratification on propensity score did not show a significant association. Weighting on propensity score shows a significant association between IV-MP patients and contralateral PVI (OR=12.9 [3.4; 94.3]; P<0.001). Improvement in visual acuity of the initially affected eye was not significantly associated with IV-MP (visual acuity difference 0.02 vs -0.28 LogMar), even in the case of early management, i.e., within the first 48hours after the onset of PVI (n=61; visual acuity difference -0.11 vs 0.25 LogMar). Complications attributable to corticosteroid therapy in the first month were significantly more frequent in the IV-MP group (31.8 vs 10.7%; P<0.05). DISCUSSION: Our data do not support the routine use of pulse IV-MP for GCA complicated by unilateral PVI to avoid bilateral ophthalmologic damage. It might be safer to not give pulse IV-MP to selected patients with high risks of glucocorticoids pulse side effects. A prospective randomised multicentre study comparing pulse IV-MP and prednisone at 1mg/kg per day is desirable.

ANCA-associated scleritis: impact of ANCA on presentation, response to therapy and outcome.

OBJECTIVES: To describe the characteristics, treatment and outcome of isolated ANCA-associated scleritis at diagnosis compared with idiopathic scleritis with negative ANCA tests. METHODS: This retrospective multicentre case-control study was performed within the French Vasculitis Study Group (FVSG) network and in three French tertiary ophthalmologic centres. Data from patients with scleritis without any systemic manifestation and with positive ANCA results were compared with those of a control group of patients with idiopathic scleritis with negative ANCA tests. RESULTS: A total of 120 patients, including 38 patients with ANCA-associated scleritis and 82 control patients, diagnosed between January 2007 and April 2022 were included. The median follow-up was 28 months (IQR 10-60). The median age at diagnosis was 48 years (IQR 33-60) and 75% were females. Scleromalacia was more frequent in ANCA-positive patients (P = 0.027) and 54% had associated ophthalmologic manifestations, without significant differences. ANCA-associated scleritis more frequently required systemic medications, including glucocorticoids (76% vs 34%; P < 0.001), and rituximab (P = 0.03) and had a lower remission rate after the first- and second-line treatment. Systemic ANCA-associated vasculitis (AAV) occurred in 30.7% of patients with PR3- or MPO-ANCA, after a median interval of 30 months (IQR 16.3-44). Increased CRP >5 mg/l at diagnosis was the only significant risk factor of progression to systemic AAV [adjusted hazard ratio 5.85 (95% CI 1.10, 31.01), P = 0.038]. CONCLUSION: Isolated ANCA-associated scleritis is mostly anterior scleritis with a higher risk of scleromalacia than ANCA-negative idiopathic scleritis and is more often difficult to treat. One-third of patients with PR3- or MPO-ANCA scleritis progressed to systemic AAV.

Prognostic factors in giant cell arteritis associated aortitis with PET/CT and CT angiography at diagnosis.

BACKGROUND: Prognosis data on giant-cell arteritis (GCA)-associated aortitis are scarce and heterogeneous. The aim of this study was to compare the relapses of patients with GCA-associated aortitis according to the presence of aortitis on CT-angiography (CTA) and/or on FDG-PET/CT. METHODS: This multicenter study included GCA patients with aortitis at diagnosis; each case underwent both CTA and FDG-PET/CT at diagnosis. A centralized review of image was performed and identified patients with both CTA and FDG-PET/CT positive for aortitis (Ao-CTA+/PET+); patients with positive FDG-PET/CT but negative CTA for aortitis (Ao-CTA-/PET+), and patients solely positive on CTA. RESULTS: Eighty-two patients were included with 62 (77%) of female sex. Mean age was 67±8 years; 64 patients (78%) were in the Ao-CTA+/PET+ group; 17 (22%) in the Ao-CTA-/PET+ group and 1 had aortitis only on CTA. Overall, 51 (62%) patients had at least one relapse during follow-up: 45/64 (70%) in the Ao-CTA+/PET+ group and 5/17 (29%) in the Ao-CTA-/PET+ group (log rank, p = 0.019). In multivariate analysis, aortitis on CTA (Hazard Ratio 2.90, p = 0.03) was associated with an increased risk of relapse. CONCLUSION: Positivity of both CTA and FDG-PET/CT for GCA-related aortitis was associated with an increased risk of relapse. Aortic wall thickening on CTA was a risk factor of relapse compared with isolated aortic wall FDG uptake.

Atypical Case of MOG Antibody-Associated Optic Neuritis with Roth Spots.

PURPOSE: To report an atypical case of MOG antibody-associated optic neuritis with Roth spots and widespread retinal hemorrhages. CASE REPORT: A 49-year-old woman complained of 1 week history painful visual loss in the left eye. Funduscopy exam showed a severe optic disc edema associated with multiple peripapillar hemorrhages, peripheral retinal hemorrhages and Roth spots in the left eye. Orbit MRI revealed an hyperintensity in the left optic nerve, enhanced with gadolinium. The serum Myelin Oligodendrocyte (MOG) antibodies was found positive. Early intravenous high dose of steroids rapidly improved visual acuity and fundus abnormalities rapidly resolved. CONCLUSION: Retinal hemorrhages can also be detected in case of optic disc edema associated with an optic neuritis, as seen in MOGAD.

Treatment of nonarteritic anterior ischemic optic neuropathy with an endothelin antagonist: ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy)-a multicentre randomised controlled trial protocol.

BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAAION) is a major cause of blindness in individuals over 50 years of age, with no available effective treatment. The oral dual endothelin receptor antagonist, bosentan, increases retinal optic nerve head blood flow in healthy humans and glaucoma patients. The objective of this trial is to assess the efficacy of bosentan administered at the acute stage in improving outcomes in NAAION patients. METHODS: ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy) is a phase III, interventional, prospective, multicentre, placebo-controlled randomised double-blind clinical trial. The primary outcome is change in the visual field mean deviation (MD) at 3 months (Humphrey 30-2 SITA standard programme). Secondary outcomes include MD and visual acuity changes up to 24 months, changes in peripapillary retinal nerve fibre and macular ganglion cell layer thickness in the affected eye, as measured by optical coherence tomography, rate of NAAION bilateralisation at 2 years, and quality-of-life. Patients over 50 years of age presenting with typical NAAION of recent onset (less than 21 days) are randomly assigned to either 125 mg oral bosentan or placebo, twice a day, during 8 weeks. Besides visits during the treatment phase, patients attend follow-up visits at 2, 3, 6, 12 and 24 months. The inclusion of patients began in August 2015 at five French University hospital ophthalmology departments and two specialised ophthalmology centres. It is planned to include 86 patients in this trial. To date we have included 72 patients and 49 have completed the full follow-up process. DISCUSSION: An endothelin receptor antagonist is a potential approach to improving the anatomical and functional prognosis of patients with NAAION. This multicentre double-blind randomised controlled trial is an opportunity to assess (1) the effect of bosentan on the structure and function of the optic nerve in NAAION, at 3 months, (2) the effect of bosentan on the bilateralisation rate at 24 months and (3) the tolerance profile of bosentan in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02377271 . Registered on March 3, 2015.

Ocular Complications of Giant Cell Arteritis: An Acute Therapeutic Emergency.

The risk of blindness, due to acute ischemic ocular events, is the most feared complication of giant cell arteritis (GCA) since the middle of the 20th century. A decrease of its rate has occurred after the advent of corticoid therapy for this vasculitis, but it seems to have stabilized since then. Early diagnosis and treatment of GCA is key to reducing its ocular morbidity. However, it is not uncommon for ophthalmological manifestations to inaugurate the disease, and the biological inflammatory reaction may be mild, making its diagnosis more challenging. In recent years, vascular imaging has opened up new possibilities for the rapid diagnosis of GCA, and ultrasound has taken a central place in fast-track diagnostic processes. Corticosteroid therapy remains the cornerstone of treatment and must begin immediately in patients with visual symptoms and suspicion of GCA. In that situation, the administration route of corticotherapy, intravenous or oral, is less important than its speed of delivery, any hour of delay worsening the prognosis.

Hidden in the Eyes-Recurrence of Systemic Hemopathies Reportedly "In Remission": Six Cases and Review of Literature.

Background and Objectives: Secondary ocular localizations of hematological malignancies are blinding conditions with a poor prognosis, and often result in a delay in the diagnosis. Materials and Methods: We describe a series of rare cases of ocular involvement in six patients with hematological malignancies, reportedly in remission, who presented secondary ocular localizations, challenging to diagnose. Two patients had an acute lymphoblastic leukemia (ALL) and developed either a posterior scleritis or a pseudo-panuveitis with ciliary process infiltration. One patient had iris plasmacytoma and developed an anterior uveitis as a secondary presentation. Two patients had a current systemic diffuse large B-cell lymphoma (DLBCL) and were referred either for intermediate uveitis or for papilledema and vitritis with secondary retinitis. Finally, one patient with an acute myeloid leukemia (AML) presented a conjunctival localization of a myeloid sarcoma. We herein summarize the current knowledge of ophthalmologic manifestations of extramedullary hematopathies. Results: Inflammatory signs were associated with symptomatic infiltrative lesions well displayed in either the iris, the retina, the choroid, or the cavernous sinus, from the admission of the patients in the ophthalmological department. These findings suggest that patients with ALL, AML, systemic DLBCL, and myeloma can present with ophthalmic involvement, even after having been reported as in remission following an effective systemic treatment and/or allograft. Conclusions: Early detection of hidden recurrence in the eyes may permit effective treatment. Furthermore, oncologists and ophthalmologists should be aware of those rare ocular malignant locations when monitoring patient's progression after initial treatment, and close ophthalmologic examinations should be recommended when detecting patient's ocular symptoms after treatment.

Cytokines, chemokines and growth factors profile in human aqueous humor in idiopathic uveitis.

To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine profiles are associated with. Serum and aqueous humor (AH) samples of 75 patients with idiopathic uveitis were analyzed by multiplex immunoassay. Infectious controls consisted of 16 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. Noninfectious controls consisted of 7 patients with Behçet disease related uveitis and 15 patients with sarcoidosis related uveitis. The control group consisted of AH and serum samples from 47 noninflammatory control patients with age-related cataract. In each sample, 27 immune mediators ± IL-21 and IL-23 were measured. In idiopathic uveitis, 13 of the 29 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-12, G-CSF, GM-CSF, MCP-1, IP-10, TNF-α and VEGF, were significantly elevated in the aqueous humor when compared to all controls. Moreover, IL-17, IP-10, and IL-21, were significantly elevated in the serum when compared to all controls. We clustered 4 subgroups of idiopathic uveitis using a statistical analysis of hierarchical unsupervised classification, characterized by the order of magnitude of concentrations of intraocular cytokines. The pathogenesis of idiopathic uveitis is characterized by the presence of predominantly proinflammatory cytokines and chemokines and vascular endothelial growth factor with high expression levels as compared to other causes of uveitis. There are indications for obvious Th-1/ IL21-Th17 pathways but also IL9-Th9 and increased IFN-γ-inducing cytokine (IL12) and IFN-γ-inducible CXC chemokine (IP-10). The combined data suggest that immune mediator expression is different among idiopathic uveitis. This study suggests various clusters among the idiopathic uveitis group rather than one specific uveitis entity.

Review of the Current Literature and Our Experience on the Value of OCT-angiography in White Dot Syndromes.

PURPOSE: To describe the application of OCT-A in various posterior uveitis disorders in our experience and to compare it with the available literature. METHODS: Eighteen eyes with the diagnoses of multifocal choroiditis (MFC), multifocal placoid pigment epitheliopathy (APMPPE), multiple evanescent white dot syndrome (MEWDS), tuberculous serpiginous-like choroiditis (SLC), serpiginous choroiditis (SC), and birdshot chorioretinopathy (BSCR) were studied. RESULTS: We found flow void of the choriocapillaris in patients with APMPPE, SC, MFC, BSCR, and in SLC. In contrast, perfusion of the choriocapillaris seemed normal in patients with MEWDS. CONCLUSIONS: We confirmed that OCT-A contributes new information on the physiopathology of white dot syndromes and inflammatory chorioretinopathies, notably on whether or not the choriocapillaris is involved. Comparing the OCT-A features allowed us to suggest that both APMPPE and SLC might be part of the same spectrum of inflammatory disease with primary involvement at the level of the choriocapillaris and secondary RPE damage.