Scleritis following intravitreal brolucizumab injection: a case series.

BACKGROUND: This study reports the first cases of scleritis following intravitreal brolucizumab (IVBr) injection for nAMD, emphasizing the need to be aware of the possibility of scleritis following IVBr injections. CASE PRESENTATION: Case 1. A 74-year-old Japanese man with nAMD complained of conjunctivitis and decreased vision in the right eye 8 days after his eighth IVBr injection. Examination revealed scleritis without anterior inflammation. Topical 0.1% betamethasone and 0.3% gatifloxacin eye drops were started. The scleritis worsened in the following 2 weeks and became painful. He underwent sub-Tenon's capsule triamcinolone acetonide (STTA) injection. Two days later, he returned with a complaint of severe vision loss. Fundus examination revealed retinal artery occlusion, vasculitis, and vitreous opacity in the right eye. Vitreous surgery was performed. CASE 2: An 85-year-old Japanese woman with nAMD in the right eye complained of reddening of the eye 27 days after her fifth IVBr injection. Examination showed conjunctivitis and scleritis without anterior inflammation in the right eye. She was started on 0.1% fluorometholone and 0.5% levofloxacin hydrate eye drops. The scleritis worsened in the following 3 weeks. Her treatment was switched to 0.1% betamethasone eye drops. One month later, the scleritis had improved and a sixth IVBr injection was administered. There was no worsening of the scleritis at that time. However, 1 month after a seventh IVBr injection, she complained of severe hyperemia and decreased vision. Fundus examination revealed vitreous opacification. She underwent STTA, and the vitreous opacity improved in 24 days. Case 3. A 57-year-old Japanese man with nAMD complained of pain and decreased vision in the right eye 21 days after a fourth IVBr injection. Examination revealed scleritis with high intraocular pressure but no anterior chamber or fundus inflammation. STTA and topical eye drops were performed. One month later, scleritis improved but visual acuity didn't due to progression of nAMD. CONCLUSIONS: Intraocular inflammation following IVBr injection may progress to the posterior segment. Scleritis can occur after IVBr injection, and topical eye drops alone may not be sufficient for initial treatment. Clinicians should consider the possibility of scleritis in patients with worsening inflammation after IVBr injection.

Efficacy, retention rate and safety of adalimumab treatment in patients with non-infectious uveitis and scleritis: a real-world, retrospective, single-centre study.

OBJECTIVES: To evaluate the outcomes of adalimumab (ADA) treatment of patients with non-infectious uveitis and scleritis, focusing on efficacy, retention rate, and safety. METHODS: This retrospective, clinical cohort study included 62 patients (104 eyes) with active ocular inflammation treated with ADA. Primary outcomes were efficacy and cumulative drug retention rate (DRR) of ADA. The secondary outcomes included changes in ocular inflammatory parameters, changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT), corticosteroid-sparing effect, impact of concomitant use of disease-modifying antirheumatic drug (DMARD) and ADA as first or ≥2nd biotherapy line on DRR, and adverse events. RESULTS: Forty-five patients (72.6%) achieved inactive disease at the end of follow-up. DRR at 6, 12, 24, and 48 months was 96.8%, 89.2%, 63.1%, and 63.1%, respectively. Of the 18 patients whose bi-weekly ADA treatment was escalated to weekly ADA due to primary or secondary inefficacy, 10 patients had inactive disease finally. BCVA improved (p < 0.001) and CMT decreased (p < 0.001) significantly at 6, 12, and 24 months after ADA therapy compared to baseline. Percentage of patients treated with ≥10 mg/day corticosteroid (61.3% vs. 6.4%) and DMARDs combined with ADA (46.8% vs. 37.1%) were lower at 6 months than at baseline. Concomitant DMARDs (p = 0.579) and use of ADA as first or ≥2nd biotherapy line (p = 0.527) had no significant effect on DRR. Most common adverse event was tuberculosis-related infections. CONCLUSIONS: ADA seems to be effective and safe with good DRR to control ocular inflammation. Escalation to weekly ADA treatment may be an effective option in patients with primary or secondary inefficacy.

Etanercept-associated episcleritis: a pediatric case report of a paradoxical adverse reaction and review of the literature.

Scleritis is an inflammation of the episcleral and scleral tissues, characterized by injection in both superficial and deep episcleral vessels. When only episcleral tissue is involved, it is referred to as episcleritis. Episcleritis is mainly idiopathic but may be secondary to an underlying rheumatologic disease. Despite being rare, drug-associated episcleritis and scleritis should also be included in the differential diagnosis. Tumor necrosis factor-alpha (TNF-α) inhibitors are generally well-tolerated, but etanercept, in particular, has the potential to cause paradoxical adverse reactions including ocular inflammations, such as uveitis, scleritis, and ocular myositis. Etanercept differs in its mechanism of action from other TNF-α inhibitors as it acts as a decoy receptor, and this may partly explain the more frequently reported etanercept-associated ocular inflammation. Etanercept may also be ineffective in preventing ocular inflammation. However, the dechallenge and rechallenge phenomena have proven there is a causative link between etanercept and new-onset ocular inflammation. We report a case of a 15-year-old boy with enthesitis-related arthritis and familial Mediterranean fever who presented with episcleritis and blepharitis while receiving etanercept treatment and subsequently showed dechallenge and rechallenge reactions. Therefore, physicians should also be aware that episcleritis should be considered a paradoxical adverse reaction to etanercept and can occur in pediatric patients. We also reviewed the English literature to provide an overview and evaluate intervention options.

Recurrent Anterior Non-necrotizing Scleritis as an Adverse Event of ChAdOx1 nCoV-19 (Vaxzevria) Vaccine.

PURPOSE: To describe a case of anterior scleritis related to SARS-CoV-2 vaccine. SARS-CoV-2 vaccines appear safe; however vaccination has triggered thromboembolic events in predisposed patients. METHODS: A retrospective case report of anterior scleritis in a woman following administration of both ChAdOx1nCoV-19 vaccine doses was studied by complete ophthalmologic examination and complementary tests. RESULTS: The patient has overcome SARS-CoV-2 infection a year prior. Ancillary tests including autoimmune and infectious diseases were negative. The chronology between ChAdOx1nCoV-19 vaccine and the sequential episodes of scleritis may have a cause-and-effect relationship. CONCLUSION: Ophthalmologists may be aware of scleritis as an ocular manifestation following ChAdOx1nCoV-19 vaccine, in otherwise healthy patients.

Adalimumab-associated Acquired Hemophilia in a Patient with Scleritis.

Acquired hemophilia A (AHA) is a rare condition that may be drug-induced. In this case report, we describe a patient who presented with extensive subcutaneous bleeding three years after beginning treatment with adalimumab for necrotizing scleritis. His workup was compatible with drug-induced AHA. He was treated with high-dose corticosteroids, cyclophosphamide, and rituximab. Adalimumab was discontinued. We present this case as an example of a rare, but potentially life-threatening, complication of adalimumab.

Effectiveness of Difluprednate for the Treatment of Anterior Scleritis.

PURPOSE: To describe the effectiveness and side effect profile of difluprednate therapy in a series of patients with anterior scleritis. DESIGN: Retrospective, interventional case series. METHODS: Data collected from all patients with anterior scleritis who used difluprednate as a single treatment agent from January 1, 2018, to January 1, 2020, including demographics, scleritis type, presence of nodules or necrosis, changes in scleritis activity, intraocular pressure (IOP), number of difluprednate drops used, best-corrected visual acuity (BCVA), and lens status. The primary outcome was clinical resolution of scleritis. Secondary outcomes included BCVA loss ≥2 lines, change in lens status or cataract surgery, and IOP ≥24 mm Hg. RESULTS: Twenty-five patients (35 eyes) were analyzed. The median age was 60 years (range 13-78); 60% were female; 64% were White. Forty percent had bilateral disease, and 44% of patients had an associated systemic disease. The majority of eyes (66%) had diffuse anterior scleritis. Eighty-three percent of eyes achieved resolution of scleritis, with a median time of resolution of 6 weeks. Eyes treated with an initial dose of ≥4 times daily were more likely to achieve disease resolution (hazard ratio [HR] = 3.43, 95% confidence interval [CI] 1.19, 9.88, P = .02). Nine eyes had IOP elevation. Four eyes lost ≥2 lines of BCVA, and 1 due to cataract progression. One eye underwent cataract surgery. CONCLUSIONS: Difluprednate alone may effectively treat non-infectious anterior scleritis with a tolerable side effect profile.

Association of Ocular Adverse Events With Inactivated COVID-19 Vaccination in Patients in Abu Dhabi.

Importance: As vaccinations against COVID-19 continue, potential ocular adverse events should be reported in detail to increase awareness among the medical community, although typically, a causal relationship cannot be established definitively. Objective: To describe ocular adverse events that occur soon after receiving an inactivated COVID-19 vaccination (Sinopharm). Design, Setting, and Participants: This case series took place from September 2020 to January 2021 at Cleveland Clinic Abu Dhabi, a tertiary referral center. Patients who reported ocular adverse events and presented within 15 days from the first of 2 doses of an inactivated COVID-19 vaccine were analyzed. Main Outcomes and Measures: Each patient underwent Snellen best-corrected visual acuity that was then converted to logMAR, applanation tonometry, and biomicroscopic examination with indirect ophthalmoscopy. Color fundus photography was obtained with a conventional 9-field fundus photography camera or with a widefield fundus photography system. Optical coherence tomography and optical coherence tomographic angiography images were obtained. Sex, race, age, and clinical data were self-reported. Results: Nine eyes of 7 patients (3 male individuals) presenting with ocular complaints following COVID-19 vaccine were included in the study. The mean (SD) age was 41.4 (9.3) years (range, 30-55 years); the mean best-corrected visual acuity was 0.23 logMAR (range, 0-1 logMAR; approximate Snellen equivalent, 20/32). The mean time of ocular adverse event manifestations was 5.2 days (range, 1-10 days). One patient was diagnosed with episcleritis, 2 with anterior scleritis, 2 with acute macular neuroretinopathy, 1 with paracentral acute middle maculopathy, and 1 with subretinal fluid. Conclusions and Relevance: In this case series study of 7 patients, the timing of transient and ocular complications 5.2 days after vaccination with an inactivated COVID-19 vaccine supported an association with the ocular findings, but a causal relationship cannot be established from this study design.

Case Report: Subconjunctival Triamcinolone Acetate-associated Scleral Necrosis: Is It Really Obsolete?

SIGNIFICANCE: Recent studies have established the safety of subconjunctival steroids for anterior scleritis, refuting scleral necrosis as a potential complication. However, presently, we report a rare case of scleral necrosis associated with subconjunctival triamcinolone acetate. PURPOSE: The purpose of this study was to report a case of scleral necrosis after subconjunctival triamcinolone acetate administration for nonresponsive anterior nodular scleritis. CASE REPORT: A 45-year-old man diagnosed with nodular anterior scleritis was administered subconjunctival triamcinolone acetate (4 mg) adjacent to the nodule after noting nonresponse for 4 months. Worsening of congestion was noted 3 weeks after the injection. Slit-lamp examination revealed diffuse congestion, 10 clock hours of anterior scleral necrosis, superior whitish depot of subconjunctival triamcinolone acetate, anterior segment flare, and few posterior synechiae. Ultrasound biomicroscopic imaging and contrast-enhanced computerized tomography showed a localized outpouching of sclera and buckling of anterior scleral wall superiorly. The result of the comprehensive blood profile and systemic evaluation undertaken to rule out any underlying autoimmune disorders and herpes zoster ophthalmicus was found negative. A diagnosis of subconjunctival triamcinolone acetate-associated scleral necrosis was made, and the patient was managed conservatively. Gradual improvement with dissolution of subconjunctival triamcinolone acetate and no recurrences till 2 years of follow-up were noted. CONCLUSIONS: Scleral necrosis is a potential complication of subconjunctival triamcinolone acetate. Judicious and cautious use of subconjunctival triamcinolone acetate is advocated for nonresolving anterior scleritis.

Drug-induced ocular inflammation.

AIM: Drug-induced ocular inflammation is rare and may be overlooked as a cause of uveitis. The main objective was to describe the causes of drug-induced ocular inflammation. Secondary objectives included uveitis complications and drug rechallenge reactions. METHODS: A retrospective chart review at Auckland District Health Board's tertiary uveitis clinic (Auckland, New Zealand) was performed. Participants were identified using the uveitis database, which consists of 2,750 subjects. Fifty eyes of 35 subjects had drug-induced inflammation. RESULTS: Drug-induced inflammation occurred in 1.3% of subjects with uveitis. Mean age was 66.8±15.6 years, and 25 subjects (71.4%) were female. Drugs responsible were bisphosphonates (24 subjects, 68.6%), brimonidine (one subject, 2.9%), etanercept (three subjects, 8.6%), immune checkpoint inhibitors (two subjects, 5.7%), BRAF inhibitors (three subjects, 8.6%), EGFR inhibitors (one subject, 2.9%) and allopurinol/perindopril (one subject, 2.9%). In subjects with bisphosphonate inflammation, anterior uveitis occurred in 22 (91.7%) and scleritis in two (8.3%). A positive rechallenge reaction occurred in two subjects with zoledronate and one with alendronate. Uveitis occurred in six subjects (17.1%) treated with cancer drugs including immune checkpoint inhibitors, BRAF inhibitors and EGFR protein kinase inhibitors. Subjects with cancer-drug-induced uveitis were managed with corticosteroids and five subjects were able to continue therapy; in one subject uveitis was uncontrollable and required drug cessation. CONCLUSIONS: Ocular inflammation caused by bisphosphonates is usually mild and resolves on medication withdrawal. Uveitis seen in association with newer cancer medications can be more severe, but in most cases it can be managed without medication cessation.

New Potential Weapons for Refractory Scleritis in the Era of Targeted Therapy.

OBJECTIVE: To assess the efficacy of biologic drugs, beyond tumor necrosis factor- (TNF-) α inhibitors, in the management of noninfectious refractory scleritis, either idiopathic or associated with systemic immune-mediated disorders. Patients and Methods. This is a retrospective study assessing the efficacy of several biologic agents (rituximab, anakinra, tocilizumab, and abatacept) and the small molecule tofacitinib in the treatment of scleritis through assessment of scleral inflammation and relapses, as well as treatment impact on best-corrected visual acuity (BCVA) and safety profile. RESULTS: Fourteen patients (19 eyes) were enrolled in the study. Scleritis inflammatory grading significantly improved from baseline to 3 months (p = 0.002) and from baseline to the last follow-up visit (p = 0.002). Scleritis relapses significantly decreased between the 12 months preceding and following biologic therapy (p = 0.007). No differences regarding BCVA were observed (p = 0.67). Regarding adverse events, only one patient developed pneumonia and septic shock under rituximab treatment. CONCLUSIONS: Our results, though limited to a low number of patients, highlight the effectiveness of different biologic therapies in the treatment of noninfectious refractory scleritis, showing to control scleral inflammation and allowing a significant reduction in the number of relapses.

Necrotizing Scleritis After Cosmetic Conjunctivectomy With Mitomycin C.

PURPOSE: To report cases of necrotizing scleritis, a sight-threatening complication that can result from cosmetic conjunctivectomy procedures. DESIGN: Retrospective case series. METHODS: The medical records of consecutive patients who underwent eye-whitening conjunctivectomy with mitoycin C (MMC) treatment performed by 1 surgeon in South Korea and were referred to the authors' clinic between January 2011 and December 2015 were reviewed. The patients in whom findings of necrotizing scleritis with active inflammation were detected in an avascular area of previous conjunctivectomy were included. RESULTS: Of a total of 231 patients who had received cosmetic eye whitening, 4 patients who met the inclusion criteria were identified. The average length of time from cosmetic eye surgery to a diagnosis of necrotizing scleritis was 51 months and all patients had unilateral findings of necrotizing scleritis. There was no underlying systemic autoimmunity or infectious etiology in all cases. Three of these 4 patients were treated with a conjunctival flap; however, all 4 received systemic anti-inflammatory treatment with oral corticosteroids. The mean follow-up duration of the patients was 22.75 months. CONCLUSIONS: Necrotizing scleritis is a severe complication that can arise after cosmetic eye-whitening conjunctivectomy with MMC. Because of the large area of the ocular surface that is treated in eye-whitening with MMC, the necrotizing scleritis that can ensue may be more extensive and severe than the surgically induced necrotizing scleritis following other periocular surgeries such as pterygium removal. Proper anti-inflammatory treatment and surgical intervention should be required for management of this complication.

Ocular complications of inflammatory bowel disease.

Though inflammatory bowel disease (IBD) has a specific predilection for the intestinal tract, it is a systemic inflammatory disorder affecting multiple organs, including the eye. Ocular complications directly related to IBD are categorized as primary and secondary. Primary complications are usually temporally associated with IBD exacerbations and tend to resolve with systemic treatment of the intestinal inflammation. These include keratopathy, episcleritis, and scleritis. Secondary complications arise from primary complications. Examples include cataract formation due to treatment with corticosteroids, scleromalacia due to scleritis, and dry eye due to hypovitaminosis A following gut resection. Some ocular manifestations of IBD can lead to significant visual morbidity and temporally associated complications can also be a herald of disease control. Furthermore, ocular manifestations of IBD can occasionally manifest before the usual intestinal manifestations, leading to an earlier diagnosis. Thus, it is important to understand the clinical presentation of possible ocular manifestations in order to initiate appropriate treatment and to help prevent significant visual morbidity.

Incidence of ocular side effects with intravenous zoledronate: secondary analysis of a randomized controlled trial.

SUMMARY: This prospective study showed that the incidence of acute anterior uveitis, confirmed by ophthalmic examination, in patients receiving intravenous zoledronate infusions as part of a randomized controlled trial for fracture prevention is 1.1%. INTRODUCTION: We prospectively investigated the incidence of ocular side effects after a single intravenous zoledronate infusion. METHODS: In a secondary analysis of a double-blind, placebo-controlled trial in which early post-menopausal women (N=1054) with normal bone density or osteopenia were randomized to infusion of zoledronate 5 mg (N=703) or placebo (N=351), we analyzed significant adverse ocular events occurring within 3 months. RESULTS: Fourteen participants reported ocular symptoms after the infusion. All were examined by an ophthalmologist and eight were diagnosed with acute anterior uveitis (AAU) and one with sectoral episcleritis. The incidence of AAU and episcleritis was 1.1% (95% CI 0.5-2.1) and 0.1% (95% CI 0.0-0.7), respectively, in the zoledronate group and 0% for both conditions in the placebo group (95% CI 0.0-0.8). The mean time from infusion to symptom onset for AAU was 3 days (range 2-4). Three cases were bilateral. AAU was mild-moderate in seven participants and severe in one. All affected eyes were treated with topical cyclopentolate 1% (to break, or minimize, posterior synechiae), and intensive, potent, topical corticosteroids with a tapering regime based on treatment response. The mean duration of topical corticosteroid was 26±10 days (range 17-44). The mean, best corrected visual acuity was 20/20 (range 20/20-20/40) at presentation, which remained unchanged after AAU resolution. None of the participants lost vision, and no long-term sequelae were reported at last follow-up (range 3-13 months post-infusion). CONCLUSIONS: Prescribers should inform patients about the possibility of ocular side effects with zoledronate infusions and refer promptly to an ophthalmologist if symptoms develop.