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Rationale: Brolucizumab is an anti-vascular endothelial growth factor agent. Clinical trials have demonstrated excellent efficacy of brolucizumab for neovascular age-related macular degeneration in terms of both visual and anatomic outcomes. However, compared with conventional anti-vascular endothelial growth factor therapy, this new treatment has a higher incidence of complications, particularly the development of occlusive retinal vasculitis. In this case report, we describe a patient who developed occlusive retinal vasculitis following brolucizumab treatment for age-related macular degeneration, followed by scleritis 141 days later., Patient Concerns: A 67-year-old Japanese man with a diagnosis of polypoidal choroidal vasculopathy in his right eye has received 18 intravitreal injections of aflibercept in the past 4 years. Because of a decline in treatment efficacy, intravitreal brolucizumab injection (IVBr) was initiated. However, 17 days after the second IVBr, the patient developed extensive occlusive retinal vasculitis with intraocular inflammation., Diagnosis: Occlusive retinal vasculitis in the right eye was diagnosed as a complication of brolucizumab therapy., Interventions: Corticosteroid treatment was initiated., Outcomes: The occlusive retinal vasculitis resolved 121 days after the second IVBr, and corticosteroid treatment was discontinued on day 138. However, on day 158 after the second IVBr, scleritis with intraocular inflammation developed. By day 184 after the second IVBr, both the scleritis and intraocular inflammation had resolved with the resumption of topical corticosteroid treatment., Lessons: This case underscores the potential for brolucizumab-induced scleritis and emphasizes the importance of recognizing and promptly managing this complication. Furthermore, it highlights the need for long-term careful follow-up in patients who develop occlusive retinal vasculitis after brolucizumab treatment., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background/aims: The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published suspected adverse drug reactions to vaccines against COVID-19. Ocular inflammatory events following COVID-19 vaccination have been reported worldwide., Methods: We analysed MHRA data on spontaneous reports of suspected ocular inflammatory events following COVID-19 vaccination between January 2021 and September 2022., Results: The MHRA received 300 UK spontaneous suspected reports of ocular inflammatory events following COVID-19 vaccination, with a calculated prevalence of 6.6 events per 1 000 000 vaccinated individuals. Anterior uveitis was the most common phenotype (58.3%), followed by optic neuritis in 39.3%. Median number of days between vaccination and onset was 8 days. Resolution of the event was seen in 52.3%., Conclusion: Ocular inflammatory events following COVID-19 vaccination have a very rare prevalence in the UK. There is no increase in the reporting rate of uveitis, optic neuritis and scleritis following COVID-19 vaccination when compared with the range of incidence in the UK population. The Yellow Card System represents a vital instrument within the domain of pharmacovigilance, empowering patients and healthcare professionals to contribute to the ongoing monitoring of medication safety., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Competing Interests: The authors declare that they have no conflict of interest.

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., (© 2024. The Author(s).)

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., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Competing Interests: Competing interests: None declared.

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.

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.

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.

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., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2021 American Academy of Optometry.)

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., Competing Interests: Nil.

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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Claudia Fabiani et al.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

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.

Importance: This case series highlights the risk of uveitis in patients treated with vemurafenib for unresectable or metastatic cutaneous melanoma., Objective: To assess the occurrence and severity of uveitis as an adverse effect of vemurafenib therapy., Design, Setting, and Patients: In this observational small case series, data were collected successively from May 1, 2012, through February 31, 2013, from patients with clinical signs of ocular inflammation treated with vemurafenib at the Department of Ophthalmology, Cochin-Hôtel-Dieu Hospital., Main Outcomes and Measures: Patients' demographics, vemurafenib dosages, and the intervals between the onset of treatment and the first ocular symptoms were recorded. The characteristics of ocular inflammatory manifestations were analyzed. The effect of the discontinuation of vemurafenib therapy on ocular manifestations was assessed, as well as the effect of rechallenging when vemurafenib was reintroduced., Results: Seven patients (mean [SD] age, 74.7 [4.0] years) had uveitis. The vemurafenib dose was 960 mg twice per day in 6 patients and a half dose in 1 patient. The mean (SD) time until the appearance of ocular signs was 5.6 (2.3) months (range, 19 days to 7 months), and inflammation ranged from mild or low-grade anterior uveitis to severe explosive panuveitis complicated by retinal detachment. Signs of ocular inflammation were always bilateral. Optical coherence tomography revealed a macular edema in only 1 of the 7 patients. Clinical improvement occurred when vemurafenib therapy was stopped in 5 of 7 patients. The rechallenge at treatment reintroduction was positive in 2 of 7 patients., Conclusions and Relevance: This small case series highlights that uveitis can be a noteworthy adverse effect of vemurafenib therapy in patients with metastatic cutaneous melanoma. However, these cases of uveitis were usually restricted to the anterior segment and manageable with local corticosteroid therapy, which justified the continuation of vemurafenib therapy because the benefits regarding the patients' survival were greater than the risk to their vision.

Background: Sweet syndrome is an uncommon skin condition, often idiopathic in origin although it may be reactive to various systemic conditions, recent infections, underlying malignancies, and medications., Objective & Method: To present a case highlighting a rare clinical presentation and to review the causes of Sweet syndrome with an emphasis on drug-induced etiologies., Results: We describe a 45-year-old woman who developed Sweet syndrome while receiving nitrofurantoin and ciprofloxacin for a urinary tract infection. Her course of disease was complicated by arthralgias, episcleritis, headaches, and erythema nodosum-like subcutaneous involvement. There was marked improvement with discontinuation of the inciting antibiotics and initiation of systemic steroids., Conclusion: This case illustrates Sweet syndrome related to nitrofurantoin and/or ciprofloxacin. This is the second report of Sweet syndrome related to these antibiotics and the first associated with ocular, joint, and neurologic involvement.

This paper presents the first reported case of risedronate-associated scleritis and conducts a review of bisphosphonates and inflammatory eye diseases. A case of scleritis associated with risedronate use in a 73-year-old Chinese woman is reported. The English medical literature was reviewed for bisphosphonates and their association with inflammatory eye diseases. Cases of ocular inflammation in patients taking bisphosphonates have been reported since the early 1990s. Reported cases include both nitrogen- and non-nitrogen-containing bisphosphonates and with both intravenous and oral use. We report the first case of risedronate-induced scleritis. The case involves a 73-year-old woman who developed scleritis following exposure to risedronate in 2007 with recurrence of scleritis upon risedronate exposure again in 2009. Discontinuation of risedronate and treatment with intravenous and topical corticosteroids resulted in both clinical and radiological improvements within 24 h. Applying Naranjo's adverse drug reaction probability scale, a causality assessment was made which categorized this reaction as definite with a score of 9. In our case, there was a strong causal relationship between the use of risedronate and scleritis. Although rare, ocular adverse effects of bisphosphonates may be serious and should be made known to prescribing physicians. This is important in the practice of rheumatology as many of the patients are prescribed this class of medication for either prevention or treatment of osteoporosis. Moreover, ocular inflammation can be a sign of systemic disease, and such patients may be referred to a rheumatologist.

Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152)-ipilimumab and tremelimumab-have been investigated in metastatic melanoma and other cancers and have shown promising results. Recently, ipilimumab was approved by the US Food and Drug Administration for the treatment of metastatic melanoma. We review the literature on managing the adverse effects and kinetics of tumor regression with ipilimumab and provide guidelines on their management. During treatment with these antibodies, a unique set of adverse effects may occur, called immune-related adverse events (irAEs). These include rashes, which may rarely progress to life-threatening toxic epidermal necrolysis, and colitis, characterized by a mild to moderate, but occasionally also severe and persistent diarrhea. Hypophysitis, hepatitis, pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have also been reported with ipilimumab. Early recognition of irAEs and initiation of treatment are critical to reduce the risk of sequelae. Interestingly, irAEs correlated with treatment response in some studies. Unique kinetics of response have been observed with CTLA-4 blockade with at least four patterns: (1) response in baseline lesions by week 12, with no new lesions seen; (2) stable disease, followed by a slow, steady decline in total tumor burden; (3) regression of tumor after initial increase in total tumor burden; and (4) reduction in total tumor burden during or after the appearance of new lesion(s) after week 12. We provide a detailed description of irAEs and recommendations for practicing oncologists who are managing them, along with the unusual kinetics of response associated with ipilimumab therapy.

Background: There have been several published reports of inflammatory ocular adverse events, mainly uveitis and scleritis, among patients taking oral bisphosphonates. We examined the risk of these adverse events in a pharmacoepidemiologic cohort study., Methods: We conducted a retrospective cohort study involving residents of British Columbia who had visited an ophthalmologist from 2000 to 2007. Within the cohort, we identified all people who were first-time users of oral bisphosphonates and who were followed to the first inflammatory ocular adverse event, death, termination of insurance or the end of the study period. We defined an inflammatory ocular adverse event as scleritis or uveitis. We used a Cox proportional hazard model to determine the adjusted rate ratios. As a sensitivity analysis, we performed a propensity-score-adjusted analysis., Results: The cohort comprised 934,147 people, including 10,827 first-time users of bisphosphonates and 923,320 nonusers. The incidence rate among first-time users was 29/10,000 person-years for uveitis and 63/10,000 person-years for scleritis. In contrast, the incidence among people who did not use oral bisphosphonates was 20/10,000 person-years for uveitis and 36/10,000 for scleritis (number needed to harm: 1100 and 370, respectively). First-time users had an elevated risk of uveitis (adjusted relative risk [RR] 1.45, 95% confidence interval [CI] 1.25-1.68) and scleritis (adjusted RR 1.51, 95% CI 1.34-1.68). The rate ratio for the propensity-score-adjusted analysis did not change the results (uveitis: RR 1.50, 95% CI 1.29-1.73; scleritis: RR 1.53, 95% CI 1.39-1.70)., Interpretation: People using oral bisphosphonates for the first time may be at a higher risk of scleritis and uveitis compared to people with no bisphosphonate use. Patients taking bisphosphonates must be familiar with the signs and symptoms of these conditions, so that they can immediately seek assessment by an ophthalmologist.

Objective: To describe 3 cases of scleritis associated with etanercept use for rheumatoid arthritis (RA) and to review the literature related to inflammatory eye diseases associated with the use of etanercept., Methods: Three cases of severe scleritis during etanercept therapy were analyzed. A systematic review of the literature in PubMed, Embase, and the Cochrane Library was performed, from 1962 to July 2010., Results: Three patients with seropositive RA developed scleritis 7-28 months after initiation of etanercept, for the first time during their long-lasting disease. In all patients the underlying disease had responded well to anti-tumor necrosis factor therapy. Ocular inflammation went into remission after discontinuation of etanercept, and no other relapses were observed. One patient experienced a dechallenge-rechallenge phenomenon (improvement in symptoms following discontinuation of the agent, then reappearance or worsening of symptoms on reexposure to the agent). Forty-two cases of inflammatory eye diseases believed to be associated with the use of etanercept have been reported in the literature: 33 uveitis, 8 scleritis, 1 orbital myositis, concerning 16 patients with RA, 10 with juvenile idiopathic arthritis, 14 with ankylosing spondylitis, and 2 with psoriatic spondyloarthropathy. Dechallenge was performed in 28 patients, leading to resolution of symptoms. Rechallenge was done in 6 cases, with clear exacerbation., Conclusion: Ocular inflammation is paradoxically a potential adverse effect of etanercept, even in previously uninvolved eyes.

The pathology of the liver is associated with many disorders including the eye. We described ocular changes following hepatitis C. The most common ophthalmic findings in hepatitis C patients treated with interferon--involve keratoconjunctivitis, scleritis, dry eye syndrome, uveitis, retinopathy, retinal hemorrhages, anterior ischemic optic neuropathy, retinal vascular changes and macular oedema, as well as electroretinogram, visual field and OCT abnormalities.

We report three cases of female patients who presented a first episode of unilateral scleritis or acute anterior uveitis while they were treated for 12-16 months by TNF inhibitor: etanercept (Enbrel((R))) 25mg twice weekly for rheumatologic diseases (rheumatoid arthritis or ankylosing spondylitis). Ocular inflammation was resistant to the usual treatment. Some cases of scleritis and uveitis are known to be drug-induced. TNF inhibitors seem to be part of them. Ocular inflammation is usually the first episode. It appears generally in the first year of the treatment by TNF inhibitors and resists to usual treatment. The general disease is usually well stabilized. In our cases, inflammation decreased only when the etanercept was discontinued.

Purpose: Uveitis and scleritis are the most serious ocular side effects of bisphosphonate therapy. The purpose of this study was to determine the 6-month rates of uveitis/scleritis following dispensing of bisphosphonates in a large veteran cohort., Methods: Two national databases (clinical and pharmacy) for fiscal year (FY) 2006 were linked to identify new diagnoses of uveitis/scleritis following the initial dispensing of bisphosphonate drugs. New diagnoses in FY 2006 were identified using International Classification of Diseases, Version 9, Clinical Modification (ICD-9-CM), in a cohort of veterans without a previous diagnosis of uveitis or scleritis using a look-back period to FY 2005. The new diagnoses were temporally aligned with initial dispensing of bisphosphonates and the rates of new cases were calculated for 1-month and 6-month time intervals., Results: There were 7.9 new cases of uveitis/scleritis per 10,000 individuals with a newly dispensed bisphosphonate that occurred within 180 days. The relative risk of uveitis/scleritis for 6 months was 1.23 (95% confidence interval: 0.85-1.79) compared to veterans not exposed to the medications. The rates of uveitis/scleritis did not differ significantly based on route of administration (oral or parenteral) or after age adjustment. Just over a third of the diagnoses were scleritis. Nearly 43% of patients with uveitis/scleritis after bisphosphonate use had a systemic diagnosis commonly associated with inflammation of the uveal tract or sclera., Conclusions: The 30-day and 6-month rates of uveitis/scleritis following the dispensing of a bisphosphonate drug are low and do not differ significantly from rates recorded for veterans not dispensed these drugs.

Purpose: To report a case of nodular scleritis following alendronate sodium., Methods: A 54 year-old male was treated with alendronate sodium 70 mg orally once per week. Eight weeks later, he experienced pain and redness of the right eye. Biomicroscopy was performed., Results: Patient was found to have inferonasal nodular scleritis. Laboratory work-up was unrevealing. Patient was given 4 mg of subtenon's triamcinolone acetate in the area of the nodular scleritis and had complete resolution. Two weeks following rechallenge with alendronate sodium resulted in recurrence of his scleritis., Conclusion: Alendronate led to nodular scleritis and rechallenge caused recurrence of scleritis.

Context: Erlotinib is a relatively new anilinoquinazoline indicated for treatment of pancreatic cancer in combination with gemcitabine. It is a tyrosine kinase inhibitor that specifically targets epidermal growth factor receptor (EGFR), which is commonly overexpressed and/or mutated in solid tumors. Active competitive inhibition of adenosine triphosphate, inhibits downstream signal transduction of ligand dependent EGFR activation. EGFR kinase inhibitors are less toxic than conventional chemotherapy as they are relatively specific for tumor cells. Common side effects include acneiform (papulopustular) rash, diarrhea, edema, pruritus, dry skin and alopecia., Case Report: This article reports the case of a 55-year-old Caucasian female with recurrent pancreatic cancer who developed episcleritis after seventeen days of treatment with erlotinib. Symptoms completely resolved four weeks after drug discontinuation., Conclusions: To our knowledge, erlotinib-induced episcleritis has not been previously described.

Ocular inflammation can arise in the form of conjunctivitis, uveitis, episcleritis and scleritis. The uveitides can be subdivided by anatomical location into anterior and posterior uveitis or categorized by location of inflammation, e.g., iritis, pars planitis or iridocyclitis. Multiple drugs have been associated with ocular inflammation and much has been written on the subject. Discussed here is a sampling of drugs representing classes of medication associated with ocular inflammation. However, this is not a comprehensive list and interested readers are encouraged to access the National Registry of Drug-Induced Ocular Side Effects (Casey Eye Institute, Portland, Oregon, www.eyedrugregistry.com) or the textbook Drug-Induced Ocular Side Effects for further information (1). The agents discussed may be administered systemically, topically or intracamerally (inside the eye). The mechanism behind ocular inflammation is frequently unknown. Prevention and treatment are based upon physician recognition and withdrawal of the drug in some instances. Consultation with an ophthalmologist is recommended, as many types of ocular inflammation can threaten vision., (Copyright (c) 2007 Prous Science. All rights reserved.)

We present a case of severe unilateral posterior scleritis associated with zoledronic acid administration that was recognized and treated in a timely manner. Subsequent use of pamidronate was associated with milder inflammation in the same eye that eventually resolved with continued monthly infusions, indicating the possibility of immunologic tolerance. Physicians prescribing these drugs should be aware of this side effect, which, if not recognized and treated appropriately, is potentially devastating. We review the published data as well as the current treatment recommendations.

An 86-year-old female was treated for osteoporosis with alendronate, an aminobisphosphonate. Six weeks after alendronate therapy began, scleritis developed in the patient's right eye. The alendronate was discontinued, and, with the administration of prednisone, the symptoms of scleritis fully resolved. Rechallenge resulted in recurrence of the symptoms. Bisphosphonates are commonly used in the management of osteoporosis and are generally safe agents. Rarely, they have been linked with ocular inflammation. This case report reviews the literature on the ocular effects of bisphosphonates and discusses a possible mechanism for the association.

In a 3-year study with 2.5 mg of ibandronate daily in postmenopausal women with at least 1 pre-existing vertebral fracture, the drug reduced new vertebral fractures by 50%, but had no effect on non-vertebral fractures. The 150-mg once-monthly formulation of ibandronate was as effective as the daily one in increasing bone mineral density and decreasing bone turnover markers. It appears to be similar to alendronate and risedronate in efficacy and tolerability, but head-to-head comparisons are lacking.

Bisphosphonates are used to inhibit bone resorption in postmenopausal women and in the management of hypercalcemia of malignancy. Recently, some drugs within this class of medicines have been proven to cause scleritis. Prior to this, bisphosphonates had been reported to cause a variety of ocular side effects, most of which are inflammatory. This review discusses the many different medicines called bisphosphonates and highlights the ocular side effect profile of each. In cases where information on dechallenge is provided, all the ocular side effects resolved after discontinuation of the medication. Recognition of adverse ocular events in association with bisphosphonate therapy should alert clinicians to the need for ophthalmic evaluation and the consideration of discontinuation of therapy in all cases of scleritis.

Purpose: To evaluate reported cases of scleritis and other ocular side effects associated with pamidronate disodium, with emphasis on previously unreported cases of scleritis., Design: Observational case series., Methods: Case reports from the National Registry of Drug-Induced Ocular Side Effects (Casey Eye Institute), the Food and Drug Administration, the World Health Organization, and the literature were reviewed to determine possible adverse ocular side effects associated with pamidronate disodium. The World Health Organization's Causality Assessment Guide was used to categorize an adverse drug reaction., Results: Seventeen cases of unilateral scleritis and one case of bilateral scleritis occurred, usually within 6 hours to 2 days after intravenous pamidronate disodium. Six patients had positive rechallenge testing with the scleritis occurring after a repeat drug exposure. Other ocular side effects with positive rechallenge data, associated with pamidronate disodium, include blurred vision, nonspecific conjunctivitis, ocular pain, bilateral anterior uveitis, and episcleritis., Conclusions: This is the first report, with rechallenge data, of any drug causing scleritis. Pamidronate disodium can cause vision-threatening diseases, which may require discontinuing the drug in some uveitis cases and, in this series, all cases of scleritis.

Ocular adverse effects of pamidronic acid are rare but well documented. Pamidronate, an inhibitor of bone resorption used primarily in the management of tumor-induced hypercalcemia and Paget's disease, is reported to cause conjunctivitis, anterior uveitis, and infrequently episcleritis and scleritis. It is hypothesized that an allergic or immunologic phenomenon caused by drug-indued immune complex formation is at fault. The reason why the uvea is a target organ is unclear. The acute inflammatory response seems unrelated to the dose of the drug, the way of administration, or the activity of Paget's disease or malignancy. We report two cases of pamidronate-induced posterior uveitis, following the WHO Causality Assessment Guide of Suspected Adverse Reactions. Uveitis and scleritis have been reported in association with a variety of topical, intraocular, periocular, and systemic medications. Seven criteria were proposed to establish causality of adverse events by drugs. Only systemically administered biphosphonates meet all seven criteria. Where pamidronate is currently considered as the drug of choice in diverse strategies, the adverse ocular effects should be well known to physicians in order to make rapid diagnosis and stop the drug causing adverse reaction.

Background: Development of central serous chorioretinopathy (CSC) following the administration of corticosteroids by diverse routes is a well-known fact. We report acute visual loss after the use of systemic corticosteroids in three patients with long-standing ocular inflammatory disorders in whom CSC could initially be misinterpreted as a worsening of the primary inflammatory condition., Methods: We analyzed the clinical findings and the fluorescein and indocyanine green (ICG) angiographic signs in those three patients., Results: The first patient had birdshot chorioretinopathy with minimal functional impairment for several years without treatment. When visual acuity and fields deteriorated, systemic corticosteroids were administered resulting in improved inflammatory and functional parameters during the first 2 months. Subsequently, the visual acuity of his left eye decreased due to CSC. The second patient had Vogt-Koyanagi-Harada disease with five episodes of acute inflammation. She was treated each time with systemic corticosteroids, but thrice her visual acuity deteriorated, caused by CSC. The third patient presented with scleritis of his right eye related to relapsing polychondritis. Massive oral corticosteroids were given, soon followed by the development of CSC in the right eye. Fluorescein and ICG angiographic signs were typical for CSC in all three patients. Cyclosporine was introduced in the two first patients and cyclophosphamide in the third patient, in parallel with tapering of oral corticosteroids. Progressive regression of CSC occurred in all three patients., Conclusion: The potentially deleterious effects of corticosteroids, favoring CSC, are well-known. They should be borne in mind when an unexpected clinical and angiographic evolution compatible with CSC develops in an uveitis patient treated with corticosteroids.

We report a patient who developed an acute symmetrical polyarthropathy, orbital myositis and posterior scleritis following inoculation with the 1993 Fluvirin (inactivated influenza vaccine: surface antigen) vaccine. We believe that this represents a hypersensitivity reaction to the vaccine as extensive investigations revealed no underlying infective, inflammatory or systemic cause. We review the current indications for vaccination against the influenza virus and the known adverse reactions to the vaccine.