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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.)

Competing Interests: Competing interests: None declared.

Purpose: To report a case of fibrinous acute anterior uveitis associated with topical interferon-α2b (IFN-α2b) treatment for ocular surface squamous neoplasia in a patient with HLA-B27 uveitis predisposition., Methods: Case report., Results: We present the case of a 57-year-old man who received topical IFN-α2b as adjuvant therapy for a previously surgically removed ocular surface squamous neoplasia with affected surgical margins. Two weeks after topical IFN-α2b initiation, the patient was diagnosed with fibrinous acute anterior uveitis. Complementary tests to rule out other causes of uveitis resulted to be negative, except for HLA-B27, which tested positive. Response to treatment with topical corticosteroids and cyclopentolate was favorable. As IFN-α2b is considered an immune enhancer and has been widely associated with autoimmune side effects, topical therapy with IFN-α2b was temporally ceased until intraocular inflammation resolved. Topical IFN-α2b was resumed, and during follow-up, no signs of uveitis were detected. The main hypothesis is that IFN-α2b acts as a trigger for intraocular inflammation in individuals with uveitis predisposition., Conclusions: Topical IFN-α2b could trigger intraocular inflammation in patients with uveitis susceptibility. It may be reasonable to use IFN-α2b cautiously in patients with a known history of uveitis or uveitis predisposition., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Anterior uveitis is a reported complication of intravenous cidofovir, almost exclusively described in human immunodeficiency virus (HIV) infected patients treated for cytomegalovirus retinitis. In this study, we report the case of an allogeneic stem cell transplant recipient with significant visual impairment and hypotony following administration of high-dose intravenous cidofovir for hemorrhagic cystitis due to BK virus., (© 2022 Wiley Periodicals LLC.)

Purpose: COVID-19 vaccines are currently undergoing long-term safety monitoring, including for ocular side effects. Uveitis following vaccination has been described previously with other vaccines and warrants evaluation for COVID-19 vaccines, especially given their widespread use., Case Reports: We present two cases of patients who developed anterior uveitis following the Moderna COVID-19 vaccine, as reported to the National Registry for Drug-Induced Ocular Side Effects. We also summarize reports of anterior uveitis following COVID-19 vaccination as reported to the World Health Organization global database of individual case safety reports., Conclusions: Based on the temporal pattern of ocular inflammation following vaccine delivery in these cases, an association may be present between uveitis and COVID-19 vaccination. Further investigation to explore this association is warranted to guide patient care.

Introduction: Ibrutinib is a small-molecule drug approved for the treatment of haematological disorders and is known to be associated with visual disturbances, but uveitis has not yet been reported as an adverse effect of this medication. We present two cases of ibrutinib-associated severe uveitis in patients with chronic lymphocytic leukaemia., Case Description: Our first case is a 65-year-old woman who presented with acute onset of bilateral fibrinous anterior uveitis 1 day after starting ibrutinib. Her vision was hand movements in the right eye and 20/120 in the left with hyperaemic discs and subretinal fluid. Ibrutinib was stopped and she experienced a significant improvement under local and oral steroid treatment. The second case is a 64-year-old male with subacute onset of bilateral hypertensive anterior uveitis with pupillary seclusion and right eye hyphaema. He was on ibrutinib for the past 9 months. His vision at presentation was 20/80 and 20/60 for the right and left eye, respectively. He responded poorly to local steroid treatment until ibrutinib was stopped due to cardiac side-effects, after which his uveitis resolved and treatment was stopped., Conclusion: The temporal association between changes in ibrutinib treatment and our patients' ocular inflammation suggests a causative link. Ibrutinib increases Th1-based immune responses which is proposed as a mechanism for drug-induced uveitis. Its antiplatelet effect may explain the fibrinous nature of the inflammation and hyphaema.

Purpose: To describe a case of herpes simplex virus 1 (HSV 1) infection following coronavirus disease 2019 (COVID-19) vaccination in an Asian Indian female., Methods: Retrospective case report., Result: A 40-year-old female presented with decreased vision, pain, and photophobia of 2 weeks duration. She reported receiving the second dose of COVISHIELD TM (ChAdOx1-S [recombinant]) 1 week prior to the onset of ocular symptoms. Left eye examination revealed granulomatous anterior uveitis. Aqueous sample from the left eye tested positive for HSV1 by polymerase chain reaction(PCR) method. She was managed with oral antiviral therapy, topical steroids, and cycloplegic agent and showed significant improvement of inflammation within 1 week and resolved within 3 weeks., Conclusion: This report demonstrates a potential association of HSV 1 anterior uveitis with COVID-19 vaccination. A high index of suspicion of viral etiology is warranted when uveitis presents with reduced corneal sensations and pigmented keratic precipitates, following a recent history of COVID-19 vaccination.

Intravesical Bacillus Calmette-Guérin (BCG) administration was used to treat bladder carcinoma in a woman in her 60s. Severe bilateral non-granulomatous anterior uveitis and gross papillitis developed subsequently. The severe BCG-induced bilateral uveitis and papillitis were treated with high dose oral corticosteroids, with topical steroids and cycloplegics. Resolution of her ocular symptoms and signs eventuated. On lumbar puncture, no evidence of systemic spread of the BCG was found. Visual acuity returned to 6/9 in each eye with subsequent resolution of papillitis. Repeat cystoscopy demonstrated no evidence of recurrent bladder tumour.Hypersensitivity reactions are well recognised with Tubercle bacilli While both hypersensitivity reactions and dissemination of BCG throughout the body have been previously documented, the literature demonstrates that this case is the first example in which papillitis and bilateral uveitis were the prominent ophthalmological features., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Bilateral acute iris transillumination (BAIT) is a relatively new clinical entity characterized by bilateral acute loss of iris pigment epithelium, iris transillumination, pigment dispersion in the anterior chamber, and sphincter paralysis. BAIT has been easily confused with other types of anterior uveitis because of pigment dispersion in the anterior chamber and some symptoms including pain, photophobia, and red eye, which is similar to those in the other types of anterior uveitis. However, inflammatory findings in these patients are not as marked as in those with other types of anterior uveitis. Therefore, systemic corticosteroid is generally not required for the treatment of pure BAIT patients because of limited intraocular inflammation. BAIT can also cause severe intraocular pressure (IOP) rise, which sometimes necessitates glaucoma surgery. Systemic corticosteroids can also increase the existing intraocular pressure rise in patients with BAIT. Therefore, it should not be used in these patients.

Purpose: To describe uveitis cases after the BNT162b2 mRNA SARS-CoV-2 vaccination., Methods: This is a multicenter, retrospective study. Vaccine-related uveitis diagnosis was supported by the classification of the World Health Organization Adverse Drug Terminology and the Naranjo criteria., Results: Twenty-one patients (23 eyes) with a mean age of 51.3 years (23-78 years) were included. Eight of the 21 patients had a known history of uveitis. The median time from previous to current attack was 1 year (0.5-15 years). There were 21 anterior uveitis cases, two with bilateral inflammation. Eight cases occurred after the first vaccination and 13 after the second vaccination. All but three presented as mild to moderate disease. Two patients developed multiple evanescent white dot syndrome after the second vaccination. The mean time from vaccination to uveitis onset was 7.5 ± 7.3 days (1-30 days). At final follow-up, complete resolution was achieved in all but two eyes, which showed significant improvement. One case of severe anterior uveitis developed vitritis and macular edema after the second vaccination, which completely resolved after an intravitreal dexamethasone injection., Conclusion: Uveitis may develop after the administration of the BNT162b2 mRNA vaccine. The most common complication was mild to moderate anterior uveitis, while multiple evanescent white dot syndrome can also occur less frequently.

Purpose : To report cases of uveitis induced by biological therapy given for cancer. Methods : Retrospective review of medical charts of patients. Results : Included were six patients aged 14-81 years. Three were treated with vemurafenib and one each with nivolumab, ipilimumab, and osimertinib. The oncological diagnoses were metastatic thyroid carcinoma, pleomorphic xanthoastrocytoma, metastatic melanoma, adenocarcinoma of the lung, and metastatic breast cancer. Ocular manifestations appeared 4-82 weeks after the biological treatment was initiated. The most common ocular presentation was anterior uveitis. Onset was sudden in all cases. The median duration of uveitis was 70 weeks. Treatment included topical or systemic corticosteroids; one patient received a single intravitreal steroid injection in one eye. Conclusions : Uveitis may rarely be induced by treatment with biological agents for cancer. Both oncologists and ophthalmologists should be aware of this potential side effect. Early detection and management can prevent permanent complications and save the patient's vision.

Purpose : To report a case of a drug-induced anterior uveitis secondary to the use ofintracameral moxifloxacin. Case report : A 64-year-old Colombian male patient presented with severe ocular pain and photophobia in his left eye 15 days after cataract surgery. In the ophthalmology and glaucoma specialist evaluation, pigment dispersion in the anterior chamber and camerular angle, severe anterior segment inflammation, and elevated intraocular pressure were observed. Poor response to treatment for a suspected viral origin and exclusion of other possible etiologies, led to the conclusion of intracameral moxifloxacin induced anterior uveitis. Conclusion and importance : We present the second published case worldwide about anterior uveitis secondary to intracameral moxifloxacin, which may rarely cause hypertensive uveitis that may be confused with viral uveitis. This provides evidence on the importance of postoperative follow-up by the surgeon for an early referral and treatment of these cases.

Purpose : To report a case of anterior uveitis in a patient under treatment with Cyclophosphamide / Bortezomid / Dexamethasone (CyBorD) protocol for Multiple Myeloma and concomitant use of Zoledronic acid. Methods : Observational case report of a 50-year-old woman presenting with acute, severe, bilateral uveitis on a medical history of Multiple Myeloma, undergoing the first cycle of CyBorD protocol, including infusion with Zoledronic acid. Results : Continuation of therapy, with parallel treatment with topical and per os steroids led to resolution of the inflammation. Three more chemotherapy cycles were performed with the same protocol including Zoledronic acid at a lower dosage and were all, uneventful. Conclusion : Our case mirrored uveitis cases with either masquerade syndrome due to Multiple Myeloma or following Zoledronic acid infusion, despite concomitant usage of Dexamethasone and Cyclophosphamide. Three consecutive rechallenges were performed without any topical prophylactic treatment and with no relapse of signs or symptoms.

Purpose : The purpose of this study is to report a case of herpetic keratouveitis that developed soon after intravitreal ranibizumab injection. Case Report : A 54-year-old man with bilateral proliferative diabetic retinopathy and severe macular edema received intravitreal ranibizumab injections in both eyes within 3 days interval. One week after the injection, patient presented with acute vision loss in his right eye. Slit-lamp biomicroscopy revealed diffuse corneal edema and severe flare in the anterior chamber with intraocular pressure (IOP) rise. After epithelial dendritic corneal ulcer was visualized, he was diagnosed with right herpetic keratouveitis that was treated with oral valacyclovir, as well as topical acyclovir ointment and prednisolone acetate drops. However, recalcitrant IOP rise had to be treated with a single session transscleral diode laser cyclophotocoagulation. Conclusion : Herpetic keratouveitis can be seen as a rare complication of intravitreal ranibizumab injection. To our best knowledge, this is the first case with herpes keratouveitis developed following intravitreal ranibizumab injection.

Aim: Nivolumab is an immune checkpoint inhibitor that has recently been widely used for metastatic malignant melanoma. We report a case who developed multiple different ocular immune-related side effects (iRAEs) related to nivolumab. Case Presentation: A 60-year-old man on nivolumab treatment for metastatic malignant melanoma developed a decrease in vision in both eyes several days after the third infusion. The initial best-corrected visual acuity (BCVA) was counting fingers in both eyes. Slit-lamp examination revealed no abnormal findings in the anterior segment of both eyes. Posterior segment evaluation showed serous retinal detachment, including the whole macula and inferior retina in both eyes, and optical coherence tomography (OCT) confirmed the diagnosis. On en face OCT analysis, hyperautoflorescent dots were noticed on the whole macular region but more intense at the inferior quadrant corresponding to serous retinal detachment. On Fluorescein Angiography (FA), no abnormality was observed. Oral corticosteroid treatment was administered. Subretinal fluid resolved one week after treatment in the right eye and two weeks after treatment in the left eye. BCVA was 20/20 in both eyes at first month of treatment. After that, oral corticosteroid treatment was tapered and stopped at the end of the second month. The patient was followed monthly. Two months after the treatment patient presented with an anterior uveitis episode with mild vision loss. Slit-lamp examination revealed 3+ cells in the anterior chamber and posterior synechia in both eyes. Posterior segment examination was normal. The patient was treated with topical corticosteroid and cycloplegic for two months. Hyperautoflorescent dots formed with serous detachment disappeared six months after the onset of serous detachment, and they did not occur during anterior uveitis episodes. Conclusions: This is the first clinical report of nivolumab-associated ocular iRAEs presenting with recurrent episodes presenting with serous retinal detachment and anterior uveitis. En face OCT imaging may help diagnose and show the activity of the posterior segment manifestation. When managed properly and observed closely following general and ocular conditions, it is possible to held iRAEs and overcome them by oral and/or topical corticosteroid therapy without interrupting the nivolumab.

Purpose : To improve awareness of delayed onset uveitis in patients with a history of intraocular tattoo ink injection. Results : A 47-year-old man underwent a scleral tattoo procedure during which there was inadvertent intraocular injection of tattoo ink into his right eye. He subsequently developed endophthalmitis, retinal detachment, and retinal necrosis. He was treated with intravitreal and oral antibiotics and underwent vitreoretinal surgical intervention. A vitreous specimen was obtained and demonstrated significantly elevated levels of several heavy metals. One month later, he developed an acute granulomatous anterior uveitis in the same eye that was managed with a combination of topical and perioperative intravitreal, intravenous, and oral corticosteroids. Conclusion : This case highlights the importance of monitoring patients with a history of intraocular tattoo ink injection for delayed onset uveitis in addition to retinal toxicity.

Purpose: This three-case report aims to highlight the ocular adverse effects induced by bisphosphonate therapy and to call clinicians' attention., Methods: Three cases of acute anterior uveitis secondary to the initial dose of zoledronate infusion were reported with focus on their symptoms, treatment regimens, and outcomes. A review of published reports provided a basis for discussion., Results: Three cases of acute anterior uveitis were either bilateral or unilateral. They demonstrated typical manifestations of bisphosphonate-induced acute anterior uveitis such as eye pain, blurred vision, conjunctival and ciliary hyperemia, keratic precipitates, and flare in the anterior chamber. After topical corticosteroid-containing comprehensive treatments, these symptoms resolved completely without any vision loss and long-term sequelae., Conclusions: Acute anterior uveitis may be part of the acute phase reaction induced by zoledronate. Patients should be informed of its symptoms in advance and be monitored closely during and after administration. Clinicians should have a good awareness of the zoledronate-associated acute anterior uveitis and to treat it in a prompt and appropriate manner.

Purpose: Detailed study of ophthalmic immune-related adverse events (AEs), including determination of incidence and recurrence rates, is of integral importance in cancer immunotherapy to inform management and treatment guidelines., Design: Retrospective registry study., Participants: Patients newly diagnosed with ophthalmic immune-related AEs between January 1, 2013, and December 31, 2017, in the American Academy of Ophthalmology's Intelligent Research in Sight (IRIS®) Registry., Methods: Data were collected from electronic health records of IRIS® Registry participating ophthalmology practices. Patients with select ophthalmic immune-related AEs were identified by International Classification of Diseases diagnosis codes. The primary exposure of interest was prior initiation of immune checkpoint inhibitors (ICIs)., Main Outcome Measures: Incidence of ophthalmic immune-related AEs within 1 year after initiation of ICI therapy was determined. Incidence rate ratios (IRRs) were derived by comparing incidence of ophthalmic immune-related AEs after ICIs versus rates of the same ocular complications in patients not taking ICIs in the entire registry population. Rates of ophthalmic immune-related AEs in patients with a past history of ocular inflammation or other specific ophthalmic condition before initiation of ICIs were examined further., Results: A total of 3123 patients who received anti-CTLA-4 or anti-programmed cell death 1 (PD-1) therapy were identified, 112 of whom demonstrated an ophthalmic immune-related AE. Incidence rates for anterior uveitis, the most common ophthalmic immune-related AE, were 8209 per 100 000 for ipilimumab (anti-CTLA-4), 2542 per 100 000 for nivolumab (anti-PD-1), 2451 per 100 000 for pembrolizumab (anti-PD-1), 5556 per 100 000 for ipilimumab plus nivolumab, and 3740 per 100 000 among all ICIs. Rates of ophthalmic immune-related AEs among patients receiving ICI therapy were higher compared with baseline rates in the general registry population (anterior uveitis IRR, 13.9; other uveitis IRR, 43.0; papilledema IRR, 38.3). Patients with a history of uveitis or other ocular inflammatory condition demonstrated high recurrence rates of ophthalmic immune-related AEs after initiating ICIs (up to 51.1%)., Conclusions: For patients initiating ICI therapy, early coordination with ophthalmic subspecialist care is important because rates of ophthalmic immune-related AEs are elevated compared with ocular complication rates in the entire registry population and patients with a history of prior autoimmune ocular disease are at high risk of recurrence of ocular complications., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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.

Background: Anterior uveitis secondary to topical brimonidine administration is rare and not well-defined. In glaucoma patients using brimonidine, one must consider this phenomenon to avoid mis-diagnosis and over-treatment with topical steroids which in turn may increase intraocular pressure (IOP). This is the largest case series including the longest patient follow-up in the current literature., Methods: Sixteen patients (26 eyes) with consultant diagnosed brimonidine-associated anterior uveitis in a tertiary referral glaucoma clinic presenting between 2015 and 2019 were included in this retrospective case series. Clinical records were taken for descriptive analysis. Main outcome measures were the key clinical features, and disease course (therapy, IOP control, patient outcome)., Results: Key features were conjunctival ciliary injection and mutton fat keratic precipitation in all eyes. The findings were bilateral in 10 patients. Time between initiation of brimonidine treatment and presentation was 1 week to 49 months. Glaucoma sub-types were mostly pseudo-exfoliative and primary open angle glaucoma. Brimonidine treatment was stopped immediately. Additionally, topical corticosteroids were prescribed in 18 eyes and tapered down during the following 4 weeks. Thirteen eyes did not need surgical or laser treatment (median follow-up time 15 months). No patient showed recurrence of inflammation after cessation of brimonidine., Conclusions: This type of anterior uveitis is an uncommon but important manifestation which should always be considered in glaucoma patients on brimonidine treatment. Although treatable at its root cause, problems may persist, especially with respect to IOP control. The latter may necessitate glaucoma surgery after the resolved episode of the uveitis.

Purpose: To report a unique case of nivolumab-induced uveitis and the results of a cytokine analysis of an intraocular fluid sample., Case Report: A 61-year-old male patient undergoing treatment for renal cell carcinoma with nivolumab presented with bilateral uveitis. Severe anterior uveitis and vitreous opacity coincided with decreased visual acuity only in his left eye. Iris damage was present in this eye because of previous complicated cataract surgery. Vitrectomy was performed to remove the vitreous opacity, and visual acuity recovered postoperatively. A cytokine analysis of an intraocular fluid sample revealed a high level of interleukin-6, granulocyte-colony stimulating factor and interferon-inducible protein-10., Conclusion: This case indicates that nivolumab-induced uveitis might be more severe in eyes with a damaged iris, and that vitrectomy should be effective for vitreous opacity. A cytokine analysis of the ocular fluid indicated that multiple types of cell might be related to the inflammation process.

A 56-year-old paramedic was admitted to hospital and treated for severe pneumonia. Shortly after initiating antibiotic treatment (including moxifloxacin), he developed bilaterally painful eyes and was diagnosed with bilateral acute anterior uveitis (AAU). Three years later, he was referred to the ophthalmology clinic with bilateral iris transillumination suggesting iris atrophy and limited pupillary dilation, indicating iris sphincter muscle paralysis. AAU typically presents unilaterally. An onset of bilateral AAU is unusual and warrants investigation for underlying systemic cause. The fluoroquinolone moxifloxacin has been reported in a limited number of cases as a causative agent of bilateral AAU and iris atrophy. This case provides additional supporting evidence that moxifloxacin may cause degradation of collagen and iris muscle in the eye, as well as elsewhere in the body, such as in blood vessels. Additionally, we present novel anterior segment ocular imaging (using optical coherence tomography) demonstrating the ability to detect iris atrophy using non-invasive imaging., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To demonstrate the anti-inflammatory action of a synthetic glucocorticoid-induced leucine zipper (GILZ98-134) peptide (GILZ-p) in a model of endotoxin-induced uveitis (EIU) in rats., Methods: The EIU model was induced in Sprague Dawley rats with an intravitreal injection of lipopolysaccharide (LPS). Synthetic GILZ-p was injected intravitreally 6 h after the LPS injection. To evaluate the anti-inflammatory effects of GILZ-p, the inflammatory response in the anterior chamber and iris of the rat eyes was evaluated with a slitlamp microscope on days 0, 1, 2, 3, and 4 after GILZ-p injection. The retinal expression of inflammatory cytokines was measured on days 0, 1, 2, 3, and 4 after GILZ-p injection. Müller cell gliosis was also detected at planned time points after GILZ-p injection., Results: Anterior segment inflammation peaked at 24 h after LPS injection in the EIU model. Compared with the controls, intravitreal GILZ-p significantly suppressed LPS-induced anterior segment inflammation in the EIU rats. The levels of retinal inflammatory factors IL-1β, TNF-α, MCP-1, and ICAM-1 were simultaneously reduced by the intravitreal GILZ-p injection. The expression of vimentin in the EIU retina was significantly reduced by GILZ-p, and the downregulated aquaporin 4 in the EIU retina was significantly restored by GILZ-p., Conclusion: The synthetic GILZ-p inhibited the inflammatory reaction in the EIU model and may have utility in the treatment of inflammatory ocular disease., (© 2019 S. Karger AG, Basel.)

Erlotinib used in the treatment of advanced non-small cell lung cancer (NSCLC) is a first-generation small-molecule tyrosine kinase inhibitor which reversibly inhibits the kinase domain of epithelial growth factor receptor (EGFR). The incidence of ocular toxicities as adverse effects (AE) of erlotinib is relatively common. However, post-marketing, acute anterior uveitis (AAU) has been reported in a small number of cases as a putative AE resulting from erlotinib therapy. We present a case of a 67-year-old, Caucasian woman, lifelong non-smoker with stage IV NSCLC who presents with decreased visual acuity and 'floaters' 6 weeks after commencing erlotinib. She was later diagnosed with erlotinib-associated bilateral AAU. This is the fifth documented case of erlotinib-associated bilateral AAU since 2010, highlighting the rarity of this AE. Thus, the possibility of AAU should always be considered in patients on EGFR-blocking therapies as significant ocular damage can occur if ophthalmic complaints are not triaged and assessed quickly., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To characterize the inflammatory response and determine the no-observable-effect level (NOEL) in cynomolgus monkey eyes after intravitreal (ITV) injection of endotoxin. Methods: The inflammatory response to endotoxin was assessed in a single-dose study in monkeys at doses of 0.01 to 0.51 endotoxin units (EU)/eye. Tolerability was assessed by clinical ophthalmic examinations, intraocular pressure measurements, fundus color photography, optical coherence tomography, and anatomic pathology. Results: ITV injection of endotoxin at ≥0.04 EU/eye resulted in a dose-related anterior segment inflammatory response. No aqueous flare or cell was noted in the 0.01 EU/eye dose group. A more delayed posterior segment response characterized by vitreous cell was observed beginning on day 5, peaking on day 15, and decreasing in some groups. Microscopic findings of mononuclear cell infiltrates in the vitreous were observed in eyes given ≥0.21 EU/eye. Conclusion: The NOEL for ITV endotoxin in cynomolgus monkeys was 0.01 EU/eye, suggesting that this species is as sensitive as rabbits to the effects of endotoxin. The vitreous cavity also appears more sensitive to endotoxin than the anterior segment/aqueous chamber. Overall, the magnitude of the inflammatory response at ≥0.04 EU/eye suggests that dose-response curve in monkeys is steeper than in rabbits. These data highlight the importance of assessing endotoxin level in ITV formulations, as levels as low as 0.04 EU/eye may confound the safety evaluations of ITV therapeutics in cynomolgus monkeys.

Dupilumab, the first biologic approved for treatment of atopic dermatitis, has demonstrated significant clinical effect and quality of life-enhancing capacity in clinical trials. In these, dupilumab-associated conjunctivitis where reported in a minority of patients. The present case series describe 10 patients treated with dupilumab where eye complications were very common. We have described patient characteristics, including FLG mutations, atopic history and clinical effect of dupilumab. Nine of 10 developed eye-complications, most commonly conjunctivitis (in 7/10). Other adverse events were herpes simplex virus uveitis and varicella-zoster virus meningitis. Although our case series is small, we conclude that dupilumab is an effective treatment option in severe atopic dermatitis, but that the risk of adverse events from the eyes and recurrence of herpes virus infections should be kept in mind. Close collaboration with an ophthalmologist is recommended, especially among patients with severe, long-lasting atopic dermatitis and/or previous eye disease.

Clinical Case: The case concerns an 81-year-old woman on treatment with a topical fixed combination of timolol and brimonidine who was diagnosed in the Emergency Department with acute anterior granulomatous hypertensive uveitis. The patient responded favourably to the withdrawal of the eye drops without showing any subsequent relapse., Discussion: Uveitis due to brimonidine is a rare adverse effect, but it must be known. Once the diagnosis is suspected, the effective treatment is the withdrawal of brimonidine, with or without the addition of topical corticosteroids to control inflammation depending on the severity of the condition. It is a process with an excellent prognosis., (Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Zoledronic acid (zoledronate) is a bisphosphonate used predominantly as a second-line treatment for post-menopausal osteoporosis. Its administration is associated with an acute phase reaction. Here, we present two cases of anterior uveitis following initial administration of zoledronate. In the first case, an 80-year-old lady presented with right eye pain and decreased visual acuity 24-hours post-infusion. Uveitis was diagnosed and sub-conjunctival injection of corticosteroids was required. In the second case, a 78-year-old lady presented with right eye pain, vomiting and decreased acuity 24-hours after infusion. She was treated with topical steroids and required cataract surgery to normalise visual acuity. Patients prescribed zoledronate should be warned of the risk of ocular side effects and asked to report promptly for treatment if they develop a red, painful eye or blurred vision.

New anticancer therapies, immune pathway inhibitors, may cause immune-related adverse events (IRAE). Immune-related ocular toxicities are rare but are potentially serious adverse events. The purpose of this article is to report a case of ocular inflammatory involvement potentially related to the immune response and the use of nivolumab, a new immunologic agent used for the treatment of a solid tumor. Despite the implication of this therapy in the occurrence of inflammation, other causes must always be ruled out. It is possible to continue this therapy in consideration of the risk/benefit ratio for each patient. Close collaboration between oncologists and ophthalmologists is necessary in the diagnosis and timely management of IRAE related to these new emerging therapies., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Bisphosphonates have become a commonly used class of medications to treat osteoporosis and other bone diseases. Zoledronate (zoledronic acid) can be dosed annually via intravenous infusion, making it an appealing option for patients and physicians. We report the case of a 68-year-old woman who developed severe, unilateral, ocular inflammation, including corneal endotheliitis, anterior uveitis with hyphema, scleritis, and orbital inflammation beginning 12 hours after receiving her first zoledronate infusion. Symptoms escalated but ultimately resolved with topical steroids and high-dose systemic corticosteroids. To our knowledge, this is the first report of unilateral diffuse inflammation of the eye and orbit, including corneal inflammation developing within 12 hours of a first zoledronate infusion.

Alkali burns to the eye constitute a leading cause of worldwide blindness. In recent case series, corneal transplantation revealed unexpected damage to the retina and optic nerve in chemically burned eyes. We investigated the physical, biochemical, and immunological components of retinal injury after alkali burn and explored a novel neuroprotective regimen suitable for prompt administration in emergency departments. Thus, in vivo pH, oxygen, and oxidation reduction measurements were performed in the anterior and posterior segment of mouse and rabbit eyes using implantable microsensors. Tissue inflammation was assessed by immunohistochemistry and flow cytometry. The experiments confirmed that the retinal damage is not mediated by direct effect of the alkali, which is effectively buffered by the anterior segment. Rather, pH, oxygen, and oxidation reduction changes were restricted to the cornea and the anterior chamber, where they caused profound uveal inflammation and release of proinflammatory cytokines. The latter rapidly diffuse to the posterior segment, triggering retinal damage. Tumor necrosis factor-α was identified as a key proinflammatory mediator of retinal ganglion cell death. Blockade, by either monoclonal antibody or tumor necrosis factor receptor gene knockout, reduced inflammation and retinal ganglion cell loss. Intraocular pressure elevation was not observed in experimental alkali burns. These findings illuminate the mechanism by which alkali burns cause retinal damage and may have importance in designing therapies for retinal protection., (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)