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PURPOSE: We describe a case vision-threatening sclerouveitis as a probable adverse drug reaction to ibrutinib. METHODS: Case report. RESULTS: Ibrutinib is an inhibitor of Bruton's kinase which has shown success in the treatment of hematological malignancies such as chronic lymphocytic leukemia. Despite being generally well tolerated, recent studies have implicated ibrutinib in several adverse events affecting organs such as the heart, intestines, and the eyes. We present the case of a patient who developed severe sclerouveitis after approximately one year of ibrutinib therapy, and suggest this is a probable adverse drug reaction associated with ibrutinib in accordance with the Naranjo algorithm, highlighting the importance of prompt management of ocular symptoms in these patients.

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OBJECTIVE: To characterize the total intraocular aqueous humour antibody profiles in cases receiving anti-vascular endothelial growth factor (anti-VEGF) for retinal vascular disease compared with controls without retinal pathology. DESIGN: Cross-sectional. PARTICIPANTS: 93 aqueous humour samples: 22 eyes undergoing cataract surgery (controls) and 71 eyes receiving intravitreal injections (IVI) (cases) for macular edema or neovascularization. METHODS: Antibody isotyping of aqueous humour was performed using Milliplex MAP Human Isotyping Multiplex Assay. Cases and controls were compared for several outcome measures. RESULTS: The primary outcome measure was total mean antibody isotype concentration quantified in the aqueous humour. Secondary outcomes included comparing aqueous humour concentrations with visual acuity, number of IVI received, type of anti-VEGF agent injected, and persistence intra-/subretinal fluid post injection. Mean immunoglobulin M (IgM) concentrations in cases were 19-fold higher compared with controls. Aqueous immunoglobulin G (IgG)1,2,3,4 and immunoglobulin A (IgA) were 2-4-fold higher in cases compared with controls. Disease-specific trends were observed, with diabetic retinopathy (DR) eyes containing the highest amounts of aqueous antibodies. Total number of injections correlated with higher titres of IgG1 (p < 0.001), IgG2 (p < 0.009), and IgG3 (p < 0.001) in all cases analyzed with the strongest correlations seen in DR eyes (r = 0.77, p < 0.001). Presence of aqueous humour antibodies correlated with worse post-IVI best-corrected visual acuity; IgG1 (p < 0.01), IgG2 (p < 0.005), IgG3 (p < 0.01), and IgA (p < 0.003) in all cases analyzed, with the strongest correlations seen in DR eyes (r = 0.74, p < 0.001). CONCLUSIONS: Intraocular antibodies are present in the aqueous humour at significantly higher concentrations in eyes receiving IVIs for retinal vascular diseases compared with controls.

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Vitamin D has emerged as a potentially important molecule in ophthalmology. To date, all ophthalmic data pertaining to vitamin D has been restricted primarily to tear and serum analysis in human patients. Considering the isolated nature of the eye, we sought to determine the presence of intraocular vitamin D in ocular disease. METHODS: 25-Hydroxyvitamin D3 (25(OH)D3) concentrations were measured in the eye and blood of 120 participants undergoing ophthalmic procedures. Ocular localization of the 1,25-dihydroxyvitamin D3-generating (CYP27B1) and deactivating (CYP24A1) hydroxylases was performed by immunohistochemistry. Gene expression of CYP27B1, CYP24A1 and VEGF-A was measured in eyes from patients with and without disease. RESULTS: 25(OH)D3 was quantified in 112 ocular samples. In 40 cataract patient samples, the average 25(OH)D3 concentration was 0.057 ng/mL, compared to 72 retinal disease patient samples, average of 0.502 ng/mL (p < 0.001). Intraocular 25(OH)D3 did not correlate with serum levels of 25(OH)D3. There was no difference between the level of 25(OH)D3 measured in the aqueous and vitreous humour. The vitamin D-specific CYPs 27B1 and 24A1, strongly localized to complementary regions of the ciliary body, retinal pigment epithelium and neural retina. Gene expression analysis confirmed retinal CYP27B1 correlated strongly with VEGF-A in eyes from diabetic patients (r = 0.92, p < 0.001). CONCLUSIONS: Our data confirms that vitamin D is present in the humours of the human eye and that local synthesis/degradation is possible via the ocular CYP27B1 and CYP24A1. This argues for a functional role for local vitamin D production and signaling in the eye and suggests that vitamin D may be an important intraocular mediator in disease pathogenesis.

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Periorbital infections after strabismus surgery are rare. We describe the first reported case of necrotizing group A streptococcal infection of the conjunctiva and Tenon's capsule complicating uneventful strabismus surgery in a 23-month-old boy, successfully managed with conservative intraoperative debridement and with targeted local and systemic antibiotics.

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PURPOSE: To investigate the effect of anti-inflammatory therapy on selective laser trabeculoplasty (SLT) outcomes. DESIGN: Randomized, double-masked, placebo-controlled trial. PARTICIPANTS: Patients with primary open-angle or pseudo-exfoliation glaucoma. METHODS: Patients undergoing SLT were randomized to receive placebo (artificial tears), prednisolone acetate 1%, or ketorolac tromethamine 0.5% eye drops 4 times per day for 5 days commencing immediately after SLT. MAIN OUTCOME MEASURES: Change in intraocular pressure (IOP) from baseline to the 1-month post-SLT visit. RESULTS: Mean change in IOP at the 1-month primary outcome time point, as well as all other time points, was not significantly different among groups (P = 0.99). Likewise, a repeated-measures, mixed-effects model did not find significant differences in IOP outcome at the 1-month time point (P = 0.95). The IOP was reduced in all groups at the 1-month post-SLT time point and all other time points, and no significant differences were found between groups using separate unadjusted cross-sectional analyses of variance (P > 0.15 for analyses at all time points). Treatment failure rates were not different among groups (P = 0.75), and at 1 year after SLT, the percentage of patients maintaining a 20% IOP reduction ranged from 18% to 22% in the 3 study groups. CONCLUSIONS: Anti-inflammatory therapy after SLT does not seem to substantially influence the IOP-lowering effect of SLT. In this study of patients with low baseline IOP, SLT showed limited efficacy in achieving a sustained reduction in IOP.

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PURPOSE: To evaluate the efficacy of prophylactic ketorolac 0.5% versus nepafenac 0.1% versus placebo on macular volume 1 month after uneventful phacoemulsification and evaluate the health-related quality-of-life (HRQOL) of topical nonsteroidal antiinflammatory drugs (NSAIDs) in the context of cataract surgery. SETTING: Hotel Dieu Hospital, Kingston, Ontario, Canada. DESIGN: Prospective placebo-controlled parallel-assignment double-masked randomized clinical trial. METHODS: In this study, patients 18 years or older scheduled for routine phacoemulsification were randomized to a placebo, ketorolac 0.5%, or nepafenac 0.1% and dosed 4 times a day starting 1 day before surgery and continuing for 4 weeks. Spectral-domain macular cube ocular coherence tomography scans measuring central subfield thickness, macular cube volume, and average macular cube thickness were performed at baseline and 1 month postoperatively. The HRQOL metrics were determined with the Comparison of Ophthalmic Medications for Tolerability (COMTOL) questionnaire. RESULTS: Each study group comprised 54 patients. One month postoperatively, although a trend toward significance occurred for nepafenac and ketorolac, analysis of the means of differences showed no statistically significant differences between the 3 study groups (P=.2901). The COMTOL analysis found no difference in tolerability, compliance, side-effect frequency and bother, and effects on HRQOL between ketorolac and nepafenac compared with the placebo. CONCLUSIONS: One month after uneventful phacoemulsification, there was no difference in macular volume between the placebo, ketorolac, and nepafenac. Ketorolac and nepafenac were well tolerated with minimal side-effect profiles. Thus, for patients without risk factors having routine surgery, prophylactic topical NSAIDs are not recommended.

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BACKGROUND: This study was undertaken to determine whether a difference exists in treatment outcome between patients treated with tranexamic acid (TEA) plus topical steroids and those treated with topical steroids alone. METHODS: A retrospective cohort study was conducted to compare treatment results for children with traumatic hyphema treated with TEA and topical steroids versus topical steroids alone. Patients were identified from a chart review of the Children's Hospital of Eastern Ontario eye clinic and the Queen's Department of Ophthalmology emergency eye clinic for charts coded "traumatic hyphema." The primary outcomes measured included visual acuity, rebleed rate, intraocular pressure, and time to hyphema resolution. Covariates were hyphema grade, the need for medications to lower intraocular pressure, and the presence of associated ocular traumatic complications. Analysis was performed with both bivariate analysis and multivariate models. RESULTS: Two hundred and fifteen patients with traumatic hyphema were included in our study. One hundred and thirty-seven patients (63.1%) received TEA plus topical steroids, and the remaining 78 patients received topical steroids alone. There was no significant difference in rebleed rate between the TEA plus topical steroid group (1.6%) and the steroid-alone group (2.6%, p = 0.60). INTERPRETATION: Patients with traumatic hyphema treated with TEA plus topical steroids did not have a significantly lower incidence of rebleed than those treated with topical steroids alone.

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