Safety and effectiveness of the fluocinolone acetonide intravitreal implant (ILUVIEN): 3-year results from the European IRISS registry study.

BACKGROUND: The ILUVIEN Registry Safety Study was a multicentre, open-label, non-randomised, observational, phase 4 study designed to assess the safety and effectiveness of the fluocinolone acetonide (FAc) implant in all indications in real-world practices in Europe. METHODS: The study included data collected prospectively and retrospectively. Patients receiving FAc implants between 2013 and 2017 were included and monitored until the last patient reached ≥3 years of follow-up. Mean intraocular pressure (IOP) data over the course of the study, along with IOP events, use of IOP-lowering therapy, mean change in visual acuity (VA) and information on supplemental therapy use were analysed post-FAc implantation. RESULTS: Six hundred and ninety-five eyes from 556 patients, with a mean±SD follow-up of 1150.5±357.36 days, were treated with a FAc implant. 96.7% of eyes had chronic diabetic macular oedema (cDMO). IOP lowering was achieved in 34.5% of eyes using topical agents and 4.3% by surgery. Seventy-three eyes (64.6% of 113 phakic) required cataract surgery during follow-up. Mean VA increased from a baseline of 52.2 letters to 57.1 letters at month 36, with improvement observed up to month 48. Supplementary therapies were given in 43.7% of eyes. When classified by length of cDMO less than or greater than the median duration those with a shorter history experienced greater VA gains than those with a longer history. CONCLUSION: This study confirms the favourable, long-term benefit-to-risk profile of the FAc implant in eyes with cDMO, with an additional benefit in patients when this therapy is administered earlier.

The Use of Sustained Release Intravitreal Steroid Implants in Non-Infectious Uveitis Affecting the Posterior Segment of the Eye.

The treatment of non-infectious uveitis affecting the posterior segment of the eye has been revolutionized by the development of sustained-release corticosteroid implants over the past decade. Their use is now supported by healthcare systems that have licensed and commissioned them on the basis of the high-quality randomised controlled trials that formed part of their development and which have informed clinicians as to their benefits and risks. In particular, they have provided an alternative mode of treatment for patients who do not wish to be systemically immunosuppressed, or in whom such immunosuppression is less desirable, such as those with unilateral disease or those with concurrent illnesses such as diabetes mellitus, renal disease or osteoporosis that are negatively impacted by systemic corticosteroids or other immunosuppressive agents. In this article, we review the evidence for the use of the major licensed corticosteroid implants and assess the advantages and disadvantages of each.

Towards an exposure narrative for metals and arsenic in historically contaminated Ni refinery soils: Relationships between speciation, bioavailability, and bioaccessibility.

Archived soils contaminated with Ni, Cu, Co, and As from legacy operations of a nickel refinery at Port Colborne, Ontario, Canada were speciated using mineral liberation analysis. Four Ni minerals were identified as fingerprint compounds of the historical refinery emissions. Cu and Co were present in solid solution in these minerals due to their presence in the refinery's feed. The highest concentrations of Ni, Cu, Co, and As in these soils were 18,553, 1915, 196, and 79mg/kg, respectively, these elevated contaminant concentrations attesting to the importance of incidental soil ingestion to the oral exposure pathway in Port Colborne. The in vitro gastric bioaccessibility (BAc) was determined for these contaminants, as was in vivo oral bioavailability (BAv), using a mass balance approach in male Sprague-Dawley rats. In spite of the elevated soil concentrations of Cu, the BAv of this physiologically important metal could not be distinguished from that in commercial rat chow, suggesting low potential for exposure. Co and As also had low apparent BAv (<2%). For Ni, baseline oral BAv of naturally sourced dietary Ni was found to be approximately 2%, as was the oral BAv of Ni from nickel sulfate hexahydrate. The mass balances of NiSO4·6H2O were fully accounted-for in urine and feces after a single gavage dose, indicating little to no organ incorporation from this highly soluble salt. Therefore, the urinary estimates of Ni BAv for these soils were assumed to represent true BAv despite variable fecal recoveries. The high Ni concentrations enabled BAc-BAv relationships to be developed for these contaminated soils. For absolute bioavailability (ABA) and relative bioavailability (RBA) the relationships were: ABA=0.0116(BAc)-0.0479 and RBA=0.5542(BAc)-2.2817. These findings will advance the development of robust exposure narratives for soil metal contamination in Port Colborne and elsewhere.

Outcomes Associated With Sustained-Release Intraocular Fluocinolone Implants in a Case of Melanoma-Associated Retinopathy Treated Without Systemic Immunosuppression.

Importance: Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome in which antiretinal antibodies crossreact with retinal ON-bipolar cells, resulting in night blindness and progressive visual field loss. Current therapeutic options include cytoreductive surgery in combination with immunoglobulin, corticosteroids, or plasmapheresis, but their effectiveness is limited and may be contraindicated, given the possible protective role of circulating autoantibodies against metastatic spread. We report 3-year follow-up of the first case (to our knowledge) of MAR treated with intravitreal long-acting steroid implants. Objective: To report on a patient with MAR who was treated with intravitreal fluocinolone acetonide implants in the absence of systemic immunosuppression. Design, Setting, and Participants: This is a 3-year follow-up of a 73-year-old woman with a history of surgical excision of a malignant melanoma of the left pinna who presented with visual symptoms of shimmering and nyctalopia. Fundus examination, fundus autofluorescence, and optical coherence tomography were normal, with no evidence of cystoid macular edema. Automated perimetry showed a reduction in visual field and full-field electroretinography (ERG) demonstrated findings consistent with generalized ON-bipolar cell dysfunction, typical of MAR. The patient was treated with bilateral fluocinolone acetonide intravitreal implants. Main Outcomes and Measures: Visual acuity, visual field, and electroretinography testing for 3 years after treatment. Results: Visual fields improved in this 73-year-old patient from 20/30 (Snellen measured as 6/9) OD and 20/16 (6/5) OS at baseline to 20/20 OU within 1 week of treatment. Detailed electroretinography monitoring indicated characteristic abnormalities that partly resolved after treatment, consistent with improved inner retinal ON-bipolar cell function. Bilateral cataracts developed approximately 2 years after injection; cataract surgery was performed uneventfully. At 3 years posttreatment, the patient remained visually stable and in systemic disease remission, with best-corrected visual acuity remaining at 20/20 OU. Conclusions and Relevance: We report what is, to our knowledge, the first case of MAR treated with intravitreal slow-release corticosteroid implants, which shows improvements in visual symptoms, visual fields, and retinal function. Sustained-release intraocular steroid implants may offer an effective and safe alternative to systemic immunosuppression in MAR, although results from 1 case should be generalized with abundant caution.

Changes in intraocular pressure after intravitreal fluocinolone acetonide (ILUVIEN): real-world experience in three European countries.

AIMS: The ILUVIEN Registry Safety Study is an ongoing, multicentre, open-label, observational study collecting real-world data on the safety and effectiveness of the 0.2 µg/day fluocinolone acetonide (FAc) implant in patients treated according to the European label requirements. METHODS: Patients included in this analysis were treated for the licensed indication of chronic diabetic macular oedema (cDMO; that is, DMO that persists or recurs despite treatment). Data presented in the current analysis were collected from patient records up to 6 March 2017. Visual acuity (VA) data, including mean change in VA over time and at last observation, intraocular pressure (IOP) over the course of the study, IOP events, use of IOP-lowering therapy and cup:disc ratio were analysed. Information on additional DMO treatments post-FAc implant was also captured. RESULTS: Five hundred and sixty-three patients (593 eyes) were enrolled on the study. Mean IOP for the overall population remained within the normal range throughout follow-up and 76.7% of patients did not require IOP-lowering therapy following treatment with the FAc implant. Sixty-nine per cent of eyes did not require additional DMO treatments. Mean VA in the overall population increased from 51.9 letters at baseline to 55.6 letters at month 12, with a significant increase of 2.9 letters at last observation. Patients with short-term cDMO experienced greater VA gains than those with long-term cDMO. CONCLUSIONS: The results of this analysis are comparable with those of other studies, including the Fluocinolone Acetate for Macular Edema study. The study reinforces the good safety and effectiveness profile of FAc, and demonstrates the benefit of early FAc treatment.

Head-to-head comparison of ranibizumab PRN versus single-dose dexamethasone for branch retinal vein occlusion (COMRADE-B).

PURPOSE: To compare the efficacy and safety of ranibizumab 0.5 mg versus dexamethasone 0.7 mg according to their European labels in macular oedema secondary to branch retinal vein occlusion (BRVO) in a 6-month, phase IIIb, randomized trial. METHODS: Patients received either monthly ranibizumab for 3 months followed by Pro re nata (PRN) treatment (n = 126) or a sustained-release dexamethasone implant followed by PRN sham injections (n = 118). Main outcomes were mean average change in best-corrected visual acuity (BCVA) from baseline to month 1 through month 6, mean changes in BCVA and foveal centre point thickness (FCPT), and adverse events (AEs). RESULTS: There was no difference in BCVA gains between the treatments prior to month 3. Best-corrected visual acuity (BCVA) gain with dexamethasone declined thereafter. From month 3 to month 6, mean BCVA change from baseline was significantly higher with ranibizumab than with dexamethasone [raw means (standard deviation):+16.2 (±11) letters versus +9.3 (±10.1) letters]. At month 6, the difference in BCVA gains from baseline was +17.3 letters in the ranibizumab versus +9.2 letters in the dexamethasone group. Patients in the ranibizumab group received a mean of 2.94 loading injections and 1.74 PRN retreatment injections, while those in the dexamethasone group received a single loading injection. Elevated intraocular pressure (IOP) and AEs were more frequent with dexamethasone than ranibizumab treatment. CONCLUSION: Ranibizumab PRN resulted in greater visual acuity (VA) gains in macular oedema following BRVO compared with single-dose dexamethasone over a 6-month study period, observed from month 3, when administered according to their European label. In clinical practice, retreatment with dexamethasone may be required prior to this point.

Safety and Biosimilarity of ior®LeukoCIM Compared to Neupogen® Based on Toxicity, Pharmacodynamic, and Pharmacokinetic Studies in the Sprague-Dawley Rat.

This study examined the safety, pharmacodynamic and pharmacokinetic similarity of the human recombinant filgrastim products ior®LeukoCIM and Neupogen® following a 28-day repeated subcutaneous dose administration in male and female Sprague-Dawley rats with a 14-day recovery period. Safety profiling was based on clinical observations, clinical pathology, and pathology findings for control rats dosed with vehicle and rats dosed either with 15, 75, and 150 µg/kg of ior®LeukoCIM or with 150 µg/kg of Neupogen®. The major adverse treatment-related clinical finding was mild to severe swelling of the hock-joint (tarsal joint) and hind limb, alone or accompanied with lameness which was more prominent in males and which had a similar frequency of occurrence for both ior®LeukoCIM and Neupogen®. All adverse findings were fully reversible. As expected, ior®LeukoCIM and Neupogen® both increased white blood cell and neutrophil levels in rats and to a similar extent for high-dose ior®LeukoCIM and Neupogen®. The pharmacokinetics of filgrastim following dosing with ior®LeukoCIM were well behaved and comparable for high-dose ior®LeukoCIM and Neupogen®. The results of this study imply that ior®LeukoCIM and Neupogen® had similar safety profiles, pharmacodynamic responses, and pharmacokinetic profiles that suggest they are biosimilar.

Intravitreal bevacizumab injections for diabetic macular edema - predictors of response: a retrospective study.

BACKGROUND: Outcomes of intravitreal antivascular endothelial growth factor injections are variable among patients with diabetic macular edema (DME). The aim of this study was to determine the ocular and systemic predictors of DME response to intravitreal bevacizumab (IVB). METHODS: Retrospective review over 2 years of 78 eyes from 54 patients. An anatomical response to IVB was defined as a 20% reduction in central macula thickness after the first course (three injections) of IVB. RESULTS: Twenty-eight percent of patients had an anatomical response after the first course of IVB. Systemic hypertension (odds ratio, 95% confidence interval: 12.1, 0.7-21) was a statistically significant predictor (P=0.025) of a good response to IVB, whereas previous macular laser was a statistically significant (P=0.0005) predictor of a poor response (0.07, 0.01-0.32). Sixty-eight percent of eyes underwent subsequent treatment for DME after the first course of IVB. The visual acuity gain at 24 months in hypertensive (0.7±3.6 letters) and nonhypertensive (5.2±3.7 letters) patients was not significantly different (P=0.41). CONCLUSION: Hypertension and previous macular laser were positive and negative predictors of response to IVB, respectively. However, long-term visual acuity changes were not significantly different between eyes with and without systemic hypertension.

Sutureless 25-Gauge Pars Plana Vitrectomy Combined with Retropupillary Fixation of an Iris-Claw Intraocular Lens.

BACKGROUND: The surgical case of a dropped intraocular lens inside the vitreous cavity constitutes a real challenge for the operating surgeon. Herein, we describe a case series where an alternative optical rehabilitation technique for late intraocular lens-bag complex dislocation has been used. METHODS: A modern vitrectomy device was used to remove the capsule with the dropped intraocular lens using sutureless 25-gauge pars plana vitrectomy. To ensure a better aesthetic result, with faster patient recovery and a reduced number of operations, the whole procedure was performed during the same operating session; an iris-claw intraocular lens for aphakia was selected for implantation. The implant was passed behind the constricted iris with the concave surface facing it. The lens was grasped with the manufacturer's holding forceps and fixed onto the posterior surface of the iris using the special enclavation needles. RESULTS: We have operated 12 eyes in two different clinical centres successfully, with minimal intra- and/or postoperative complications. CONCLUSION: We believe that this is a viable solution for the visual rehabilitation of patients, who would otherwise need more than one operation for a lens exchange.

Raised Intraocular Pressure in Nonjuvenile Idiopathic Arthritis-Uveitis Children: Risk Factors and Effect on Retinal Nerve Fiber Layer.

PURPOSE: To determine risk factors for intraocular pressure (IOP) elevation and glaucoma in children with nonjuvenile idiopathic arthritis-related uveitis and any IOP-related changes in the retinal nerve fiber layer (RNFL) thickness. PATIENTS AND METHODS: Clinical data were collected from children attending a tertiary referral uveitis clinic between May 2010 and October 2012. We assigned 206 eyes of 103 children into 32 normal eyes, 108 normotensive uveitics (NU), 41 hypertensive uveitics (HU: raised IOP without glaucomatous disc), and 25 glaucomatous uveitics (GU: raised IOP with glaucomatous disc). Risk factors for raised IOP, glaucoma and steroid response (SR) were evaluated and RNFL thickness across groups was compared with determine changes related to raised IOP. RESULTS: IOP elevation occurred in 40 patients (38.8%) or 66/174 eyes with uveitis (37.9%); and SR occurred in 35.1% of all corticosteroid-treated eyes. Chronic uveitis was a significant risk factor for raised IOP [odds ratio (OR)=9.28, P=0.001], glaucoma, and SR (OR=8.4, P<0.001). Higher peak IOP was also a risk factor for glaucoma (OR=1.4, P=0.003). About 70% of SR eyes were high responders (IOP increase >15 mm Hg from baseline), associated with younger age and corticosteroid injections. Although no significant RNFL thinning was detected between HU and NU eyes, significant thinning was detected in the inferior quadrant of GU (121.3±28.9 µm) compared with NU eyes (142.1±32.0 µm, P=0.043). CONCLUSIONS: Children with chronic uveitis are at higher risk of raised IOP and glaucoma. Thinning of the inferior RNFL quadrant may suggest glaucomatous changes in uveitic children with raised IOP.

Long-term Outcomes of Rituximab Therapy in Ocular Granulomatosis with Polyangiitis: Impact on Localized and Nonlocalized Disease.

PURPOSE: To evaluate the long-term outcomes of rituximab (RTX) treatment in patients with ocular granulomatosis with polyangiitis (GPA) with localized or generalized disease. DESIGN: Retrospective cohort. PARTICIPANTS: Thirty-seven patients with ocular GPA receiving RTX in a multidisciplinary vasculitis clinic between 2004 and 2013. METHODS: A total of 100 patients who received a course of RTX were identified, and notes were reviewed. Baseline demographic details, clinical characteristics (including organ involvement), drugs used, and outcome measures were recorded. MAIN OUTCOME MEASURES: The percentage in remission (inactive disease with prednisolone ≤7.5 mg with or without maintenance treatment) at 6 months, time to remission, percentage relapsing, side effects, B-cell count, antineutrophil cytoplasm antibody titers, induction, and maintenance regimens. RESULTS: The median follow-up time after the first RTX course was 36.5 months. Twenty patients had scleritis, and 17 patients had orbital disease; 86% achieved remission at 6 months. The percentage in remission versus partial remission was not statistically significant between patients with scleritis and patients with orbital disease (85% vs. 15% with scleritis and 82% vs. 18% with orbital disease; P = 1.00). The percentage relapsing was not statistically significant (P = 0.33) between scleritis (60%) and orbital disease (41%). Localized disease (ocular ± ear-nose-throat/lung) was observed in 57%, and generalized disease (ocular plus other organs) was observed in 43%, the former having a median duration of disease of 40 months. There was no statistically significant difference (P = 0.37) in the percentage in remission between localized and generalized ocular disease. Relapses occurred in 51%, with localized disease being a significant risk factor for relapse. Fifty percent of patients with generalized disease versus none with localized disease received cyclophosphamide (CYP) as part of the induction regimen. Patients who received CYP during induction had significantly (P = 0.027) lower ratios of baseline 12-month proteinase 3 titers than patients who did not have CYP. Infections were observed in 16% of patients, with 8% requiring hospital admission. CONCLUSIONS: Our long-term data suggest that RTX is effective for inducing disease remission in localized and generalized ocular GPA. Localized disease is a significant risk factor for relapse, which may be related to less use of CYP in the induction regimen.

Treatment of diabetic maculopathy.

Diabetic maculopathy is an important cause of severe sight impairment. There has been a significant evolution in its treatment over the past decade and laser treatment is now largely being superseded by intravitreal injections of anti-vascular endothelial growth factor agents or corticosteroids.

Bilateral sequential non-arteritic anterior ischaemic optic neuropathy following repeat influenza vaccination.

A 68-year-old man developed bilateral sequential non-arteritic anterior ischaemic optic neuropathy, each episode occurring with a close temporal relationship to influenza vaccination.

Long-term clinical outcome and causes of vision loss in patients with uveitis.

PURPOSE: To evaluate the long-term clinical and functional outcome, risks, and causes of vision loss and burden of disease among patients with uveitis. DESIGN: Cross-sectional study. PARTICIPANTS: The study included 1076 patients diagnosed with uveitis who attended the uveitis clinic at Moorfields Eye Hospital, London, United Kingdom, between 2011 and 2013. METHODS: Information was gathered from the notes of all patients who were examined in the clinic. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), causes of moderate vision loss (MVL; 20/50-20/120), and severe vision loss (SVL; ≤ 20/200). RESULTS: The study included 1799 eyes of 1076 patients with an average follow-up of 7.97 ± 0.17 years (median, 5.6 years; range, 1 month-54 years; 8159 patient-years; 14 226 eye-years). Average BCVA remained stable for patients with anterior uveitis (20/30 at baseline to 20/33 at 10 years), as well as for those with nonanterior uveitis (20/50 at baseline to 20/47 at 10 years). Vision loss was noted in 19.2% of eyes, with an incidence for MVL of 0.01 per eye-year or 0.02 per patient-year and for SVL of 0.01 per eye-year or 0.02 per patient-year. Patients were more at risk of vision loss if they had non-anterior uveitis disease, vitreous opacities, retinal detachment, cystoid macular edema (CME), macular scarring, macular hole, optic neuropathy, or macular ischemia. Chronic CME was the most common cause of MVL (3.55%), and macular scarring was the most common cause for irreversible SVL (4%). Among 525 patients (48.7%) who received oral prednisolone, 320 (61%) required a dose of more than 40 mg/day and 130 (24.8%) also required 1 or more second-line agents. Patients were reviewed on average 33.7 ± 0.7 times or 5.9 ± 0.46 times/year. CONCLUSIONS: Long-term functional outcome among uveitis patients is good, with BCVA remaining stable for more than 10 years of follow-up. In cases when vision loss occurs, it is related mainly to retinal changes. The burden on clinical services is similar regardless of the severity of disease or the risk of vision loss.

Birdshot chorioretinopathy.

PURPOSE OF REVIEW: Birdshot chorioretinopathy remains incompletely understood, but new insights into its pathogenesis have been reported recently, and treatment and monitoring options have also expanded. Central visual acuity may remain good until the late stages of the disease, but loss of visual field and peripheral retinal function is common. RECENT FINDINGS: The underlying pathogenesis of the disease has long been believed to be T-cell driven, but examination of the IL-17 pathway has now further refined the potential underlying mechanism. New imaging techniques, including extended depth imaging of the choroid with optical coherence tomography, have demonstrated promise in detecting disease activity earlier, enabling targeted treatment to be given. Treatment options have expanded with the advent of the biological agents, and these may yet improve outcomes, particularly in refractory patients. SUMMARY: Laboratory research continues to investigate the underlying mechanisms of disease, but our understanding remains frustratingly incomplete for a disease with such a clear HLA association. Clinical research is increasingly being driven to improve the phenotyping of affected patients so that those at risk of visual loss can be identified early and treated more aggressively with individually targeted therapies such as the newer biological agents, but how successful this approach will ultimately prove to be remains to be seen.

Safety and biosimilarity of ior(®) EPOCIM compared with Eprex(®) based on toxicologic, pharmacodynamic, and pharmacokinetic studies in the Sprague-Dawley rat.

This study examined the safety, pharmacodynamic (PD), and pharmacokinetic (PK) biosimilarity of the human recombinant erythropoietin (EPO) products ior(®) EPOCIM and Eprex(®) following a 28-day repeated intravenous dose administration in male and female Sprague-Dawley rats with a 14-day recovery period. Safety profiling was based on clinical observations, clinical pathology, and pathology findings for control rats dosed with vehicle and rats dosed either with 30, 300, and 600 I.U./kg of ior(®) EPOCIM or 600 I.U. of Eprex(®) . Adverse findings for both ior(®) EPOCIM and Eprex(®) were similar and were a consequence of thrombotic events (ulcerative skin lesions, swollen hock joints/lameness, stomach ulcers) and decreased body weight gains, all known adverse reactions to this class of drug in rats. With the exception of stomach ulcers, all other adverse findings were fully reversible. Neither drug stimulated the production of antidrug antibodies. As expected, ior(®) EPOCIM and Eprex(®) both increased reticulocyte, red blood cell, hemoglobin, and hematocrit levels in rats. The PK of EPO following dosing with ior(®) EPOCIM was well behaved and consistent with the literature. The results of this study imply that ior(®) EPOCIM and Eprex(®) had safety profiles, PD responses, and toxicokinetic profiles that were biosimilar.

Evaluation of retinal nerve fiber layer thickness in eyes with hypertensive uveitis.

IMPORTANCE: Uveitic glaucoma is among the most common causes of irreversible visual loss in uveitis. However, glaucoma detection can be obscured by inflammatory changes. OBJECTIVE: To determine whether retinal nerve fiber layer (RNFL) measurement can be used to detect glaucoma in uveitic eyes with elevated intraocular pressure (IOP). DESIGN, SETTING, AND PARTICIPANTS: Comparative case series of RNFL measurement using optical coherence tomography performed from May 1, 2010, through October 31, 2012, at a tertiary referral center. We assigned 536 eyes with uveitis (309 patients) in the following groups: normal contralateral eyes with unilateral uveitis (n = 72), normotensive uveitis (Uv-N) (n = 143), raised IOP and normal optic disc and/or visual field (Uv-H) (n = 233), and raised IOP and glaucomatous disc and/or visual field (Uv-G) (n = 88). EXPOSURES: Eyes with uveitis and elevated IOP (>21 mm Hg) on at least 2 occasions. MAIN OUTCOMES AND MEASURES: Comparison of RNFL values between groups of eyes and correlation with clinical data; risk factors for raised IOP, glaucoma, and RNFL thinning. RESULTS: Mean (SD) global RNFL was thicker in Uv-N (106.4 [21.4] µm) compared with control (96.0 [9.0] µm; P < .001) eyes and was thicker in Uv-N eyes with active (119.6 [23.2] µm) compared with quiescent (102.3 [20.8] µm; P = .001) uveitis, which in turn was not significantly different from control eyes (P = .07). Compared with Uv-N eyes, significant RNFL thinning was seen in all quadrants except the temporal in Uv-G eyes and significant thinning in the inferior quadrant of Uv-H eyes with no evidence of disc or visual field changes (P = .03). Risk factors for elevated IOP were male sex and anterior uveitis. Age, higher peak IOP, longer duration of follow-up, and uveitis-induced elevation of IOP were risk factors for glaucoma and RNFL defect. CONCLUSIONS AND RELEVANCE: Screening for glaucomatous RNFL changes in uveitis must be performed during quiescent periods. Thinning of the inferior quadrant suggests that glaucomatous damage, more than uveitic ocular hypertension, is in fact occurring. Measurement of RNFL may detect signs of damage before disc or visual field changes and therefore identifies a subgroup that should receive more aggressive treatment.

Treatment with repeat dexamethasone implants results in long-term disease control in eyes with noninfectious uveitis.

PURPOSE: To describe the long-term outcome of eyes with uveitis after repeated treatment with dexamethasone implants (Ozurdex; Allergan, Inc., Irvine, CA). DESIGN: Retrospective, observational case series. PARTICIPANTS: Thirty-eight eyes of 27 patients with uveitis that were treated with 61 dexamethasone implants. METHODS: All eyes underwent dexamethasone pellet implantation. Anatomic and functional outcomes, as well as ocular complications, were noted. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), central retinal thickness (CRT), vitreous haze score, and presence of increased intraocular pressure or cataract. RESULTS: Average follow-up was 17.3 ± 1.8 months after the first implant (median, 13.3 months; range, 3-54.5 months; 54.65 eye-years), with 14 eyes (36.9%) receiving a single implant and 24 eyes (63.1%) receiving multiple implantations. After the first implantation, average BCVA improved significantly from 0.47 ± 0.05 logarithm of the minimum angle of resolution (logMAR) units (Snellen equivalent, 20/60) to 0.27 ± 0.07 logMAR (Snellen equivalent, 20/37; P<0.001); CRT decreased by 263 ± 44.22 µm (P = 0.003), although macular edema persisted in 50% of eyes, and the percentage of eyes achieving a vitreous haze score of 0 increased from 58% to 83% (P = 0.03). The median duration of therapeutic effect after the first injection was 6 months (range, 2-42 months), with a similar response achieved after each repeat implantation. The accumulated effect of repeat dexamethasone implants resulted in a continued improvement in BCVA (R(2) = 0.91; P<0.0001), with significant improvement and stabilization of CRT. After repeated implantations, 2 eyes had progression of posterior subcapsular opacities, although neither required surgery. There were 7 instances of increased intraocular pressure of more than 21 mmHg at a rate of 0.13 per eye-year, all of which responded to pharmacologic treatment. CONCLUSIONS: The accumulated effect of repeat dexamethasone pellet implantations improves retinal thickness and resolves ocular inflammation, resulting in restoration of ocular function. Ocular complications were minimal, with no eyes requiring surgery for increased ocular pressure or progression of cataract.

Clinical and imaging features predictive of orbital granulomatosis with polyangiitis and the risk of systemic involvement.

OBJECTIVE: Granulomatosis with polyangiitis (GPA), previously Wegener's granulomatosis, requires prompt diagnosis and systemic review to exclude life-threatening disease. However, early diagnosis of orbital GPA may be difficult because anti-neutrophil cytoplasmic antibody (ANCA) and anti-PR3 antibody screening can be negative at presentation and orbital biopsies taken for diagnosis may not show the classic features of GPA. This study was designed to compare GPA with other causes of orbital inflammation and to identify the presenting clinical and imaging features most likely to predict GPA and its systemic spread. DESIGN: Retrospective noninterventional comparative case series. PARTICIPANTS: A total of 247 patients who had undergone orbital biopsies for clinical presentations with orbital inflammation were identified from the Institute of Ophthalmology pathology database. METHODS: Patients were divided into GPA and non-GPA groups on the basis of their final clinical diagnosis. Clinical and imaging features of these 2 groups were compared to determine those predictive of GPA, and patients with GPA also had long-term evaluation for systemic involvement. MAIN OUTCOME MEASURES: A diagnosis of orbital GPA and development of systemic GPA were the main outcome measures. RESULTS: Features highly suggestive of GPA were sinonasal symptoms, sinonasal changes, or paranasal bone erosion on imaging (P < 0.001). Bony erosion was independent of ANCA status or systemic involvement. Twenty-two percent of patients (8/37) with GPA had evidence of systemic involvement at presentation, and no patient presenting with solely orbital GPA developed later systemic disease over a median follow-up of 2.7 years. CONCLUSIONS: A high index of suspicion should be maintained for GPA when a patient presents with an orbital mass and sinonasal symptoms or imaging shows sinonasal involvement or paranasal bone erosion. No patient with solely orbital GPA involvement at presentation developed systemic disease, suggesting that orbital GPA can remain localized in the long-term.

Outcomes of changing immunosuppressive therapy after treatment failure in patients with noninfectious uveitis.

PURPOSE: To evaluate the outcomes of changing immunosuppressive therapy for noninfectious uveitis after failure. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with noninfectious uveitis managed at 2 tertiary uveitis clinics in the United Kingdom and Australia. METHODS: Participants with a history of using immunosuppressive therapy were identified in clinics, and notes were reviewed by doctors trained in uveitis therapy. Each treatment episode/course (starting or changing a therapy) was identified, and demographic details, clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or biologicals), and drug doses were obtained. MAIN OUTCOME MEASURES: For each treatment episode, the reasons for changing therapy, corticosteroid-sparing effects, and control of inflammation were determined. RESULTS: A total of 147 patients were identified who underwent 309 different treatment episodes. Fifty-five percent of patients eventually required a change in treatment after their first treatment episode/course. Forty-five episodes involved switching from one ISA to another, with 50% to 100% of these patients achieving "success" (prednisolone ≤10 mg and sustained control) with the new ISA. A combination of ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of these patients. Biological agents were used in 45 episodes, the most common one being infliximab, which achieved success in 80% of patients. CONCLUSIONS: Our data suggest that control of inflammation can be achieved after switching or combining ISAs.