Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration

Purpose: To evaluate the safety and efficacy of repeat injections of Brimonidine Drug Delivery System (Brimo DDS) Generation 2 (Gen 2) containing 400-μg brimonidine in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Design: A phase IIb, randomized, multicenter, double-masked, sham-controlled, 30-month study (BEACON). Participants: Patients diagnosed with GA secondary to AMD and multifocal lesions with total area of > 1.25 mm2 and ≤ 18 mm2 in the study eye. Methods: Enrolled patients were randomized to treatment with intravitreal injections of 400-μg Brimo DDS (n = 154) or sham procedure (n = 156) in the study eye every 3 months from day 1 to month 21. Main Outcome Measures: The primary efficacy endpoint was GA lesion area change from baseline in the study eye, assessed with fundus autofluorescence imaging, at month 24. Results: The study was terminated early, at the time of the planned interim analysis, because of a slow GA progression rate (∼ 1.6 mm2/year) in the enrolled population. Least squares mean (standard error) GA area change from baseline at month 24 (primary endpoint) was 3.24 (0.13) mm2 with Brimo DDS (n = 84) versus 3.48 (0.13) mm2 with sham (n = 91), a reduction of 0.25 mm2 (7%) with Brimo DDS compared with sham (P = 0.150). At month 30, GA area change from baseline was 4.09 (0.15) mm2 with Brimo DDS (n = 49) versus 4.52 (0.15) mm2 with sham (n = 46), a reduction of 0.43 mm2 (10%) with Brimo DDS compared with sham (P = 0.033). Exploratory analysis showed numerically smaller loss over time in retinal sensitivity assessed with scotopic microperimetry with Brimo DDS than with sham (P = 0.053 at month 24). Treatment-related adverse events were usually related to the injection procedure. No implant accumulation was observed. Conclusions: Multiple intravitreal administrations of Brimo DDS (Gen 2) were well tolerated. The primary efficacy endpoint at 24 months was not met, but there was a numeric trend for reduction in GA progression at 24 months compared with sham treatment. The study was terminated early because of the lower-than-expected GA progression rate in the sham/control group. Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references

Real-Life ILUVIEN (Fluocinolone Acetonide) Case Study: Rapid Drying of the Macula and Improved Vision within 2 Years after Therapy Initiation

Importance: A case showing sustained structural and functional responses 2 years after a single treatment with ILUVIEN (0.2 µg/day fluocinolone acetonide, FAc) despite suboptimal responses to ranibizumab. Observations: A 68-year-old female patient with diabetic macular oedema (DME) from type 2 diabetes mellitus was first diagnosed in October 2010 and had a baseline visual acuity (VA) of 46 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the left eye. Central foveal thickness (CFT) was 712 microns. The patient was treated with 11 intravitreal injections of ranibizumab (5 in combination with a small-interfering RNA agent), and by March 2014, VA and CFT were largely unchanged (55 ETDRS letters and 774 microns). The patient was treated with ILUVIEN as she had a pseudophakic lens and a clearly suboptimal response to the prior therapy with ranibizumab. An implant releasing FAc at a dosage of 0.2 µg/day was administered in March 2014, and the optical coherence tomography indicated that the macula was dry after 7 days (CFT was below 300 microns). This was sustained at 6, 12, and 24 months after the treatment. VA improved by 5 letters within 7 days and by 15 letters within 14 days, and this was maintained after 24 months. Throughout the duration of this study, the intraocular pressure was ≤22 mm Hg, and no glaucoma medication was administered. Conclusions and Relevance: In real-life UK practice, this DME patient showed a suboptimal response to multiple intravitreal injections of ranibizumab. When subsequently treated with a single injection of ILUVIEN, there were large and rapid improvements in VA and CFT that were maintained for the following 2 years

Cost advantage of fluocinolone acetonide implant (ILUVIEN®) versus ranibizumab in the treatment of chronic diabetic macular oedema

A cost analysis model was developed to evaluate the 3-year cost of treating vision impairment associated with chronic diabetic macular oedema (DMO) with either a single fluocinolone acetonide (FAc) implant or with 14 ranibizumab injections in the National Health Service (NHS) in England. The model accounts for the overall direct cost of treatment in both pseudophakic and phakic eyes including the cost of the drugs, the cost of administering the drugs, the cost of monitoring the patient, the cost of additional interventions required, and the cost of managing adverse events.The model indicates a considerable cost saving with the FAc implant irrespective of lens status even allowing for the additional cost of cataract extraction surgery in the majority of steroid-treated phakic patients. Using NHS list prices, the total treatment cost over a 3-year period for one eye is calculated to be £14,273 with multiple ranibizumab injections, £8205 with an FAc implant in a pseudophakic eye and £8932 with an FAc implant in a phakic eye – resulting in an overall cost saving with the implant of £6068 per pseudophakic eye and £5341 per phakic eye. The FAc implant remains the dominant treatment when up to 60% of patients receive the FAc implant and at least 40% of patients receive 14 ranibizumab injections.The results presented here indicate that 3 years of treatment with a single FAc implant offers a considerable cost saving over 3 years of treatment with ranibizumab (assumed to comprise 14 injections) in both phakic and pseudophakic eyes

Case Series Investigating the Efficacy and Safety of Bilateral Fluocinolone Acetonide (ILUVIEN®) in Patients with Diabetic Macular Edema: 10 Eyes with 12 Months Follow-up

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>.</b> <a href="https://link.springer.com/article/10.1007/s40123-016-0049-3?view=classic">https://link.springer.com/article/10.1007/s40123-016-0049-3?view=classic</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data:report 2

Purpose: To report the findings at 1 year of a study comparing repeated intravitreal bevacizumab (ivB) and modified Early Treatment of Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) in patients with persistent clinically significant diabetic macular edema (CSME).Design: Prospective, randomized, masked, single-center, 2-year, 2-arm clinical trial.Participants: A total of 80 eyes of 80 patients with center-involving CSME and at least 1 prior MLT.Methods: Subjects were randomized to either ivB (6 weekly; minimum of 3 injections and maximum of 9 injections in the first 12 months) or MLT (4 monthly; minimum of 1 treatment and maximum of 4 treatments in the first 12 months).Main Outcome Measures: The primary end point was the difference in ETDRS best-corrected visual acuity (BCVA) at 12 months between the bevacizumab and laser arms.Results: The baseline mean ETDRS BCVA was 55.7 +/- 9.7 (range 34-69) in the bevacizumab group and 54.6 +/- 8.6 (range 36-68) in the laser arm. The mean ETDRS BCVA at 12 months was 61.3 +/- 10.4 (range 34-79) in the bevacizumab group and 50.0 +/- 16.6 (range 8-76) in the laser arm (P = 0.0006). Furthermore, the bevacizumab group gained a median of 8 ETDRS letters, whereas the laser group lost a median of 0.5 ETDRS letters (P = 0.0002). The odds of gaining >= 10 ETDRS letters over 12 months were 5.1 times greater in the bevacizumab group than in the laser group (adjusted odds ratio, 5.1; 95% confidence interval, 1.3-19.7; P = 0.019). At 12 months, central macular thickness decreased from 507 +/- 145 mu m (range 281-900 mu m) at baseline to 378 +/- 134 mu m (range 167-699 mu m) (P<0.001) in the ivB group, whereas it decreased to a lesser extent in the laser group, from 481 +/- 121 mu m (range 279-844 mu m) to 413 +/- 135 mu m (range 170-708 mu m) (P = 0.02). The median number of injections was 9 (interquartile range [IQR] 8-9) in the ivB group, and the median number of laser treatments was 3 (IQR 2-4) in the MLT group.Conclusions: The study provides evidence to support the use of bevacizumab in patients with center-involving CSME without advanced macular ischemia

Diabetic retinopathy and diabetic macular oedema pathways and management: UK Consensus Working Group

The management of diabetic retinopathy (DR) has evolved considerably over the past decade, with the availability of new technologies (diagnostic and therapeutic). As such, the existing Royal College of Ophthalmologists DR Guidelines (2013) are outdated, and to the best of our knowledge are not under revision at present. Furthermore, there are no other UK guidelines covering all available treatments, and there seems to be significant variation around the UK in the management of diabetic macular oedema (DMO). This manuscript provides a summary of reviews the pathogenesis of DR and DMO, including role of vascular endothelial growth factor (VEGF) and non-VEGF cytokines, clinical grading/classification of DMO vis a vis current terminology (of centre-involving [CI-DMO], or non-centre involving [nCI-DMO], systemic risks and their management). The excellent UK DR Screening (DRS) service has continued to evolve and remains world-leading. However, challenges remain, as there are significant variations in equipment used, and reproducible standards of DMO screening nationally. The interphase between DRS and the hospital eye service can only be strengthened with further improvements. The role of modern technology including optical coherence tomography (OCT) and wide-field imaging, and working practices including virtual clinics and their potential in increasing clinic capacity and improving patient experiences and outcomes are discussed. Similarly, potential roles of home monitoring in diabetic eyes in the future are explored. The role of pharmacological (intravitreal injections [IVT] of anti-VEGFs and steroids) and laser therapies are summarised. Generally, IVT anti-VEGF are offered as first line pharmacologic therapy. As requirements of diabetic patients in particular patient groups may vary, including pregnant women, children, and persons with learning difficulties, it is important that DR management is personalised in such particular patient groups. First choice therapy needs to be individualised in these cases and may be intravitreal steroids rather than the standard choice of anti-VEGF agents. Some of these, but not all, are discussed in this document

Systemic corticosteroid use in UK Uveitis practice: results from the ocular inflammation steroid toxicity risk (OSTRICH) study.

OBJECTIVES To ascertain adherence to an international consensus target of ≤7.5 mg/day of prednisolone for maintenance systemic corticosteroid (CS) prescribing in uveitis and report the frequency of courses of high-dose systemic CS in the UK. METHODS We conducted a national, multicentre audit of systemic CS prescribing for uveitis at 11 UK sites between November 2018 and March 2019. High-dose CS was defined as (1) maintenance >7.5 mg prednisolone for >3 consecutive months, or (2) >1 course ≥40 mg oral CS or ≥500 mg intravenous (IV) methylprednisolone in the past 12 months. Case notes of patients exceeding threshold CS doses were reviewed by an independent uveitis specialist and judged as avoidable or not, based upon a scoring matrix. RESULTS Of 667 eligible patients, 285 (42.7%) were treated with oral or IV CS over the preceding 12 months; 96 (33.7%) of these exceeded the threshold for high-dose CS. Twenty-five percent of prescribing in patients on excess CS was judged avoidable; attributed to either prescribing long-term CS without evidence of consideration of alternative strategies, prescribing error or miscommunication. More patients received immunomodulatory therapy (IMT) in the group treated with CS above threshold than below threshold (p < 0.001) but there was no significant difference in doses of IMT. CONCLUSION 33% of patients had been prescribed excessive corticosteroid when compared to the reference standard. An analysis of decision-making suggests there may be opportunity to reduce excess CS prescribing in 25% of these patients