Fluocinolone Acetonide Insert Research Articles

Long-Term Results of 0.19mg Fluocinolone Acetonide Insert for Treatment of Non-Infectious Uveitis in Clinical Practice

ABSTRACT Purpose To evaluate the long-term outcomes of patients with non-infectious uveitis treated with 0.19 mg fluocinolone acetonide insert (FAi) for up to 36 months in clinical practice. Methods A retrospective study conducted at a single uveitis center. Results Fifty eyes of 39 patients were included. Mean best corrected visual acuity (BCVA) and central retinal thickness (CRT) remained stable until month 36 after FAi implantation (61.04 vs. 70.25 letters and 370.8 vs. 332.5 µm, respectively). The recurrence rate was 34% (17 eyes) after 36 months, of which 82% (14 eyes) received high-dose corticosteroids before FAi. Mean intraocular pressure (IOP) remained unchanged (13.38 vs. 15.74 mmHg), while most phakic eyes (13 of 14 eyes) required cataract surgery. Conclusions We show that FAi effectively prevents recurrences of non-infectious uveitis for up to three years in clinical practice, comparable with randomized clinical trials. Patients who received high-dose corticosteroids before FAi have an increased risk for early recurrence and should be considered for scheduled re-treatment.

0.18 MG FLUOCINOLONE ACETONIDE INSERT FOR THE TREATMENT OF CHRONIC POSTOPERATIVE PSEUDOPHAKIC CYSTOID MACULAR EDEMA.

To report the outcomes of the 0.18 mg fluocinolone acetonide insert (FAi) in the treatment of chronic (>6 months) postoperative cystoid macular edema after cataract surgery. This was a retrospective consecutive case series of eyes with chronic postoperative cystoid macular edema treated with the FAi. Visual acuity, intraocular pressure, optical coherence tomography metrics, and supplemental therapies were extracted from the charts before and at 3, 6, 12, 18, and 21 months after FAi placement, when available. Nineteen eyes of 13 patients with chronic postoperative cystoid macular edema after cataract surgery underwent FAi placement with an average follow-up of 15.4 months. Ten eyes (52.6%) had a ≥2-line gain in visual acuity. Sixteen eyes (84.2%) had a ≥20% reduction in optical coherence tomography central subfield thickness. Eight eyes (42.1%) had complete resolution of CME. Improvements in central subfield thickness and visual acuity were sustained throughout individual follow-up. Compared with 18 eyes (94.7%) requiring local corticosteroid supplementation before FAi, only six eyes (31.6%) required supplementation after FAi. Similarly, of the 12 eyes (63.2%) that were on corticosteroid drops before FAi, only 3 (15.8%) required drops after FAi. Eyes with chronic postoperative cystoid macular edema after cataract surgery treated with the FAi had improved and sustained visual acuity and optical coherence tomography metrics, along with a reduction in supplemental treatment burden.

IOP Elevation in Patients Treated With Fluocinolone Acetonide Insert for Chronic Noninfectious Uveitis Affecting the Posterior Segment.

Characterize timing of intraocular pressure (IOP) elevation in patients treated with fluocinolone acetonide insert (FAi) for uveitis. A post-hoc subset analysis of data from a randomized, prospective, double-masked, sham-controlled, 3-year, phase 3 clinical trial with 129 participants with noninfectious posterior uveitis randomly assigned to receive 0.18-mg fluocinolone acetonide insert or sham injection. The number of eyes with IOP of 30 mm Hg or greater at different time points were recorded. The incidence of FAi eyes that reached IOP 30 mm Hg or greater was 17.2%. The mean number of days to first IOP response was 241. IOP elevations were divided into four time periods: under 1 month (33%), 3 to 6 months (33%), 6 to 18 months (26.7%), and greater than 18 months (6.7%). Ten cases of elevated IOP were managed medically and five required surgical management. Visual field analysis revealed no significant change in mean deviation compared to patients' own, untreated eyes (P > .05). IOP elevations occurred in 15 out of 87 patients treated with the FAi. The onset of elevated IOP was fairly evenly distributed across the 36-month trial. Patients should be regularly evaluated for increased IOP, which can be successfully managed by traditional means. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:387-390.].

Intravitreal Fluocinolone 0.19mg Implant in the Management of Chronic Non-Infectious Uveitis: 12-Month Outcomes from a Single Tertiary Centre

ABSTRACT Aim To present efficacy and safety of 0.19 mg fluocinolone acetonide insert (FAi) to treat chronic noninfectious uveitis (NIU) in a single referral center. Methods A retrospective observational clinical study of 11 eyes with NIU complicated by chronic cystoid macular edema (CMO). Results The main indication for treatment was chronic CMO in all 11 eyes. The mean central retinal thickness (CRT) at baseline was 435 μm ± 176, improving to 296 μm ± 67 at 12 months. Raised intraocular pressure (IOP) was the commonest adverse event. An IOP >21 mmHg was observed in three eyes, and >30 mmHg in one eye, managed with topical therapy. The mean best corrected visual acuity (BCVA) was stable at 12 months. There were no observed recurrences of uveitis. Two eyes received adjunctive treatment for worsening CRT. Conclusions Our results suggest FAi is an effective maintenance treatment for NIU with favorable functional and anatomical outcomes.

Fluocinolone acetonide vitreous insert for chronic diabetic macular oedema: a systematic review with meta-analysis of real-world experience

We conducted a meta-analysis of real-world studies on the 0.19 mg Fluocinolone Acetonide (FAc) intravitreal implant for chronic diabetic macular oedema (DMO), comparing these findings with the Fluocinolone Acetonide for Diabetic Macular Edema (FAME) study. The primary outcome was mean change of best corrected visual acuity (BCVA) at 24 months. Secondary outcomes were 36-month mean BCVA, mean central macular thickness (CMT) change, rates of eyes receiving supplementary intravitreal therapy, cataract surgery, intraocular pressure (IOP)-lowering drops and glaucoma surgery. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Nine real-world studies were included. The FAc implant yielded a significantly improved BCVA at 24 and 36 months (24-month MD = 4.52; 95% CI 2.56–6.48; 36-month MD = 8.10; 95% CI 6.34–9.86). These findings were comparable with the FAME study. The FAc implant yielded significantly reduced 24- and 36-month CMT. Pooled proportions of cataract surgery, IOP-lowering drops and glaucoma surgery were 39%, 27% and 3%, respectively, all lower than the FAME study. Pooled estimate of supplementary intravitreal therapy was 39%, higher than the 15.2% of the FAME study. This meta-analysis of real-world studies confirms favorable visual and anatomical outcomes following FAc insert for chronic DMO. In real-life studies more than one third of patients received supplementary intravitreal therapy, an issue that needs to be further explored.

Local treatment of infectious and noninfectious intermediate, posterior, and panuveitis: current concepts and emerging therapeutics.

Local therapeutics play an important role in the management of infectious and noninfectious uveitis (NIU) as well as certain masquerade syndromes. This review highlights the established therapeutics and those under investigation for the management of uveitis. An injectable long-acting fluocinolone acetonide insert was recently approved by the Food and Drug Administration for the treatment of NIU affecting the posterior segment. Intravitreal methotrexate, sirolimus, and anti-vascular endothelial growth factor (VEGF) agents are being evaluated for efficacy in NIU. Intravitreal foscarnet and ganciclovir are important adjuncts in the treatment of viral retinitis as are methotrexate and rituximab for the management of vitreoretinal lymphoma. Local injectable steroids with greater durability are now available for NIU but comparative efficacy to other treatment modalities remains to be determined. Local steroid-sparing immunosuppressive agents are undergoing evaluation for efficacy in NIU as are anti-VEGF agents for uveitic macular edema. Local antivirals may improve outcomes in cases of viral retinitis. Local chemotherapeutics can help induce remission in vitreoretinal lymphoma.

Effect of a Fluocinolone Acetonide Insert on Recurrence Rates in Noninfectious Intermediate, Posterior, or Panuveitis: Three-Year Results

To examine the 36-month efficacy and safety of a 0.2 μg/day fluocinolone acetonide insert (FAi) to treat noninfectious uveitis of the posterior segment (NIU-PS). Phase 3, prospective, double-masked, multicenter study (clinicaltrials.gov, NCT01694186). Adults (≥18 years old) with a diagnosis of NIU-PS in ≥1 eye for ≥1 year and ≥2 recurrences of uveitis requiring systemic corticosteroid, immunosuppressive treatment, or intraocular corticosteroids. Participants were randomized 2:1 to FAi or sham (injection plus standard of care) treatment. The primary outcome was the difference between the proportion of FAi-treated and sham-treated patients who had a uveitis recurrence. Secondary outcomes included time to first recurrence, number of recurrences, best-corrected visual acuity (BCVA) change from baseline, resolution of macular edema, and number of adjunctive treatments. One hundred twenty-nine participants (n= 87 FAi-treated; n= 42 sham-treated) were enrolled. Over 36 months of treatment, cumulative uveitis recurrences were significantly reduced with FAi compared with sham (65.5% vs. 97.6%, respectively; P < 0.001); time to first recurrence was commensurately longer (median 657.0 and 70.5 days, respectively; P < 0.001). The number of recurrences per eye was significantly lower in the FAi-treated compared with the sham-treated group (mean 1.7 vs. 5.3, respectively, P < 0.001). At 36 months, more FAi-treated eyes had a ≥15-letter increase in BCVA from baseline and fewer FAi-treated eyes had investigator-determined macular edema at month 36 compared with sham-treated eyes (33.3% vs. 14.7% and 13.0% vs. 27.3% for BCVA and macular edema, respectively). Fewer FAi compared with sham-treated participants required adjunctive treatments (57.5% vs. 97.6%, respectively). Intraocular pressure (IOP) was similar for both study groups at month 36 (mean ± standard deviation 14.5±5.1 and 14.8±5.3, respectively), and approximately half as many eyes in the FAi-treated group when compared with the sham-treated group underwent IOP-lowering surgery (5.7% vs. 11.9%). Cataract surgery was required more frequently over 36 months in the FAi-treated compared with the sham-treated group (73.8% vs. 23.8% of eyes, respectively). Fluocinolone acetonide insert-treated eyes had significantly reduced uveitis recurrence rates throughout the study duration, significantly increased recurrence-free durations, fewer recurrence episodes among those with recurrences, less adjunctive therapy, and an acceptable side-effect profile compared with sham-treated eyes.

Withdrawn: Reduced Risk of Recurrence of Noninfectious Posterior Segment Uveitis After 0.18-mg Fluocinolone Acetonide Insert: Randomized Trial

Abstract Purpose To evaluate the safety and efficacy of 0.18 mg fluocinolone acetonide intravitreal (FAi) insert in chronic non-infectious uveitis affecting the posterior segment of the eye. Design Prospective, multicenter, randomized, doubled-masked, sham-controlled, 3-year, phase 3 clinical trial. Methods Eligible patients were randomized in a 2:1 ratio to receive either FAi (0.18 mg) insert (N=87) or sham injection (N=42). Primary efficacy endpoint was the recurrence of uveitis within 6 months. Secondary endpoints were recurrence within 12 months, resolution of macular edema, change in best corrected visual acuity, intraocular pressure (IOP) and adverse events. Results Uveitis recurrence rates were significantly lower in FAi group compared to sham at 6 (18.4 vs 78.6%; p Conclusion FAi demonstrated significant benefit in extending anti-inflammatory effect and reducing the likelihood of uveitis flares through 12 months. A higher proportion of FAi eyes had elevated IOP, but IOP-lowering medication and surgeries were used in similar proportions in both groups. Additional data from this three-year study will provide further insight into the safety, efficacy, and duration of effect of this treatment.

Comparison of data characterizing the clinical effectiveness of the fluocinolone intravitreal implant (ILUVIEN) in patients with diabetic macular edema from the real world, non-interventional ICE-UK study and the FAME randomized controlled trials

Objective: To compare the effectiveness and safety of the fluocinolone acetonide (FAc) intravitreal implant between the observational Iluvien Clinical Evidence study in the United Kingdom (ICE-UK) and the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) randomized controlled trials (RCTs) in people with diabetic macular edema (DME). Clinical Trials Registration: NCT00344968.Methods: This study selected patients randomized to receive 0.2 µg/day FAc insert (FAc treated eyes) or sham injection (control eyes) from the FAME RCTs, and patients’ first FAc treated eye and non-FAc treated fellow (control) eye from the ICE-UK study. Outcomes included change in visual acuity (VA), central foveal thickness (CFT), and intraocular pressure (IOP).Results: After 12 months follow-up, mean change in VA was 5.0 letters improvement (p < .001) and 1.6 letters improvement (p = .003) in FAME FAc treated and control eyes, and 3.8 letters (p = .012) and –2.1 letters (p = .056) in ICE-UK FAc treated and control eyes, respectively. Mean change in CFT was –144 µm (p < .001) vs –72 µm (p < .001) in FAME FAc treated and control eyes and –113 µm (p < .001) vs –13 µm (p < .001) in ICE-UK FAc treated and control eyes. For eyes with a follow-up of 12 months, 77 (22.3%) and 15 (8.6%) FAME FAc treated and control eyes and 25 (18.7%) and six (4.3%) ICE-UK FAc treated and control eyes required emergent IOP-lowering therapy.Conclusions: Statistically significant improvements in VA 12 months after FAc implantation were observed in both the real-world study and in the RCTs. The improvement in VA and CFT in the RCTs was marginally greater than in the real-world study; however, recruits in the real-world study had more severe visual morbidity at baseline. Whilst there were many changes in the care of people with DME over this time, these data all support the value of treatment with FAc intravitreal implant.

Effect of an Injectable Fluocinolone Acetonide Insert on Recurrence Rates in Chronic Noninfectious Uveitis Affecting the Posterior Segment: Twelve-Month Results

To assess the safety and efficacy of an intravitreal fluocinolone acetonide (FA) insert to manage inflammation associated with chronic noninfectious posterior uveitis. Multicenter, randomized, prospective, doubled-masked, sham-controlled, 3-year phase 3 clinical trial. One hundred twenty-nine participants with recurrent noninfectious posterior uveitis were assigned randomly to FA insert (n= 87) or sham injection (n= 42). The more severely affected eye in participants with bilateral disease was designated as the study eye. The insert (FA, 0.18 mg) was injected into the vitreous cavity; sham injection mimicked the insert delivery procedure. Ophthalmic examinations, OCT, and ocular tolerability and discomfort assessments were conducted; study visits were on days 7 and 28 and months 2, 3, 6, 9, and 12. Uveitis recurrence was treated as needed. The 6-month recurrence rate was the primary outcome measure. The 6-month (28% and 91%) and 12-month (38% and 98%) uveitis recurrence rates were significantly lower (P < 0.001) with FA insert vs. sham, respectively. Fewer recurrences per study eye (mean, 0.7 vs. 2.5), lower incidence of 15-letter or more decrease in best-corrected visual acuity (14% vs. 31%), and reduced systemic (19% vs. 40%) and local (7% vs. 62%) uveitis adjunctive treatments were observed with FA insert vs. sham, respectively. The FA insert group showed higher rates of cataract. Intraocular pressure-lowering treatment use was similar between groups. No deaths, treatment-related study discontinuations, or unanticipated safety signals were observed through 12 months. Chronic noninfectious posterior uveitis was managed successfully in this study population; FA insert eyes experienced fewer uveitis recurrence episodes, required fewer adjunctive treatments, and demonstrated less visual acuity loss compared with sham eyes. The FA insert treatment group showed higher rates of cataract; delivery by injection was not associated with an increase in ocular adverse events or any other safety measures not typically associated with local steroid use, suggesting the procedure is appropriate for an officesetting.

Steroid Therapy in Diabetic Retinopathy and Diabetic Macular Edema

Diabetic macular edema (DME) is the leading cause of blindness in patients with diabetic retinopathy worldwide. Therapeutic alternatives now include focal/grid laser photocoagulation, vitreoretinal surgery, and intraocular injection of anti-angiogenic and steroid molecules. In patients with recalcitrant DME, especially in those cases when anti-vascular endothelial growth factor (VEGF) agents are contraindicated or a treatment regimen with fewer intravitreal injections is required, intravitreal administration of steroids represents a fundamental alternative. Three intravitreal corticosteroid options for DME treatment are currently available including the dexamethasone delivery system, the fluocinolone acetonide insert, and off-label intravitreal triamcinolone acetonide. All of these drugs are associated with the risk of cataract progression and intraocular pressure elevation. In patients unresponsive to anti-VEGF therapy, pseudophakic, at low risk for glaucoma, or who have significant cardiovascular risk, treatment with long-lasting intraocular steroids is suggested.

Intravitreal Steroids in Diabetic Macular Edema.

Over the past decade, great strides have been made in the management of diabetic macular edema (DME). Therapeutic alternatives now include focal/grid laser photocoagulation, vitreo-retinal surgery, and intraocular injection of anti-angiogenic and steroid molecules. Intravitreal administration of steroids represents a fundamental alternative for recalcitrant and naive eyes with DME, especially in those cases when anti-vascular endothelial growth factor (VEGF) agents are contraindicated or a treatment regimen with fewer intravitreal injections is required. Currently, 3 intravitreal corticosteroid options for DME treatment are available: the dexamethasone delivery system, the fluocinolone acetonide insert, and off-label intravitreal triamcinolone acetonide. All 3 agents are associated with risk of cataract progression and intraocular pressure elevation, but they maintain a good safety profile. In patients who remain unresponsive to anti-VEGF therapy, are pseudophakic, at low risk for glaucoma, or who have significant cardiovascular risk, treatment with long-lasting intraocular steroids is suggested. There still remain many unanswered questions about intravitreal drugs, regarding dose, frequency, the correct regimen of each treatment, and the potential long-term side effects.

Update on corticosteroids for diabetic macular edema.

Diabetic macular edema (DME) remains an important cause of visual loss. Although anti-vascular endothelial growth factor (VEGF) agents are generally used as first-line treatments for patients with center-involving DME, there is an important role for corticosteroids as well. Corticosteroids may be especially useful in pseudophakic patients poorly responsive to anti-VEGF therapies, in patients wishing to reduce the number of required injections, and in pregnant patients. Intravitreal triamcinolone acetonide has been used for many years but is not approved for this indication. An extended-release bioerodable dexamethasone delivery system and an extended-release nonbioerodable fluocinolone acetonide insert have both achieved regulatory approval for the treatment of DME. All intravitreal corticosteroids are associated with risks of cataract progression, elevation of intraocular pressure, and endophthalmitis. There is no current consensus regarding the use of corticosteroids, but they are valuable for selected patients with center-involving DME.

An updated review of long-term outcomes from randomized controlled trials in approved pharmaceuticals for diabetic macular edema

Diabetic macular edema (DME) is a major sight-threatening cause in diabetic patients. We review the long-term outcome of four approved pharmacotherapy for treating DME, including intravitreal injections of corticosteroids (dexamethasone implants and fluocinolone acetonide inserts) and anti-vascular endothelial growth factor (VEGF) (ranibizumab and aflibercept). They all show superior ability to improve vision and reduce macular thickness, comparing with sham injections or macular focal/grid laser treatment. Anti-VEGF agents result in low incidence of severe ocular or systemic adverse effects, but glaucoma and cataract should be aware after intravitreal corticosteroids. Prompt treatment with these agents can lead to a better outcome

Long-Term Outcome of Approved Pharmacotherapy for Diabetic Macular Edema: A Review of Randomized Controlled Trials in Fluocinolone Acetonide Implants, Dexamethasone Implants, Aflibercept and Ranibizumab

Diabetic macular edema (DME) is a major sight-threatening cause in diabetic patients. The pathophysiology of macular edema involves both the presence of inflammation and angiogenic stimulant regarding vascular endothelial growth factor (VEGF) [1]. Intravitreal injections of anti-VEGF, including ranibizumab [2-8], bevacizuamb [9], pegaptanib [10], aflibercept [11] are proven to be effective for managing DME. Intravitreal injections of corticosteroids, potent anti-inflammatory agents, such as fluocinolone acetonide implants (Retisert) [12], fluocinolone acetonide inserts (Iluvein) [13,14], dexamethasone implants [15,16], and triamcinolone acetonide [2] have been shown to be beneficial to DME. The Food and Drug Administration of US and European Medicines Agency have approved intravitreal injections of fluocinolone acetonide inserts (Iluvein), dexamethasone implants, aflibercept, and ranibizumab for treating DME. Herein the long-term outcome of the randomized controlled studies in these approved pharmacotherapies will be reviewed.

Fluocinolone acetonide and its potential in the treatment of chronic diabetic macular edema

Diabetic macular edema (DME) is a potentially sight-threatening disease that predominantly affects patients with type 2 diabetes. The pathogenesis is complex, with many contributing factors involved. In addition to overexpression of vascular endothelial growth factor in the diabetic eye, there is an inflammatory pathway that contributes to the breakdown of the blood-retina barrier and nonperfusion. In addition to vascular endothelial growth factor inhibitors, clinical and experimental investigations underline the great potential of steroids in the treatment of DME. Fluocinolone acetonide is currently the only corticosteroid approved for the treatment of DME in Europe. It is manufactured as an intravitreal insert, releasing fluocinolone acetonide at a rate of 0.2 μg per day. Phase III clinical studies have demonstrated that the beneficial effect of the fluocinolone acetonide insert lasts up to 3 years. Improvement in visual acuity was especially remarkable in patients with a prolonged duration of DME of at least 3 years at the initiation of therapy. Cataract formation occurs in nearly all phakic eyes treated, and needs to be considered when the indication for treatment is made. Given the efficacy versus potential complications of the insert, fluocinolone acetonide represents a promising second-line treatment option in patients with DME. Fluocinolone appears to be especially beneficial for patients whose options for visual recovery have seemed limited up until now.

Aqueous Levels of Fluocinolone Acetonide after Administration of Fluocinolone Acetonide Inserts or Fluocinolone Acetonide Implants

To compare aqueous levels of fluocinolone acetonide (FAc) after administration of FAc inserts or FAc implants (Retisert; Bausch & Lomb, Rochester, NY). Comparison of pharmacokinetics from 2 prospective, interventional, clinical trials. Thirty-seven patients with diabetic macular edema (DME) (Fluocinolone Acetonide in Human Aqueous [FAMOUS] Study, C-01-06-002) and 7 patients with uveitis (NA-00019318). Aqueous FAc was measured after administration of FAc implants or 0.2 μg/day (low dose, ILUVIEN; Alimera Sciences Inc., Alpharetta, GA) or 0.5 μg/day (high dose) FAc inserts. The primary end point was aqueous levels of FAc. At 1 month after administration for subjects who received 1 treatment, mean aqueous FAc levels were 2.17 (low dose) and 3.03 ng/ml (high dose) for FAc inserts and 6.12 ng/ml for FAc implants with maximum levels of 3.83, 6.66, and 13.50 ng/ml, respectively. At 3 months, mean FAc levels were 1.76, 2.15, and 6.12 ng/ml, respectively. Between 6 and 36 months after low-dose inserts, aqueous levels of FAc were remarkably stable, ranging from 1.18 to 0.45 ng/ml. After high-dose inserts, mean FAc levels were stable between 6 and 24 months, ranging from 1.50 to 0.84 ng/ml and then decreasing to 0.35 ng/ml at 30 months and 0.15 ng/ml at 36 months. In implant-containing eyes, mean FAc levels remained >6 ng/ml through 15 months, the last time point with measurements from at least 6 eyes. Low- and high-dose FAc inserts both provide stable long-term release of FAc with comparable peak levels in the aqueous: slightly >2 ng/ml for approximately 3 months followed by steady-state levels between 1.0 and 0.5 ng/ml through 36 months for low-dose inserts versus levels between 1.5 and 1.1 ng/ml through 24 months for high-dose inserts. Steady-state aqueous levels after FAc implants were >6 ng/ml. These results provide new insights that aid in the interpretation of efficacy trials and indicate that there is a dose effect for steroid-induced ocular hypertension. In susceptible patients, prolonged aqueous levels of FAc >1 ng/ml moderately increased the risk of glaucoma and levels >6 ng/ml posed a markedly increase risk.

Sustained Delivery Fluocinolone Acetonide Vitreous Inserts Provide Benefit for at Least 3 Years in Patients with Diabetic Macular Edema

To assess long-term efficacy and safety of intravitreal inserts releasing 0.2 μg/d (low dose) or 0.5 μg/d (high dose) fluocinolone acetonide (FAc) in patients with diabetic macular edema (DME). Two randomized, sham injection-controlled, double-masked, multicenter clinical trials. Subjects with persistent DME despite ≥1 macular laser treatment were randomized 1:2:2 to sham injection (n = 185), low-dose insert (n = 375), or high-dose insert (n = 393). Subjects received study drug or sham injection and after 6 weeks were eligible for rescue laser. Based on retreatment criteria, additional study drug or sham injections could be given after 1 year. Percentage of patients with improvement of ≥15 letters from baseline. Secondary outcomes included other parameters of visual function and foveal thickness. At month 36, the percentage of patients who gained ≥15 in letter score using the last observation carried forward method was 28.7% (low dose) and 27.8% (high dose) in the FAc insert groups compared with 18.9% (P = 0.018) in the sham group, and considering only those patients still in the trial at month 36, it was 33.0% (low dose) and 31.9% (high dose) compared with 21.4% in the sham group (P = 0.030). Preplanned subgroup analysis demonstrated a doubling of benefit compared with sham injections in patients who reported duration of DME ≥3 years at baseline; the percentage who gained ≥15 in letter score at month 36 was 34.0% (low dose; P<0.001) or 28.8% (high dose; P = 0.002) compared with 13.4% (sham). An improvement ≥2 steps in the Early Treatment Diabetic Retinopathy Study retinopathy scale occurred in 13.7% (low dose) and 10.1% (high dose) compared with 8.9% in the sham group. Almost all phakic patients in the FAc insert groups developed cataract, but their visual benefit after cataract surgery was similar to that in pseudophakic patients. The incidence of incisional glaucoma surgery at month 36 was 4.8% in the low-dose group and 8.1% in the high-dose insert group. In patients with DME FAc inserts provide substantial visual benefit for up to 3 years and would provide a valuable addition to the options available for patients with DME.

Long-term Benefit of Sustained-Delivery Fluocinolone Acetonide Vitreous Inserts for Diabetic Macular Edema

To assess the efficacy and safety of intravitreal inserts releasing 0.2 μg/day (low dose) or 0.5 μg/day (high dose) fluocinolone acetonide (FA) in patients with diabetic macular edema (DME). Two parallel, prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trials. Subjects with persistent DME despite at least 1 macular laser treatment were randomized 1:2:2 to sham injection (n = 185), low-dose insert (n = 375), or high-dose insert (n = 393). Subjects received study drug or sham injection at baseline and after 6 weeks were eligible for rescue laser. Based on retreatment criteria, additional study drug or sham injections could be given after 1 year. The primary outcome was the percentage of patients with improvement from baseline best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Trial (ETDRS) letter score of 15 or more at month 24. Secondary outcomes included other parameters of visual function and foveal thickness (FTH). The percentage of patients with improvement from baseline ETDRS letter score of 15 or more at month 24 was 28.7 and 28.6 in the low- and high-dose insert groups, respectively, compared with 16.2 in the sham group (P = 0.002 for each). Benefit occurred for both doses compared with sham at 3 weeks and all subsequent time points. The mean improvement in BCVA letter score between baseline and month 24 was 4.4 and 5.4 in the low- and high-dose groups, respectively, compared with 1.7 in the sham group (P = 0.02 and P = 0.016). At all time points compared with sham, there was significantly more improvement in FTH. Subjects requiring cataract surgery were more frequent in the insert groups, and their visual benefit was similar to that of subjects who were pseudophakic at baseline. Glaucoma requiring incisional surgery occurred in 3.7%, 7.6%, and 0.5% of the low-dose, high-dose, and sham groups, respectively. Both low- and high-dose FA inserts significantly improved BCVA in patients with DME over 2 years, and the risk-to-benefit ratio was superior for the low-dose insert. This is the first pharmacologic treatment that can be administered by an outpatient injection to provide substantial benefit in patients with DME for at least 2 years.