Chronic Diabetic Macular Edema Research Articles

Surgical Treatment for Diabetic Macular Edema

Diabetic macular edema (DME) is defined as excess fluid accumulation within the retina in the macular area, and when it is centered on the fovea it is the most common cause of decreased visual acuity in patients with diabetic retinopathy. The development of diabetic macular edema is closely related to the duration of diabetes, poor glycemic control, and type 2 diabetes on insulin therapy. The first-line therapy in diabetic macular edema has been the intravitreal injection of anti-vascular endothelial growth factors (VEGF). Other treatment modalities are intravitreal corticosteroid injection and focal laser photocoagulation. However, the efficacy of intravitreal therapy may decrease significantly over time, especially in the presence of vitreomacular traction, tight posterior hyaloid, or epiretinal membrane (ERM). At this stage, pars plana vitrectomy (PPV) is preferred as an alternative treatment method in eyes with chronic DME resistant to intravitreal injections. The vitreous of diabetic patients contains high amounts of VEGF and Angiotensin 2, which cause DME, and cytokines such as interleukin-6 and ICAM-1. In addition, due to the enzymes, it contains, the vitreous causes cross-linking and thickening of the collagen fibers in its structure, causing tight adhesion and traction on the macula. The mechanism of action of pars plana vitrectomy in macular edema can be explained by removing the vitreous and vitreomacular tractions. Vitrectomy may also increase retinal oxygenation. Selection of the appropriate case is important. The undisturbed integrity of the outer retinal layers including the external limiting membrane(ELM) and the ellipsoid zone, no preoperative foveal ischemia, and performing surgery early before ELM is damaged, have been found to be related to better postoperative visual acuity gain. Further, prospective, randomized, controlled studies with large series including detailed parameters and long follow-up evaluating the efficacy of surgical treatment in diabetic macular edema are warranted.

Effectiveness and safety of fluocinolone acetonide intravitreal implant in diabetic macular edema patients considered insufficiently responsive to available therapies (REACT): a prospective, non-randomized, and multicenter study

ObjectiveTo assess the effectiveness and safety of the intravitreal fluocinolone-acetonide implant (FAc-i) in patients with chronic diabetic macular edema who did not sufficiently respond to other available therapies.MethodsThis was a multicenter, prospective, non-randomized, and phase-IV observational study conducted on patients with recurrent-DME who were insufficient responders to currently available therapies (REACT-Study). The primary end-point was the mean change in best-corrected-visual-acuity from baseline to month-24 values.ResultsThirty-one eyes from 31 patients were included in the study. Mean age was 68.0 ± 7.7 years, and 10 (32.3%) were women. Study patients had received 5.3 ± 7.3 previous DME treatments before starting the study. In the overall study sample, BCVA improved from 56.1 ± 12.3 letters at baseline to 62.4 ± 17.0 letters at month-24 (p = 0.0510). The eyes with a baseline BCVA < 70 ETDRS letters had a significant improvement in BCVA from 53.2 ± 10.2 letters at baseline to 61.5 ± 17.9 letters at month-24 (p = 0.0165). In the overall study population, central-subfoveal-thickness (CST) was significantly reduced from 474.0 ± 135.1 µm at baseline to 333.4 ± 135.6 at month-24 (p < 0.0001). Similarly, macular-volume (MV) was significantly reduced from 10.7 ± 2.7 mm3 at baseline to 9.6 ± 2.9 mm3 (p = 0.0027) at month-24. Among the 31 study eyes, 19 (61.3%) required an additional treatment for DME. Throughout the study, 9 (29.0%) eyes required ocular hypotensive medication for controlling their intraocular-pressure and 5 (16.1%) eyes underwent cataract surgery.ConclusionsIn DME eyes who did not sufficiently respond to previous therapies, the FAc-i was associated with an improvement in visual and anatomic outcomes. There were no unexpected adverse-events.Trial registration numberEudraCT identifier: 2016-001680-37.

The role and efficacy of vitrectomy for the management of refractory diabetic macular edema: Systematic review and meta-analysis

This study aimed to evaluate the role and efficacy of vitrectomy in the management of chronic diabetic macular edema (DME) refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF) and corticosteroid treatments. A systematic review and meta-analysis were performed by searching the Embase, Medline, and gray literature. Eight hundred and thirty-nine studies were retrieved and eight were selected (three for quantitative synthesis and five for qualitative synthesis). Visual acuity (VA) and central macular thickness (CMT) were compared between the vitrectomy-treated and control groups (treated with anti-VEGF and intravitreal corticosteroid injection) using the standardized mean difference (SMD) with 95% confidence intervals (CIs) and P-values. There was no significant difference in post-operative VA between the vitrectomy-treated and control groups (SMD = −0.31, 95% CI: −0.76, 0.14, P = 0.18). However, CMT was significantly lower in the vitrectomy group than in the control group (SMD = −0.31, 95% CI: −0.76, 0.14, P = 0.18). In addition, the incidence of postoperative complications was higher in the control groups than that in the vitrectomy group.This systematic review and meta-analysis suggest that vitrectomy may be viable for the management of chronic DME refractory to anti-VEGF and corticosteroid agents. Although there was no significant difference in VA, the CMT was significantly reduced in the vitrectomy group. Moreover, the incidence of post-operative complications was lower in the vitrectomy group than that in the control group. Further studies are needed to confirm these findings and identify patient subgroups that may benefit from vitrectomy.

Fluocinolone Acetonide Implant Injected 1Month after Dexamethasone Implant for Diabetic Macular Oedema: the ILUVI1MOIS Study.

The aim of this study was to assess the efficacy and safety of fluocinolone acetonide implant (FAci) injected 1month after the last dexamethasone intravitreal implant (DEXi) in chronic diabetic macular oedema (DME) patients. Retrospective multicentric study conducted in pseudophakic patients with chronic DME frequently treated with dexamethasone intravitreal implant (DEXi; time to DME recurrence ≤ 6months), receiving FAci 1month after the last DEXi, with at least a 6-month follow-up. Best-corrected visual acuity (BCVA), central macular thickness (CMT) on optical coherence tomography, intraocular pressure (IOP) and additional treatments were assessed on the day of FAci injection (M0), 1 (M1) and 3months (M3) later and then every 3months. A total of 41 eyes from 34 patients were included. At M0, patients' mean age was 68.7 ± 9.8years, the mean DME duration was 63.9 ± 22.9months, the mean interval between two DEXi was 14.2 ± 3.3weeks. M12 data were available for 71% of patients. At baseline, the mean BCVA, CMT and IOP were 63.2 ± 16.6letters, 299.4 ± 103.3µm, and 16.2 ± 4.5mmHg, respectively, and remained stable during the follow-up. At M12, 14% of patients required additional intravitreal treatments. In pseudophakic patients with chronic DME showing good response to DEXi but requiring repeated injections every < 6months, switching to FAci 1month after the last DEXi was effective and safe. Further prospective randomized controlled studies are needed to confirm these findings, and to determine the best interval between the last DEXi and the first FAci.

Surgical Management of Diabetic Macular Edema

Diabetic macular edema (DME) is the accumulation of fluid in the extracellular space within the macula and is a major cause of visual impairment among patients with diabetes. First-line treatment for DME includes pharmacotherapy with intravitreal anti-vascular endothelial growth factor medications and intravitreal corticosteroids. Alternative therapeutic strategies include laser photocoagulation for non-center involving DME, and surgical options such as pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peel in cases with vitreoretinal interface anomalies or DME refractory to pharmacotherapy, and the Port Delivery System (PDS) for sustained release of anti-vascular endothelial growth factor (VEGF) medication. Our aim is to review the existing literature on surgical management of DME including imaging changes in chronic DME and the clinical relevance of surgical intervention. Imaging changes associated with DME and a worse prognosis include disorganization of the retinal layer, disruption of both the external limiting membrane (ELM) and ellipsoid zone, and vitreomacular interface abnormalities. Studies involving pars plana vitrectomy with and without ILM peel show anatomic improvement but may not always be associated with significant change in visual outcomes. Early studies lacked detailed imaging of the retinal layers and PPV was likely performed as a last resort. In addition, the novel PDS is surgically implanted into the pars plana and works as a drug reservoir with controlled release of drug. However, it has been recalled in patients with wet age-related macular degeneration due to issues with dislodgement. Surgical interventions for DME include pars plana vitrectomy with and without ILM peel and new surgical therapies for DME such as the PDS and subretinal gene therapy have the potential to reduce the risk of DME progression.

Visual function and retinal morphological changes after single suprachoroidal delivery of fluocinolone acetonide (Iluvien®) implant in eyes with chronic diabetic macular edema

BackgroundTo assess the efficacy and safety of supra-choroidal (SC) Iluvien in the management of chronic diabetic macular edema (DME).MethodsA retrospective interventional non-comparative consecutive case series including patients with chronic DME who received an SC Iluvien implant. All patients had persistent central macular thickness (CMT) ≥ 300µ after previous treatment with anti-vascular endothelial growth factor (VEGF) agents or laser photocoagulation. The main outcome measures were improvement of best-corrected visual acuity (BCVA), reduction of CMT, and detection of ocular hypertension/glaucoma or cataract formation. Friedman’s two-way ANOVA was used to analyze BCVA, intraocular pressure (IOP), and DME across different time points. P-value = 0.05.ResultsThe study included 12 eyes of 12 patients. Six patients (50%) were males. The median age was 58 years (range 52–76 years). The median duration of DM was 13 years (range 8–20 years). Ten patients (83.3%) were phakic and 2 patients (17%) were pseudophakic. The median pre-operative BCVA was 0.07 (range 0.05–0.8). The median pre-operative CMT was 544µ (range 354–745µ). The median pre-operative IOP was 17 mmHg (range 14-21mmHg). The median follow-up period was 12 months, range (12–42). Post-operatively, the median final BCVA was 0.15 (range 0.03-1), p 0.02, the median CMT was 404µ (range 213–747), p 0.4 and the median IOP was 19.5 mmHg (range 15–22), p 1. Two out of 10 phakic patients (20%) developed nuclear sclerosis grade I by 12 months. Six patients (50%) developed a transient rise in IOP < 10 mmHg from the baseline that resolved within 3 weeks with antiglaucoma drops.ConclusionSC Iluvien is potentially effective in improving visual function, reducing macular edema, and reducing the incidence of steroid-induced cataracts and glaucoma.

Efficacy of 190 mcg fluocinolone acetonide intravitreal implant: microperimetry and OCT real-life data.

Fluocinolone acetonide is a valid alternative treatment for patients with chronic diabetic macular edema (DME) with poor response to anti-vascular endothelial growth factor (VEGF) therapy. The purpose of this study is to report the efficacy and safety of ILUVIEN® implant in pseudophakic eyes with persistent DME. This is a single-centre pilot-study of 8 patients with persistent DME treated with the ILUVIEN implant, despite previous anti-vascular endothelial growth factor and/or steroid treatment. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) central retinal thickness, intraocular pressure (IOP) and microperimetric data were evaluated at baseline and month 1, 3 and 6 post treatment. All data are presented as mean and standard deviation. At baseline, 1, 3 and 6 months, we had BCVA of 0.26±0.22, 0.38±0.27, 0.48±0.27 and 0.46±0.24; IOP of 15.00±2.67, 15.50±3.16, 14.88±2.42 and 15.63±2.67 mmHg; macular thickness of 652±231, 487±278, 475±287 and 413±211 µm; macular sensitivity of 6.83±4.20, 6.13±3.72, 7.68±3.40 and 7.71±3.33 dB; bivariate contour elliptic area (BCEA) 95.4% 3.8±3.42, 6.06±10.06, 3.05±2.46 and 2.59±2.19°2. According to the results of our study, fluocinolone acetonide (FAc) is a valid therapy option despite some limitations. It has been evidenced that FAc is more effective in patients with mild central macular thickening, while in those with modest to severe central macular thickness (CMT), different therapy strategies should be considered.

Clinical efficacy and safety of intravitreal fluocinolone acetonide implant for the treatment of chronic diabetic macular oedema: five-year real-world results.

To report 5-year real-world efficacy and safety data following the treatment of chronic diabetic macular oedema (DMO) with the intravitreal 0.19 mg fluocinolone acetonide implant(ILUVIEN). Retrospective cohort study of 31 eyes treated with ILUVIEN for chronic DMO at a tertiary centre in Birmingham (UK). Best corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded at baseline, and then at 1-,2-,3-, and 5-years. Safety was assessed based on intraocular pressure (IOP) -lowering medication, surgery, and other complications. BCVA significantly improved 1-year post-ILUVIEN (+4.2 letters, p < 0.05) and gradually reverted to baseline levels over the 5-year period of follow-up (+0.2 letters at year-5). A significant and sustained CRT reduction was observed throughout the 5-years. The proportion of eyes on IOP-lowering medication increased from 16% at baseline, to 70% at 5-years (p < 0.001) with eyes on a mean of 1.3 medications. Laser trabeculoplasty (n = 2), cyclodiode laser (n = 1), and trabeculoplasty and trabeculotomy (n = 1, in the same eye; 3.2%) were required for uncontrolled IOP. Other complications included endophthalmitis (n = 1) and vitreous haemorrhage (n = 1). 58% of eyes required additional intravitreal injections, with a mean 29.2 months to first injection. We observed a 69% reduction in treatment burden following treatment with ILUVIEN implant. Our real-world results confirm the efficacy of the ILUVIEN implant over 5 years, with two-thirds of eyes having improved or stable visual acuity 5 years after ILUVIEN, and an overall sustained improvement in anatomical outcome. Although the rate of IOP-lowering medications use was higher than previously reported, the rate of incisional IOP-lowering surgery and other complications remained low and in keeping with rates reported in larger studies.

Spontaneous resolution of treatment‐resistant foveal capillary macroaneurysms in retinal diseases

AbstractPurpose: Capillary macroaneurysms (CMAs), may be observed in many retinal diseases causing chronic macular edema. A targeted photocoagulation can be efficient to close extrafoveal CMAs. However, treatment of foveal CMAs can be challenging. We report 2 cases of foveal CMAs with chronic edema resistant to intravitreal injections (IVI), which spontaneously resolved after discontinuation of treatment.Methods: Patients with foveal aneurysms greater than 150 μm in diameter, related to retinal diseases and treatment‐resistant were evaluated with ophthalmologic examination and multimodal imaging.Results: Case 1: a 74‐year old female with retinal branch vein occlusion complicated with chronic macular edema was referred for treatment. Foveal macroaneurysm was detected on indocyanine green angiography (ICGA) and was resistant to ranibizumab followed by aflibercept monthly IVI. Six months after stopping treatment, macular edema spontaneously resolved with occlusion of the CMA.Case 2: a 82‐year old patient was treated for a chronic diabetic macular edema on his left eye. He received regular IVI of ranibizumab, aflibercept and dexamethasone implant without improvement. A retrofoveal CMA was noted on ICGA. After 4 months without IVI, the central macular thickness and the vision improved spontaneously.Conclusions: Chronic macular edema related to foveal CMAs is usually resistant to anti‐VEGF and steroid intravitreal injections. In some cases, spontaneous resolution of the macroaneurysm can occur when treatment is stopped.

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

BackgroundThe 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...

Treatment of chronic diabetic macular oedema with intravitreal fluocinolone acetonide implant; real-life analysis of outcomes during overall treatment period.

To assess the clinical efficacy of the fluocinolone acetonide (FA) intravitreal implant (Iluvien, Alimera Sciences) over a 12-month period in a population resistant to treatment with first-line anti-VEGF agents. This study is a retrospective cohort study assessing functional and anatomical outcomes in 13 eyes of 12 patients treated for diabetic macular oedema (DMO) with a single fluocinolone implant (FA) (Iluvien) under real-world conditions. The follow-up period includes the time of first intravitreal treatment (incl anti-VEGF or short-lasting steroids) given until 12 months post FA implant insertion. Primary outcomes were best corrected visual acuity (BCVA), measured using the modified Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale, and central foveal thickness (CFT), measured using Topcon 3DOCT-2000 (Topcon Inc) SD-OCT imaging. Mean BCVA and CFT were measured before anti-VEGF treatment, after anti-VEGF treatment, at the time of Iluvien implant insertion, and 6 and 12 months after Iluvien implant insertion. The t-paired sample test was used to ascertain statistical significance of changes in comparison of two samples while the ANOVA analysis was used in comparison of three or more samples. The baseline BCVA (SD) of the cohort prior to initiation of anti-VEGF treatment was 47.45 (12.27) ETDRS letters whilst the mean CFT (SD) was 579 (203) microns. Following completion of anti-VEGF therapy, the mean improvement in vision was 8.9 ETDRS letters (p = 0.1) whilst the mean reduction in CFT was 197 microns (p = 0.028). Mean BCVA (SD) at the time of insertion of the FA implant was 55.15 (11.16) ETDRS letters and mean (SD) CFT at time of insertion of the FA was 454.62 μm (109.51). Following the 12-month treatment period with the FA implant, BCVA (SD) was 62.15 (10.25) ETDRS letters (p = 0.0331) and the mean (SD) CFT was 404.36 μm (142.92), a change of -50.26 μm from baseline (p = 0.0369). This study has shown that statistically significant improvements in BCVA and CFT can be achieved over a 12-month period with the Iluvien implant. The implant has been shown to be a safe option in the treatment of DMO and may have a role to play in achieving good functional and anatomical outcomes in DMO while also reducing the frequency of follow-up appointments required to maintain stable vision in the working-age population.

Efficacy and Safety of Intravitreal Fluocinolone Acetonide Implant for Chronic Diabetic Macular Edema Previously Treated in Real-Life Practice: The REALFAc Study.

Diabetic macular edema (DME) is the main cause of visual impairment in diabetic patients and a chronic disease requiring long-term treatments. The fluocinolone acetonide (FAc) implant has recently been approved to treat DME in patients considered insufficiently responsive to available therapies. This study evaluates the functional and anatomical efficacy of the FAc implant in real-life practice. A total of 62 eyes with chronic DME were included and followed for a mean of 13.9 (+7.5) months. Previous treatment included at least anti-vascular endothelial growth factor (VEGF) in 83.9% of eyes, dexamethasone implant (DEX-I) in 100% of eyes, vitrectomy in 29.0% of eyes, and laser photocoagulation (either panretinal or focal photocoagulation) in 75.8% of eyes. The mean baseline best corrected visual acuity (BCVA) was 64.0 (+/−17.2) letters (median: 67.5 letters) with a mean DME duration of 60.3 (+/−30.6) months. The maximum BCVA gain occurred at 21 months with a mean gain of 5.0 (+/−12.7) letters. A total of 50.0% of eyes gained ≥5 letters during follow-up. Patients with lower BCVA at baseline had the lowest final BCVA (p < 0.001) but the highest BCVA gain (p = 0.02). The best overall improvement in mean central macular thickness (CMT) occurred at 18 months (p < 0.0001). The improvement in BCVA was inversely associated with the decrease in CMT and showed a decrease when CMT increased (DME recurrence). According to the history of vitrectomy, we did not find any significant difference in mean final BCVA (p = 0.1) and mean BCVA gain (p = 0.2) between eyes previously vitrectomized or not. A total of 23 eyes (37.1%) required additional treatment for DME, and 17.7% required an IOP-lowering procedure during follow-up. In conclusion, this real-life observational study demonstrated the efficacy and safety of the FAc implant in patients with chronic DME already treated with other available therapies.

Prognostic biomarkers of chronic diabetic macular edema treated with a fluocinolone acetonide intravitreal implant

Background: This study aimed to investigate retinal imaging biomarkers, such as disorganization of the retinal inner layers (DRIL) and/or ellipsoid zone (EZ) disruption by spectral domain optical coherence tomography (SD-OCT), and functional outcomes in eyes treated with 0.2 µg/day of a fluocinolone acetonide intravitreal implant (FAc) after an insufficient response to previous treatments.&#x0D; Methods: This was a retrospective comparative study of 18 eyes (15 patients) with persistent and/or recurrent diabetic macular edema (DME) treated with FAc. Eyes were divided according to the number of prior intravitreal treatments: group 1 (n = 8) with less than or equal to 6 injections (early switch) and group 2 (n = 10) with &gt; 6 injections (late switch). Outcomes included percentage of eyes with DRIL and/or EZ disruption at baseline and analysis of the best corrected visual acuity (BCVA) using ETDRS letters, central macular thickness (CMT), DRIL, and EZ disruption at the last observation.&#x0D; Results: Group 2 revealed a significantly higher percentage of DRIL and/or EZ disruption than group 1 (P &lt; 0.05). At the last observation, group 1 revealed a higher percentage of eyes achieving vision stability/improvement, gaining greater than or equal to15 letters, and achieving greater than or equal to 70 letters (P &gt; 0.05 for all comparisons). The mean BCVA gain was 8.8 and 0.7 letters for groups 1 and 2 (P = 0.397). Both groups revealed a significant mean CMT reduction (&gt;20% reduction from the baseline value), without a significant statistical difference between them (P = 0.749). After treatment, most eyes from both groups showed resolution of DRIL and EZ disruption.&#x0D; Conclusions: Patients with DME presenting with a lower percentage of DRIL and/or EZ disruption at baseline had better functional outcomes, supporting the possible benefit of an early switch to FAc after insufficient response to previous treatments. Future randomized studies with a larger patient cohort are warranted to confirm our conclusions.&#x0D; How to cite this article: Lopes BO, Brizido MS, Aerts F, Pina SM, Simoes PS, Miranda MI. Prognostic biomarkers of chronic diabetic macular edema treated with a fluocinolone acetonide intravitreal implant. Med Hypothesis Discov Innov Ophthalmol. 2021 Summer; 10(2): 50-58. https://doi.org/10.51329/mehdiophthal1421

Efficacy and safety of intravitreal Fluocinolone Acetonide microimplant (ILUVIEN®) in patients with chronic diabetic macular edema: 1 year follow-up.

Evaluate the efficacy and safety of intravitreal 0.19 mg fluocinolone acetonide (FAc) micro implant in patients with chronic diabetic macular edema (cDME). Prospective study recruiting subjects with cDME. Inclusion criteria: cDME for at least 2 years documented with OCT imaging; pseudophakia; previous treatments with laser photocoagulation and intravitreal injections of anti-VEGF and/or dexamethasone. Exclusion criteria: phakia; ocular hypertension; tractional component visible on OCT; glaucoma; previous vitrectomy. Outcome measures included best-corrected visual acuity (BVCA), intraocular pressure (IOP), and central macular thickness (CMT), measured 1, 3, 6, and 12 months post-injection. Data were compared with the Friedman test and significance was set at p < 0.05. A total of 18 eyes with a median duration of cDME of 45 months (25-118 months). The 77% of subjects either maintained or improved their BVCA. About 17% and 33% of subjects showed an improvement of 15 ETDRS letters or more at 3 and 12 months respectively. The 17% and 28% of subjects showed a CMT <250 microns at 3 and 12 months, respectively. The median change in CMT thickness was of -370 and -373.5 microns at 3 and 12 months post-injection respectively (p-value is 0.025). Changes in median IOP at 3 and 12 months post-injection were not statistically significant (p-value is 0.210). Ocular hypertension (OHT) was detected in two eyes (11%). The FAc micro implant has proved efficacy in improving and/or maintaining BVCA in 77% of patients with cDME up to 12 months post-injection. Ocular hypertension is the most common side effect but responds well to topical therapy.

Extended real-world experience with the ILUVIEN\xae (fluocinolone acetonide) implant in the United Kingdom: 3-year results from the Medisoft\xae audit study

BackgroundThis study aimed to assess the long-term effectiveness of the 0.2 μg/day fluocinolone acetonide (FAc) implant over ≥3 years for patients with diabetic macular oedema.MethodsA retrospective audit of pseudo-anonymised data from patients with chronic diabetic macular oedema (cDMO) and treated with the FAc implant across 14 UK clinical sites. Safety and clinical effectiveness were measured.ResultsTwo-hundred and fifty-six eyes had ≥3 years of follow-up (mean 4.28 years), during which a mean of 1.14 FAc implants were used per eye. Mean best-recorded visual acuity (BRVA) increased from 52.6 to 56.7 letters at month 3 and remained stable thereafter; this trend was also seen in pseudophakic eyes. The proportion of patients attaining a BRVA ≥6/12 increased from 17% at baseline to 27% 1 month after FAc implant and remained stable above 30% from month 12 onwards. Eyes with no prior history of intraocular pressure (IOP)-related events required significantly less treatment-emergent IOP-lowering medication than those with a prior history of IOP events (17.9% vs. 50.0% of eyes; p < 0.001). The incidence of an IOP increase of ≥10 mmHg, use of IOP-lowering medication, laser trabeculoplasty and IOP-lowering surgery was 28.9%, 29.7%, 0.8% and 2.7%, respectively, for the whole cohort. There were significant reductions in mean central foveal thickness and macular volume (p < 0.001).ConclusionsThe FAc implant was well tolerated, with predictable and manageable IOP-related events while delivering a continuous microdose of corticosteroid to eyes with cDMO, providing prolonged vision preservation and a reduced number of treatments.

The impact of vitrectomy on outcomes achieved with 0.19 mg fluocinolone acetonide implant in patients with diabetic macular edema.

There is a lack of consensus on the use of intravitreal corticosteroid therapies in patients with diabetic macular edema (DME) and prior vitrectomized eyes in clinical practice. Retro-IDEAL was a 3-year retrospective, multicenter study in patients with chronic DME (i.e. DME that persists or recurs despite treatment) treated with ILUVIEN® (0.2 µg daily fluocinolone acetonide intravitreal implant), who had suboptimal outcomes with first-line vascular endothelial growth-factor inhibitors and other DME therapies. A total of 81 eyes (63 patients) were included of which 39 eyes had undergone prior vitrectomy (PV group) while 42 eyes had not undergone prior vitrectomy (NPV). Baseline characteristics were balanced; however, more patients had proliferative diabetic retinopathy in the PV group vs. the NPV group (21.62% vs 9.38%, respectively). Over 36 months, mean visual acuity (VA) increased in both groups with a tendency for more ETDRS letters being gained in the NPV group (+5.33) vs. the PV group (+2.42). By month 36, central retinal thickness was reduced to ⩽300 µm in two-thirds of the eyes in both groups and the mean change from baseline in intraocular pressure was similar in both groups (+0.50 mmHg -0.75 mmHg; NPV and PV group). These long-term data suggest that the 0.2 μg/day FAc implant is effective in both vitrectomized and non-vitrectomized patients, with a manageable safety profile, and improved VA and reduced supplemental therapies for patients with a suboptimal response to first-line DME therapies. Clinicians may consider utilizing the FAc implant earlier in the DME disease process.

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.

Real-World Efficacy and Safety of Fluocinolone Acetonide Implant for Diabetic Macular Edema: A Systematic Review.

To assess real-world outcomes of fluocinolone acetonide (FAc) implant in treating diabetic macular edema (DME), a systematic literature review was conducted on PubMed in order to identify publications assessing the efficacy and safety of the FAc implant in DME in daily practice. Case reports and randomized controlled trials were excluded. Twenty-two observational real-world studies analyzing a total of 1880 eyes were included. Mean peak visual gain was +8.7 letters (11.3 months post-FAc injection) and was greater for lower baseline best corrected visual acuity (BCVA) and for more recent DME. Mean central retinal thickness (CRT) decreased 34.3% from baseline. 77.0% of the analyzed studies reported both BCVA improvement of at least five letters and a CRT decrease by 20% or more. Rescue therapy was needed more frequently when FAc was administered for chronic DME. FAc-induced ocular hypertension was reported in 20.1% of patients but only 0.6% needed surgery. Cataract extraction was performed in 43.2% of phakic patients. Adequate patient selection is essential for optimal FAc response and better safety profile. Currently positioned as second- or third-line treatment in the management algorithm, FAc implant decreases treatment burden and provides better letter gain when administered for more recent DME.

One-year outcomes of Aflibercept for refractory diabetic macular edema in Bevacizumab nonresponders.

Purpose:A sub-population of patients with diabetic macular edema (DME) responds less effectively to off-label use of Bevacizumab. Approval of Aflibercept for DME has offered Bevacizumab nonresponders an alternative therapeutic option. Herein, we investigate the anatomical and functional changes associated with Aflibercept treatment in Bevacizumab nonresponders with chronic DME in a Canadian setting.Methods:A retrospective study of eyes with persistent DME that were switched to Aflibercept due to nonresponse following ≥6 consecutive monthly Bevacizumab injections was performed. Anatomical and functional changes and the predictors of response were assessed using patients' characteristics prior to receiving their first (baseline) and seventh consecutive Aflibercept injections (follow-up).Results:Twenty-four eyes were included, with a mean age of 63.9 ± 10.7 years, an average of 16.8 ± 8.5 Bevacizumab injections prior to switching to Aflibercept, and mean follow-up duration of 11.8 ± 1.7 months following switching to Aflibercept. Best-corrected visual acuity (BCVA) improved significantly from 0.49 ± 0.13 to 0.41 ± 0.11 logMAR (P < 0.001) and central subfield thickness (CST) decreased by 119.4 μm from 409.4 ± 85.8 μm to 290.0 ± 64.5 μm (P < 0.001), with 50% of eyes showing complete anatomical response. Worse BCVA and higher CST at baseline predicted greater vision improvements (P = 0.001 and P = 0.035, respectively) while a larger decrease in CST was associated with greater baseline CST (P = 0.001) and better glycemic control (P = 0.039).Conclusion:Our data from a real-world clinical setting highlight the efficacy of Aflibercept as an alternative therapeutic option for DME recalcitrant to Bevacizumab, with potential additional benefit to those with worse vision, greater CST, and better glycemic control at baseline.

Optical Coherence Tomography Biomarkers: Vitreous Status Influence in Outcomes for Diabetic Macular Edema Therapy with 0.19-mg Fluocinolone Acetonide Implant

Background: The 0.19-mg fluocinolone acetonide (FAc) implant (ILUVIEN^®; Alimera Sciences Ltd., Hampshire, UK) was approved for the treatment of vision impairment associated with chronic and refractory diabetic macular edema (DME). Objectives: To quantitatively assess functional and structural features in nonvitrectomized and vitrectomized DME patients after being treated with an FAc implant. Methods: Retrospective review of patients with DME receiving a single intravitreal injection of the FAc implant. The study was designed to analyze the presence of quantitative structural OCT biomarkers at baseline and 12 months after FAc therapy according to vitreous status. Results: A total of 41 eyes from 30 patients were included in this study. At 12 months after injection, vitrectomized patients had a lower central foveal thickness (p = 0.017) and fewer hyperreflective dots (p = 0.028) compared with nonvitrectomized. Thirty (73%) patients presented a significant functional improvement with 17 (42%) increasing at least 15 ETDRS letters. Overall, 22 (54%) eyes had a complete resolution of DME at the 12-month visit. Patients who needed additional therapy had a higher prevalence of subretinal fluid (42 vs. 3%, p = 0.005) at baseline. Conclusions: This study supports the effectiveness of the FAc implant and reports significant changes at 12 months after FAc injection.