Chronic Diabetic Macular Edema Research Articles

Persistent Macular Thickening After Ranibizumab Treatment for Diabetic Macular Edema With Vision Impairment

The prevalence of persistent diabetic macular edema (DME) after months of anti-vascular endothelial growth factor therapy and its effect on visual acuity are unknown. To assess subsequent outcomes of eyes with DME persisting for 24 weeks after initiating treatment with 0.5 mg of ranibizumab. We performed post hoc, exploratory analyses of a randomized clinical trial from March 20, 2007, through January 29, 2014, from 117 of 296 eyes (39.5%) randomly assigned to receive ranibizumab with persistent DME (central subfield thickness ≥250 μm on time domain optical coherence tomography) through the 24-week visit. Four monthly intravitreous injections of ranibizumab and then as needed per protocol. Cumulative 3-year probabilities of chronic persistent DME (failure to achieve a central subfield thickness <250 μm and at least a 10% reduction from the 24-week visit on at least 2 consecutive study visits) determined by life-table analyses, and at least 10 letter (≥2 line) gain or loss of visual acuity among those eyes. The probability of chronic persistent DME among eyes with persistent DME at the 24-week visit decreased from 100% at the 32-week visit to 81.1% (99% CI, 69.6%-88.6%), 55.8% (99% CI, 42.9%-66.9%), and 40.1% (99% CI, 27.4%-52.4%) at the 1-, 2-, and 3-year visits, respectively. At 3 years, visual acuity improved in eyes with and without chronic persistent DME through the follow-up period, respectively, by a mean of 7 letters and 13 letters from baseline. Among 40 eyes with chronic persistent edema through 3 years, 17 (42.5%) (99% CI, 23.1%-63.7%) gained 10 letters or more from baseline, whereas 5 (12.5%) (99% CI, 2.8%-31.5%) lost 10 letters or more from baseline. These data suggest less than half of eyes treated for DME with intravitreous ranibizumab have persistent central-involved DME through 24 weeks after initiating treatment. Among the 40% that then have chronic persistent central-involved DME through 3 years, longer-term visual acuity outcomes appear to be slightly worse than in the 60% in which DME does not persist. Nevertheless, when following the treatment protocol used in this trial among eyes with vision impairment from DME, long-term improvement in visual acuity from baseline is typical and substantial (≥2-line) loss of visual acuity is likely uncommon through 3 years, even when central-involved DME chronically persists.

What Is Chronic or Persistent Diabetic Macular Edema and How Should It Be Treated?

What Is Chronic or Persistent Diabetic Macular Edema and How Should It Be Treated?

Case Series Investigating the Efficacy and Safety of Bilateral Fluocinolone Acetonide (ILUVIEN(®)) in Patients with Diabetic Macular Edema.

IntroductionPatients with diabetic macular edema (DME), a chronic, vision-limiting condition, may be insufficiently responsive to standard-of-care anti-vascular endothelial growth factor (VEGF) and/or laser therapies. One approved treatment for such patients is 0.2 μg/day fluocinolone acetonide (FAc) sustained-release implant; however, data are limited for treatment strategies in patients with bilateral chronic DME insufficiently responsive to standard-of-care therapies.MethodsSix pseudophakic patients with bilateral, chronic DME previously treated with laser and anti-VEGF therapy (and intravitreal triamcinolone acetonide in 10 eyes) were retrospectively investigated for visual and anatomical outcomes, 6 months post-0.2 μg/day FAc implant in both eyes.ResultsAt baseline, the mean best corrected visual acuity (BCVA) was approximately 6/38 or 43 [standard deviation (SD) ±17.4] Early Treatment Diabetic Retinopathy Study (ETDRS) letters; mean central retinal thickness (CRT) was 648 μm (SD ±160). Mean change in BCVA was +10 letters (SD ±12.2 letters), with 4/12 eyes maintaining or achieving driving vision (≥70 letters) and 3/12 eyes having unchanged BCVA. CRT was reduced 6 months after 0.2 μg/day FAc implant in 11/12 eyes. The mean intraocular pressure (IOP) was 16.1 mmHg [mean change of 1.1 mmHg (SD ±3.6)].ConclusionIn a real-world setting, 0.2 μg/day FAc implant in both eyes was a feasible, effective choice for patients with severe bilateral DME, without notable increases in IOP.FundingPublication charges were funded by Alimera Sciences Ltd. Medical writing assistance for this study was provided by QXV Communications and funded by Alimera Sciences Ltd.Electronic supplementary materialThe online version of this article (doi:10.1007/s40123-016-0045-7) contains supplementary material, which is available to authorized users.

Letter to the editor: dexamethasone intravitreal implant in the treatment of diabetic macular edema.

Dear editor I read “Dexamethasone intravitreal implant in the treatment of diabetic macular edema” published July 2015 by Dugel et al.1 This article is very interesting in terms of providing an outline of the role of inflammation in the pathogenesis of diabetic macular edema and explaining the value of corticosteroids in the treatment of diabetic macular edema. However, I would like to draw your attention to the data presented for ILUVIEN® (fluocinolone acetonide; FAc) in Table 2, which has been presented incorrectly and does not reflect the approved product and dose in Europe. ILUVIEN is indicated in Europe for the treatment of vision impairment associated with chronic diabetic macular edema, considered insufficiently responsive to available therapies2 and is approved in Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Ireland, Italy, Luxembourg, the Netherlands, Norway, Poland, Portugal, Spain, Sweden, and the United Kingdom. ILUVIEN was launched in the United Kingdom in April 2013, Germany in May 2013, and Portugal in January 2015.3 ILUVIEN contains 190 µg of FAc and delivers 0.2 µg of FAc per day. Dugel et al1 presented the data for the 0.5 µg of FAc per day, which was studied in the FAME studies but is not the approved dose in Europe. This needs to be explained to the reader as the data that are relevant to the currently marketed product are those of the 0.2 µg of FAc per day release rate.2,4 Thus, Table 2 presented in Dugel et al has been amended to reflect the data for ILUVIEN. Parameter ILUVIEN Therapeutic indication For the treatment of vision impairment associated with chronic DME, considered insufficiently responsive to available therapies2 Active drug Fluocinolone acetonide (FAc)2 Formulation Non-biodegradable implant (polyimide tube)2 Dose 190 µg of FAc with a daily release rate of 0.2 µg2 Duration of action (months) Up to 36 months. This is underpinned by a pharmacokinetic study in human eyes, which showed that following a single intravitreal injection of ILUVIEN, there was a stable delivery of 0.2 µg of FAc per day that was sustained and therefore detectable after 36 months.2,4 This is complemented by efficacy data that show mean improvements in BCVA and central foveal thickness, from baseline levels, for up to 36 months2,5 License approval Status: a. European countries where an ILUVIEN license has been granted b. European countries where ILUVIEN has been launched a. Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Ireland, Italy, Luxembourg, the Netherlands, Norway, Poland, Portugal, Spain, Sweden, the United Kingdom3 b. United Kingdom, April 2013; Germany, May 2013; and Portugal, January 20153 Phase III clinical trial in DME: FAME studies: FAME A and FAME B2,5 Trial design: a. Description of the FAME studies b. The primary endpoint c. The number of patients studied in the FAME studies a. FAME A and B studies were performed under a single protocol as randomized, double-masked, sham injection-controlled, parallel-group, multicenter studies conducted over a 36-month period and included a pre-planned subgroup analysis to assess efficacy in chronic DME patients2,5 b. The primary endpoint for the FAME studies was 24 months but the studies show ILUVIEN was efficacious for up to 36 months, and this is the basis for the license and indication being approved in Europe. Both FAME A and B trials independently met the primary efficacy endpoint of ≥15 letter improvement in BCVA over baseline c. A total of 956 subjects were randomized2,5 Efficacy (% patients): Chronic DME patients: 15-ETDRS-letter BCVA gain at 3 years 34.0% vs 13.4% (0.2 µg FAc per day vs sham control) of subjects achieved a ≥15 letter improvement from baseline BCVA after 3 years2,5 Ocular safety (% patients): Release rate of 0.2 µg FAc per day vs sham control: a. Elevated IOP a. 38.4% vs 14.1% required IOP-lowering drops2,5 b. Cataract-related adverse events b. 81.7% vs 50.4% where cataract was considered an adverse event2,5 c. Incisional glaucoma surgery (IOP-lowering surgery) c. 4.8% vs 0.5% underwent IOP-lowering surgery2,5 View it in a separate window Abbreviations: DME, diabetic macular edema; BCVA, best-corrected visual acuity; FAME, Fluocinolone Acetonide for Diabetic Macular Edema; ETDRS, Early Treatment Diabetic Retinopathy Study; IOP, intraocular pressure. A number of papers have been published on the pharmacokinetic,4 safety, and efficacy of ILUVIEN,5 and the reader can access the summary of product characteristics for ILUVIEN online.2

INTRAVITREAL DEXAMETHASONE IMPLANT IN PATIENTS WITH RANIBIZUMAB PERSISTENT DIABETIC MACULAR EDEMA.

To study the efficacy of intravitreal injection (IVI) of dexamethasone implant as second-line treatment in patients with resistant chronic diabetic macular edema nonresponsive to 6 monthly consecutive IVI of ranibizumab. A retrospective study was conducted over 9 months. Best-corrected visual acuity and central macular thickness were noted. Patients with best-corrected visual acuity ≤20/40 using Snellen chart, central macular thickness ≥300 μm, and poor response to 6 monthly consecutive IVI of ranibizumab were included. Patients received IVI of dexamethasone implant and were examined at 1, 3, 6, and 9 months. Thirteen eyes of 12 patients were included (6 men and 6 women; mean age, 64 ± 7.8 years). Best-corrected visual acuity increased by a mean of 5.58 letters at Month 1 (P = 0.017), 4.61 at Month 3 (P = 0.05), 4.61 at Month 6 (P = 0.042), and 5.77 at Month 9 (P = 0.017). Central macular thickness decreased from 594 μm to 402 μm at Month 1 (P = 0.0002), 428 μm at Month 3 (P = 0.002), 459 μm at Month 6 (P = 0.02), and 489 μm at Month 9 (P = 0.03). Mean number of dexamethasone IVI was 1.07. Two patients (15.3%) developed elevated intraocular pressure, and 1 patient was operated for cataract at 6 months (9% of phakic patients). Intravitreal injection of dexamethasone implant seems as an effective second-line treatment in diabetic macular edema persistent after 6 monthly consecutive intravitreal ranibizumab injections in real life.

Outer retinal tubulation in diabetic macular edema following anti-VEGF treatment

BackgroundTo address the presence and features of outer retinal tubulation (ORT) found in diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (anti-VEGF) and to differentiate between ORT and cystoid DME, which have different plans of management.MethodsThis was a retrospective review of a total of 514 patients investigated with spectral domain optical coherence tomography (OCT) in patients with diabetic macular edema treated with anti-VEGF. ORT was seen in 12 eyes of 11 patients. The morphologic characteristics of ORT and its progress over time were examined using OCT data. The retinal images were obtained by horizontal and vertical scans to analyze the possible presence of ORT and to explore their morphologic features and location in the retinal layers.ResultsORT was seen in DME treated with anti-VEGF. ORT was shown as round or ovoid hyporeflective spaces with hyperreflective borders on the B-scans, measuring 30 to 120 μm high and 30 to 1775 μm wide. The tubules generally remained stable over time. In a retinal practice specializing in advanced diabetic retinopathy clinic, this ORT was seen in 12 eyes of 11 patients during a 12-month period. ORT presented either after receiving 0.05 mL open-label intravitreal injections of 0.5 mg ranibizumab or 1.25 mg bevacizumab.ConclusionORT is found in DME treated with anti-VEGF that may show damage to the outer retina secondary to the severity and chronicity of the DME. ORT may be a result of underlying chronic and severe diabetic macular edema that may occur later possibly secondary to retinal layers rearrangement after several anti-VEGF injections. It is important to differentiate between ORT and cystoids DME. The presence of the ORT entity alone without the presence of DME does not require further anti-VEGF re-injections.

A novel intravitreal fluocinolone acetonide implant (Iluvien(®)) in the treatment of patients with chronic diabetic macular edema that is insufficiently responsive to other medical treatment options: a case series.

BackgroundIluvien® is a novel, nonbiodegradable, sustained-release drug delivery system (0.2 μg/d fluocinolone acetonide [FAc]) indicated in Europe for the treatment of vision impairment associated with chronic diabetic macular edema (DME), considered insufficiently responsive to available therapies.ObjectiveTo evaluate the safety and efficacy of 190-μg FAc implant in patients with chronic DME refractory to other medical treatment options in a clinical setting.MethodsRetrospective registry data were collected by using standard case report forms (CRFs). Prior to intravitreal injection of the FAc implant, all patients were treated either with a vascular endothelial growth factor (VEGF) antagonist and/or a steroid (triamcinolone, dexamethasone implant). Patients were excluded from receiving FAc if they had a known history of elevated intraocular pressure (IOP) following corticosteroid therapy, glaucoma, ocular hypertension, or any contraindications cited in the summary of product characteristics. Best-corrected visual acuity (BCVA) was the main study parameter. Central fovea thickness (CFT) and IOP were measured concurrently. These parameters were recorded prior to and after the injection of the 190-μg FAc implant (between 1 week and 9 months). Injections were performed between May 2013 and March 2014.ResultsFifteen eyes from ten patients were treated. Thirteen eyes (nine patients) were pseudophakic, and seven eyes (five patients) were vitrectomized prior to receiving therapy. BCVA improved in eleven eyes (73.3%), remained unchanged in two eyes (13.3%), and decreased slightly in two eyes (13.3%) at the last follow-up visit versus baseline levels. IOP increased in two patients and was controlled using fixed-combination of IOP-lowering eyedrops or sectorial cyclocryotherapy (n=1).ConclusionThe 190-μg FAc implant was efficacious and showed a favorable benefit-to-risk profile in the patient population with chronic DME of this case series that were refractory to other therapies. The longer-term efficacy and safety in a real-life setting is still being assessed in this center. FAc may offer an important treatment option for patients with chronic DME refractory to other treatment options.

Comment on: "Use of the Fluocinolone Acetonide Intravitreal Implant for the Treatment of Noninfectious Posterior Uveitis: 3-Year Results of a Randomized Clinical Trial in a Predominantly Asian Population".

I read “Use of the fluocinolone acetonide intravitreal implant for the treatment of noninfectious posterior uveitis (NIPU): 3-year results of a randomized clinical trial in a predominantly Asian population” (December 2014) [1]. This article is certainly of interest, especially regarding the effectiveness of 0.59 and 2.1 mg doses of fluocinolone acetonide (FAc) intravitreal implant for the treatment of NIPU in a predominantly Asian patient population. However, I would like to make sure that your readership does not confuse the FAc intravitreal implant reported by Sangwanet al. (i.e., Retisert; contains 0.59 mg of FAc) with the FAc implant (ILUVIEN®; contains 190 μg of FAc) licenced in Europe for the indication ‘… for the treatment of vision impairment associated with chronic diabetic macular edema (DMO), considered insufficiently responsive to available therapies [2]’. This letter highlights the key differences between Retisert and ILUVIEN. These products are licenced by different manufacturers. Retisert is manufactured by Bausch & Lomb (Rochester, NY, USA) and ILUVIEN is manufactured by Alimera Sciences (based in Atlanta, Georgia, USA and Aldershot, UK). These products contain and deliver different amounts of FAc. Retisert delivers 0.59 mg of FAc with an initial rate of 0.6 mg of FAc per day, which decreases over the 1st month to a steady rate of 0.3–0.4 μg FAc per day [3]. ILUVIEN contains a total of 190 μg of FAc with an average daily release of 0.2 μg of FAc per day [2, 4]. These products release FAc for different amounts of time. Retisert releases 0.3–0.4 μg FAc per day for between 30 [3, 4] and 36 months [1]. In contrast, ILUVIEN releases 0.2 μg FAc per day for up to 36 months [4]. These products are administered differently. Retisert is surgically implanted into the posterior segment of the affected eye through a pars plana incision. ILUVIEN is an intravitreal implant that is inserted using a 25-gage needle into the vitreous cavity in the posterior eye with the optimal placement being inferior to the optic disc and posterior to the equator [2]. These products have different indications. In Europe, Retisert is not licensed whereas ILUVIEN is licensed and indicated for “… the treatment of vision impairment associated with chronic diabetic macular oedema, considered insufficiently responsive to available therapies.” [2]. In the USA, Retisert is indicated for “…the treatment of chronic noninfectious uveitis affecting the posterior segment of the eye” [3] and not for DMO. The indication for ILUVIEN in the USA is for “…or the treatment of diabetic macular edema in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure” [5]. I would like to highlight that ILUVIEN was designed to improve on the performance of Retisert to deliver the lowest dose of corticosteroid, currently under investigation, to the retina [6]. Furthermore, I would like to point the reader in the direction of Kane et al. [6] which explains the development history and characteristics of Retisert and ILUVIEN. The paper by Campochiaro et al. [4] is also very helpful as it compares the aqueous levels of FAc after the administration of Retisert or ILUVIEN. John Hall, MD Senior Vice President, Medical Director Europe

Dexamethasone Intravitreal Implant for Chronic Diabetic Macular Edema Resistant to Intravitreal Bevacizumab Treatment

Purpose: To evaluate the safety and efficacy of intravitreal dexamethasone implant (Ozurdex) in patients with chronic diabetic macular edema (DME) resistant to prior intravitreal bevacizumab (IVB) treatment.Materials and Methods: Thirty eyes of 30 patients were administered intravitreal Ozurdex and examined at baseline and 1, 3, and 6 months postinjection in this prospective study. Main outcomes were the best corrected visual acuity (BCVA, logMAR), central foveal thickness (CFT), mean cube volume (MCV), and intraocular pressure (IOP). Patients had a CFT over 275 µm (measured by OCT) and were unresponsive to 3 consecutive IVB injections. All data are presented as mean ± standard deviation.Results: The mean BCVA significantly increased from 0.56 ± 0.38 to 0.41 ± 0.27 (p < 0.001), and 0.44 ± 0.28 (p = 0.008) at 1 and 3 months, respectively. At months 1, 3, and 6, the mean CFT significantly decreased from 517 ± 136 µm at baseline, to 290 ± 60 µm (p < 0.001), 314 ± 88 µm (p < 0.001) and 411 ± 126 µm (p = 0.01), respectively. However, the mean CFT (p < 0.001) and MCV (p = 0.01) significantly increased and BCVA significantly decreased (p = 0.04) at 6 month compared to 3 month. Compared to baseline, IOP increased significantly at 1 week (p = 0.01), 1 month (p = 0.01) and 3 months (p = 0.04). However eyes with IOP higher than 21 mmHg were treated and well controlled with topical anti-glaucoma monotherapy. Macular edema recurrence occurred in 25 eyes (CFT ranged from 321 µm to 800 µm) at 6 months.Conclusion: Dexamethasone intravitreal implant may be an effective and safe alternative in treatment of chronic DME nonresponsive to regular IVB. However, its therapeutic efficacy decreases between the third and sixth months following the injection.

Real-world Experience of Fluocinolone Acetonide (0.2 μg/day) Intravitreal Implant in the Treatment of Diabetic Macular Oedema

Fluocinolone acetonide intravitreal implant (ILUVIENR, FAc intravitreal implant) is approved for clinical use in Europe and US for the treatment of diabetic macular oedema (DMO). In Europe, the implant is indicated for chronic DMO patients who are insufficiently responsive to available therapies. The use of FAc intravitreal implants has been shown to be effective in pivotal clinical trial studies. Case reports and case series of FAc intravitreal implants in chronic DMO are now emerging and combined analysis of these reveals interesting findings that complement the findings in the clinical studies. Visual improvement and central retinal thickness reductions are similar to those of the clinical trials, which is surprising given that treatments often perform less well in the real-world. In addition, the incidence of intraocular pressure (IOP) elevations is lower than reported in the clinical studies. However, further follow-up is ongoing and this needs to be confirmed in a larger population of subjects. This article reviews some of these important real-world data and their likely impact on future chronic DMO treatment practice as well as the impact in terms of the functional benefit to patients with impaired vision.

Navigated Laser Photocoagulation of Chronic Diabetic Macular Edema

Objective: This paper deals with a retrospective evaluation of the effect of navigated photocoagulation of chronic DME with the NAVILAS device. Methods: The cohort comprised 18 eyes with clinically significant DME. The age range was 41-82 years (median 68) and the monitoring time in all eyes lasted for 12 months. The following examination techniques were employed: best corrected visual acuity (BCVA) tested on ETDRS charts, biomicroscopic examination of the fundus in artificial mydriasis, colour photography, fluorescent angiography (FAG), and optical coherence tomography (OCT, spectral domain Cirrus, C. Zeiss). The values of BCVA and OCT were statistically tested by means of a non-parametric pair test (Wilcoxon). The performed therapy included 1 focal laser treatment of the macula, 9 grid photocoagulations of the macula, and 8 direct photocoagulations of leaking microaneurysms. Laser treatment was done using navigated photocoagulation by NAVILAS device. Results: The initial BCVA ranged between 0.1 and 0.8 (average 0.5); at the end of the monitoring period the range of BCVA was 0.1 to 1.0 (average 0.5). No statistically significant difference was found between the pre- operative and post-operative values of BCVA. The average value of the thickness of the macula in the central field on OCT was 360 µm prior to the intervention and 322 µm at the end of the monitoring time. This difference was statistically significant (p=0.015 Wilcoxon). After laser treatment with a NAVILAS device there was an anatomical improvement in DME. The sight functions (BCVA) remained stabilized. Conclusion: Navigated photocoagulation of the macula for DME showed in the present cohort of patients a favourable and functional benefit of the used method.

Sustained Delivery Fluocinolone Acetonide Vitreous Implants: Long-Term Benefit in Patients with Chronic Diabetic Macular Edema

To present the safety and efficacy of intravitreal implants releasing 0.2 μg/day fluocinolone acetonide (FAc) in patients with chronic versus nonchronic diabetic macular edema (DME). To assess ocular characteristics, anatomic changes, and re-treatment and ancillary therapies that may explain the differential treatment effect seen with intravitreal implants releasing FAc 0.2 μg/day in patients with chronic and nonchronic DME. An overall benefit-to-risk assessment for the FAc 0.2-μg/day and FAc 0.5-μg/day doses has been reported previously. Preplanned subgroup analysis of chronic (duration of diagnosis, ≥3 years) and nonchronic (duration of diagnosis, <3 years) DME in patients from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials. Patients with persistent DME despite 1 or more macular laser treatment were randomized 1:2:2 to sham injection (n = 185), FAc 0.2 μg/day (n = 375), or FAc 0.5 μg/day (n = 393). Patients received study drug or sham injection and after 6 weeks were eligible for rescue laser. Based on re-treatment criteria, additional masked study drug could be given after 1 year. Percentage of patients with improvement of 15 letters or more from baseline. Secondary outcomes included other parameters of visual function and foveal thickness. At month 36, the difference between FAc 0.2 μg/day and sham control in the percentage of patients who gained 15 letters or more was significantly greater in chronic DME patients (FAc 0.2 μg/day, 34.0% vs. sham, 13.4%; P<0.001), compared with patients with nonchronic DME (FAc 0.2 μg/day, 22.3% vs. sham, 27.8%; P = 0.275). The greater response in patients with chronic DME was not associated with baseline ocular characteristics, changes in anatomic features, or differences in re-treatment or ancillary therapies. The ocular adverse event profile for FAc 0.2 μg/day was similar regardless of DME duration. This is the first published analysis correlating duration of diagnosis of DME with treatment effect. In patients with chronic DME, FAc 0.2 μg/day provides substantial visual benefit for up to 3 years and would provide an option for patients who do not respond to other therapy.

TREATMENT OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR–RESISTANT DIABETIC MACULAR EDEMA WITH DEXAMETHASONE INTRAVITREAL IMPLANT

To investigate the efficiency of intravitreal dexamethasone implant in patients with chronic diabetic macular edema nonresponsive to three consecutive monthly intravitreal injections of anti-vascular endothelial growth factor administered previously. Fifteen patients (16 eyes) were included in this 4-month prospective clinical trial. Main observed outcomes were the changes between initial and monthly visits in best-corrected visual acuity, central foveal thickness, and intraocular pressure (IOP). Patients included had central foveal thickness of >225 μm (measured by optical coherence tomography) and were nonresponsive to previously administered 3 consecutive monthly intravitreal injections of 1.25-mg bevacizumab. Administration of intravitreal dexamethasone implant was performed at baseline, and patients were followed-up monthly. Statistically significant changes from baseline were observed in best-corrected visual acuity (at 2 months), central foveal thickness (at 1, 2, and 3 months), and IOP (at Months 1, 2, and 3) as follows: mean best-corrected visual acuity significantly increased from 0.29 Snellen lines at baseline to 0.39 lines after 2 months (P = 0.0381). At Months 1, 2, and 3, the mean central foveal thickness significantly decreased, from 462 μm at baseline, to 366 μm (P = 0.0343), 346 μm (P = 0.0288), and 355 μm (P = 0.0370), respectively. When compared with baseline IOP of 15.38 mmHg (12-19 mmHg), IOP increased significantly at Months 1, 2, and 3: 18.93 mmHg (range, 16-24 mmHg; P = 0.0003), 19.5 mmHg (range, 16-27 mmHg; P = 0.0003), and 17.5 mmHg (range, 15-21 mmHg; P = 0.0048), respectively. Dexamethasone intravitreal implant may present an alternative option in the treatment of chronic diabetic macular edema nonresponsive to three consecutive monthly bevacizumab injections administered previously. However, IOP measures were only slightly increased. It seems that the effect of dexamethasone may last till 4 months after initial injection.

Volcano like pattern in optical coherence tomography in chronic diabetic macular edema

In this article we herein report an interesting vitreo-macular interface abnormality associated with chronic diabetic cystoid macular edema. It is an observational case study of three diabetic patients examined in the diabetic clinic. All the patients had proliferative diabetic retinopathy with chronic macular edema. A serial cross sectional OCT examination and tracking of both the longitudinal progression of macular thickening and vitreo-macular interface revealed cystoid macular edema with a characteristic hyperreflective vitreous shadow emerging from the vitreofoveal interface. All the patients had dehiscence of inner retinal layers.This particular morphological feature at the vitreo-foveolar interface, which we name as “volcano sign”, has not been described earlier. The probable mechanism of such a finding probably could be due to slow progressive leakage of chronic cytoid fluid into the vitreous with condensation of the overlying vitreous. Vitreo-macular traction followed by posterior vitreous detachment probably would have contributed to such a morphological event.

Changing Perspectives in Diabetic Macular Oedema – Recognising and Understanding Chronic Diabetic Macular Oedema

The satellite symposium moderated by Usha Chakravarthy entitled ‘Changing Perspectives in Diabetic Macular Oedema: Recognising and Understanding Chronic Diabetic Macular Oedema’ was convened at the 2014 EURETINA Congress. The symposium discussed the multiple processes involved in chronic diabetic macular oedema (DMO) and the use of medications, in particular, corticosteroids in its management. As DMO progresses, inflammatory cytokines are up-regulated relative to vascular endothelial growth factor (VEGF) and these promote various pathways that ultimately result in retinal damage in chronic disease. It is important therefore that treatments for chronic DMO address this altered inflammatory cytokine profile to effectively manage the condition. ILUVIEN®, a 190 μg intravitreal implant in applicator (with a daily release rate of 0.2 μg/day fluocinolone acetonide [FAc] implant) is a second-line therapy indicated for the treatment of chronic DMO. This implant has been shown in phase III trials to lead to marked improvements in visual acuity and in retinal thickness in patients with chronic DMO that were insufficiently response to first-line therapy (i.e. laser). Clinical trial data strongly support the use of the FAc implant in chronic DMO and now ‘real world’ data from its use in regular clinical practice are becoming available and interim results complement those reported in a clinical trial setting.

Managing Insufficiently Responsive DMO Patients Post-NICE Guidance

A satellite symposium, chaired by Usha Chakravarthy, was held at the Royal College of Ophthalmologists Annual Congress in Birmingham, entitled Managing Insufficiently Responsive DMO Patients Post-NICE Guidance. While therapies targeting vascular endothelial growth factor (VEGF), such as ranibizumab, have proven benefit in the treatment of diabetic macular oedema (DMO), patients with disease of longer duration may not respond as well to these therapies, a result of the more complex pathophysiology of chronic DMO, involving retinal inflammation. Corticosteroids offer a multi-factorial treatment approach, acting on numerous biochemical and anatomical pathways, unlike ranibizumab and bevacizumab, which inhibit VEGF and consequently confer their benefits through the modification of a single pathway. The ILUVIEN® intravitreal implant, contains 190 μg of fluocinolone acetonide (FAc), with an average release rate of 0.2 μg/ day for up to 36 months. Its benefits are most pronounced in patients with chronic DMO. ILUVIEN is indicated for the treatment of vision impairment associated with chronic DMO, considered insufficiently responsive to available therapies. The effectiveness of ILUVIEN was demonstrated in phase III clinical trials, and these benefits are being replicated in routine clinical practice. In this symposium, the speakers described clinical scenarios that demonstrated the utility of ILUVIEN in patients with DMO that are insufficiently responsive to currently available first-line therapies.

The Treatment of Diabetic Macular Oedema with ILUVIEN® Intravitreal Implant Following Prior Anti-VEGF Therapy – Case Study

Diabetic macular oedema (DMO) is the main cause of vision loss in diabetic retinopathy. The ILUVIEN® intravitreal implant, which contains fluocinolone acetonide and is administered by injection into the vitreous cavity, should be considered if the patient is not responding to anti-vascular endothelial growth factor (VEGF) therapy, and the patient fulfils the recommendations of the National Institute for Health and Care Excellence (NICE) Technology Appraisal 301. The efficacy and safety of the ILUVIEN implant has been demonstrated in clinical studies, and a pre-planned subgroup analysis has shown that it is particularly beneficial in patients with chronic DMO. This case study is the first report in the UK of the effectiveness of the ILUVIEN implant in a patient in whom therapy with ranibizumab did not result in sustained improvements in terms of visual outcomes and foveal thickness.

Comparison of Diabetic Macular Edema Treatment Patterns and Outcomes by European and US Retina-treating Ophthalmologists

AIM:To uncover and evaluate diabetic macular edema (DME) patient treatment patterns in the US and the largest EU countries.METHODS:Quantitative analyses of self-report data from retina-treating ophthalmologists via 30-minute Internet-based surveys. Data were collected across the US (one study) and EU (two studies— EU-1 and EU-2) between November 2011 and January 2013. Visual outcomes and rates of treatment success or failure were evaluated.RESULTS:Respondents were surveyed across the US (n=71) and EU (EU-1: n=180; EU-2: n=106). Nearly one-third of treated patients (US 38.6 %; EU-1 37.8 %; EU-2 30.7 %) reached a plateau in vision improvement. Geographical comparison showed no significant difference in responses between the US and the EU (EU-1, EU-2) (p&gt;0.05).CONCLUSIONS:These data help to quantify the size of the chronic DME patient population in the US and EU, which is not achieving an acceptable functional outcome with current therapy. The paper provides solid empirical evidence regarding similarities in DME patient treatment and outcomes in the US and EU. The global and reproducible similarities in terms of physicians’ perceptions of the threshold of DME treatment burden and the visual outcomes when treatment benefit is limited are compelling. This is especially interesting within the present context where information regarding the effect of current treatments is limited. Diabetes is growing around the world at epidemic proportions, and these data provide insight into the impact DME may have on healthcare systems.

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.

Intravitreal ILUVIEN® Implant for Diabetic Macular Oedema – Early Case Experiences

Diabetic macular oedema (DMO) is an important cause of vision loss and challenges remain in the treatment of this progressive disease. Corticosteroids provide a comprehensive treatment approach, lowering the concentration of inflammatory cytokines and growth factors such as vascular endothelial growth factor (VEGF). However, intravitreal injections are often short-lived and are associated with intraocular side effects. The ILUVIEN® intravitreal implant contains fluocinolone acetonide and is administered by injection into the vitreous cavity. Its efficacy and safety have been demonstrated in clinical studies, and a subgroup analysis has shown that it is particularly beneficial in patients with long-standing DMO – a group with poor visual outcomes and limited treatment options. As a result, the ILUVIEN implant has been approved in Europe for the treatment of visual impairment due to chronic DMO considered insufficiently responsive to available therapies. These data have been supported by real-use clinical experience and two cases are presented that demonstrate the effectiveness of the ILUVIEN implant in two patients where prior therapies including ranibizumab have not produced a sustained beneficial effect.