Diabetic macular oedema [DMO] is a prevalent and sight-threatening condition among diabetic patients, which can cause irreversible blindness. Since angiogenesis and inflammation are two key elements in the etiopathogenesis of DMO, intravitreal injections of vascular endothelial growth factor inhibitors [anti-VEGF] and sustained released intravitreal corticosteroid implants are currently considered as treatments of choice. The introduction, 10 years ago, of the 0.19 mg fluocinolone acetonide [FAc] implant for treating eyes with vision impairment associated with recurrent and persistent DMO represented an important advance. Since then, two randomized-control trials and many real-world studies have shown its good efficacy/safety profile and the replicability of its treatment regimen. The FAc implant is, in general terms well tolerated, although it is associated with intraocular pressure-[IOP] and cataract-related adverse events [AEs]. Most IOP-related AEs are effectively controlled with ocular-hypotensive therapies. The objective of this paper is to review the role of FAc implant in the treatment of DMO over the 10 years since its launch, as well as its impact on clinical practice outcomes.

To describe effects of sustained-release steroid delivery devices on intraocular pressure (IOP) in eyes with glaucoma drainage devices.

Retrospective case series of eyes with steroid implants (dexamethasone or fluocinolone acetonide) and prior glaucoma drainage devices (Ahmed, Baerveldt) without uveitis. Outcomes included IOP, IOP rise, central foveal thickness, and IOP medications.

We included 14 eyes (14 patients, 38% men, 94% pseudophakic). Mean age at steroid implantation was 64 ± 12 years. Baerveldt (64%) was more common than Ahmed (36%). Tubes were in the anterior chamber (57.1%), sulcus (28.6%), and pars plana (14.3%). Ozurdex (93%) was more common than Yutiq (7%). Mean IOP was 13.5 ± 3.4 mmHg preimplant, 11.8 ± 3.7 mmHg at month 1, 13.3 ± 3.6 mmHg at month 3 ( P = 0.35), and 11.3 ± 3.8 mmHg at 1 year ( P = 0.032). Mean antihypertensive medication was unchanged at month 3 ( P = 1.0) and -0.36 medication at last follow-up ( P = 0.35). Mean central foveal thickness change was -204 ± 158 µ m ( P = 0.001). There were no cases of endophthalmitis.

Intravitreal steroid implants were safe and effective for the treatment of postsurgical CME in patients with pre-existing glaucoma drainage devices. There was no increase in IOP and no increase in antihypertensive drops.

Background/Objectives: Chronic macular edema (CME) is a common complication of diabetic retinopathy or non-infectious uveitis affecting the posterior segment (NIU-PS). Alongside anti-VEGF therapy, glucocorticoids are frequently used to manage CME. Given the heterogeneous nature of patients' medical history, their social conditions, and disease manifestations, individualized treatment is essential for optimal outcomes. This study assesses the effectiveness of intravitreal fluocinolone acetonide (FA) (Iluvien®) in treating persistent and recurrent macular edema in clinical practice at the University Hospital of Erlangen-Nuremberg, Germany. Methods: A total of 46 eyes with diabetic macular edema (DME) (21 eyes) and NIU-PS (25 eyes) were retrospectively analyzed over a follow-up period of up to 36 months. Since persistent retinal thickness fluctuations are linked to long-term retinal damage and functional decline, this study analyzed central retinal thickness (CRT)-including its fluctuations measured as CRT amplitude-alongside BCVA as the primary outcomes. Results: After an initial decrease in CRT in the first year after FA treatment, the maximum CRT amplitude significantly decreased in the following years. For patients with DME, CRT amplitude reduced from 271.4 µm to 91.57 µm in the first year (p = 0.0056) and 106.0 µm in the second year (p = 0.0109). For patients with NIU-PS, CRT amplitude decreased from 185.2 µm to 87.7 µm in the first year (p = 0.0131) and 97.3 µm in the second year (p = 0.0375). Mean BCVA remained stable in both cohorts. Conclusions: Intravitreal FA proved to be effective in reducing and stabilizing CRT in patients with chronic DME and NIU-PS without losing visual acuity, reducing treatment burden.

Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus and may result in irreversible visual loss. Laser treatment has been the gold standard treatment for diabetic macular edema and proliferative diabetic retinopathy for many years. Of late, intravitreal therapy has emerged as a cornerstone in the management of DR. Among the diverse pharmacotherapeutic options, anti-vascular endothelial growth factor agents have demonstrated remarkable efficacy by attenuating neovascularization and reducing macular edema, thus preserving visual acuity in DR patients.

Diabetic retinopathy (DR) is a leading global cause of vision impairment, with its prevalence increasing alongside the rising rates of diabetes mellitus (DM). Despite the retina's complex structure, the underlying pathology of DR remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) and recent advancements in multi-omics analyses have revolutionized molecular profiling, enabling high-throughput analysis and comprehensive characterization of complex biological systems. This review highlights the significant contributions of scRNA-seq, in conjunction with other multi-omics technologies, to DR research. Integrated scRNA-seq and transcriptomic analyses have revealed novel insights into DR pathogenesis, including alternative transcription start site events, fluctuations in cell populations, altered gene expression profiles, and critical signaling pathways within retinal cells. Furthermore, by integrating scRNA-seq with genetic association studies and multi-omics analyses, researchers have identified novel biomarkers, susceptibility genes, and potential therapeutic targets for DR, emphasizing the importance of specific retinal cell types in disease progression. The integration of scRNA-seq with metabolomics has also been instrumental in identifying specific metabolites and dysregulated pathways associated with DR. It is highly conceivable that the continued synergy between scRNA-seq and other multi-omics approaches will accelerate the discovery of underlying mechanisms and the development of novel therapeutic interventions for DR.

to evaluate long-term effectiveness and safety of fluocinolone acetonide (FAc) implant used as second-line treatment in patients with persistent diabetic macular edema (DME).

retrospective data chart review of 241 pseudophakic eyes of 178 patients treated with FAc from July 2017 to December 2021 in 10 medical retinal units in Italy. The primary endpoint was the change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 2 years. A Student's paired t-test was used. Additional therapies for DME and intraocular pressure (IOP)-related events were also evaluated.

efficacy of FAc was assessed in a subset of 111 eyes with at least 24 months of follow-up. Mean BCVA increased at 2 years by 5.1 ETDRS letters (95%CI = 2.6-7.5; p < 0.001) while mean CMT decreased by 189 µm (95% CI 151-227; p < 0.001). Thirty-eight of these eyes (34.2%) needed additional intravitreal treatments, mainly anti-VEGF. Safety was evaluated on the entire cohort of 241 eyes treated with FAc. Overall, 66 eyes (27.4%) required emergent IOP-lowering medications (typically within the first-year post FAc) while 14 eyes (5.8%) underwent trabeculectomy, mostly during the second year of follow-up.

FAc implant provides a substantial long-term functional and anatomical benefit when used as second-line treatment in eyes with DME. IOP rise can be adequately managed with topical agents although some eyes may require IOP-lowering surgery.

The high prevalence of Diabetic macular edema (DME) is a real global health problem. Its complex pathophysiology involves different pathways. Over the last decade, the introduction of intravitreal treatments has dramatically changed the management and prognosis of DME. Among the different treatment options, inhibitors of vascular endothelial growth factor (anti-VEGF) and intravitreal steroids implants represent the first-line therapy of DME. We conducted a review of electronic databases to compile the available evidence about the clinical management of DME in a clinical setting, with a special focus on treatment-naïve patients. Anti-VEGF therapies represent a valuable option for treating DME patients. However, many patients do not respond properly to this treatment and, due to its administration regimen, many patients receive suboptimal treatment in real life. Current evidence demonstrated that in patients with DME, DEX-i improved significantly both anatomic and visual outcomes. Besides eyes with insufficient anti-VEGF respond or recalcitrant DME cases, DEX-i can be effectively and safely used in treatment-naïve DME patients as first line therapy. DEX-i may be considered first line therapy in different clinical scenarios, such as DME eyes with a greater inflammatory component, patients with cardiovascular events, vitrectomized eyes, or those requiring cataract surgery. In conclusion, there are still many points for improvement pending in the clinical management of the patient with DME. Since DME treatment must follow a patient-tailored approach, selecting the best therapeutic approach for each patient requires a good understanding of the pathophysiology of DME.

Ophthalmic treatment demands precision and consistency in delivering therapeutic agents over extended periods to address many conditions, from common eye disorders to complex diseases. This diversity necessitates a range of delivery strategies, each tailored to specific needs. We delve into various delivery cargos that are pivotal in ophthalmic care. These cargos encompass biodegradable implants that gradually release medication, nonbiodegradable implants for sustained drug delivery, refillable tools allowing flexibility in treatment, hydrogels capable of retaining substances while maintaining ocular comfort, and advanced nanotechnology devices that precisely target eye tissues. Within each cargo category, we explore cutting-edge research-level approaches and FDA-approved methods, providing a thorough overview of the current state of ophthalmic drug delivery. In particular, our focus on nanotechnology reveals the promising potential for gene delivery, cell therapy administration, and the implantation of active devices directly into the retina. These advancements hold the key to more effective, personalized, and minimally- invasive ophthalmic treatments, revolutionizing the field of eye care.

Diabetic macular edema (DME) is a common complication of diabetic retinopathy. Treatment with intravitreal injections is effective in most cases but is associated with a high therapeutic burden for patients. This implies the need for long-term treatments, such as the fluocinolone acetonide (FAc) implant. A review of basic science, pharmacology, and clinical data was conducted to provide a state-of-the-art view of the FAc implant in 2024. Although generally well tolerated, the FAc implant has been associated with ocular hypertension and cataract, and caution should be advised to the patients in this regard. By synthesizing information across these domains, a comprehensive evaluation can be attained, facilitating informed decision-making regarding the use of the FAc implant in the management of DME. The main objective of this review is to provide clinicians with guidelines on how to introduce and use the FAc implant in a patient with DME.

To determine whether the types and rates of post-surgical complications associated with the Port Delivery System with ranibizumab (PDS) are comparable with those reported for other ocular implants that cross the sclera.

Systematic literature reviews were conducted to determine the long-term (≥ 18-month) safety of ocular implants that cross the sclera in clinical trials and real-world studies. Complication types and rates were compared with those reported for the PDS in phase III clinical trials (Archway, Pagoda, and Pavilion).

Sixteen clinical trials (24 publications) and 43 real-world studies were identified reporting 30 complications in eyes with 15 implant types and 8 ocular diseases. Implants were associated with an acceptable, well-characterized safety profile, with most complications resolving spontaneously or with treatment. Device-related complications were reported in 0.7% (0.0-5.0%) of study eyes in clinical trials and 1.3% (0.0-14.5%) of eyes in real-world studies. Rates of conjunctival complications were 2.1% (0.0-22.8%) and 2.2% (0.9-4.6%), respectively. The overall types and rates of adverse events of special interest reported for the PDS in phase III trials (cataract, conjunctival bleb, vitreous hemorrhage, conjunctival erosion, conjunctival retraction, endophthalmitis, implant dislocation, retinal detachment, and hyphema) were within the ranges reported for other ocular implants.

The rates of complications reported in phase III clinical trials for the PDS were within the ranges reported for other ocular implants that cross the sclera. This suggests that the long-term safety of the PDS is consistent with other ocular devices established in ophthalmology clinical practice.

PROSPERO international prospective register of systematic reviews: CRD5202234129, CRD42022343129.

The aim of this study was to evaluate real-life data on the functional and anatomical outcome of intravitreal fluocinolone acetonide (FAc) in patients with refractory diabetic macular edema (DME).

Retrospective study on 44 eyes with chronic DME that received intravitreal FAc implant and were previously treated with intravitreal dexamethasone, triamcinolone, or anti-vascular endothelial growth factor. We assessed best-corrected visual acuity (BCVA), central maximum thickness (CMT), and foveal thickness (FT) as measured by spectral-domain optical coherence tomography (Spectralis OCT; Heidelberg Engineering). Secondary outcomes were intraocular pressure (IOP), adverse events, time to additional treatments.

The FAc implant significantly reduced the CMT (baseline 541.23 ± 155.29 µm, p < 0.001) and FT (baseline 460.34 ± 139.28 µm, p < 0.001) for up to 36 months. Despite postoperative visual improvement over time, BCVA did not significantly shift from baseline (0.55 ± 0.38 logMAR, p = 0.568). The FAc implant effect diminished after 21.34 ± 12.74 months. IOP increased in 9% of eyes (n = 4) but was well controlled under topical (n = 1) or surgical therapy (n = 3).

Even though patients' visual recovery does not benefit significantly, the FAc implant addresses the important pillars of chronic DME therapy regarding reduced injection frequency and reduced DME.

Despite significant advancements in ocular drug delivery, challenges persist in treating posterior segment diseases like macular edema (ME) and age-related macular degeneration (AMD). Suprachoroidal (SC) injections are a promising new method for targeted drug delivery to the posterior segment of the eye, providing direct access to the choroid and retina while minimizing systemic exposure and side effects. This review examines the anatomical and physiological foundations of the SC space; evaluates delivery devices such as microcatheters, hypodermic needles, and microneedles; and discusses pharmacokinetic principles. Additionally, advancements in gene delivery through SC injections are explored, emphasizing their potential to transform ocular disease management. This review also highlights clinical applications in treating macular edema, diabetic macular edema, age-related macular degeneration, choroidal melanoma, and glaucoma. Overall, SC injections are emerging as a promising novel route for administering ophthalmic treatments, with high bioavailability, reduced systemic exposure, and favorable safety profiles. Key therapeutic agents such as triamcinolone acetonide, dexamethasone, AAV-based gene therapy, and axitinib have shown promise. The field of suprachoroidal injection is progressing rapidly, and this review article, while attempting to encapsulate most of the published preclinical and clinical studies, mainly focuses on those that are published within 2023 and 2024.

Persistent diabetic macular edema (DME) remains a problem in clinical practice, with many patients having a suboptimal response to the standard of care (SOC). Evidence supports the long-term efficacy of intravitreal fluocinolone acetonide (FAc) implant (ILUVIEN®) in patients that have responded sub-optimally, although there is still scarce data from real-world Portuguese practices. We aimed to monitor the current SOC in selected Portuguese practices prior to FAc implantation and then assess the long-term effectiveness and safety of the FAc implant.

The study included patient data from five Portuguese public hospitals.

This was a non-interventional, multicenter audit of data collected from Retina.pt registry from patients with persistent or recurrent DME despite treatment.

Outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP). Results were compared at regular times over 36 months.

This study included 222 eyes from 152 patients. A significant decrease in BCVA (P < 0.001) and a significant increase in CMT (P = 0.013) were observed prior to FAc. A significant increase in BCVA was registered at 6 months after FAc implant administration (P < 0.001), which was maintained during follow-up. No relevant changes in IOP were observed. Treatment burden was reduced as a result of treatment with FAc (P < 0.001 for anti-VEGF, corticosteroids, or both treatments) in the full population.

In Portuguese practice, data showed that pre-FAc implantation, some patients did not respond to SOC treatment and/or they were undertreated. Following FAc implant administration, there were rapid, sustained, long-term visual and anatomical improvements, and a marked reduction in treatment burden.

Purpose: To evaluate the real-world clinical and safety outcomes of a 0.19 mg fluocinolone acetonide intravitreal implant to treat diabetic macular edema (DME). Methods: This retrospective analysis comprised patients treated with a single fluocinolone acetonide intravitreal implant for the clinical indication of ME secondary to diabetic retinopathy. Primary outcomes included changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and the frequency of DME-related treatments 12 months before and up to 36 months after fluocinolone acetonide administration. Safety outcomes were also assessed. Results: One hundred forty-eight eyes (115 patients) were followed for a mean (±SD) of 12.3 ± 4.2 months before and 29.4 ± 14.5 months after fluocinolone acetonide administration. A 0.8-letter decrease (Early Treatment Diabetic Retinopathy Study) in the mean BCVA was observed at month 24. The BCVA was 70 letters (20/40 Snellen equivalent) or more in 20.6% of eyes at baseline and in 23.7% of eyes 24 months after implant administration. The mean CST was 379.9 μm and 323.7 μm, respectively. The CST was 300 μm or less in 58.7% of eyes at month 24 (P < .001). The mean frequency of intravitreal antivascular endothelial growth factor injections or laser photocoagulation decreased from 4.9 to 1.5 per year after fluocinolone acetonide administration (P < .001). Implant migration to the anterior chamber occurred in 3 eyes, 2 of which were vitrectomized and later required removal. Conclusions: The 0.19 mg fluocinolone acetonide intravitreal implant provided long-term stabilization of VA and macular anatomy in patients with DME, despite a significant reduction in treatment frequency.

To report the long-term functional, anatomical and safety outcomes of 0.2 μg/day fluocinolone acetonide 0.19mg in patients with persistent or recurrent diabetic macular edema (DME).

Retrospective, observational, single-center study of patients with recurrent or persistent DME. All patients received 0.2 μg/day of fluocinolone acetonide 0.19mg, and data were collected at baseline and months 1, 3, 6, 12, 24 and 36 after implantation. Outcomes measured included best-corrected visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP), and safety outcomes.

A total of 28 eyes from 28 patients were included. The mean age was 66.5 years (95% CI 62.8-70.2) with a mean duration of DME of 8.8 years (95% CI 7.7-10.0). Only two eyes were phakic. Mean follow-up was 25.4 months (95% CI 21.2-29.6). Mean BCVA at baseline was 48.6 ETDRS letters (95% CI 41.3-55.8) and improved as early as month 1 of follow-up with a mean gain in BCVA of 7.8 (95% CI 4.3-11.3) ETDRS letters (p<0.001). Statistically significant improvements in BCVA were also observed at months 6, 12 and 24. At baseline, patients had a mean CMT of 530.5µm (95% CI 463.0-598.0), and a decrease in CMT was observed, starting at the first month of follow-up (mean CMT reduction of -170.5µm, 95% CI -223.8- -117.1; p<0.001). Statistically significant decreases in CMT were also observed at months 6, 12, 24, and 36, with the maximum decrease observed at month 12 (p<0.001). Mean IOP at baseline was 16.4mmHg (95% CI 15.3-17.5) and nine eyes (32.1%) had an IOP ≥21mmHg during follow-up.

Our results support the effectiveness and safety profile of fluocinolone acetonide. Although additional long-term real-world evidence is required, fluocinolone acetonide may represent a safe strategy for daily, low-dose, sustained and localized release to the posterior segment of the eye, providing both functional and anatomical benefits in DME.

Diabetic macular edema (DME) is a common complication of diabetes mellitus and a leading cause of visual impairment worldwide. It is defined as the diabetes-related accumulation of fluid, proteins, and lipids, with retinal thickening, within the macular area. DME affects a significant proportion of individuals with diabetes, with the prevalence increasing with disease duration and severity. It is estimated that approximately 25-30% of diabetic patients will develop DME during their lifetime. Poor glycemic control, hypertension, hyperlipidemia, diabetes duration, and genetic predisposition are recognized as risk factors for the development and progression of DME. Although the exact pathophysiology is still not completely understood, it has been demonstrated that chronic hyperglycemia triggers a cascade of biochemical processes, including increased oxidative stress, inflammation, activation of vascular endothelial growth factor (VEGF), cellular dysfunction, and apoptosis, with breakdown of the blood-retinal barriers and fluid accumulation within the macular area. Early diagnosis and appropriate management of DME are crucial for improving visual outcomes. Although the control of systemic risk factors still remains the most important strategy in DME treatment, intravitreal pharmacotherapy with anti-VEGF molecules or steroids is currently considered the first-line approach in DME patients, whereas macular laser photocoagulation and pars plana vitrectomy may be useful in selected cases. Available intravitreal steroids, including triamcinolone acetonide injections and dexamethasone and fluocinolone acetonide implants, exert their therapeutic effect by reducing inflammation, inhibiting VEGF expression, stabilizing the blood-retinal barrier and thus reducing vascular permeability. They have been demonstrated to be effective in reducing macular edema and improving visual outcomes in DME patients but are associated with a high risk of intraocular pressure elevation and cataract development, so their use requires an accurate patient selection. This manuscript aims to provide a comprehensive overview of the pathology, epidemiology, risk factors, physiopathology, clinical features, treatment mechanisms of actions, treatment options, prognosis, and ongoing clinical studies related to the treatment of DME, with particular consideration of intravitreal steroids therapy.

To assess ocular, visual, and anatomical outcomes following the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) and incisional intraocular pressure (IOP)-lowering surgery in diabetic macular edema.

From a 36-month, phase 4, open-label, observational study (N = 202 eyes, 159 patients), 8 eyes (7 patients) required IOP-lowering surgery post-FAc; eyes were segregated by FAc-induced (n = 5, 2.47%) versus neovascular glaucoma (NVG)-related (n = 3, 1.49%) IOP elevations and assessed for IOP, best corrected visual acuity (BCVA), central subfield thickness (CST), and cup-to-disc ratio (c/d).

Changes at 36 months were +5.4 letters BCVA (P > 0.05) and +0.09 c/d (P = 0.0217); IOP and CST were unchanged. FAc-induced-group eyes required fewer IOP-lowering medications than NVG-group eyes (2.0 versus 4.0; P < 0.01) but for longer duration (15.2 versus 2.6 months; P < 0.001).

Post-FAc IOP-lowering surgery, regardless of cause, largely did not affect the outcomes measured; these procedures, then, may not meaningfully threaten positive outcomes. [Ophthalmic Surg Lasers Imaging Retina 2024;55:22-29.].

To evaluate effects of the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN) on intraocular pressure (IOP) in patients with diabetic macular edema (DME).

Secondary analysis of a 36-month, phase IV, nonrandomized, open-label, observational study.

The study included 202 eyes from 159 patients who received the 0.19-mg FAc implant after a successful prior steroid challenge per the United States label indication.

Study eyes were assessed for IOP values, incidence of IOP elevations, and best-corrected visual acuity (BCVA) for up to 36 months post-FAc implant.

Mean IOP was stable over 36 months post-FAc; IOP change from baseline peaked at 2.12 mmHg at 9 months, then declined to baseline levels. At 36 months, eyes had a 32.5% cumulative probability of an IOP event > 25 mmHg and a 15.6% probability of an IOP event > 30 mmHg (Kaplan-Meier). The probability of requiring IOP-lowering medication at any time by month 36 was 38.3%. A total of 78% of eyes did not have IOP elevations > 25 mmHg if similar values were seen with the previous steroid challenge. Although 7.4% of eyes had an IOP > 30 mmHg during a scheduled study visit, most exceeded this threshold only once (60%). Regardless of IOP status, mean BCVA remained stable.

Over 36 months, the 0.19-mg FAc implant was associated with relatively stable IOPs in patients with DME, and there was no significant impact of IOP elevations identified regarding their effects on long-term visual outcomes. The probability that a prior corticosteroid challenge will not predict an IOP elevation > 25 mmHg over 36 months post-FAc is 22%; therefore, routine IOP monitoring should be scheduled.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Diabetic macular edema (DME) is a common sight-threatening complication of diabetic retinopathy (DR) and the leading cause of severe visual impairment among the working-age population. Several therapeutic options are available for the management of DME, including intravitreal corticosteroids. They have been traditionally used as second-line treatment, due to the risk of intraocular pressure increase and cataract-related adverse events. However, attention has recently been focused on the primary or early use of intravitreal corticosteroids, due to growing evidence of the crucial role of inflammation in the pathogenesis of DME. Furthermore, intravitreal steroid implants offer the additional advantage of a longer duration of action compared to anti-vascular endothelial growth factor agents (anti-VEGF). This review aims to summarize the available evidence on the efficacy and safety profile of dexamethasone (DEX) intravitreal implant, with a specific focus on clinical scenarios in which it might be considered or even preferred as first-line treatment option by adequate selection of patients, considering both advantages and possible adverse events. Patients with contraindications to anti-VEGF, DME with high inflammatory OCT biomarkers, pseudophakic patients and phakic patients' candidates to cataract surgery as well as vitrectomized eyes may all benefit from first-line DEX implant. Additionally, DME not responders to anti-VEGF should be considered for a switch to DEX implant and a combination therapy of DEX implant and anti-VEGF could be a valid option in severe and persistent DME.

To 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.

This 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.

Thirty-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.

In 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.

EudraCT identifier: 2016-001680-37.

Purpose: To assess the impact of retinal thickness variability (RTV) control on visual and treatment burden outcomes in patients with diabetic macular edema (DME) who received the 0.19 mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien, Alimera Sciences). Methods: This post hoc analysis examined the outcomes of a 3-year, phase 4, nonrandomized, open-label observational study. Retinal thickness was measured as central subfield thickness (CST). RTV was quantified by CST area under the curve (CST-AUC), retinal thickness amplitude (RTA), and retinal thickness standard deviation (RTSD). Visual outcomes were measured as best-corrected visual acuity (BCVA), and treatment burden was measured as the number of yearly supplemental DME treatments. Results: The percentage of eyes with a CST ≤300 µm fluctuated throughout the study but was significantly increased relative to baseline at 36 months (baseline: 32.9% vs 36 months: 46.8%; P < .05). FAc significantly reduced RTV in all measures more than 36 months (P < .0001). When divided into quartiles, eyes with the best RTV control post FAc had the greatest BCVA gains and improved disease control (ie, reduced need for supplemental therapy). The last-observed BCVA letter score exhibited linear correlations with CST-AUC (R2 = -0.100), RTA (R2 = -0.125), and RTSD (R2 = -0.162). A multivariate linear regression with baseline BCVA as a covariate displayed improved correlations with the last-observed BCVA, CST-AUC (R2 = -0.448), RTA (R2 = -0.432), and RTSD (R2 = -0.436). Conclusions: The sustained corticosteroid release of the 0.19 mg FAc implant reduced RTV in patients with DME, which directly correlated with significantly improved vision and a reduced supplemental treatment burden.

The ILUVIEN Registry Safety Study was a multicentre, open-label, non-randomised, observational, phase 4 study designed to assess the safety and effectiveness of the fluocinolone acetonide (FAc) implant in all indications in real-world practices in Europe.

The study included data collected prospectively and retrospectively. Patients receiving FAc implants between 2013 and 2017 were included and monitored until the last patient reached ≥3 years of follow-up. Mean intraocular pressure (IOP) data over the course of the study, along with IOP events, use of IOP-lowering therapy, mean change in visual acuity (VA) and information on supplemental therapy use were analysed post-FAc implantation.

Six hundred and ninety-five eyes from 556 patients, with a mean±SD follow-up of 1150.5±357.36 days, were treated with a FAc implant. 96.7% of eyes had chronic diabetic macular oedema (cDMO). IOP lowering was achieved in 34.5% of eyes using topical agents and 4.3% by surgery. Seventy-three eyes (64.6% of 113 phakic) required cataract surgery during follow-up. Mean VA increased from a baseline of 52.2 letters to 57.1 letters at month 36, with improvement observed up to month 48. Supplementary therapies were given in 43.7% of eyes. When classified by length of cDMO less than or greater than the median duration those with a shorter history experienced greater VA gains than those with a longer history.

This study confirms the favourable, long-term benefit-to-risk profile of the FAc implant in eyes with cDMO, with an additional benefit in patients when this therapy is administered earlier.

These guidelines are a consensus of French glaucoma and retina experts on the management of ocular hypertension (OHT) observed in a third of the cases after corticosteroid implant intravitreal injections. They update the first guidelines published in 2017. Two implants are marketed in France: the dexamethasone implant (DEXi) and the fluocinolone acetonide implant (FAci). It is essential to assess the pressure status before injecting a patient with a corticosteroid implant. A molecule-specific monitoring of the intraocular pressure is needed throughout the follow-up and at the time of reinjections. Real-life studies have allowed optimizing the management algorithm by significantly increasing the safety of these implants. Corticosteroid testing with DEXi should be performed before switching to FAci to optimize pressure tolerance of FAci. Beyond topical hypotensive treatments, selective laser trabeculoplasty may be considered in the therapeutic arsenal for the management of steroid-induced OHT and subsequent injections.

These are the recommendations of French glaucoma and retina experts on the management of ocular hypertension (OHT) observed in 1/3 of cases after intravitreal steroid implant injections. They are an update to the recommendations first published in 2017. There are two implants on the French market: the dexamethasone (DEXi) and fluocinolone acetonide (FAci) implants. It is important to know the pressure status before injecting a patient with a steroid implant. Monitoring of the IOP adapted to the specific drug is necessary throughout follow-up and reinjections. Real-life studies have made it possible to optimize the management algorithm by significantly increasing the safety of use of these implants. A corticosteroid test with DEXi is necessary before switching to FAci to optimize the pressure tolerance of the latter. In addition to topical glaucoma medications, SLT laser can be considered in the therapeutic arsenal for the management of steroid-induced OHT and future injections.

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.

Analysis of a 3-year, Phase 4, open-label, observational study evaluating the association of baseline best-corrected visual acuity (BCVA) with visual, treatment burden, and retinal thickness variability (RTV) outcomes and intraocular pressure (IOP)-related events after the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant.

Data from patients with diabetic macular edema (DME) who did not have a clinically significant rise in IOP after previous corticosteroid treatment (N = 202 eyes from 159 patients) were segregated by baseline BCVA of ≥20/40 or <20/40 and analyzed for BCVA, number of yearly supplemental DME treatments, RTV, and incidence of IOP-related events.

At 36 months post-FAc, eyes with better baseline BCVA (≥20/40) maintained baseline BCVA, whereas vision in eyes with worse baseline BCVA (<20/40) increased by approximately 7 letters to 61.34 letters (Snellen equivalent approximately 20/60; P < 0.05). Treatment burden and RTV decreased post-FAc regardless of baseline BCVA. Eyes with better baseline BCVA (≥20/40) had numerically fewer IOP-related events post-FAc versus eyes with worse baseline BCVA (<20/40), including a lower incidence of incisional IOP-lowering surgery.

The 0.19-mg FAc implant improved RTV and treatment burden regardless of baseline BCVA. Better baseline BCVA (≥20/40) was associated with long-term BCVA maintenance. Although eyes with worse baseline BCVA (<20/40) experienced significantly improved BCVA, it never rose to the level of those with better baseline BCVA. These data indicate that early, effective intervention in DME, before significant vision loss occurs, is key to maintaining visual outcomes.

To assess treatment burden in patients with diabetic macular edema (DME) after the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN).

Prospective and retrospective analyses of a 36-month, phase 4, open-label, observational study.

Setting: Multicenter.

Included patients had DME and previously received corticosteroid treatment without a clinically significant rise in intraocular pressure (IOP) (N = 202 eyes in 159 patients). Patients were not randomized.

Prospective, observational treatment burden data were analyzed for their relationship to safety and functional efficacy outcomes across 36 months.

Outcomes included the mean number of yearly treatments, supplemental-free probability over time, best-corrected visual acuity, and monitoring of IOP-related events.

Over 36 months, the mean number of yearly treatments decreased from 3.5 before FAc to 1.7 after FAc; at 36 months, 68.3% of patients required 0 to 2 treatments per year. After FAc, the percentage of eyes requiring supplemental therapy decreased vs before FAc (P < .0001 for each). Through 36 months, 25% of FAc-treated eyes did not require supplemental treatment. At 36 months, mean best-corrected visual acuity increased by 4.5 letters vs a decline of 6.4 letters in the 36 months before FAc. IOP elevations >25 mm Hg occurred in 18.2% of eyes that did not receive supplemental treatment after FAc vs 27.2% of eyes that received supplemental treatments, which included additional intraocular steroids.

Over 36 months, the FAc implant is associated with improved visual outcomes and better disease control as measured by a significant reduction in yearly treatment burden in patients with DME.

Fluocinolone acetonide (FAc) intravitreal implant (Iluvien®) is a corticosteroid implant indicated for the treatment of diabetic macular oedema (DMO) in patients who have previously received conventional treatment without good response, non-infectious posterior uveitis, and as an off-label treatment of the macular oedema secondary to retinal vein occlusion. FAc is a non-biodegradable 0.19 mg intravitreal implant which is designed to release FAc over 3 years at a rate of approximately 0.2 mcg per day. The aim of this review is to describe the special pharmacological properties of Iluvien and display the outcomes of the most important clinical trials and real-world studies regarding its efficacy and safety for the management of the above retinal disorders.

To assess the efficacy and safety of supra-choroidal (SC) Iluvien in the management of chronic diabetic macular edema (DME).

A 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.

The 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.

SC Iluvien is potentially effective in improving visual function, reducing macular edema, and reducing the incidence of steroid-induced cataracts and glaucoma.

To better understand the level of agreement among retina specialists on the role of inflammation in diabetic retinopathy (DR) and diabetic macular edema (DME), and the use of 0.19-mg fluocinolone acetonide (FAc) implant in DME treatment, a consensus survey was drafted and disseminated to retina specialists across the United States.

Using the modified Delphi method, a list of 12 consensus statements were generated by the coauthors based on short-answer responses to an initial survey. In total, 56 retina specialists completed the entire consensus survey. Except for two multiple-choice questions, there were 10 consensus statements that used a modified Likert scale to indicate their level of agreement to the statement: Agree = 3, Mostly Agree = 2, Mostly Disagree = 1, Disagree = 0. Percentage agreement and 95% confidence intervals (CIs) were calculated, and a consensus threshold was set at > 80% agreement for each statement.

Seven of 10 consensus statements using the modified Likert scale reached consensus, including those on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. The remaining three statements displayed high agreement with average scores > 80%, but the 95% CIs were below threshold. These included the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use. Two multiple-choice questions focused on clinical situations in which corticosteroids would be used as baseline therapy for DME (pseudophakic eye [73%], recent stroke/myocardial infarction [66%], and pregnancy/breastfeeding [66%]) and which delivery route satisfies the steroid challenge for the FAc implant (intravitreal [100%], sub-tenon/periocular [73%], and topical [57%]).

Physicians highly agreed on the role of inflammation in pathophysiology of DR/DME, injection burden and patient adherence, and efficacy and safety of the FAc implant. However, full consensus was not found on the impact of the FAc implant on DR progression, FAc as baseline therapy for DME, and the effectiveness of the steroid challenge to mitigate intraocular pressure risk after FAc use. [Ophthalmic Surg Lasers Imaging Retina. 2023;54(3):166-173.].

Diabetic macular edema (DME) is a major ocular complication of diabetes mellitus (DM), leading to significant visual impairment. DME's pathogenesis is multifactorial. Focal edema tends to occur when primary metabolic abnormalities lead to a persistent hyperglycemic state, causing the development of microaneurysms, often with extravascular lipoprotein in a circinate pattern around the focal leakage. On the other hand, diffusion edema is due to a generalized breakdown of the inner blood-retinal barrier, leading to profuse early leakage from the entire capillary bed of the posterior pole with the subsequent extravasation of fluid into the extracellular space. The pathogenesis of DME occurs through the interaction of multiple molecular mediators, including the overexpression of several growth factors, including vascular endothelial growth factor (VEGF), insulin-like growth factor-1, angiopoietin-1, and -2, stromal-derived factor-1, fibroblast growth factor-2, and tumor necrosis factor. Synergistically, these growth factors mediate angiogenesis, protease production, endothelial cell proliferation, and migration. Treatment for DME generally involves primary management of DM, laser photocoagulation, and pharmacotherapeutics targeting mediators, namely, the anti-VEGF pathway. The emergence of anti-VEGF therapies has resulted in significant clinical improvements compared to laser therapy alone. However, multiple factors influencing the visual outcome after anti-VEGF treatment and the presence of anti-VEGF non-responders have necessitated the development of new pharmacotherapies. In this review, we explore the pathophysiology of DME and current management strategies. In addition, we provide a comprehensive analysis of emerging therapeutic approaches to the treatment of DME.