In-situ forming biodegradable implants for sustained Fluocinolone acetonide release to the posterior eye: In-vitro and in-vivo investigations in rabbits.

Delivering medication to the posterior segment of the eye presents a significant challenge. Intravitreal injection has emerged as the preferred method for drug delivery to this area. However, current injectable non-biodegradable implants for fluocinolone acetonide (FA) require surgical removal after prolonged drug release, potentially affecting patient compliance. This study aimed to develop an in-situ forming biodegradable implant (ISFBI) optimal formulation containing PLGA504H and PLGA756S (50:50 w/w%) with the additive NMP solvent. The goal was to achieve slow and controlled release of FA over a two-month period with lower burst release, following a single intravitreal injection. Through morphology, rheology, stability and in-vitro release evaluations, the optimal formulation demonstrated low viscosity (0.12-1.25 Pa. s) and sustained release of FA at a rate of 0.36 µg/day from the third day up to two months. Furthermore, histopathology and in-vivo studies were conducted after intravitreal injection of the optimal formulation in rabbits' eye. Pharmacokinetic analysis demonstrated mean residence time (MRT) of 20.02 ± 0.6 days, half-life (t1/2) of 18.80 ± 0.4 days, and clearance (Cl) of 0.29 ± 0.03 ml/h for FA in the vitreous humor, indicating sustained and slow absorption of FA by the targeted retinal tissue from vitrea over the two-month period and eliminating through the anterior section of the eye, as revealed by its presence in the aqueous humor. Additionally, FA exhibited no detection in the blood and no evidence of systemic side effects or damage on the retinal layer and other organs. Based on these findings, it can be concluded that in-situ forming injectable biodegradable PLGA implants can show promise as a long-acting and controlled-release system for intraocular drug delivery.

Feasibility study and techno-economic assessment of power-to-gas (P2G) technology based on solid oxide electrolysis (SOE).

Power-to-Gas (P2G) is considered as a promising energy storage technology in a long-time horizon. The rapid growth in the share of intermittent renewables in the energy mix is driving forward research and development in large-scale energy storage. This paper presents a feasibility analysis of a power-to-gas system in terms of various operating points and capacities. The analysis was performed using a system model, which features a solid oxide electrolyzer (SOE), a CO2 separation unit, and a methanation reactor as the key components. For the purposes of the techno-economic assessment (TEA) of the system, the CAPEX/OPEX estimation was performed and the cost structure defined. The model proposed in the study enables system-level optimization, including technical and economic criteria, considering two nominal scales: 10 kW and 40 GW, which corresponds to the nominal capacity of SOE in each case. According to the study, in an SOE-based P2G system, the cost of synthetic natural gas (SNG) production will fall by 15-21% by 2030 and 29-37% by 2050. SNG production would cost 3.15-3.75 EUR2023/kgSNG in 2030 and 2.6-3.0 EUR2023/kgSNG in 2050 for systems with SOE power >10 MW. Generally, product cost reductions occur as a result of material development and large-scale production, which influences the system's CAPEX. According to the research, the technology will break even by 2050. The large-scale power-to-gas system with a total of 40 GW installed capacity delivers a product price of 2.4 EUR2023/kgSNG with the average conversion efficiency of 68%.

Ocular, Visual, and Anatomical Outcomes in Eyes Requiring Incisional Intraocular Pressure-Lowering Surgery Following the 0.19-mg Fluocinolone Acetonide Intravitreal Implant.

BACKGROUND AND OBJECTIVE: 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. PATIENTS AND METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.].

Retinal changes after fluocinolone acetonide implant (ILUVIEN®) for DME: SD-OCT imaging assessment using ESASO classification.

INTRODUCTION: A detailed understanding of the anatomical and structural changes occurring in the retina following intravitreal fluocinolone acetonide implantation may help improve the management and prognosis of persistent or recurrent diabetic macular edema (DME). METHODS: Overall, 45 eyes (from 35 patients) with refractory center-involved DME received an intravitreal fluocinolone acetonide implant. They were monitored at baseline and at 6, 12, 24, and 36 months for best-corrected visual acuity (BCVA), central foveal thickness (CFT), and the seven retinal parameters used in the classification of diabetic maculopathy recently developed at the European School for Advanced Studies in Ophthalmology (ESASO). RESULTS: Within 6 months of implantation, significant improvements were evident in BCVA, CFT, maculopathy stage, and the percentage of eyes with: intraretinal cysts; CFT > 30% above the upper normal value; and disrupted or absent ellipsoid zone (EZ) and/or external limiting membrane (ELM). Significant improvements were still maintained at 36 months post-implantation. At month 36, early treatment with the implant (i.e., after < 6 previous intravitreal injections for DME) trended toward being more effective than later treatment in improving BCVA, CFT, maculopathy stage, and the percentage of eyes with CFT > 30% above the upper normal value. However, statistical significance was not achieved. CONCLUSION: In persistent or recurrent DME, fluocinolone acetonide implantation can be effective in improving maculopathy stage and reducing the percentage of eyes with: intraretinal cysts; CFT > 30% above the upper normal value; and disrupted or absent EZ and/or ELM. It can also increase BCVA and reduce CFT.

The 0.19-mg Fluocinolone Acetonide Intravitreal Implant for Diabetic Macular Edema: Intraocular Pressure-Related Effects over 36 Months.

PURPOSE: 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). DESIGN: Secondary analysis of a 36-month, phase IV, nonrandomized, open-label, observational study. PARTICIPANTS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intravitreal fluocinolone acetonide 0.19 mg (ILUVIEN®) in patients with non-infectious uveitis: real-world effectiveness and safety outcomes at 12 months.

PURPOSE: This study assessed the effectiveness of the 0.19-mg fluocinolone acetonide (FAc) implant by multimodal measurements in patients with non-infectious uveitis (NIU) in a real-world setting in Spain. METHODS: A prospective study of patients who had NIU including uveitic macular oedema (UME) with ≥ 12 months follow-up was done. Exclusion criteria include infectious uveitis and uncontrolled glaucoma or ocular hypertension requiring more than 2 medications. Effectiveness was assessed using a multicomponent outcome measure that included nine outcomes. Effectiveness was defined as all components being met at every timepoint. Secondary outcome measures were onset or progression of glaucoma and investigator-reported adverse events. RESULTS: Twenty-six eyes from 22 patients were included, with 96.2% having an indication including UME. During the 12-month study, the FAc implant was effective in 15 (57.7%) eyes, reaching effectiveness as soon as 2 weeks post-implantation. Mean best-corrected visual acuity and mean central macular thickness (CMT) were significantly improved vs. baseline at all timepoints (all comparisons p < 0.01). During the 12-month study, inflammation markers (anterior chamber cells and vitreous haze) had also significantly declined. Factors predicting effectiveness at month 12 were systemic corticosteroid dose pre-FAc, higher immunomodulatory therapy (IMT) load at baseline and thicker retinal nerve fibre layer (RNFL) at baseline (all p < 0.05). Factors predicting failure were male gender, thinner RNFL at baseline and treatment ineffectiveness at 1 month (all p < 0.05). In parallel, corticosteroid and IMT use also declined significantly. No significant increase in IOP was detected. CONCLUSION: The FAc implant is safe and effective at treating NIU over 12 months in a real-world setting in Spain.

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.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION NUMBER: EudraCT identifier: 2016-001680-37.

PSEUDOMONAS ENDOPHTHALMITIS AFTER 0.59 MG FLUOCINOLONE ACETONIDE SURGICAL IMPLANT IN A PATIENT WITH A LONG-STANDING CRAWFORD TUBE.

PURPOSE: The purpose of this study was to report a case of Pseudomonas aeruginosa endophthalmitis after surgical 0.59 mg fluocinolone acetonide implant in a patient with a long-standing Crawford tube. METHODS: This was a retrospective case review. RESULTS: A 52-year-old woman with a history of bilateral sarcoid-associated panuveitis and nasolacrimal duct obstructions treated with dacryocystorhinostomies and long-standing Crawford tubes underwent placement of a surgical fluocinolone acetonide implant. The Crawford tube was visible throughout the surgery and notably exhibited small amounts of rotation and prolapse with manipulation of the eye. On postoperative Day 4, the patient presented urgently with pain and decreased visual acuity. Endophthalmitis was suspected, and a vitreous tap and intravitreal injections of vancomycin and amikacin were performed. Cultures grew P. aeruginosa. Initially she responded to treatment with no evidence of intraocular infection or inflammation by postoperative Week 3. However, at postoperative Week 4, the patient returned with a yellow purulent subconjunctival nodule and surrounding scleral injection. A second nodule appeared 2 weeks later. The patient was treated with topical and systemic antibiotics. The nodules responded well to treatment showing notable consolidation and revealing an area of scleral thinning as they regressed. CONCLUSION: We present a case of P. aeruginosa endophthalmitis and presumed scleritis after the surgical fluocinolone acetonide implant placement in an eye with a Crawford nasolacrimal tube effectively treated with topical, intravitreal, and systemic antibiotics. Long-standing nasolacrimal duct hardware may allow reflux of nasopharyngeal and nasolacrimal bacteria, contaminating the ocular surface during surgery.

SPONTANEOUS FORMATION AND RESOLUTION OF A LAMELLAR HOLE IN A PATIENT SUCCESSFULLY TREATED FOR DIABETIC MACULAR EDEMA WITH A FLUOCINOLONE ACETONIDE IMPLANT.

PURPOSE: The purpose of this study was to report a case of spontaneous formation and resolution of a lamellar macular hole in a patient with diabetic macular edema treated with steroid implants. METHODS: This study is a case report. RESULTS: A 53-year-old man presented with blurry vision and was found to have diabetic macular edema that remained refractory to treatment despite multiple short-term intravitreal steroid implants. He was eventually treated with an intravitreal fluocinolone acetonide implant and was subsequently noted to have developed a lamellar macular hole that then resolved spontaneously without any additional therapy. CONCLUSION: There can be spontaneous formation and resolution of lamellar holes in the treatment of diabetic macular edema because of reorganization of the inner retinal layers, without significant impact on visual acuity. To the best of our knowledge, this finding has not been previously reported.

Incidence and treatment approach of intraocular pressure elevation after various types of local steroids for retinal diseases.

PURPOSE: For the treatment of macular edema, in addition to the use of antivascular endothelial growth factors, steroids are also used intravitreally and sub-Tenon. Side effects include among others cataract formation and elevation of intraocular pressure (IOP). The aim of this retrospective study was to elicit the IOP elevation after administration of various steroidal medication, the time of onset, and the efficacy of the administered IOP-lowering therapies. METHODS: We included 428 eyes with a postoperative (n = 136), diabetic (n = 148), uveitic macular edema (n = 61), and macular edema after retinal vein occlusion (n = 83). These patients were treated with one or more diverse steroidal agents once or multiple times. These drugs included: triamcinolone acetonide (TMC) as intravitreal injection (TMC IVI) or sub-Tenon (TMC ST), as well as dexamethasone (DXM) and fluocinolone acetonide (FA) intravitreally. An increase of IOP of ≥ 25 mmHg was designated as pathological. A steroid response in anamnesis, the time of onset of IOP rise from the first administration, and the therapy administered were documented. RESULTS: Of 428 eyes, 168 eyes (39.3%) had IOP elevation up to a mean of 29.7 (SD ± 5.6) mmHg, which occurred at a median of 5.5 months. Steroids most frequently leading to rise of IOP included DXM (39.1% of all eyes receiving that drug), TMC IVI (47.6%), TMC ST combined with DXM (51.5%), DXM with FA (56.8%), and TMC IVI with DXM (57.4%). A Kaplan-Meier analysis and the Log Rank test showed a significant difference (p < 0.001). IOP rise was treated as follows: 119 conservatively (70.8%), and 21 surgically (12.5%, cyclophotocoagulation 8.3%, filtering surgery 1.8%, in 4 the steroidal drug implant was removed 2.4%), and 28 eyes received no therapy (16.7%). Sufficient IOP regulation was achieved in 82 eyes (68.9%) with topical therapy. In 37 eyes (31.1%) with persistently elevated intraocular pressure, topical therapy had to be continued over the follow-up of 20 ± 7 months. CONCLUSIONS: IOP increases after any type of steroid application are not rare. Results of our study let us suspect that especially therapy with intravitreal dexamethasone, either as a monotherapy or in combination with another steroid, tends to increase IOP more than other steroids. Regular IOP checks are necessary after each steroid administration, with possible initiation of long-term conservative and/or surgical therapy if necessary.

Functional and Morphological Responses to Fluocinolone Acetonide 0.19 mg in Noninfectious Uveitic Macular Edema Evaluated as the Area-Under-the-Curve.

Purpose: This study investigated the impact of baseline clinical and optical coherence tomography (OCT) factors on the response to a 0.19-mg fluocinolone acetonide (FAc) implant in patients with noninfectious uveitic macular edema evaluated by the area under the curve over 24 months. Methods: A retrospective study was conducted of eyes of patients with noninfectious uveitic macular edema undergoing FAc treatment, with follow-up from baseline to 24 months. The area under the curve (AUC) of best-corrected visual acuity (BCVA) and the central macular thickness (CMT) were calculated using the trapezoidal rule. Clinical and OCT data at the time of FAc administration were collected, and associations with AUC of BCVA and CMT changes were investigated. Results: Twenty-three patients were enrolled. BCVA and CMT significantly improved after FAc implantation (P < 0.05). AUCBCVA and AUCCMT were 0.41 ± 0.33 logarithm of minimal angle of resolution/6 months and 320.15 ± 321.64 µm/6 months, respectively. Better baseline BCVA (coefficient [coef.] = 0.83, P < 0.001) and macular thickness reduction after FAc administration (coef. = -0.0001, P < 0.05) were associated with better BCVA after FAc treatment. In contrast, baseline OCT biomarkers such as ellipsoid zone reflectivity and choroidal vascularity index, sex, or disease duration before FAc injection showed no correlation with AUCBCVA and AUCCMT (P > 0.05). The younger the patient at the time of FAc injection, the greater the reduction in CMT (coef. = 1.76, P < 0.05). Conclusions: Among all clinical and morphological baseline factors, Baseline BCVA was the strongest predictor for AUCBCVA, while no association with baseline OCT features was observed. Overall, improvement of BCVA and CMT after FAc injection was maintained over 24 months. This study is registered in the German Clinical Trials Register under the DRKS-ID: DRKS00024399.

INJECTABLE FLUOCINOLONE IMPLANT FOR THE MANAGEMENT OF CHRONIC POSTSURGICAL CYSTOID MACULAR EDEMA IN VITRECTOMIZED EYES.

PURPOSE: Long-acting injectable steroids are changing the treatment paradigm for patients with chronic intraocular inflammation and cystoid macular edema (CME). We report the use of the fluocinolone implant 0.18 mg in patients with chronic postsurgical CME after pars plana vitrectomy. METHODS: This is a retrospective case series of 24 vitrectomized eyes which received fluocinolone implant for the management postsurgical CME. Clinical outcomes and requirement for rescue therapy were studied. RESULTS: Median length of follow-up was 19.3 months (range 8.3-23.2 months). There was an improvement in median central subfield thickness from 412 µ m (range 167-806 µ m) to 311 µ m (range 157-686 µ m) after fluocinolone implant ( P < 0.001). The injection burden decreased significantly after study treatment ( P < 0.001); however, there was no significant change in visual acuity ( P = 0.334). Eighteen eyes had control of CME that did not require additional intravitreal therapy. Four eyes had initially controlled but recurrent CME requiring intravitreal steroid therapy at median of 7.8 months (range 7.6-15.4 months). One eye never attained sufficient inflammatory control despite rescue therapy. CONCLUSION: Fluocinolone implant can be an effective treatment in vitrectomized patients with chronic postsurgical CME and can help decrease the overall injection burden.

BETTER BASELINE VISION LEADS TO BETTER OUTCOMES AFTER THE 0.19-mg FLUOCINOLONE ACETONIDE INTRAVITREAL IMPLANT IN DIABETIC MACULAR EDEMA.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

INTRAVITREAL FLUOCINOLONE ACETONIDE IMPLANT FOR RADIATION RETINOPATHY: Report of Preliminary Findings.

PURPOSE: To assess the efficacy of a 0.18 mg intravitreal fluocinolone acetonide (FA) implant (Yutiq, EyePoint Pharmaceuticals, Watertown, MA) as a treatment option for patients with radiation retinopathy-related cystoid macular edema. METHODS: A retrospective review of seven patients treated for uveal melanoma who developed radiation retinopathy-related cystoid macular edema. They were initially treated with intravitreal anti-vascular endothelial growth factor and/or steroid injections and then transitioned to intravitreal FA implant. Primary outcomes include best-corrected visual acuity, central subfield thickness, and number of additional injections. RESULTS: After FA implant insertion, best-corrected visual acuity and central subfield thickness remained stable in all patients. The variance in best-corrected visual acuity decreased from 75.5 ETDRS letters (range 0-199 letters) to 29.8 (range 1.2-134) after FA implant insertion. Mean central subfield thickness was 384 µ m (range 165-641) and 354 µ m (range 282-493) before and after FA implant insertion, resulting in a 30- µ m mean reduction. The number of intravitreal injections (average 4.9, range 2-10) decreased after intravitreal FA implant insertion with only two patients requiring one additional FA implant (average 0.29, range 0-1) over a mean of 12.1 months (range 0.9-18.5) follow-up. CONCLUSION: Intravitreal FA implant is an effective treatment for cystoid macular edema radiation retinopathy. The slow release of steroid allows for sustained control of macular edema, which correlated with stable visual acuity and decreased injection burden for patients.

Intravitreal Fluocinolone Acetonide Implant (ILUVIEN®) for the Treatment of Retinal Conditions. A Review of Clinical Studies.

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.

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

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The 0.19-mg Fluocinolone Acetonide Implant for the Treatment of Diabetic Macular Edema: An Expert Consensus.

BACKGROUND AND OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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%]). CONCLUSIONS: 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.].

[Comparison of available clinical and imaging tools to assess good positioning of a fluocinolone acetonide implant (Iluvien®) in the vitreous cavity after injection]. / Comparaison des moyens clinique et d'imagerie disponibles en pratique clinique pour objectiver la présence de l'implant d'acétonide de fluocinolone (Iluvien®) dans la cavité vitréenne après injection.

INTRODUCTION: Sustained-release corticosteroid implants are injected into the vitreous cavity using preloaded pens. The fluocinolone (FAc) implant is approximately half the size of the dexamethasone implant (Dex-I). It is simply introduced in the vitreous base rather than propelled into the vitreous cavity as is Dex-I. Verification of its positioning after injection is thus difficult by indirect ophthalmoscopy. The goal of our study is to compare the performance of available clinical and imaging tools to confirm the presence of the FAc in the vitreous cavity following injection. METHODS: Twelve eyes of 12 consecutive patients were included in a retrospective, single-center, observational study carried out at the Bordeaux University Hospital, France. All patients were injected with the FAc after pupil dilation, and presence of the implant was immediately checked by indirect biomicroscopy, wide-field retinography (Clarus®, Carl-Zeiss-Meditec, Dublin, CA, USA) and ultra-wide-field retinography (California®, Optos, Edinburgh, United-Kingdom). Seven days later, a B-mode ultrasonography (10MHz, AVISO, Quantel-medical, France) and an UBM ultrasonography (50MHz, AVISO, Quantel-medical, France) were performed. RESULTS: Indirect biomicroscopy and wide-field retinography detected 4/12 implants (33.3%). Ultra-wide-field retinophotography detected 6/12 implants (50%). All the implants seen using indirect biomicroscopy and wide-field retinography were also visualized with ultra-wide-field. B-mode ultrasonography showed 5/12 implants (41.6%) and UBM 9/12 implants (75%). Finally, one implant dislocated into the anterior chamber and was seen in the iridocorneal angle on gonioscopy. CONCLUSION: Objective confirmation of the proper positioning of the FAc implant in the vitreous cavity is mandatory. If both indirect ophthalmoscopy and anterior examination fail to detect it, ultra-wide field retinography along with UBM ultrasonography, if necessary, appear to be the two best imaging modalities to use.

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

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