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Purpose: To compare the outcomes of early or late switching from intravitreal (IV) anti-vascular endothelial growth factor (anti-VEGF) injection to IV Dexamethasone (DEX) implant injection in treatment-naïve patients with macular edema secondary to branch retinal vein occlusion., Methods: This study included 68 eyes of 68 treatment-naïve BRVO patients who started anti-VEGF treatment. After the loading dose, the patients were divided into two groups: Early DEX group (n:34) (DEX implant treatment started after 3 loading doses) and Late DEX group (n:34) (DEX implant treatment started after 6 months). Visual acuity and examination findings were recorded at baseline, 3rd, 6th, and 12th month follow-ups. Optical coherence tomography data were recorded for central macular subfield thickness assessment., Results: A total of 30 (44.1%) women and 38 (55.9%) men participated, and the average age was 67.6 ± 6.4 years. The mean letter gains at week 52 was 15.1 and 20.9 in the Early DEX and Late DEX groups, respectively. The group with the highest gain of ≥15 letters was the Late DEX group (26/34 patients) and the gain of ≥15 letters was 14/34 in the Early DEX group (p: 0.006). At week 52, the anatomical gain was 115.3 µm and 136.9 µm in the Early DEX and Late DEX groups, respectively., Conclusions: A gain of 15 or more letters was demonstrated to be higher in patients who switched to DEX implant late after anti-VEGF treatment. If it is necessary to switch, the late switch may be more effective for more visual gain at the end of the first year.

Objectives: To assess the risk factors for resistance to first-line therapy and long-term response to dexamethasone intravitreal implant (Ozurdex ® ) of patients with macular oedema (MO) secondary to rhegmatogenous retinal detachment repair (RRDR)., Methods: This was a retrospective, consecutive cohort study conducted in patients who underwent RRDR between January 2014 and December 2020 in the Rothschild Foundation Hospital and experienced postoperative MO (POMO) with a follow-up of at least 18 months., Results: Of the 1152 patients screened, 36 eyes (3.1%) experienced POMO. The mean follow-up duration was 45.2 months (18.0-80.5 months). Twenty-five eyes (69.4%) were resistant to first-line therapy and received at least one Ozurdex ® injection (mean number: 2.7 [1-12]). The multivariate analysis showed an increased risk of resistance in patients who underwent perfluorocarbon liquid (PFCL)-assisted drainage (adjusted odds ratio: 8.65; 95% confidence interval: 1.97-15.33; p = 0.01). Significant differences in best-corrected visual acuity and central macular thickness were found between before Ozurdex ® injection and the last follow-up visit: from 0.57 ± 0.47 LogMAR to 0.34 ± 0.32 LogMAR (p = 0.02) and from 483.0 ± 124.0 µm to 354.6 ± 96.5 µm (p = 0.001), respectively. The absence of serous retinal detachment and the presence of hyperreflective foci at baseline were associated with a higher resistance and a poorer response to Ozurdex ® . Two patients (8%) experienced hypertony, that was well controlled with hypotonic drops., Conclusion: MO secondary to RRDR is challenging. Ozurdex ® could be reasonably proposed as first-line treatment, at least when MO occurs following PFCL-assisted drainage, given the favourable long-term benefit/risk ratio., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

This study investigates the impact of glycosylated hemoglobin (HbA1c) on the efficacy of intravitreal dexamethasone (DEX) implants in patients with diabetic macular edema (DME) over a 12-month period. We retrospectively reviewed 90 DME patients treated with DEX implants, categorizing them based on baseline HbA1c levels (≤ 7% and > 7%) and 12-month changes in HbA1c ("improved", "stable", "worsened"). At the 2-month mark, the mean central subfield thickness (CST) reduction in the HbA1c ≤ 7% group was - 147.22 ± 113.79 µm compared to -130.41 ± 124.50 µm in the > 7% group (p = 0.506). Notably, 12-month outcomes between these groups showed no significant difference. The "improved" HbA1c subgroup experienced a more pronounced CST reduction at 2 months (p = 0.042), with outcomes leveling off with other groups by 12 months. Conclusively, DEX implant outcomes in DME were not influenced by either baseline HbA1c levels or their changes over time. This suggests that local alterations in the inflammation milieu may have a potentially stronger impact on DME treatment outcomes, highlighting the importance of considering local factors in DME treatment., (© 2024. The Author(s).)

Background and Objective: Intravitreal dexamethasone implant (DEXI) has been placed as an effective option to treat diabetic macular edema (DME). However, there is no consensus on the best time to introduce it. We conducted a study to evaluate anatomical and functional behavior after the first DEXI according to previous treatment., Research Design and Methods: This retrospective, real-world study between 2013 and 2020 investigated changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT at months 2 and 6 after the first DEXI in DME. Patients were divided into naive, early switch (≤3 anti-VEGF injections), or late switch (>3 anti-VEGF injections) groups., Results: Among 112 consecutive eyes, mean BCVA and CMT improved significantly in all groups at month 2, with no difference between them. However, this improvement was not maintained at 6 months. The Naíve group presented better BCVA all over the study period. The previously treated groups, which started with worse initial visual acuity, showed more visual gain without reaching the BCVA of the naive group. CMT performance was similar between groups., Conclusions: There was similar anatomical and functional behavior in all groups. Poorer visual acuity at baseline was associated with worse functional outcome despite good anatomic response.

Introduction: We describe a case of acute exudative polymorphous vitelliform maculopathy (AEPVM) that recurred 9 years after the initial event. To the best of our knowledge, this is the first report of recurrent AEPVM showing recovery of retinal and retinal pigment epithelium (RPE) function and good visual outcome following treatment with intravitreal corticosteroid., Case Description: A 45-year-old Caucasian woman first presented with AEVPM in 2009. Her condition spontaneously resolved and she remained stable over several years. 9 years later, her condition recurred with bilateral reduction in visual acuity. Fundus examination revealed multiple small yellowish subretinal lesions across the posterior pole in both eyes. Optical coherence tomography (OCT) showed bilateral cystoid macular oedema (CMO). She was referred for electrophysiology and her electrooculogram findings were in keeping with severe generalised RPE dysfunction bilaterally, with a light peak to dark trough ratio (Arden index) of 110%, comparable to her initial presentation 9 years earlier. She was initially treated with oral steroids with some improvement. However, the maculopathy in the left eye recurred on cessation of oral treatment. A sustained-release 700ug dexamethasone intravitreal implant (Ozurdex®) was inserted in the left eye to which she responded remarkably, with improvement in visual acuity and complete resolution of the CMO. A year later, at her most recent clinic visit in March 2021, there was no evidence of any further recurrence., Conclusion: Our case demonstrates clinical and imaging findings consistent with recurrence of AEPVM with CMO that has been successfully treated with Ozurdex®., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest other than writing assistance being funded by Alimera Sciences Ltd.

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 mm 3 at baseline to 9.6 ± 2.9 mm 3 (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., (© 2023. The Author(s).)

Background/objectives: To describe the visual and clinical outcomes of patients with post endothelial keratoplasty (EK) cystoid macular oedema (CMO) refractory to topical treatment with intravitreal sustained-release dexamethasone implant (Ozurdex)., Subjects/methods: 131 eyes from 111 patients undergoing solitary or combined EK (52 DSAEK (40.0%) and 79 DMEK (60.0%)) at Southend University Hospital between January 2020 and February 2022 with a minimum follow-up of 6 months were evaluated. Patients suspected of having CMO underwent spectral-domain macular optical coherence tomography (SD-OCT) Patients with diabetes were not included in this series., Results: CMO was identified in 5.3% (n = 7) of cases, with 2 of these patients responding to topical corticosteroid treatment. The remaining 5 patients underwent intravitreal dexamethasone implant, with 1 patient requiring repeat implant due to CMO recurrence. All presented within 2 months postoperatively. 4 out of 5 eyes treated with intravitreal dexamethasone achieved a Snellen BCVA ≤6/9.5. 1 patient had an uncontrolled rise in intraocular pressure (IOP) despite maximal medical treatment requiring an urgent PreserFlo Ab-Externo MicroShunt., Conclusions: The use of intravitreal sustained-release dexamethasone implant in the management of post EK CMO refractory to topical therapy is effective and safe in most cases, but patients should be monitored and treated promptly for any secondary IOP response.

Introduction: To report a successful application of dexamethasone implants in the treatment of a massive amount of persistent subretinal fluid (SRF) following a tractional retinal detachment (TRD) surgery., Case Report: A 44-year-old woman was found to have SRF 1 week after a diabetic TRD surgery. The central macular thickness (CMT) reached up to 1.47 mm and remained high after a month's observation. For better restoration, 2 dexamethasone implants (Ozurdex) were applied at postoperative week 5 and 32 respectively and got good outcomes. The SRF decrease showed a close correlation with Ozurdex treatments: The CMT declined quickly in the next 16 weeks both after 2 times of Ozurdex applications (the linear regression slopes of CMT changes: -12.54 and -22.94, respectively). In contrast, in the interval of 2 injections, the CMT had few changes (the slope: -4.667) even if applying an anti-VEGF agent. Eventually, SRF was completely resolved 48 weeks after the surgery., Discussion: Dexamethasone implant can be an option for effective treatment of persistent SRF after TRD repair, especially in some refractory cases. However, the mechanism remains unclear, and the treatment regimen needs to be explored based on more clinical trials.

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). AUC BCVA and AUC CMT 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 AUC BCVA and AUC CMT ( 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 AUC BCVA , 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.

Aim: To evaluate effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX) monotherapy in the AUSSIEDEX study non-responder subgroup, defined by diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF) agents., Methods: This prospective, open-label, observational, real-world study included pseudophakic and phakic (scheduled for cataract surgery) eyes that did not achieve a ≥5-letter best corrected visual acuity (BCVA) gain and/or clinically significant central subfield retinal thickness (CRT) improvement after 3-6 anti-VEGF injections for DME (N=143 eyes), regardless of baseline BCVA and CRT. After an initial DEX injection (baseline visit), reinjection was permitted at ≥16-week intervals., Primary Endpoints: changes in mean BCVA and CRT from baseline to week 52. Safety assessments included adverse events., Results: Of 143 eyes, 53 (37.1%) and 89 (62.2%) switched to DEX after 3-6 (early) and >6 (late) anti-VEGF injections, respectively; 1 (0.7%) had missing information. With 2.3 injections (mean) over 52 weeks, the change in mean BCVA from a baseline of 57.8 letters was not significant at week 52. Mean CRT improved significantly from a baseline of 417.8 μm at week 52 (mean change -60.9 μm; p<0.001). Outcomes were similar in eyes switched to DEX early and late. No unexpected adverse events were reported; no filtration surgeries were required., Conclusion: To date, AUSSIEDEX is the largest prospective, real-world study of DEX monotherapy for treatment-naïve or anti-VEGF-refractory DME. Following early or late switch from anti-VEGF agents, DEX significantly improved anatomic outcomes at 52 weeks without new safety concerns, supporting use in anti-VEGF-refractory DME., Trial Registration Number: NCT02731911., Competing Interests: Competing interests: Financial arrangements of the authors with companies whose products may be related to the present report are listed below, as declared by the authors. PM, MD, PhD: Advisory board member for and honoraria from Allergan (an AbbVie company), Bayer, and Novartis. JA, MD: Advisory board member for and honoraria from Alcon, Allergan (an AbbVie company), Apellis, Bayer, Novartis, and Roche. SF-B, MD, PhD: Consultant for Allergan (an AbbVie company), Bayer, Novartis, and Roche. HKK, MD: Scientific advisory member for Allergan (an AbbVie company). AAC, MD, PhD: Advisor for Alcon, Allergan (an AbbVie company), Apellis, Bayer, Novartis, and Roche. JT, RN: Employee of Allergan (an AbbVie company) at the time the study was conducted, and current employee of Pfizer. SS, BS, RN: Employee of Allergan (an AbbVie company) at the time the study was conducted., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: 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)., Methods: 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., Results: 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., Conclusions: 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., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objective: To evaluate the effectiveness and safety of intravitreal dexamethasone implant (IDI) in diabetic macular edema (DME) patients with and without prior vitrectomy. Methods: A retrospective cohort study was conducted on DME patients who received IDI treatment at the Aier Eye Hospital, Beijing from March 2018 to August 2020. Patients were divided into two groups according to whether they had undergone vitrectomy or not. Clinical and follow-up data, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), occurrence of ocular and systemic complications, and time to DME recurrence and retreatment, were collected before and after IDI injection at 15 days, 1, 2, 3, and 6 months. Statistical analyses were performed using t -test, Mann-Whitney U -test, χ 2 test or Fisher's exact test, and generalized estimating equations. Results: Thirty-six patients (41 eyes) were included, with 19 patients (21 eyes) in the vitrectomy group and 17 patients (20 eyes) in the non-vitrectomy group. Compared with baseline, BCVA of eyes in the vitrectomy group was significantly improved at 15 days after IDI injection, with values of 1.00 (0.52, 1.31) and 0.61 (0.30, 1.00), respectively ( Z =-2.10, P =0.036); BCVA of eyes in the non-vitrectomy group was significantly improved at 1 month after IDI injection, with values of 0.76 (0.60, 1.35) and 0.52 (0.10, 0.70), respectively ( Z =-2.24, P =0.025). Compared with baseline, CMT of eyes in both groups was significantly reduced at all follow-up time points after 15 days of IDI injection (all P <0.05). In the vitrectomy group, CMT before and 15 days after injection were 487 (438, 661) μm and 389 (340, 553) μm, respectively ( Z =-3.45, P <0.001); in the non-vitrectomy group, CMT before and 15 days after injection were 486 (410, 641) μm and 323 (290, 396) μm, respectively ( Z =-4.07, P <0.001). There were no statistically significant differences in BCVA and CMT between the two groups at all follow-up time points (all P >0.05). The time to DME recurrence was 3.0 (3.0, 4.0) months in the vitrectomy group and 5.0 (4.0, 5.0) months in the non-vitrectomy group, with no significant difference between the two groups ( P =0.675). Four eyes (19.0%) in the vitrectomy group and three eyes (15.0%) in the non-vitrectomy group had high IOP, with no significant difference ( P =0.529). No severe ocular or systemic complications were observed in any patients. Conclusions: IDI treatment is safe and effective in DME patients with and without prior vitrectomy, with similar efficacy, but with faster onset of action in patients with prior vitrectomy. There was no significant difference in DME recurrence within 6 months after IDI injection between the two groups.

Purpose: To evaluate the effectiveness of in---travitreal bevacizumab injections following a single dexamethasone implant in the treatment of macular edema secondary to branch and central retinal vein occlusion., Methods: This was a prospective interventional non-comparative study, 44 eyes of patients with naïve macular edema related to branch and central retinal vein occlusion were treated with a dexamethasone implant. Patients were followed-up at four-week intervals from the second to the sixth month. If persistent or recurrent macular edema occurred during this period, the patient was treated with intravitreal bevacizumab injections on an as-needed basis. The outcome measures were best-corrected visual acuity and central macular thickness changes., Results: The mean best-corrected visual acuity changed from 0.97 ± 0.33 LogMAR at baseline to 0.54 ± 0.40 at the six-month post-implant examination (p<0.00001). Improvement ≥3 Snellen lines were seen in 20 eyes (45.54%). The mean central macular thickness at baseline was 670.25 ± 209.9 microns. This had decreased to 317.43 ± 112.68 microns at the six-month follow-up (p<0.00001). The mean number of intravitreal bevacizumab injections received in the six months post-implant was 2.32. The mean time from dexamethasone implant to first anti-VEGF injection was 3.45 months., Conclusions: Intravitreal bevacizumab injections following a single dexamethasone implant were found to improve best-corrected visual acuity and central macular thickness in patients with macular edema due to branch and central retinal vein occlusion at six months, with few intravitreal injections required.

Purpose: The purpose of this study is to evaluate clinical outcomes of autoimmune retinopathy (AIR) in the patients treated with intravitreal dexamethasone implant (IDI)., Method: Twenty-one eyes of 11 AIR patients treated with at least 1 injection of IDI were retrospectively reviewed. Clinical outcomes before and after treatment, including best corrected visual acuity (BCVA), optic coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinography (ff-ERG), and visual field (VF) at last visit within 6 and/or 12 months, were recorded., Results: Among all the patients, 3 had cancer-associated retinopathy (CAR) and 8 had non-paraneoplastic-AIR (npAIR) with mean followed up of 8.52 ± 3.03 months (range 4-12 months). All patients achieved improved or stable BCVA within 6 and/or 12 months after the treatment. Cystoid macular edema (CME) in 2 eyes and significant retinal inflammation in 4 eyes were markedly resolved after single injection. Central retinal thickness (CFT) in all eyes without CME, ellipsoid zone (EZ) on OCT in 71.4% of eyes, ERG response in 55% of eyes, and VF in 50% of eyes were stable or improved within 6 months after treatment. At last visit within 12 months, both BCVA and CFT remained stable in the eyes treated with either single or repeated IDI; however, progression of EZ loss and damage of ERG response occurred in some patients with single IDI., Conclusion: Clinical outcomes, including BCVA and parameters of OCT, ERG, and VF, were stable or improved after IDI in a majority of AIR patients. Local treatment of AIR with IDI was a good option to initiate the management or an alternative for the patients' refractory to the systemic therapy but with limited side effect., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To assess the safety and efficacy of intraoperative dexamethasone intravitreal (DEX) implant in patients with diabetic macular edema (DME) undergoing femtosecond laser assisted cataract surgery (FLACS)., Methods: In this single-center retrospective study, the charts of patients who underwent combined FLACS and DEX implant in the previous three months were reviewed. Primary outcome measures were ocular complications; secondary outcome measures were the change of best-corrected visual acuity (BCVA) and central retinal thickness (CRT)., Results: 20 eyes of 20 patients were included. None developed intraoperative or postoperative complications. Mean BCVA was 20/120 (logMAR, 0.78 ± 0.31) at baseline and improved significantly to 20/63 (logMAR, 0.52 ± 0.24; p = 0.01), 20/58 (LogMAR, 0.48 ± 0.28; p < 0.001) and to 20/58 (LogMAR, 0.48 ± 0.31; p < 0.001) at month 1,2 and 3, respectively. A mean improvement of 0.30 LogMAR was recorded at month 1 and 3. Mean CRT decreased significantly from 416.6 ± 76.1 μm at baseline to 322.4 ± 46.4 μm (p < 0.001), to 300.7 ± 29.7 μm (p < 0.001), and to 319.8 ± 54.7 μm (p < 0.001) at month 1,2 and 3, respectively. Comparing to the 1-month follow-up, the largest mean reduction in CRT (112.4 ± 68.9 µm) was observed at month 2 (p = 0.001). Fourteen patients (70%) had an improvement of CRT over the first 2 months followed by a recurrence of edema at month 3., Conclusion: DEX implant following FLACS seems to be a safe and effective approach for patients with coexisting cataract and DME.

Purpose: To show an alternative surgical technique for the introduction of the intravitreal fluocinolone acetonide (FAc) implant (Iluvien ® ) into the vitreous cavity using a 23-gauge (G) trocar if it is retained during its implantation in the subconjunctival space., Methods: We describe the surgical procedure performed to solve the complication: The FAc implant was extracted from the subconjunctival space using flat retinal forceps. A 23-G trocar was inserted 3,5 mm to the limbus. The same flat retinal forceps were used to take the FAc implant and introduce it into the vitreous cavity using a 23-G trocar., Results: The patient's best corrected visual acuity (BCVA) (Snellen) improved from 20/200 to 20/63 and the central macular thickness (CMT) was reduced from 610 microns (µm) to 215 µm after one week of the FAc implantation. He remained stable after 3 months of follow-up, with a BCVA of 20/63 and a CMT of 191 µm. His intraocular pressure (IOP) remained stable and the integrity of the implant was checked by indirect ophthalmoscopy., Conclusion: The introduction of the intravitreal FAc implant using a 23-gauge trocar constitutes a valid alternative if it is retained during its implantation in the subconjunctival space.The functionality of the implant remained intact in our patient.

Purpose: To compare the direct costs associated with the dexamethasone intravitreal implant (DEX-i) in treatment-naïve and previously treated eyes with diabetic macular edema (DME) in a real clinical setting., Methods: Retrospective and single-center study conducted in a real clinical scenario. Consecutive DME patients, either naïve or previously treated with vascular endothelial growth factor inhibitors (anti-VEGF), who received treatment with one or more DEX-i between May 2015 and December 2020, and who were followed-up for a minimum of 12 months, were included in the study. The cost analysis was performed from the perspective of the Andalusian Regional Healthcare Service. The primary effectiveness endpoint was the probability of achieving an improvement in best-corrected visual acuity (BCVA) ≥ 15 ETDRS letters after 1 year of treatment. The incremental cost-effectiveness ratio (ICER) of different improvements in BCVA was calculated., Results: Forty-nine eyes, twenty-eight (57.1%) eyes from the treatment-naïve group and twenty-one (42.9%) from the previously treated group, were included in the analysis. The total cost of one year of treatment was significantly lower in the treatment-naïve eyes than in the previously treated eyes [Hodges-Lehmann median difference: EUR 819.1; 95% confidence interval (CI): EUR 786.9 to EUR 1572.8; p < 0.0001]. The probability of achieving a BCVA improvement of ≥15 letters at month 12 was significantly greater in the treatment-naïve group than in the previously treated group (rate difference: 0.321; 95% CI: 0.066 to 0.709; p = 0.0272). The Cochran-Mantel-Haenszel Odds Ratio of achieving a BCVA improvement of ≥15 letters at month 12 was 3.55 (95% CI: 1.09 to 11.58; p = 0.0309). In terms of ICER, the treatment-naïve group showed cost savings of EUR 7704.2 and EUR 5994.2 for achieving an improvement in BCVA ≥ 15 letters at month 12 and at any of the measured time points, respectively., Conclusions: DEX-i was found to be more cost-effective in treatment-naïve eyes than in those previously treated with anti-VEGF. Further studies are needed to determine the most cost-effective treatment based on patient profile.

Purpose: To evaluate the effectiveness of 0.19-mg fluocinolone acetonide implant (FAi) for preventing inflammatory relapses in noninfectious uveitis with posterior segment involvement in standard clinical practice. Further, to assess the value of remission induction therapy with intraocular and periorbital administered high-dose corticosteroids before FAi., Methods: A retrospective cohort study in a tertiary referral center specialized in uveitis management. The primary study outcomes were the best-corrected visual acuity (BVCA) and central retinal thickness (CRT) within a 12-month observation period. The secondary outcomes were intraocular pressure (IOP) and intraocular inflammation. The main safety measures were IOP increase and cataract formation., Results: In total, 76 eyes of 57 patients received FAi. Locally administered high-dose corticosteroids were applied in 68.4% of all eyes before FAi. BCVA remained stable within the 12-month observation period (63.21 vs. 62.95, difference 0.26 letters; 95% CI: - 6.31 to 6.84; p > 0.9). Significant CRT reduction upon FAi was sustained after 12 months (362.7 vs. 309.1 μm, difference 53.57 μm; 95% CI: 1.55 to 105.6; p = 0.04). Intraocular inflammation was reduced until 9 months of follow-up (0.82 vs. 0.3, difference 0.53; 95% CI: 0.11 to 0.95; p = 0.007). A mean IOP increase (13.68 vs. 15.6; difference - 1.92; 95% CI: - 3.85 to 0.004; p = 0.0507) and cataract development (20% of all phakic eyes) were noted., Conclusion: We observed similar levels of FAi effectiveness for the treatment of noninfectious uveitis in standard clinical practice compared to previous randomized clinical trials. Moreover, remission induction therapy before FAi can benefit patients with increased baseline uveitis activity., (© 2022. The Author(s).)

Purpose: To assess treatment burden in patients with diabetic macular edema (DME) after the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN)., Design: Prospective and retrospective analyses of a 36-month, phase 4, open-label, observational study., Methods: Setting: Multicenter., Patient Population: 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., Observation Procedures: Prospective, observational treatment burden data were analyzed for their relationship to safety and functional efficacy outcomes across 36 months., Main Outcome Measures: Outcomes included the mean number of yearly treatments, supplemental-free probability over time, best-corrected visual acuity, and monitoring of IOP-related events., Results: 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., Conclusions: 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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the cost-effectiveness of early- versus late-switch to the intravitreal-dexamethasone implant (DEX-i) in patients with diabetic macular edema (DME) who did not adequately respond to vascular endothelial growth factor inhibitors (anti-VEGF)., Methods: Retrospective analysis of a multicenter Clinical Data Registry. The registry included DME eyes who received 3 intravitreal anti-VEGF injections (early-switch) or > 3 intravitreal anti-VEGF injections (late-switch) before switching to DEX-i injections. The primary outcome was to estimate the incremental cost needed to obtain a best-corrected visual acuity (BCVA) improvement ≥ 0.1 or a central-retinal thickness CRT ≤ 250 μm., Results: The analysis included 108 eyes, 32 (29.6%) and 76 (70.4%) in the early- and late-switch groups, respectively. Early-switch strategy was associated with a cost saving of €3,057.8; 95% CI: €2,406.4-3,928.4, p < 0.0001). Regarding incremental-cost-effectiveness ratio, late-switch group was associated with an incremental cost of €25,735.2 and €13,533.2 for achieving a BCVA improvement ≥ 0.1 at month 12 and at any of the time-point measured, respectively. At month 12, 38 (35.2%) eyes achieved a BCVA improvement ≥ 0.1. At month 12, 52 (48.1) eyes had achieved a CRT ≤ 250 micron. As compared to baseline, the mean (95% CI) CRT reduction was - 163.1 (- 212.5 to - 113.7) µm and - 161.6 (- 183.8 to - 139.3) µm in the early-switch and late-switch groups, respectively, p = 0.9463., Conclusions: In DME eyes, who did not adequately respond to anti-VEGF, switching to DEX-i at early stages (after the first 3-monthly injections) was found to be more cost-effective than extending the treatment to 6-monthly injections of anti-VEGF., (© 2022. The Author(s).)

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., Competing Interests: Yusuf Mushtaq and Maryam M Mushtaq are co-first authors for this study. Lorenzo Motta and Georgios D Panos are co-correspondence authors for this study. The authors report no conflicts of interest in this work., (© 2023 Mushtaq et al.)

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.

Uveitis is a type of ocular inflammatory disease caused by various etiologies, for which corticosteroids are the main treatment. Dexamethasone Intravitreal implant (DEX-I) has been widely used in the treatment of uveitis across the world. Then, new indications and complications appeared. This review aims to summarize the use of DEX-I in uveitis in the past 10 years. We summarized the clinical data (baseline characteristics, efficacy and safety) and discussed controversies by retrospectively analyzing the articles and cases published in PubMed and Web of Science using the terms "Ozurdex", OR "intravitreal dexamethasone implant", AND "uveitis" from 2010 to 2022. DEX-I is effective in reducing edema, improving inflammation and improving vision when treating various conditions of uveitis including infectious, no-infectious, pediatric uveitis, and surgery-related applications. The efficacy of DEX-I as a monotherapy is related to the following: etiology and course of disease, treatment of systemic diseases, patients' toleration after multiple injections, economic situation, etc. In addition, intravitreal corticosteroids implantation may replace systemic therapy in some patients. In terms of safety, the incidence of high intraocular pressure is about 20.52%, and the incidence of cataract is about 15.51%. DEX-I can effectively treat non-infectious uveitis and some infectious uveitis such as suspected tuberculosis, and its safety is controllable. Further studies are necessary to evaluate the effect of monotherapy and to expand more indications.

Objective: We aimed to compare visual and anatomical outcome in vitrectomized and non-vitrectomized eyes treated with dexamethasone (DEX) implant due to diabetic macular oedema (DMO)., Design: Multicenter, retrospective, interventional study., Participants: 236 eyes from 234 patients with DMO with or without previous vitrectomy performed with follow-up of 12 months., Methods: Records were reviewed for cases of DMO treated with DEX implant in vitrectomized and not vitrectomized eyes. Best corrected visual acuity (BCVA), central subfoveal thickness (CST), and intraocular pressure (IOP) were recorded at baseline and 12 months after treatment with DEX implants. Correlations between vitreous status and visual and anatomical outcome, as well as safety profile were analysed., Main Outcome Measures: BCVA and CST over follow-up period., Secondary Outcomes: cataract rate formation, intraocular pressure increase, number of implants needed., Results: The non-vitrectomized group included 130 eyes (55.1%), the vitrectomized group included 106 eyes (44.9%). The groups were well balanced for age and gender (p = 0.540, and p = 0.053, respectively). Both groups showed statistically significant improvement in BCVA and CST (for all groups: p < 0.001). There was no significant difference between the groups in terms of change in vision (p = 0.89) and anatomy (p = 0.65). The mean number of DEX implants given during follow-up was 3.5 in both groups, and there was no significant difference between the groups (p = 0.81)., Conclusion: We demonstrated similar anatomical and functional efficacy of DEX implant in non-vitrectomized and vitrectomized eyes. Its efficacy was not influenced by full vitrectomy for diabetic retinopathy complications. Safety profile was well balanced between groups., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Introduction: The aim of this study was to evaluate the outcomes and complications associated with the use of same-day bilateral intravitreal dexamethasone (DEX) implants for the treatment of diabetic macular edema (DME)., Methods: This retrospective analysis of an open-label, multicenter, consecutive case series included 130 eyes of 65 patients with bilateral DME who were treated with intravitreal DEX implants. The patients were divided into two groups: a control group (comprising 40 eyes treated with an alternating unilateral regimen) and a study group (comprising 90 eyes treated with concomitant bilateral DEX implants). All patients were followed up monthly after implantation. The changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to sixth month after implantation, and ocular adverse effects such as intraocular pressure, cataract, and tolerability of bilateral implantation were reviewed. The primary endpoint was to assess the safety of the same-day bilateral treatment protocol. The secondary endpoints focused on evaluating the functional and anatomical changes associated with bilateral simultaneous or alternating implantations., Results: At 6 months after implantation, mean BCVA increased and CRT decreased in both groups. Moreover, no serious ocular adverse effects were observed. In addition, no differences were observed between the two groups in the number of patients who required extra follow-up visits or the number of extra visits made in addition to the treatment schedule., Conclusions: Same-day bilateral intravitreal DEX implants are associated with a low complication rate and are well tolerated by patients. This safe practice may optimize efficiency and reduce the burden on both the health-care system and patients, when used to treat bilateral DME., (© 2023 S. Karger AG, Basel.)

Purpose: To provide consensus on the clinical use of intravitreal dexamethasone (DEX) implant for the treatment of diabetic macular edema (DME) in Turkey., Methods: A panel of 22 retina experts prepared 77 statements of recommendation, and 80 retinal specialists practicing in Turkey were chosen to vote either in support or against each one. A Delphi-based method was used through which the ophthalmologists were able to view all of the results anonymously after two rounds and modify their subsequent answers. The survey was conducted via a mini website, and statements without consensus were resent to the specialists with the latest vote results a week later., Results: A total of 72 ophthalmologists answered the first and second round questions. After the first stage, consensus was achieved on 55 of the statements, leaving 22 without agreement. After the second stage, consensus was reached on 11 of the remaining statements. Strong consensus was achieved on statements regarding the etiopathogenesis of DME and the first-line indications and safety of the DEX implant procedure. The panel recommended the use of DEX implant for patients with an arterial thromboembolic event in the last three months and also agreed that pro re nata DEX implant treatment not only provides better outcomes for DME patients but also reduces the treatment burden for those who could not receive an adequate number of anti-vascular endothelial growth factor (VEGF) injections., Conclusion: This study provides clinical consensus and recommendations about the use of DEX implant in the clinical practice of DME management in Turkey.

Cystoid macular edema (CME) is the most common cause of decreased visual acuity after both vitrectomy and cataract surgery. Various strategies have been used for its treatment, such as intravitreal corticosteroids. The intravitreal fluocinolone acetonide implant (Iluvien ® ) is approved for the treatment of persisting diabetic macular edema and for the prevention of recurrence of non-infectious uveitis affecting the posterior segment. There are very few reports about its off-label use for post-surgical CME. We present four clinical cases of post-surgical CME (three following vitrectomy and one following cataract surgery in a vitrectomized eye 2 years ago). All of them had been previously treated with an average of four injections of intravitreal dexamethasone implant (Ozurdex ® ), with repeated recurrence of CME. After treatment with Iluvien, three cases showed improvement of both visual acuity and macular anatomy, with resolution of the macular edema. One patient required additional treatment with Ozurdex during follow-up, further improving CME. Two of the cases required topical pressure lowering treatment, and none required filtering surgery. Iluvien could be an effective therapeutic option for persistent non-diabetic macular edema after vitrectomy or cataract surgery refractory to other intravitreal therapies, with the benefit of being able to provide longer recurrence-free periods.

Purpose: To investigate the efficacy and safety of dexamethasone (DEX) implant in eyes with diabetic macular edema (DME) over 12-months., Methods: In this retrospective study charts from a single center were analysed, including naïve and pre-treated patients. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) were evaluated at baseline, months 1-2, 3-4, 5-6 and 7-12., Results: Data of 77 eyes were analysed (58.4% were pre-treated with anti-VEGF inhibitors). Mean baseline BCVA values for the whole sample, pre-treated and naïve patients, were 60.94 (SD 13.74), 60.85 (SD 13.80) and 61.01 (SD 13.86) letters, respectively. In the whole sample BCVA changes against baseline were significant (p < 0.05) at months 1-2, 3-4 and 7-12. In the pre-treated group changes were statistically significant at months 1-2 and 7-12. No statistically significant differences were found in the naïve group and between subgroups.In the whole group and the pre-treated group, CRT changes against baseline were significant (p < 0.05) at all time points, while in the naïve group changes were only significant at time point months 3-4. No statistically significant differences were found between subgroups.IOP increases were moderate and successfully managed with topical medication., Conclusion: After treatment with DEX implant, BCVA increased and CRT decreased significantly in the whole population at all time points. No significant differences were found between naïve and pre-treated patients. Changes in BCVA and CRT in the naïve group were not statistically significant. This was most likely attributable to the small sample size. The data underlines the importance of DEX implant as an efficacious and safe alternative to VEGF- inhibitors in real world practice.

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

Purpose: To assess the impact of preoperative intravitreal dexamethasone implant (DexI) on functional and anatomic outcomes in patients with diabetic macular edema (DME) who underwent phacoemulsification cataract surgery., Methods: Prospective and non-comparative study conducted on consecutive DME patients undergoing cataract surgery. DexI was administered 15 days before surgery and in a pro re nata regime after surgery. Main outcome measures were mean change in central retinal thickness (CRT), central subfield thickness (CST), total macular volume (TMV), and central subfield volume (CSV) from baseline to month-12. Secondary outcome was mean change in best corrected visual acuity (BCVA)., Results: Forty eyes were included in the study. CRT significantly decreased from 410.4  ±  64.8 µm at baseline to 303.2  ±  24.3 µm at month-12, p  < 0.0001. Similarly, CST was significantly reduced from 436.4  ±  120.4 µm at baseline to 322.9  ±  54.2 µm at month-12, p  < 0.0001. Total macular volume and CSV were significantly reduced from 9.95  ±  1.68 mm3 and 0.38  ±  0.11 mm 3 at baseline to 8.49  ±  0.83 mm 3 and 0.31  ±  0.05 mm 3 at month-12, respectively ( p  < 0.0001 each, respectively). BCVA significantly improved from 0.26  ±  0.17 Snellen equivalent at baseline to 0.65  ±  0.19 at month-12, p  < 0.0001. Mean DexI administered during the study were 2.0  ±  0.3. Neither DME subtype nor previous treatment status had any effect on functional or anatomic outcomes. Regarding safety, one (2.5%) eye developed ocular hypertension, which was successfully controlled with topical hypotensive treatment., Conclusions: DexI was and effective and safe strategy for managing DME in diabetic patients undergoing uneventful cataract surgery.

Purpose: The intravitreal dexamethasone implant (DEX-I) is an alternative to anti-VEGF for the first-line treatment of diabetic macular oedema (DME). However, several questions remain regarding its routine use and its place in certain situations not always specified in current recommendations. A national consensus approach was, therefore, initiated by French retinal experts., Methods: An iterative Delphi consensus approach was used. A steering committee (SC) of seven experts analysed data from the literature to formulate statements divided into five key areas of treatment. These statements were submitted to the independent and anonymous electronic vote of 87 French retina experts among whom 39 expressed their opinion and therefore constituted the voting panel., Results: After two rounds of voting, 22 and 7 of 38 statements received a strong consensus and a good consensus, respectively. The consensus level was higher for statements regarding first-line indications and safety of DEX-I compared to those regarding efficacy assessment, reprocessing time or pathophysiological biomarkers. The panellists recommended the preferential use of DEX-I for patients with limited availability for multiple injections, those who needed to undergo cataract surgery or who had a recent cardiovascular history, and as a therapeutic alternative to anti-VEGF in patients with a history of vitrectomy, retinal serous detachment, hyper-reflective points or dry exudates in optical coherence tomography (OCT). However, some statements proposed by SC experts were not validated., Conclusion: This study provides some key recommendations to clinicians treating diabetic macular oedema, which may be useful when using intravitreal dexamethasone implants in daily practice.

Purpose: To investigate the changes in vitreous inflammatory and angiogenic cytokine levels, primarily interleukin-(IL)-6, following intravitreal injection of the 0.19 mg fluocinolone acetonide (FAc, ILUVIEN®) implant in patients with diabetic macular edema., Methods: A single-center phase IV study involving 12 patients' eyes with diabetic macular edema. Vitreous fluid samples were obtained prior to intravitreal injection of the fluocinolone acetonide implant and then again over a 6-month period. Vitreous samples were examined using a cytometric bead array to measure IL-6, IL-8, IP-10, MCP-1, VEGF, and CD54. PIGF and PEDF were measured using an enzyme-linked immunosorbent assay. Changes in the cytokine and chemokine expression patterns were analyzed. Clinical parameters such as BCVA and center point thickness (CPT) were also examined., Results: There were mean reductions in all parameters between baseline and month 6. Significant changes (p < 0.05 versus baseline) were observed in the expression of IL-6, IP-10, MCP-1, and CD54 following the administration of fluocinolone acetonide implant. VEGF and PIGF increased at month 1 before declining at month 6, though this trend was not significant. CPT decreased rapidly between screening and the first follow-up visit, and this decrease was sustained. BCVA remained relatively stable throughout., Conclusion: This study demonstrated changes in vitreous inflammatory and angiogenic cytokine levels following intravitreal injection of the FAc implant in patients with diabetic macular edema. Data show that the fluocinolone acetonide implant led to rapid and sustained reductions of some inflammatory cytokines with improvement of the overall clinical picture., (© 2022. The Author(s).)

Purpose: To evaluate the mid-term safety and effectiveness of intravitreal dexamethasone implant (DEX-i) for treating unresponsive to medical therapy cystoid macular edema (CME) in vitrectomized eyes for endophthalmitis., Methods: Retrospective and interventional case series study conducted on vitrectomized eyes for endophthalmitis that developed a CME that did not adequately respond to medical therapy, who underwent 0.7-mg DEX-i. Main outcome measures were changes in central retinal thickness (CRT) and best corrected visual acuity (BCVA)., Results: Eleven eyes were included in the study. Microbiological findings of vitreous biopsies were 7 (63.6%) staphylococcus epidermidis; 3 (27.3%) Pseudomonas aeruginosa; and 1 (9.1%) Propionibacterium acnes. Median (interquartile range, IqR) duration of CME was 4.0 (3.0-4.0) months. Median (IqR) time between vitrectomy and DEX-i was 9.0 (9.0-11.0) months. Median CRT was significantly decreased from 548.0 (412.8-572.5) µm at baseline to 308.0 (281.3-365.5) µm at month 6 (p = 0.0009, Friedman test). Median BCVA significantly improved from 38.0 (30.5-44.8) letters at baseline to 50.0 (46.8-53.0) letters at month 6 (p < 0.0001, Friedman), with 9 (81.8%) eyes gaining ≥ 10 letters. Elevation of intraocular pressure was observed in one (9.1%) eye, which was successfully controlled with medical therapy. No recurrence of endophthalmitis or other complications was observed. Eight (72.7%) eyes required an additional DEX-i, while 3 (27.3%) were successfully controlled with only one DEX-i. CME recurrence occurred in 5 (62.5%) Gram-positive and 3 (100.0%) Gram-negative bacteria (p = 0.2357)., Conclusion: In vitrectomized eyes for endophthalmitis affected by CME unresponsive to medical therapy, DEX-i had an acceptable safety profile and achieved favorable outcomes. The possibility of suppressing mechanisms for infection control should be taken into account, although correct management of endophthalmitis and long time without reactivation before DEX-i reduce the risk., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of the present study was to describe foveal eversion patterns in diabetic macular edema (DME) and to assess their relationship with the course of the disease and the outcome. The study was designed as prospective, observational, with two years of follow-up. DME patients were divided in two groups, one treated by combined anti-VEGF injections and dexamethasone (DEX) implants, and the other treated by fluocinolone acetonide (FAc) implant with additional anti-VEGF retreatments if needed. Main outcome measures were foveal eversion prevalence, foveal eversion patterns, best-corrected visual acuity (BCVA), central macular thickness (CMT), structural OCT metrics, number of intravitreal injections. One hundred and forty-six eyes (146 patients; 80 males; mean age 67 ± 8 years) affected by already treated DME, with 84 eyes treated with anti-VEGF/DEX treatments (mean of 10 ± 3 injections) and 62 treated with FAc implant. Looking at the treatments administered before the inclusion into the study, 84 eyes (58%) were treated with anti-VEGF injections, whereas 62 eyes (42%) underwent a combination of anti-VEGF and corticosteroids implants. DME eyes showed statistically significant improvements of LogMAR BCVA and CMT over the 2-year follow-up. Foveal eversion was found in 83 eyes (57%), categorized as follows: Pattern 1a (16;19%); Pattern 1b (22;27%) and Pattern 2 (45;54%). BCVA improvement was detected in all the subgroups, excepting for Pattern 2, which showed also significantly worse structural OCT parameters. Pattern 1b and Pattern 2 were characterized by significantly higher prevalence of persistent DME (64% and 89% of cases, respectively). Foveal eversion patterns were correlated with progressively worse DME outcome. Foveal eversion may be associated to the loss of foveal homeostasis, with consequent poor response to intravitreal treatments and worse DME outcome., (© 2022. The Author(s).)

Background: Diabetic Macular Edema (DME) is the most common cause of vision loss in diabetic patients. Currently, the Vascular Endothelial Growth Factor inhibitors (anti-VEGFs) are used as the first line of DME treatment and corticosteroid implants are usually used as a second-line treatment. These implants are a safe and effective therapeutic option that can improve the quality of life of DME patients by reducing the intravitreal injections number. We determined the economic impact related to DME, also from the social perspective, and the consequences of the increased use of the dexamethasone implant., Methods: The analysis compares two scenarios: the first based on the current rate of recourse to the therapeutic alternatives available in the Italian healthcare setting (as is) and the second based on the assumption of an increased recourse to dexamethasone implants (to be). The results are expressed both in terms of the resource absorption associated with the two scenarios and in terms of the cost differential yielded by their comparison., Results: The increased use of the dexamethasone implant allows considerable savings in terms of healthcare professionals' time, follow-up and productivity lost by patients/caregivers. These savings would reduce healthcare costs for the management of DME patients in Italy by €2,058,238 in 5 years., Conclusions: To optimize the healthcare resources allocation, it is necessary to implement treatments that yield not only cost reductions but also a clinical benefit for patients. The dexamethasone implant use is an example of DME management that generates value for patients, health system and society., Competing Interests: GC, MB, MV, FA, RR, FB, and AC worked as consultants of HTA Italia Srl, which received funds from Allergan S.p.A. The sponsor had no role in conducting or designing the study., (Copyright © 2022 Calabrò, Basile, Varano, Amore, Ricciardi, Bandello and Cicchetti.)

Background: Frequent intravitreal anti-VEGF injections are impractical for many Aboriginal patients with diabetic macular oedema (DMO). The longer acting intravitreal dexamethasone implant (DEX-implant) is approved for DMO but has not been assessed in an Aboriginal population., Methods: This was a prospective, multicentre, randomised, single-masked, non-inferiority clinical trial. Aboriginal adults from Western Australia with DMO were randomised to receive 3-monthly DEX-implant, or monthly intravitreal bevacizumab. The primary outcome was the change in best corrected visual acuity (BCVA) at 12 months., Results: The final endpoint was analysed for 24 DEX-implant and 28 bevacizumab injection eyes. Mean BCVA improved by 4.0 letters (-0.08 LogMAR) in the DEX-implant group and worsened by 5.5 letters (0.11 LogMAR) in the bevacizumab group. Before adjusting for cataract surgery, the upper bound of the two-sided 90% CI for the DEX-implant was 3.5 letters (0.07 LogMAR), which met non-inferiority criteria. The BCVA of remote participants who received the DEX-implant improved by 5.5 letters (0.11 LogMAR), compared to an 18.5 letter (0.37 LogMAR) decline for bevacizumab (p = 0.04). The incidence of steroid-induced ocular hypertension for the DEX-implant was 33.3%., Conclusions: Before adjusting for the effect of cataract surgery, the DEX-implant was non-inferior to bevacizumab for treating DMO in Aboriginal participants. In remote participants, the DEX-implant surpassed non-inferiority to achieve superior outcomes to bevacizumab. The incidence of steroid-induced hypertension was comparable to that reported in non-Aboriginal populations. We provide guidelines for the judicious use of DEX-implant among Aboriginal people, and a framework for performing ophthalmic clinical trials in Aboriginal communities., (© 2022 Royal Australian and New Zealand College of Ophthalmologists.)

Center-involving diabetic macular edema (DME) is a leading cause of vision impairment in working-age adults. While its management is particularly challenging in a poorly compliant population, continuous innovation and the advent of new molecules have improved its outcome. The control of glycemia and of systemic aggravating factors remain essential to slow down progression of disease complications including DME. The indications for macular laser photocoagulation has progressively been phased out as a standard of care and replaced by local intraocular anti-VEGFs biologics and glucocorticoids (GCs). Intravitreal GCs in controlled-release drug delivery systems have allowed to reduce injection frequency and treatment burden. The non biodegradable Fluocinolone Acetonide (FAc) implant allows a long-lasting stabilization of both functional and anatomic improvements. However, adequate patient selection and monitoring through regular follow-up are essential for optimal results. Based on their experience and the latest literature, the aim of the present review is to provide international expert panel consensus on the place of the FAc implant in the treatment algorithm of DME, as well as its safety profile and how to manage it.

Background: Prevention of non-infectious uveitis of the posterior segment (NIU-PS) recurrence using 0.2 μg/day fluocinolone acetonide implant (FAi) was assessed over 3 years (NCT01694186). Outcomes for FAi-treated and fellow eyes with NIU-PS were compared, to evaluate FAi versus conventional treatment strategies., Methods: Eligible subjects had >1-year recurrent NIU-PS history and either ≥2 separate recurrences requiring treatment, or corticosteroid therapy (systemic or ocular) in the 12 months preceding study entry. Bilateral disease was present and analysed in 59/87 FAi-treated participants. Recurrence rates, best-corrected visual acuity (BCVA) changes, cataract surgery, intraocular pressure (IOP) events and adjunctive medication use were compared for FAi-treated and fellow eyes., Results: Over 36 months, more FAi-treated than fellow eyes remained recurrence-free (28.8% vs. 5.1%, P = 0.001; mean 1.9 vs. 4.7 recurrences, respectively, P < 0.0001). FAi-treated eyes gained +9.6 letters BCVA, versus a loss of -4.4 in fellow eyes (P < 0.0001). Systemic medications were given to 42.4% of subjects. Intra/periocular adjunctive injections were lower in FAi-treated than fellow eyes (20.3% vs. 66.1%, P < 0.0001); topical corticosteroid use was also lower in FAi-treated than fellow eyes (27.1% vs 52.5%, P = 0.0041). IOP-related events occurred at similar rates in both FAi-treated and fellow eyes, excepting IOP-lowering surgery (5.1% vs. 15.3%, respectively; P = 0.1251). Cataract surgery occurred in 72.0% of FAi-treated and 37.0% of fellow eyes., Conclusions: In subjects with bilateral NIU-PS, continuous, low-dose corticosteroid with 0.2 μg/day FAi reduced recurrence and adjunctive medication requirements, and improved vision over 36 months, providing greater protection against ocular inflammation than a reactive approach using standard of care., (© 2021. The Author(s).)

Purpose: To assess the long-term safety and efficacy of the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien; Alimera Sciences, Inc) in patients with diabetic macular edema (DME)., Design: Three-year, phase 4, nonrandomized, open-label observational study., Participants: Patients with DME who previously received corticosteroid treatment without a clinically significant rise in intraocular pressure (IOP; all eyes, n = 202 eyes of 159 patients; 36-month completion, n = 94 eyes)., Methods: A prospective, observational study in which patients received a 0.19-mg FAc intravitreal implant at baseline and then were observed for safety-, visual-, anatomic-, and treatment burden-related outcomes for up to 36 months., Main Outcome Measures: Primary safety outcomes included changes in IOP and interventions to manage IOP elevations. Secondary outcomes included changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and adjunctive DME treatment frequency RESULTS: At 36 months after FAc implantation, study eyes showed a mean CST change of -60.69 μm (P < 0.0001) and a mean BCVA change of +3.61 letters (P = 0.0222) compared with baseline. Overall median treatment frequency decreased from 3.4 treatments/year in the 36 months before FAc implantation to 1 treatment/year in the 36 months after FAc implant, a treatment burden reduction of 70.5%. Furthermore, among the group that completed 36 months of treatment (n = 94 eyes), 25.53% of eyes remained rescue free through 36 months. Mean IOP remained stable throughout the study, and IOP increases to more than 30 mmHg occurred in 10.89% of eyes. Intraocular pressure-related procedures were infrequent, with a surgical rate of 2.97%, with 1.49% attributable to steroid use (vs. surgeries attributable primarily to neovascular glaucoma). In addition, an IOP response of < 25 mmHg after the steroid challenge predicted that 96.92% of eyes would have a similar outcome to 0.19-mg FAc implant at the last visit. Intraocular pressure increases that did occur were manageable with standard treatments (n = 202 eyes)., Conclusions: In patients with DME, the 0.19-mg FAc implant provided improved visual outcomes and reduced treatment burden compared with previous treatments while maintaining a favorable safety profile., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate intravitreal 0.19 mg fluocinolone acetonide implant (FAi) (Iluvien®) for the treatment of chronic non-infectious uveitis with associated cystoid macular edema (CME)., Methods: A retrospective review of medical reports from a single Danish tertiary centre including 20 patients (20 eyes), treated with 0.19 mg FAi for non-infectious uveitic CME. The primary endpoints were change in best corrected visual acuity (BCVA) and central retinal thickness (CRT). The secondary endpoints were recurrence rate, change in systemic treatment, and intraocular pressure (IOP)., Results: Mean follow-up of the 20 eyes was 2.3 ± 1.1 years. BCVA improved at 6 (p = 0.13), 12 (p = 0.05), 18 (p = 0.03), and 24 months and CRT decreased at 6 (p = 0.004), 12 (p = 0.006), 18, and 24 months after 0.19 mg FAi. Within 18 months after implantation, four of 14 patients (28.6%) relapsed. Three of five patients discontinued systemic corticosteroids within 4 months and one patient continued with reduced dose. Five of 10 patients receiving disease-modifying antirheumatic drugs (DMARDs) at time of implantation discontinued within 1 year. No patients started new systemic treatment. Eight eyes were treated with topical IOP-lowering medication at the time of implantation, of these two later underwent trabeculectomy. There were no complications associated with previous glaucoma surgery., Conclusion: This long-term follow-up study showed that intravitreal treatment with 0.19 mg FAi should be considered in the treatment of chronic non-infectious uveitic CME in selected patients. This treatment is safe even in selected glaucoma patients and may offer reduction or cessation of local or systemic anti-inflammatory treatment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Zebrafish embryos are widely used for drug discovery, however, administering drugs to adult zebrafish is limited by current protocols that can cause stress. Here, we developed a drug formulation and administration method for adult zebrafish by producing food-based drug pellets that are consumed voluntarily. We applied this to zebrafish with BRAF-mutant melanoma, a model that has significantly advanced our understanding of melanoma progression, but not of drug resistance due to the limitations of current treatment methods. Zebrafish with melanomas responded to short-term, precise and daily dosing with drug pellets made with the BRAFV600E inhibitor, vemurafenib. On-target drug efficacy was determined by phospho-Erk staining. Continued drug treatment led to the emergence, for the first time in zebrafish, of acquired drug resistance and melanoma relapse, modelling the responses seen in melanoma patients. This method presents a controlled, non-invasive approach that permits long-term drug studies and can be widely applied to adult zebrafish models., Competing Interests: Competing interests E.E.P. is the Editor-in-Chief at Disease Models & Mechanisms but was not included in any aspect of the editorial handling of this article or peer review process., (© 2022. Published by The Company of Biologists Ltd.)

Introduction: The aim of this study was to describe functional and anatomical changes (best-corrected visual acuity [BCVA], central macular thickness [CMT], and central macular volume [CMV]) in patients with macular edema (ME) secondary to retinal vein occlusion (RVO) treated with intravitreal dexamethasone implant (IDI) and identify its clinical predictors in a real-world setting., Methods: Data from 111 patients who underwent IDI to treat RVO-associated ME were retrospectively reviewed. Demographic, preoperative, and postoperative variables were assessed using a logistic regression analysis to determine predictors of visual and anatomical improvement., Results: Mean BCVA, CMT, and CMV improved from baseline after IDI ( p  < 0.001). The strongest predictors of different treatment outcomes were: a baseline BCVA ⩽60 ETDRS letters (OR = 50.600; p  < 0.001) and first IDI injection (OR = 2.988; p  < 0.001) for BCVA gain ⩾15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters; a baseline BCVA ⩽60 ETDRS letters (OR = 7.893; p  = 0.002) and non-chronic ME (OR = 3.875; p  = 0.019) for BCVA ⩾80 ETDRS letters achievement; a baseline CMT ⩾400 µm (OR = 49.083; p   <  0.001) and a baseline CMV ⩾12 mm 3 (OR = 4.235; p  < 0.001) for CMT reduction ⩾50%; and a baseline CMT ⩾400 µm (OR = 11.471; p   <  0.001) and a baseline CMV ⩾12 mm 3 (OR = 10.284; p  < 0.001) for CMV reduction ⩾15%., Conclusion: This study confirmed the effectiveness of IDI to treat ME secondary to RVO and identified new predictive factors for two visual (⩾15 ETDRS letters gain and BCVA ⩾80 ETDRS letters) and two anatomical outcomes (>50% CMT and >15% CMV reduction).

Purpose: To determine the prognostic characteristics of optical coherence tomography (OCT) parameters by evaluating diabetic macular edema (DME) patients with early dexamethasone (DEX) shift after three doses of intravitreal ranibizumab (RNB) injection., Methods: Fifty-four eyes of 34 patients who had DEX implant after three doses of RNB were included in this retrospective study. Early DEX shift includes patients who received direct DEX implant replacement after three doses of RNB load. Baseline OCT values and factors affecting best corrected visual acuity (BCVA) and central macular thickness (CMT) response were analyzed with logistic regression analyses., Results: The presence of subretinal fluid and hyperreflective spot (HRS) >20 were found to be a negative predictive factor for anatomical response. ( p  = 0.009, p  = 0.001, respectively) Low initial BCVA creates a positive effect on visual gain.( p  = 0.041) Giant outer nuclear layer cysts, completely disrupted inner segment-outer segment and HRS > 20 have a negative effect on visual gain. ( p  = 0.025, p  = 0.043, p  = 0.023, respectively) According to the receiver operating characteristic analysis, the subretinal fluid volume threshold at which >20% reduction in CMT occurs was determined to be 0.85 mm 3 . (sensitivity 70%, specificity 84% area under the curve 0.817, p  = 0.021)., Conclusion: The presence of high number of HRS and high subretinal fluid volume at the baseline negatively affect prognosis even in patient groups with early DEX shift.

Purpose: To assess the efficacy and safety of dexamethasone 0.7 mg implants (DEX-I) in patients with diabetic macular edema (DME) either naïve to therapy or refractory to anti-VEGF treatment, in a single-center, real-world setting., Methods: Patients diagnosed with DME and treated with DEX-I were retrospectively enrolled in the study and split in two groups: naïve (Group 1, n  = 64) and refractory (Group 2, n  = 64) to treatment. Patients were evaluated at baseline, at 1 month, and every 3 months after each DEX-I implant. Main outcome measures were change in best-corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline to follow-up visits., Results: Significant improvements in BCVA were observed in treatment-naïve patients at 6 months following the first and second DEX-I injection ( p  = 0.0023 and p  = 0.0063, respectively), with significant reductions in mean CMT at 6 months after all DEX implants. In treatment-refractory patients, mean CMT was significantly reduced from baseline to 6 months ( p  < 0.05) after all DEX-I injections, although no changes were observed in BCVA., Conclusions: DEX-I improved visual acuity and macular edema mostly in treatment-naïve patients, suggesting DEX-I may be a viable first-line treatment option in DME.

Background: This study aimed to assess the long-term effectiveness of the 0.2 μg/day fluocinolone acetonide (FAc) implant over ≥3 years for patients with diabetic macular oedema., Methods: A retrospective audit of pseudo-anonymised data from patients with chronic diabetic macular oedema (cDMO) and treated with the FAc implant across 14 UK clinical sites. Safety and clinical effectiveness were measured., Results: Two-hundred and fifty-six eyes had ≥3 years of follow-up (mean 4.28 years), during which a mean of 1.14 FAc implants were used per eye. Mean best-recorded visual acuity (BRVA) increased from 52.6 to 56.7 letters at month 3 and remained stable thereafter; this trend was also seen in pseudophakic eyes. The proportion of patients attaining a BRVA ≥6/12 increased from 17% at baseline to 27% 1 month after FAc implant and remained stable above 30% from month 12 onwards. Eyes with no prior history of intraocular pressure (IOP)-related events required significantly less treatment-emergent IOP-lowering medication than those with a prior history of IOP events (17.9% vs. 50.0% of eyes; p < 0.001). The incidence of an IOP increase of ≥10 mmHg, use of IOP-lowering medication, laser trabeculoplasty and IOP-lowering surgery was 28.9%, 29.7%, 0.8% and 2.7%, respectively, for the whole cohort. There were significant reductions in mean central foveal thickness and macular volume (p < 0.001)., Conclusions: The FAc implant was well tolerated, with predictable and manageable IOP-related events while delivering a continuous microdose of corticosteroid to eyes with cDMO, providing prolonged vision preservation and a reduced number of treatments., (© 2021. The Author(s).)