Efficacy and Safety of 0.19-mg Fluocinolone Acetonide Implant in Postoperative Cystoid Macular Edema after Pars Plana Vitrectomy: the ILUCYD study.

PURPOSE: To assess the efficacy and safety of 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien®) in treating chronic postoperative cystoid macular edema (PCME) after pars plana vitrectomy. DESIGN: Retrospective multicentric case series in clinical settings. SUBJECTS: Patients with chronic PCME who underwent vitrectomy in tertiary care centers in France. All eyes had a documented good response to the DEX implant prior to FAc implantation. METHODS: Review of charts and OCT scans of patients treated with a FAc intravitreal implant. MAIN OUTCOME MEASURES: The primary endpoints were the best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Secondary endpoints were the intraocular pressure (IOP); proportion of patients maintaining a BCVA ≥20/40; need for additional non-study treatment; differences between eyes that underwent a single and multiple surgeries and OCT biomarkers of better BCVA. RESULTS: Forty-nine eyes of 49 patients with a mean follow-up of 24.5 ± 3.9 months were included. The mean BCVA increased from 0.40 ± 0.26 logMAR at baseline to 0.32 ± 0.24 logMAR at month 24 (M24) (p=0.0035). The mean CRT decreased from 409.37 ± 139.43 µm at baseline to 340 ± 91 µm at M24 (p=0.0001). The mean IOP was 14.0 ± 4 mmHg at baseline and remained stable at 14.03 ± 4.1 mmHg at M24 (p=0.99). During the follow-up, the IOP exceeded 21 mmHg in 9 eyes. The IOP rise was controlled with topical therapy in all eyes except one, which required cyclophotocoagulation. The BCVA was ≥20/40 in 47% of eyes (95% CI: 34%-61%) at baseline and in 58% of eyes at M24 (95% CI: 41%-73%). At M18, the likelihood of achieving a BCVA ≥20/40 was higher in eyes with intact external limiting membrane and ellipsoid zone. Additional dexamethasone implant (DEXi) was injected in 14 eyes (28.57%). The treatment burden of 2.45 ± 1.35 DEXi/year was decreased to 0.57 ± 0.60 DEXi/year after FAc implantation (p=0.001). CONCLUSION: FAc implant improved the BCVA and reduced the CRT in eyes with chronic PCME after vitrectomy. The IOP rise could be anticipated by the previous response to corticosteroids. FAc implant in eyes with chronic PCME also allowed reducing the treatment burden.

Pros and cons of internal limiting membrane peeling during epiretinal membrane surgery: a randomised clinical trial with microperimetry (PEELING).

BACKGROUND: After idiopathic epiretinal membrane (iERM) removal, it is unclear whether the internal limiting membrane (ILM) should be removed. The objective was to assess if active ILM peeling after iERM removal could induce microscotomas. METHODS: The PEELING study is a national randomised clinical trial. When no spontaneous ILM peeling occurred, patients were randomised either to the ILM peeling or no ILM peeling group. Groups were compared at the month 1 (M1), M6 and M12 visits in terms of microperimetry, best-corrected visual acuity (BCVA) and optical coherence tomography findings. The primary outcome was the difference in microscotoma number between baseline and M6. RESULTS: 213 patients were included, 101 experienced spontaneous ILM peeling and 100 were randomised to the ILM peeling (n=51) or no ILM peeling group (n=49). The difference in microscotoma number between both groups was significant at M1 (3.9 more microscotomas in ILM peeling group, (0.8;7.0) p=0.0155) but not at M6 (2.1 more microscotomas in ILM peeling group (-0.5;4.7) p=0.1155). Only in the no ILM peeling group, the number of microscotomas significantly decreased and the mean retinal sensitivity significantly improved. The ERM recurred in nine patients in the no ILM peeling group (19.6%) versus zero in the ILM peeling group (p=0.0008): two of them underwent revision surgery. There was no difference in mean BCVA and microperimetry between patients experiencing or not a recurrence at M12. CONCLUSION: Spontaneous ILM peeling is very common. Active ILM peeling prevents anatomical ERM recurrence but may induce retinal impairments and delay visual recovery. TRIAL REGISTRATION: NCT02146144.

Mannose-coupled AAV2: A second-generation AAV vector for increased retinal gene therapy efficiency.

Inherited retinal diseases are a leading and untreatable cause of blindness and are therefore candidate diseases for gene therapy. Recombinant vectors derived from adeno-associated virus (rAAV) are currently the most promising vehicles for in vivo therapeutic gene delivery to the retina. However, there is a need for novel AAV-based vectors with greater efficacy for ophthalmic applications, as underscored by recent reports of dose-related inflammatory responses in clinical trials of rAAV-based ocular gene therapies. Improved therapeutic efficacy of vectors would allow for decreases in the dose delivered, with consequent reductions in inflammatory reactions. Here, we describe the development of new rAAV vectors using bioconjugation chemistry to modify the rAAV capsid, thereby improving the therapeutic index. Covalent coupling of a mannose ligand, via the formation of a thiourea bond, to the amino groups of the rAAV capsid significantly increases vector transduction efficiency of both rat and nonhuman primate retinas. These optimized rAAV vectors have important implications for the treatment of a wide range of retinal diseases.

Intravitreal air tamponade after AAV2 subretinal injection modifies retinal EGFP distribution.

The subretinal injection protocol for the only approved retinal gene therapy (voretigene neparvovec-rzyl) includes air tamponade at the end of the procedure, but its effects on the subretinal bleb have not been described. In the present study, we evaluated the distribution of enhanced green fluorescent protein (EGFP) after subretinal injection of AAV2 in non-human primates (NHP) without (group A = 3 eyes) or with (group B = 3 eyes) air tamponade. The retinal expression of EGFP was assessed 1 month after subretinal injection with in vivo fundus photographs and fundus autofluorescence. In group A (without air), EGFP expression was limited to the area of the initial subretinal bleb. In group B (with air), EGFP was expressed in a much wider area. These data show that the buoyant force of air on the retina causes a wide subretinal diffusion of vector, away from the injection site. In the present paper, we discuss the beneficial and deleterious clinical effects of this finding. Whereas subretinal injection is likely to become more common with the coming of new gene therapies, the effects of air tamponade should be explored further to improve efficacy, reproducibility, and safety of the protocol.

Optical Coherence Tomography Angiography in Diabetic Macular Edema Treated with Intravitreal Aflibercept: A 48-Week Observational Study (the DOCTA Study).

INTRODUCTION: Central vision loss due to diabetic macular edema (DME) is related to the macular edema itself but also, in some cases, to alterations of the foveal avascular zone (FAZ). The aim of this trial was to study changes in macular vessels in eyes with DME treated with aflibercept using optical coherence tomography angiography (OCTA). METHODS: This was a longitudinal, prospective, noncontrolled, single-arm study. The primary objective was the quantitative assessment of macular vessels over time in patients with DME treated with intravitreal aflibercept during a 48-week follow-up using OCTA. RESULTS: Twenty-six DME eyes from 26 patients were included (mean age, 64.6 years; women, 53.8%; prior anti-VEGF treatment, 46.1%). Each eye received a mean (SD) of 7.2 (2.2) injections. The following parameters of the FAZ did not change during the 48-week follow-up: the mean (SD) FAZ area varied from 0.19 (0.19) mm2 at baseline (n = 22) to 0.23 (0.20) mm2 at week 48 (n = 15), boundary from 1.54 (1.21) to 2.04 (1.20) mm, and circularity from 0.45 (0.33)% to 0.57 (0.20)%. There was no change in perfusion density and vessel density of the macula in the 3-mm circle. As expected, mean central retinal thickness, macular volume, and visual acuity improved during follow-up. CONCLUSION: No change in macular perfusion was observed in eyes with DME during a 48-week follow-up after intravitreal injections of aflibercept. Randomized controlled trials using OCT angiography in large populations with extended observation periods are needed to assess changes in macular vessels after intravitreal anti-VEGF treatment.

Efficacy and safety of Aflibercept for the treatment of inflammatory choroidal neovascularization: The ALINEA study.

PURPOSE: To evaluate mean change in best-corrected visual acuity (BCVA) at 52 weeks in patients with inflammatory choroidal neovascularization (CNV) treated with aflibercept. METHODS: We conducted a prospective non-comparative open-label trial. Following one mandatory intravitreal injection of aflibercept, patients were treated under a pro re nata (PRN) dosing regimen with monthly visits. RESULTS: A total of 19 patients were included, but one presented exclusion criteria; 16 patients were followed for the whole 52-week study, and data for the primary endpoint analysis were available for 14. At baseline, mean BCVA and mean central retinal thickness (CRT) were 64.53 (±19.64) letters and 351.79 (±97.77) µm, respectively. At 52 weeks, the mean change in BCVA was +9.50 (±12.90) letters [95%CI = +2.05-+16.95]. One patient had lost more than 15-letters at 24 weeks, and another one at 52 weeks. CRT change was -62.77 (±100.73) µm at 24 weeks and -66.53 (±97.47) µm at 52 weeks. There was a mean number of 3.56 (±3.29) intravitreal injections at 52 weeks (min = 1; max = 12). No serious ocular adverse events related to the treatment were reported. CONCLUSIONS: Our study shows that aflibercept is clinically effective, both anatomically and functionally in the treatment of inflammatory CNV. Following the first injection, the PRN strategy appears sufficient for treating most choroidal neovessels.

IMPACT study: Impact of adherence to anti-VEGF intravitreal injections for macular disease during COVID 19-related confinement in France.

PURPOSE: The aim of this study was to evaluate the impact of adherence to French coronavirus disease 2019 (COVID 19)-related guidelines for intravitreal injection (IVI) practice on the visual outcomes of patients treated with anti-vascular endothelial growth factor (VEGF) agents for macular diseases during the first lockdown period. METHODS: Observational multicentre study including all patients from 18 centres with an IVI initially planned during the lockdown. Visual acuity (VA, ETDRS) was recorded at 1 and 4 months after lockdown. French COVID 19-related guidelines recommended maintaining IVI practice. We defined three groups of patients: A, adherent to guidelines; NA+, non-adherent with delayed IVIs; and NA-, non-adherent without IVIs performed during the lockdown. Risk factors for non-adherence and visual loss were studied. RESULTS: A total of 3020 eyes of 3020 patients, aged 77.8 ± 11.6 years, 59.8% women, were included. 59.3% were non-adherent(46.7% NA+, 12.6% NA-). A smaller decrease in VA at 4 months was observed in the A group than the NA+ and NA- group (-0.2 ± 6.7, -0.3 ± 6.9 and -1.5 ± 6.9, respectively [p < 0.001]). Factors associated with non-adherence were in multivariable analysis, older age, hospital practice, low-density population areas, high viral incidence areas, longer intervals between injection and treat and extent protocol. Factors associated with visual loss at 4 months in multivariable analysis were, being in the NA- group, older age, T&E and fixed regimens. CONCLUSION: Strict adherence to guidelines was associated with better visual outcome, although most of our patients did not attend as planned. Identification of patients at risk could help in the future in case of a new pandemic lockdown.

Final 4-year results of the RAINBOW real-world study: intravitreal aflibercept dosing regimens in France in treatment-naïve patients with neovascular age-related macular degeneration.

PURPOSE: The purpose of this study is to evaluate real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in routine clinical practice in France. METHODS: RAINBOW (NCT02279537) was an ambispective, observational, 4-year study assessing IVT-AFL effectiveness, treatment patterns, and safety in patients with nAMD in France. Treatment-naïve patients prescribed IVT-AFL and treated according to local practice (pro re nata or treat-and-extend) were eligible. Three treatment cohorts were retrospectively identified based on their treatment pattern within the first 12 months: regular (3 initial monthly IVT-AFL injections received within 45-90 days after the first injection in month 0 and followed by injections every 2 months), irregular with the initial monthly injections, and irregular without the initial monthly injections. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to month 12. The 48-month results are described here. RESULTS: Overall, the study included 516 patients (each with one study eye), and 30.2% of patients completed 48 months of IVT-AFL treatment. Mean change in BCVA from baseline (56.5 letters) to month 48 for patients with an assessment at both time points was + 1.1 (regular cohort, n = 47), + 0.1 (irregular cohort with initial monthly injections, n = 115), and - 1.3 letters (irregular cohort without initial monthly injections, n = 26), representing a decrease from the gains achieved at month 12. Mean number of IVT-AFL injections received by month 48 in the treatment cohorts was 14.9, 13.7, and 11.9, respectively. The safety profile of IVT-AFL was consistent with previous studies. CONCLUSION: In RAINBOW, the 48-month results demonstrate a lack of long-term effectiveness of IVT-AFL treatment of nAMD due to progressive undertreatment in routine clinical practice in France. These real-world findings highlight the importance of 3 initial monthly IVT-AFL injections followed by continuous proactive treatment beyond the first year to achieve optimal functional outcomes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02279537.

Recommendations for the management of diabetic macular oedema with intravitreal dexamethasone implant: A national Delphi consensus study.

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.

Validity of the French version of Catquest-9SF and use of an electronic notepad for entering patient-reported outcome measures.

BACKGROUND: The Catquest-9SF questionnaire is a patient reported outcome measure that quantifies the visual benefits from cataract surgery. The purpose of this study was to translate and adapt the Catquest-9SF questionnaire for France, to assess its psychometric properties via Rasch analysis, and to assess its validity when completed using an electronic notepad. METHODS: The Catquest-9SF questionnaire was translated following the guidelines of the International Society for Pharmacoeconomics and Outcomes Research. Catquest-9SF and clinical data were collected from patients before and after routine cataract surgery. All questionnaire data were collected via an electronic notepad. Rasch analysis was performed to assess psychometric properties, and sensitivity to change was analysed for patients with complete paired pre- and post-operative questionnaires. RESULTS: A complete filled-in preoperative questionnaire was obtained for 848 patients. Rasch analysis showed good precision (person separation: 2.32, person reliability: 0.84), ordered category probability curves, no item misfit, and unidimensionality. The respondents were slightly more able than the level of item difficulty (targeting: -1.12 logits). Sensitivity was analysed on 211 paired questionnaires, and the postoperative questionnaires showed a clear ceiling effect. The effect size was 2.6. The use of an electronic notepad for completing the questionnaire worked out very well after some adjustments. CONCLUSIONS: The French version of Catquest-9SF has good psychometric properties and is suitable for use in French-speaking patients. The use of the Catquest-9SF questionnaire in an electronic format showed good validity.

Functional and anatomical outcomes after successful repair of macula-off retinal detachment: a 12-month follow-up of the DOREFA study.

PURPOSE: To report visual and anatomical outcomes and determine predictors of good visual acuity (VA) recovery after macula-off rhegmatogenous retinal detachment (RD). METHODS: Prospective multicentre study including 115 eyes from 115 patients successfully operated on for RD, with assessment of VA and spectral-domain optical coherence tomography (SD-OCT) macular images at 1, 3, 6 and 12 months after surgery. RESULTS: Over the follow-up period, VA significantly improved from median [IQR] 62 [46; 72] ETDRS letters at 1 month to 75 [67; 80] ETDRS letters at 12 months (p < 0.001) with a concomitant decreased number of eyes with any SD-OCT lesions (p < 0.001). The presence of subretinal fluid (SRF) significantly decreased (p < 0.001), as did the number of photoreceptor (PR) layer lesions (p = 0.04). At 12 months, lesions in the PR layer and poor VA recovery were significantly associated with a longer time to surgery (p = 0.007 and p < 0.001, respectively). The rate of patients without PR lesions increased from 40.9% at 1 month to 60.0% at 6 months and 73.9% at 12 months (p < 0.001). The incidence of epiretinal membrane (ERM) significantly increased (p < 0.001), while cystoid macular oedema (CME) remained stable over time. Visual acuity (VA) at 3 months postoperatively was a good reflection of final VA recovery (p < 0.001). CONCLUSION: Visual acuity (VA) improved in parallel with the decreasing number of eyes with SD-OCT lesions after macula-off rhegmatogenous RD. A long time to surgery was the only preoperative factor associated with poor VA recovery after retinal detachment surgery.

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

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

Tele-ophthalmology for screening for eye diseases in older patients with cognitive complaints.

INTRODUCTION: Population-based studies show a significant increase in the prevalence of visual impairment in older patients. However, older patients and patients with lower Mini-Mental State Examination (MMSE) scores have few ophthalmological assessments. The main objective of our study was to evaluate the feasibility of tele-ophthalmological screening for ophthalmological diseases in older patients referred for cognitive assessment. METHODS: This monocentric prospective study included patients referred to a memory clinic for cognitive assessment. All patients underwent a geriatric assessment comprising a cognitive assessment associated with tele-ophthalmological screening undertaken by an orthoptist, including undilated retinal photography. The retinal photographs were subsequently sent to an ophthalmologist. We identified patients who were not eligible for ophthalmological assessment, for patients that had to come back due to poor-quality retinal photographs and finally for detected eye diseases. The association between the geriatric variable and newly detected eye diseases was analysed in univariable and multivariable analyses. RESULTS: The mean age of the 298 patients included was 83.5 years ± 5.65; 29.5% were male. The mean MMSE score was 20.8 ± 5.2; 66.3% of patients had a diagnosis of dementia. Eighteen patients (6.0%) were not eligible for ophthalmological examination and 13 patients (4.6%) were asked to come back owing to poor-quality retinal photographs. Forty-one patients (13.7%) had a newly detected eye disease. In multivariable analysis, patients with a lower MMSE had significantly more newly identified eye diseases. DISCUSSION: The tele-ophthalmological screening method identified unknown ophthalmological diseases requiring specialised management in this older population with cognitive complaints.

Inflammatory optic neuropathy in granulomatosis with polyangiitis can mimick isolated idiopathic optic neuritis.

OBJECTIVE: We describe a clinico-radiological presentation of inflammatory optic neuropathy that mimicked optic neuritis. METHODS: Retrospective single-center case series and literature review of optic neuropathy without orbital pseudotumor. RESULTS: Five local patients fulfilled the inclusion criteria. Clinical presentation revealed rapidly progressive severe unilateral visual loss, retrobulbar pain (n = 4), and paralytic strabismus (simultaneous = 2, protracted = 2) without proptosis. Optic nerve abnormality was not appreciated on initial scan review. Patients did not have any general activity of the granulomatosis with polyangiitis. Upon follow-up magnetic resonance imaging and initial imaging review, all patients revealed orbital apex anomalies. Visual acuity improved in three patients who received high-dose intravenous glucocorticosteroids immediately. Relapse was frequent and visual outcome was poor (final vision > 20/40 in two patients only). Literature review identified 16 well-documented cases of granulomatosis with polyangiitis-related isolated optic neuropathies. Magnetic resonance imaging revealed no abnormality (n = 6), optic nerve and/or sheath involvement (n = 9), apex infiltration (n = 3), and/or pachymeningitis (n = 7). CONCLUSION: Granulomatosis with polyangiitis is a rare yet potentially blinding cause of inflammatory optic neuropathy. Optic neuropathy in granulomatosis with polyangiitis may occur in the absence of systemic symptoms of disease activity and is challenging to distinguish from other inflammatory and non-inflammatory disorders affecting visual acuity. Several clinical and imaging clues suggest that optic neuropathy results from the development of an extravascular granulomatous process within the optic nerve sheath in the orbital apex, a place that is difficult to image. In a granulomatosis with polyangiitis patient with unexplained visual loss and a seemingly normal workup (fundoscopy, biology, and imaging), clinician should keep a high index of suspicion.

UVEITIS TREATED WITH DEXAMETHASONE IMPLANT.

PURPOSE: To evaluate the real-life efficacy and safety of the intravitreal dexamethasone implant in uveitis. METHODS: This retrospective observational multicentric study included 152 eyes treated exclusively by 358 dexamethasone implant injections. The main outcome measures included change in the best-corrected visual acuity, central macular thickness, and vitreous haze score. RESULTS: Patients were treated with dexamethasone implant for macular edema (51.3%), vitritis with macular edema (40.1%), vitritis (5.3%), and other causes (3.3%). The mean duration of follow-up was 19.0 months. The mean gain in best-corrected visual acuity during follow-up was +12.1 letters. An improvement in best-corrected visual acuity ≥5, 10, and 15 letters was found in 64.5, 50.7, and 35.5% of cases, respectively. 59.7% of eyes with macular edema at baseline were found to be anatomical responders. Vitritis resolution (vitreous haze = 0+) was obtained in 81.4% of cases. Ocular hypertension (intraocular pressure ≥25 mmHg and/or gain ≥10 mmHg from baseline) occurred in 28.3% of patients. No filtering surgery/laser therapy was required. A total of 40.2% of phakic subjects underwent cataract surgery on average 11.2 months after the first injection. CONCLUSION: This study confirms the efficacy and safety of the dexamethasone implant in noninfectious uveitis. Cataract and ocular hypertension were not uncommon but easily manageable.

Does internal limiting membrane peeling during epiretinal membrane surgery induce microscotomas on microperimetry? Study protocol for PEELING, a randomized controlled clinical trial.

BACKGROUND: The epiretinal membrane (ERM) is a degenerative condition associated with age, which can cause loss of vision and/or metamorphopsia. The treatment of symptomatic ERM involves surgical removal including a vitrectomy followed by peeling of the ERM using a microforceps. As the internal limiting membrane (ILM) is adherent to the ERM, it is sometimes removed with it (spontaneous peeling). If ILM remains in place, it can be removed to reduce ERM recurrence. However, it is important to clarify the safety of ILM peeling, while it increases surgical risks and cause histological disorganization of the retina that can lead to microscotomas, may be responsible for definitive visual discomfort. METHODS: PEELING is a prospective, randomized, controlled, single-blind, and multicentered trial with two parallel arms. This study investigates the benefit/risk ratio of active ILM peeling among individuals undergoing ERM surgery without spontaneous ILM peeling. Randomization is done in the operating room after ERM removal if ILM remains in place. After randomization, the two groups-"active peeling of the ILM" and "no peeling of the ILM"-are compared during a total of three follow-up visits scheduled at month 1, month 6, and month 12. Primary endpoint is the difference in microscotomas before surgery and 6 months after surgery. Patients with spontaneous peeling are not randomized and are included in the ancillary study with the same follow-up visits and the same examinations as the principal study. Relevant inclusion criteria involve individuals aged > 18 years living with idiopathic symptomatic ERM, including pseudophakic patients with transparent posterior capsule or open capsule or lensed patients with age-related cataracts. The calculated sample size corresponds to 53 randomized eyes (one eye/patient) per arm that means 106 randomized eyes (106 randomized patients) in total and a maximum of 222 included patients (116 spontaneous peeling). DISCUSSION: ILM peeling is often practiced in ERM surgery to reduce ERM recurrence. It does not impair postoperative visual acuity, but it increases the surgical risks and causes anatomical damages. If active ILM peeling is significantly associated with more microscotomas, it may contraindicate the ILM peeling during primitive idiopathic ERM surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02146144. Registered on 22 May 2014. Recruitment is still ongoing.

Impact of intravitreal aflibercept dosing regimens in treatment-naïve patients with neovascular age-related macular degeneration: 2-year results of RAINBOW.

BACKGROUND: To review treatment outcomes from real-world data of patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) injection. METHODS: RAINBOW (ClinicalTrials.gov, NCT02279537) is an ongoing, observational, 4-year study to monitor the effectiveness and safety of IVT-AFL in patients with nAMD in clinical practice in France. Treatment-naïve patients diagnosed with nAMD who had been prescribed IVT-AFL by their treating physician were eligible. The regimens of interest were regular treatment interval cohort (patients who received three initial monthly IVT-AFL injections followed by regular injections every 2 months) and two irregular treatment interval cohorts (with and without three initial monthly injections). Here we describe results at 24 months in patients according to IVT-AFL treatment regimen. RESULTS: The mean change in best-corrected visual acuity (BCVA) with IVT-AFL from baseline to 24 months was + 3.0 letters in the overall population (P < 0.05 vs baseline). The mean change was positive for the regular and irregular treatment interval cohorts with initial doses (+ 4.9 and + 4.0 letters, respectively; P < 0.05 vs baseline) and negative for the irregular treatment interval cohort without initial doses (- 2.5 letters; P = 0.365 vs baseline) at 24 months. The mean overall number of IVT-AFL injections over 12 and 24 months was 6.0 and 8.8, respectively. The most common ocular adverse events were lack of efficacy (6.3%), vitreous floaters (2.7%), and increased lacrimation (1.7%). CONCLUSIONS: In the real-world RAINBOW study, visual outcomes observed at 24 months were consistent with results from the primary endpoint at 12 months. In this study, treatment-naïve patients who received three initial IVT-AFL doses and regular IVT-AFL treatment over the first 24 months experienced better visual outcomes than patients who received no initial doses and an irregular treatment regimen. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT02279537). Registered 29 October 2014.

Complications of cosmetic iris implants: French series of 87 eyes.

PURPOSE: Iris intraocular implants were developed to manage congenital or traumatic iris defects. However, they are also used to change the color of patient eyes. The aim of this retrospective series was to report complications in patients managed in France after cosmetic implantation. SETTING: Ophthalmological institutions and private ophthalmologists in France. DESIGN: Multicenter retrospective observational study. METHODS: Questionnaires were sent to all ophthalmology departments in university hospitals and to private ophthalmologists. This questionnaire listed demographic and clinical data for each implanted eye with a focus on safety, the description of ocular complications (corneal edema, endothelial cell loss, increased intraocular pressure, and intraocular inflammation), and the therapeutic management implemented. RESULTS: Forty-four questionnaires (87 eyes) were collected, and ultimately, 33 questionnaires (65 eyes) were considered complete and analyzed. Two types of implants were identified. Of the 65 eyes analyzed, only 5 eyes (7.7%) did not experience any complication and 60 eyes (92.3%) had at least 1 complication. The most commonly reported complication was corneal decompensation (78.5%). The diagnosis of glaucoma was made in over half (52.3%) of the cases. Explantation was needed in 81.5% of cases. The mean final visual acuity was 0.45 ± 0.08 logarithm of the minimum angle of resolution (logMAR) (0 to 2 logMAR). CONCLUSIONS: Several ocular complications with a decreased mean visual acuity were described in a young healthy population. In addition, patient information on the safety of this procedure appeared insufficient.

Comparison of two techniques used in routine care for the treatment of inflammatory macular oedema, subconjunctival triamcinolone injection and intravitreal dexamethasone implant: medical and economic importance of this randomized controlled trial.

BACKGROUND: Whether they are injected peri- or intraocularly, corticosteroids are still essential tools in the therapeutic arsenal for treating inflammatory macular oedema. A few years ago, however, only triamcinolone acetonide was available to ophthalmologists. While this compound was initially developed for rheumatological or dermatological use, it has been increasingly deployed in ophthalmology, despite still being off-label. In 2011, the system for delivery of dexamethasone from a biodegradable, injectable implant into the vitreous cavity obtained approval for use in inflammatory macular oedema. While the efficacy and safety of triamcinolone in macular oedema, including inflammatory oedema, have already been studied, there are currently no publications on subconjunctival triamcinolone injections, which are simple, effective and well tolerated. To date, the dexamethasone 700 µg implant has been authorized for the treatment of noninfectious intermediate and posterior uveitis, but there have been no studies to evaluate the efficacy and safety of the different peri- and intraocular strategies, including the treatment of inflammatory macular oedema. METHODS: This protocol is therefore designed to compare the efficacy and safety of peri- and intraocular corticosteroid injections in the treatment of inflammatory macular oedema. In this ongoing study, 142 patients will be included, and the oedematous eye will be randomised to treatment with either subconjunctival triamcinolone injection or an intravitreal implant containing 700 µg dexamethasone. Follow-up is planned for 6 months with monthly visits. Each visit will include visual acuity measurement, a slit lamp examination, fundoscopy, intraocular pressure measurement, laser flare measurement (if available) and spectral domain optical coherence tomography. DISCUSSION: The results of this trial will have a real impact on public health if it is shown that a Kenacort retard® (i.e. triamcinolone) injection costing just €2.84 and performed in the physician's office (with no additional overhead costs) is at least as effective as the dexamethasone 700 µg implant (Ozurdex®; costing approximately €960 with the injection performed in a dedicated room), with no increased side effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02556424. Registered on 22 September 2015.