Switch to faricimab after initial treatment with aflibercept in eyes with diabetic macular edema.

PURPOSE: To assess the effectiveness of a switch to faricimab in individuals affected by DME and previously treated with aflibercept. METHODS: In this retrospective, single-center study, DME patients previously treated with at least 3 injections of aflibercept then switched to faricimab were enrolled. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline, at the time of the switch and at 6 months follow-up. At transition to faricimab, patients were categorized as "good visual responders" (≥ 5 letters from baseline) or "poor visual responders" (< 5 letters), and as "good anatomical responders" (any reduction in edema compared to baseline) or "poor anatomical responders" (no reduction or worsening of edema). Changes in BCVA and CST were recorded at 6 months after the switch to faricimab. RESULTS: 100 eyes of 100 patients (61 female, 61%) were switched to faricimab after a mean of 6.8 ± 3.3 aflibercept injections. At the 6 months follow-up, only "poor visual responders" (N = 62) demonstrated a meaningful increase in BCVA (Δswitch-6M = + 5 letters; P = 0.007), coupled with a reduction in CST (Δswitch-6M = - 67.9 µm; P = 0.004); participants with "poor anatomical response" upon transitioning exhibited a significant functional gain (Δswitch-6M = + 4.5 letters; p = 0.05) but limited CST enhancements (Δswitch-6M = - 95.1 µm; p = 0.05). CONCLUSIONS: Faricimab shows a positive impact on anatomical and functional metrics in DME cases refractory to aflibercept.

Overlapping retinal phenotypes in a consanguineous family harboring mutations in CRB1 and RS1.

PURPOSE: To describe and distinguish overlapping retinal phenotypes in a consanguineous family harboring mutations in CRB1 and RS1, two different genes that are associated with splitting of the central neurosensory retina. METHODS: Retrospective case series. RESULTS: Three siblings and their father had decreased vision from early childhood, but the father was unavailable for clinical examination. The proband, an 11-year old boy, had clinical features classic for CRB1-retinopathy (nummular pigmentary degeneration, relatively plump vessels, thickened retinal by optical coherence tomography with cystoid splitting in the central macula). The younger brother had right eye cataract with retinal detachment (presumed traumatic) and neurosensory retinal splitting in the central and peripheral retina with nummular pigmentary changes. It was assumed both brothers had the same disease until examination of the older sister, who had bilateral central and peripheral neurosensory retinal splitting in a pattern classic for X-linked retinoschisis and without any evidence for CRB1-retinopathy. The mother had an unremarkable clinical examination. ERG testing and directed genetic testing of CRB1 and RS1 for the family members confirmed CRB1-retinopathy in the proband, X-linked retinoschisis in the younger brother (hemizygous RS1 mutation), and X-linked retinoschisis in the older sister (homozygous RS1 mutation). The mother was confirmed as a carrier for both mutations. DISCUSSION: A consanguineous family affected by retinal degenerative disease may have homozygous mutations in more than one gene, and this includes the possibility of homozygosity for X-linked disease. Electroretinography can be useful in distinguishing CRB1-retinopathy from X-linked retinoschisis.

Diabetic macular edema outcomes in eyes treated with fluocinolone acetonide 0.2 µg/d intravitreal implant: real-world UK experience.

PURPOSE: To conduct an observational, multicenter study to evaluate real-world clinical efficacy and safety of the 0.2 µg/day fluocinolone acetonide (FAc) implant in the treatment of patients with chronic diabetic macular edema (DME) in 3 large hospital ophthalmology departments in the United Kingdom. METHODS: Fluocinolone acetonide implants were inserted into the study eyes following a suitable washout period; phakic eyes received FAc implant following cataract surgery. Follow-up visits took place 2-4 weeks postinjection and then at 3, 6, and 12 months; change in central macular thickness (CMT) from baseline was measured by optical coherence tomography and best-corrected visual acuity (BCVA) was also assessed. Adverse events and changes in intraocular pressure (IOP) were recorded in order to evaluate the safety profile for the FAc implant. RESULTS: Improvements in BCVA and CMT were observed from 3 months and sustained for the duration of observation. At 12 months, the overall mean change from baseline CMT was -126 µm and mean increase in BCVA from baseline was 5.1 letters. Increases in IOP following FAc implant were easily managed with IOP-lowering medication. Implant migration into the anterior chamber occurred in 2 eyes where prior vitrectomy had resulted in a posterior capsule defect; this was rectified and resolved. CONCLUSIONS: The results of this study provide further efficacy and safety profile data for FAc implant treatment of chronic DME in a real-world clinical setting; the FAc implant appears to be a valuable therapeutic approach for patients with chronic DME who have suboptimal response to other treatment options.

A Novel Technique for Repositioning of a Migrated ILUVIEN(®) (Fluocinolone Acetonide) Implant into the Anterior Chamber.

INTRODUCTION: Fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN(®); Alimera Sciences Limited, Aldershot, UK) has been approved in the UK for the treatment of chronic diabetic macula edema, insufficiently responsive to available therapies. It is inserted into the vitreous cavity through a 25-gauge needle. Migration of the implant to the anterior chamber (AC) can occur through gaps in the posterior capsule especially in vitrectomized eyes. Early removal of AC-dislocated FAc implant is essential to prevent corneal edema and damage from raised intraocular pressure. AIM: To demonstrate a simple and novel technique, with a previous capsular tear, for removal of AC-migrated FAc implant and reinsertion into the vitreous cavity without compromising implant integrity. METHOD: A side port incision was created with a keratome and an anterior chamber maintainer introduced and secured. Subsequently, a corneal incision was created at 12 o'clock through which a 23-gauge backflush needle (flute needle) was advanced into the anterior chamber and passive suction used to secure the implant. The flute needle was then placed through the defect in the posterior capsule and the exit port blocked, causing loss of suction and allowing the implant to fall into the posterior segment. The sulcus intraocular lens (IOL) was centralized simply by manipulating it approximately 180 degrees to provide adequate anterior capsule support. RESULTS: The FAc implant was successfully removed from AC in two patients and reinserted into the vitreous cavity without damage or complications either for the eye or the implant. IOL in both patients were repositioned to close the gap in posterior capsule. After 2 months, the implant remains in the vitreous cavity. This paper presents data from one of these cases. CONCLUSION: Using 23-gauge flute needle to retrieve dislocated FAc implant is a safe and easy technique. FUNDING: Alimera Sciences Ltd.

Apoptosis in proliferative vitreoretinopathy.

PURPOSE: To study the involvement of apoptosis using different apoptosis markers in PVR pathogenesis. METHODS: The presence of mRNA coding for Fas, Fas ligand (FasL), and TNF-related apoptosis inducing ligand (TRAIL) was investigated in vitreous samples from 46 consecutive patients-25 with PVR, 11 with retinal detachment (RD) not complicated by PVR, and 10 with macular hole (MH)-using RT-PCR. From previously examined vitreous samples, 21 PVR, 9 RD, and 10 MH were examined for their levels of TGF-beta2 protein with sandwich ELISA kits. Five epiretinal membranes excised from five patients with PVR were also examined for apoptotic cell death using the terminal deoxytransferase (TdT) mediated dUTP-biotin nick end labeling (TUNEL) technique. RESULTS: FAS mRNA was detected in 72% of patients with PVR, 55% of patients with RD and 20% of patients with MH. TRAIL mRNA was detected in 67% of patients with PVR, 89% of patients with RD, and 20% of patients with MH. FasL mRNA was detected in 20% of patients with PVR, 9% of patients with RD, and 10% of patients with MH. The median levels of Fas and TRAIL mRNA were significantly higher (P < 0.05) in patients with PVR than in those with MH hole but between patients with PVR and those with RD the difference was not significant (P > 0.05). A significant difference was detected between RD and MH for TRAIL mRNA levels (P = 0.008). For FasL, no significant difference between groups was found. TGF-beta2 was detected in all investigated vitreous samples. A significant difference was found between the PVR and MH groups (P = 0.001) and between the RD and MH groups (P = 0.004), but not between the PVR and RD groups (P < 0.05). The level of TGF-beta2 was significantly correlated to the level of TRAIL mRNA (r = 0.86), but no correlation was found between TGF-beta2 and Fas mRNA levels (r = 0.21). Four of five examined PVR epiretinal membranes showed positive staining for apoptotic cells using the TUNEL technique. CONCLUSIONS: Apoptosis is one of the mechanisms that is involved in PVR pathogenesis. Different apoptosis markers suggest different pathways occur in PVR, including Fas/FasL, TRAIL, and TGF-beta2 mediated processes.