The Combination of PlGF Inhibition and MMC as a Novel Anti-Scarring Strategy for Glaucoma Filtration Surgery

The complementary effects of mitomycin-C (MMC) and anti-placental growth factor (PlGF) therapy were explored and compared to the combined administration of MMC and aflibercept. Additionally, the effect of PlGF (inhibition) on IOP was investigated, since aqueous PlGF is known to be upregulated in glaucoma patients.status: publishe

Phase I trial on robot assisted retinal vein cannulation with ocriplasmin infusion for central retinal vein occlusion

PURPOSE: To evaluate the safety and feasibility of robot-assisted retinal vein cannulation with Ocriplasmin infusion for central retinal vein occlusion. METHODS: Prospective phase I trial including four patients suffering from central retinal vein occlusion (CRVO). Diagnosis was confirmed by preoperative fluo-angiography and followed by a standard three-port pars plana vitrectomy. Afterwards, a custom-built microneedle was inserted into a branch retinal vein with robotic assistance and infusion of Ocriplasmin started. Primary outcomes were the occurrence of intra-operative complications and success of cannulation. Secondary outcomes were change in visual acuity, central macular thickness (CMT) and venous filling times (VFT) during fluo-angiography two weeks after the intervention. RESULTS: Cannulation with infusion of ocriplasmin was successful in all four eyes with a mean total infusion time of 355 ± 204 seconds (range 120-600 seconds). Best corrected visual acuity (BCVA) remained counting fingers (CF) in case 3 and 4, increased in case 1 from CF to 0.9LogMAR and decreased in case 2 from 0.4 to 1.3 LogMAR. CMT and VFT both showed a trend towards significant decrease comparing preoperative measurements with two weeks postintervention (1061 ± 541 μm versus 477 ± 376 μm, p = 0.068) and 24 ll 4 seconds versus 15 ± 1 seconds, p = 0.068, respectively). In one eye a needle tip broke and could be removed with an endoforceps. There were no other intervention-related complications. CONCLUSION: Robot-assisted retinal vein cannulation is feasible and safe. Local intravenous infusion with Ocriplasmin led to an improved retinal circulation.status: publishe

Longitudinal In Vivo Characterization of the Streptozotocin-Induced Diabetic Mouse Model: Focus on Early Inner Retinal Responses

Purpose: The goal of this study was to perform an extensive temporal characterization of the early pathologic processes in the streptozotocin (STZ)-induced diabetic retinopathy (DR) mouse model, beyond the vascular phenotype, and to investigate the potential of clinically relevant compounds in attenuating these processes. Methods: Visual acuity and contrast sensitivity (CS) were studied in the mouse STZ model until 24 weeks postdiabetes onset. ERG, spectral domain optical coherence tomography (SD-OCT), leukostasis, and immunohistochemistry were applied to investigate neurodegeneration, inflammation, and gliosis during early-, mid- and late-phase diabetes. Aflibercept or triamcinolone acetonide (TAAC) was administered to investigate their efficacy on the aforementioned processes. Results: Visual acuity and CS loss started at 4 and 18 weeks postdiabetes onset, respectively, and progressively declined over time. ERG amplitudes were diminished and OP latencies increased after 6 weeks, whereas SD-OCT revealed retinal thinning from 4 weeks postdiabetes. Immunohistochemical analyses linked these findings to retinal ganglion and cholinergic amacrine cell loss at 4 and 8 weeks postdiabetes onset, respectively, which was further decreased after aflibercept administration. The number of adherent leukocytes was augmented after 2 weeks, whereas increased micro- and macroglia reactivity was present from 4 weeks postdiabetes. Aflibercept or TAAC showed improved efficacy on inflammation and gliosis. Conclusions: STZ-induced diabetic mice developed early pathologic DR hallmarks, from which inflammation seemed the initial trigger, leading to further development of functional and morphologic retinal changes. These findings indicate that the mouse STZ model is suitable to study novel integrative non-vascular therapies to treat early DR.status: publishe

IL-33trap-mediated IL-33 neutralization does not exacerbate choroidal neovascularization, but fails to protect against retinal degeneration in a dry age-related macular degeneration model

The progressive and sight-threatening disease, age-related macular degeneration (AMD), is a growing public health concern due to ageing demographics, with the highest unmet medical need for the advanced stage of dry AMD, geographic atrophy. The pathogenesis underlying AMD is driven by a complex interplay of genetic and environmental factors. There is ample evidence that inflammation is strongly involved in AMD development. Interleukin-33 (IL-33) has been proposed to be critically involved in retinal degeneration, but a protective role in eye pathophysiology was also demonstrated. The current study investigated the therapeutic potential of IL-33trap, a novel IL-33-neutralizing biologic, in dry AMD/geographic atrophy and, based on controversial data regarding the protective versus detrimental functions of IL-33 in neovascularization, evaluated the risk of progression to wet AMD by IL-33 neutralization. Repeated intravitreal (IVT) injections of IL-33trap in the mouse laser-induced choroidal neovascularization model did not exacerbate neovascularization or leakage, while it significantly inhibited inflammatory cell infiltration in the retinal pigment epithelium and choroid. On the contrary, IVT treatment with IL-33trap significantly induced retinal inflammation and could not prevent retinopathy induction in the mouse sodium iodate (NaIO3) model. Overall, these data suggest a complex and dichotomous role of IL-33 in eye pathology and indicate that IL-33 neutralization is not able to prevent onset and progression of dry AMD pathogenesis

Robot-assisted retinal vein cannulation in an in vivo porcine retinal vein occlusion model

Purpose To evaluate the feasibility of robot-assisted retinal vein cannulation for retinal vein occlusion. Methods Prospective experimental study performed in in vivo porcine eyes. A standard three port pars plana vitrectomy was followed by laser-induced branch retinal vein occlusion. Consequently, a retinal vein cannulation with the help of a surgical robot and a microneedle was performed. Complete success was defined as a stable intravenous position of the needle tip confirmed by blood washout for at least 3 min. Secondary outcomes were the occurrence of intra-operative complications and technical failures. Results Cannulation was successful in 15 of 18 eyes with a complete success rate (duration of infusion of more than 3 min) of 73% after exclusion of two eyes from analysis due to failure in establishing a blood clot. There were no technical failures regarding the robotic device. The intravessel injections of ocriplasmin in two of two eyes led to a clot dissolution. In a subset of five eyes, a second cannulation attempt at the border of the optic disc resulted in a stable intravessel position and infusion during 362 (±138) seconds. Conclusion Robot-assisted retinal vein cannulation with prolonged infusion time is technically feasible. Human experiments are required to analyse the clinical benefit of this new therapy.status: publishe