Management of diabetic tractional retinal detachments: surgical experiences from a large tertiary academic institution.

Purpose Of Review: Management of diabetic tractional retinal detachments (TRDs) remains technically challenging. The purpose of this review is to provide an updated overview of current surgical techniques and important considerations when treating this condition.

Recent Findings: Recent advances in imaging have provided critical insights into hyaloid status and tractional forces in diabetic TRDs, greatly aiding surgical planning.

Outcomes After Switching to Faricimab for Refractive Macular Edema in Treatment-Experienced Eyes with Neovascular Age-Related Macular Degeneration.

Purpose: To examine response to faricimab in neovascular age-related macular degeneration (nARMD) refractory to traditional anti-vascular endothelial growth factor (anti-VEGF) agents.

Patients And Methods: Retrospective chart review was conducted on eyes with nARMD with persistent subretinal and/or intraretinal fluid despite previously receiving ≥15 injections with ≥2 different anti-VEGF agents. Best corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters were collected at baseline, initial post-injection visit, and most recent visit with OCT following last faricimab.

Chronic hypotony and uveitis managed with pars plana vitrectomy, silicone oil tamponade, and permanent keratoprosthesis.

Purpose: We report a case of silicone oil placement after Boston Type 1 keratoprosthesis implantation for improvement and maintenance of intraocular pressure in a patient with chronic hypotony secondary to chronic uveitis.

Methods: Observational case report.

Results: A 54-year-old female with a history of bilateral chronic panuveitis and subsequent hypotony presented with progressive corneal decompensation and band keratopathy in her better-seeing left eye.

Peptide-Based Nanoparticles for Systemic Extrahepatic Delivery of Therapeutic Nucleotides.

Peptide-based nanoparticles (PBN) for nucleotide complexation and targeting of extrahepatic diseases are gaining recognition as potent pharmaceutical vehicles for fine-tuned control of protein production (up- and/or down-regulation) and for gene delivery. Herein, we review the principles and mechanisms underpinning self-assembled formation of PBN, cellular uptake, endosomal release, and delivery to extrahepatic disease sites after systemic administration. Selected examples of PBN that have demonstrated recent proof of concept in disease models in vivo are summarized to offer the reader a comparative view of the field and the possibilities for clinical application.

An unusual presentation of peripapillary pachychoroid syndrome.

Purpose: Peripapillary pachychoroid syndrome (PPS) is a recently described entity of the pachychoroid disease spectrum and is characterized by thickening of the nasal choroid and peripapillary fluid pockets. This case illustrates the remarkable natural history of this recently described disorder.

Observation: This case report describes a patient with PPS who presented with severe cystoid macular edema (CME) that spontaneously resolved without treatment.

Posterior Uveitis Associated with Cemiplimab.

Purpose: The immune checkpoint inhibitors (ICPIs) comprise a class of oncologic immunotherapies. The most recent US Food and Drug Administration-approved ICPI is cemiplimab (Libtayo®). Cemiplimab, like the other ICPIs, blocks checkpoint receptors in order to disinhibit T-cells so that they may detect and eliminate tumor cells.

Traumatic Retinal Detachment in Patients with Self-Injurious Behavior: An International Multicenter Study.

Purpose: To describe the clinical characteristics, surgical outcomes, and management recommendations in patients with traumatic rhegmatogenous retinal detachment (RRD) resulting from self-injurious behavior (SIB).

Design: International, multicenter, retrospective, interventional case series.

Participants: Patients with SIB from 23 centers with RRD in at least 1 eye.

Volumetric Analysis of Vascularized Serous Pigment Epithelial Detachment Progression in Neovascular Age-Related Macular Degeneration Using Optical Coherence Tomography Angiography.

Purpose: To analyze the evolution of type 1 neovascularization associated with vascularized serous pigment epithelial detachment (vsPED) using three-dimensional, volumetric, en face optical coherence tomography angiography (OCTA).

Methods: This was a retrospective case series from four tertiary medical centers. OCTA images were analyzed at baseline and at the 3-, 6-, 12-, 18-, and 24-month follow-up visit when available.

Pseudoflow with OCT Angiography in Eyes with Hard Exudates and Macular Drusen.

Purpose: To analyze "pseudoflow," a false positive flow-artifact observed with optical coherence tomography angiography (OCTA) of stationary hyperreflective structures corresponding to hard exudates and macular drusen.

Methods: Retrospective case series of patients with hard exudates (due to diabetic macular edema [DME] or retinal vein occlusion [RVO]) or macular drusen (due to nonneovascular, or dry, age-related macular degeneration [AMD]) studied with OCTA by using volume-based projection artifact removal (3D PAR).

Results: OCTA of 20 eyes (10 DME/10 RVO) with hard exudates were analyzed.

Anti-JNK2 peptide-siRNA nanostructures improve plaque endothelium and reduce thrombotic risk in atherosclerotic mice.

Background: A direct and independent role of inflammation in atherothrombosis was recently highlighted by the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) trial, showing the benefit of inhibiting signaling molecules, eg, interleukins. Accordingly, we sought to devise a flexible platform for preventing the inflammatory drivers at their source to preserve plaque endothelium and mitigate procoagulant risk.

Methods: p5RHH-siRNA nanoparticles were formulated through self-assembly processes.

Radial Hemorrhage in Henle Layer in Macular Telangiectasia Type 2.

Importance: Radial hemorrhage in the outer plexiform layer of Henle may be a complication of macular telangiectasia type 2 (MacTel 2) and may occur because of microvascular abnormalities of the deep retinal capillary plexus in the absence of subretinal neovascularization.

Objective: To describe the multimodal imaging findings, including cross-sectional and en face optical coherence tomography (OCT), of radial hemorrhage in the outer plexiform layer of Henle, which may be a complication of MacTel 2.

Design, Setting, And Participants: This retrospective case series from 2 tertiary referral centers (Stein Eye Institute, Los Angeles, California; New England Eye Center, Boston, Massachusetts) between January 1, 2012, and December 31, 2017, describes 3 patients with MacTel 2 complicated by characteristic radial hemorrhage in the outer plexiform layer of Henle.

A role for peptides in overcoming endosomal entrapment in siRNA delivery - A focus on melittin.

siRNA has the possibility to revolutionize medicine by enabling highly specific and efficient silencing of proteins involved in disease pathogenesis. Despite nearly 20 years of research dedicated to translating siRNA from a research tool into a clinically relevant therapeutic, minimal success has been had to date. Access to RNA interference machinery located in the cytoplasm is often overlooked, but must be considered when designing the next generation of siRNA delivery strategies.

Peptide-siRNA nanocomplexes targeting NF-κB subunit p65 suppress nascent experimental arthritis.

The NF-κB signaling pathway is implicated in various inflammatory diseases, including rheumatoid arthritis (RA); therefore, inhibition of this pathway has the potential to ameliorate an array of inflammatory diseases. Given that NF-κB signaling is critical for many immune cell functions, systemic blockade of this pathway may lead to detrimental side effects. siRNAs coupled with a safe and effective delivery nanoplatform may afford the specificity lacking in systemic administration of small-molecule inhibitors.

Mechanisms of nanoparticle-mediated siRNA transfection by melittin-derived peptides.

Traditional peptide-mediated siRNA transfection via peptide transduction domains exhibits limited cytoplasmic delivery of siRNA due to endosomal entrapment. This work overcomes these limitations with the use of membrane-destabilizing peptides derived from melittin for the knockdown of NFkB signaling in a model of adult T-cell leukemia/lymphoma. While the mechanism of siRNA delivery into the cytoplasmic compartment by peptide transduction domains has not been well studied, our analysis of melittin derivatives indicates that concurrent nanocomplex disassembly and peptide-mediated endosomolysis are crucial to siRNA transfection.

RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee.

Studies of DNA methylation from fungi, plants, and animals indicate that gene body methylation is ancient and highly conserved in eukaryotic genomes, but its role has not been clearly defined. It has been postulated that regulation of alternative splicing of transcripts was an original function of DNA methylation, but a direct experimental test of the effect of methylation on alternative slicing at the whole genome level has never been performed. To do this, we developed a unique method to administer RNA interference (RNAi) in a high-throughput and noninvasive manner and then used it to knock down the expression of DNA methyl-transferase 3 (dnmt3), which is required for de novo DNA methylation.

Melittin derived peptides for nanoparticle based siRNA transfection.

Traditional transfection agents including cationic lipids and polymers have high efficiency but cause cytotoxicity. While cell penetrating peptide based transfection agents exhibit improved cytotoxicity profiles, they do not have the efficiency of existing lipidic agents due to endosomal trapping. As a consequence, we propose an alternative method to efficient peptide based siRNA transfection by starting with melittin, a known pore-forming peptide.

Programmable nanoparticle functionalization for in vivo targeting.

The emerging demand for programmable functionalization of existing base nanocarriers necessitates development of an efficient approach for cargo loading that avoids nanoparticle redesign for each individual application. Herein, we demonstrate in vivo a postformulation strategy for lipidic nanocarrier functionalization with the use of a linker peptide, which rapidly and stably integrates cargos into lipidic membranes of nanocarriers after simple mixing through a self-assembling process. We exemplified this strategy by generating a VCAM-1-targeted perfluorocarbon nanoparticle for in vivo targeting in atherosclerosis (ApoE-deficient) and breast cancer (STAT-1-deficient) models.

Probing the surface-enhanced Raman scattering properties of Au-Ag nanocages at two different excitation wavelengths.

The surface-enhanced Raman scattering (SERS) properties of bimetallic Au-Ag nanocages has been thoroughly investigated by changing the nanocage composition, localized surface plasmon resonance (LSPR) peak position and excitation wavelength. We found a significant dependency on excitation wavelength for the Au-Ag nanocages, independent of the underlying LSPR, which can be extended to other bimetallic SERS substrates. While it is well-understood that plasmon damping can occur for Au nanoparticles when their LSPR peaks are close to interband transition frequencies and thereby attenuate SERS intensities, this study probes an additional aspect and shows that SERS intensities are reduced when the excitation light source is near interband transition frequencies regardless of the LSPR location.

The polarity protein Par1b/EMK/MARK2 regulates T cell receptor-induced microtubule-organizing center polarization.

Engagement of a T cell to an APC induces the formation of an immunological synapse as well as reorientation of the microtubule-organizing center (MTOC) toward the APC. How signals emanating from the TCR induce MTOC polarization is not known. One group of proteins known to play a critical role in asymmetric cell division and cell polarization is the partitioning defective (Par) family of proteins.

Nanostructure of Er3+ doped silicates.

We demonstrate nanostructural evolution resulting in highly increased photoluminescence in silicates doped with Er3+ ions. High-resolution transmission electron microscopy (HRTEM) imaging, nano-energy dispersed X-ray (NEDX) spectroscopy, X-ray diffraction (XRD) and photoluminescence analysis confirm the local composition and structure changes of the Er3+ ions upon thermal annealing. We studied two types of amorphous nanopowder: the first is of the composition SiO2/18Al2O3/2Er2O3 (SAE), synthesized by combustion flame-chemical vapor condensation, and the second is with a composition of SiO2/8Y2O3/2Er2O3 (SYE), synthesized by sol-gel synthesis (composition in mol%).