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The authors review favorable outcomes in patients with thyroid eye disease–compressive optic neuropathy after corticosteroid treatment and orbital radiation.

This pilot study demonstrates the short-term safety of single intravitreal injections of 2 mg (0.08 mL) ziv-aflibercept in patients with choroidal neovascular membranes. No signs of toxicity were seen on clinical examination or with electroretinographic testing at one month. Further studies are needed to determine the long-term safety and clinical efficacy of the 2-mg dose.

The effectiveness of different instrument approach charts to deliver minimum visibility and altitude information during airport equipment outages was investigated. Eighteen pilots flew simulated instrument approaches in three conditions: (a) normal operations using a standard approach chart (standard-normal), (b) equipment outage conditions using a standard approach chart (standard-outage), and (c) equipment outage conditions using a prototype decluttered approach chart (prototype-outage). Errors and retrieval times in identifying minimum altitudes and visibilities were measured. The standard-outage condition produced significantly more errors and longer retrieval times versus the standard-normal condition. The prototype-outage condition had significantly fewer errors and shorter retrieval times than did the standard-outage condition. The prototype-outage condition produced significantly fewer errors but similar retrieval times when compared with the standard-normal condition. Thus, changing the presentation of minima may reduce risk and increase safety in instrument approaches, specifically with airport equipment outages.

Combining biomolecules such as enzymes with nanoparticles has much to offer for creating next generation synergistically functional bionanomaterials. However, almost nothing is known about how these two disparate components interact at this critical biomolecular-materials interface to give rise to improved activity and emergent properties. Here we examine how the nanoparticle surface can influence and increase localized enzyme activity using a designer experimental system consisting of trypsin proteolysis acting on peptide-substrates displayed around semiconductor quantum dots (QDs). To minimize the complexity of analyzing this system, only the chemical nature of the QD surface functionalizing ligands were modified. This was accomplished by synthesizing a series of QD ligands that were either positively or negatively charged, zwitterionic, neutral, and with differing lengths. The QDs were then assembled with different ratios of dye-labeled peptide substrates and exposed to trypsin giving rise to progress curves that were monitored by Förster resonance energy transfer (FRET). The resulting trypsin activity profiles were analyzed in the context of detailed molecular dynamics simulations of key interactions occurring at this interface. Overall, we find that a combination of factors can give rise to a localized activity that was 35-fold higher than comparable freely diffusing enzyme–substrate interactions. Contributing factors include the peptide substrate being prominently displayed extending from the QD surface and not sterically hindered by the longer surface ligands in conjunction with the presence of electrostatic and other productive attractive forces between the enzyme and the QD surface. An intimate understanding of such critical interactions at this interface can produce a set of guidelines that will allow the rational design of next generation high-activity bionanocomposites and theranostics.

We report the development of a quantum dot (QD)–peptide–fullerene (C60) electron transfer (ET)-based nanobioconjugate for the visualization of membrane potential in living cells. The bioconjugate is composed of (1) a central QD electron donor, (2) a membrane-inserting peptidyl linker, and (3) a C60electron acceptor. The photoexcited QD donor engages in ET with the C60acceptor, resulting in quenching of QD photoluminescence (PL) that tracks positively with the number of C60moieties arrayed around the QD. The nature of the QD-capping ligand also modulates the quenching efficiency; a neutral ligand coating facilitates greater QD quenching than a negatively charged carboxylated ligand. Steady-state photophysical characterization confirms an ET-driven process between the donor–acceptor pair. When introduced to cells, the amphiphilic QD–peptide–C60bioconjugate labels the plasma membrane by insertion of the peptide–C60portion into the hydrophobic bilayer, while the hydrophilic QD sits on the exofacial side of the membrane. Depolarization of cellular membrane potential augments the ET process, which is manifested as further quenching of QD PL. We demonstrate in HeLa cells, PC12 cells, and primary cortical neurons significant QD PL quenching (ΔF/F0of 2–20% depending on the QD–C60separation distance) in response to membrane depolarization with KCl. Further, we show the ability to use the QD–peptide–C60probe in combination with conventional voltage-sensitive dyes (VSDs) for simultaneous two-channel imaging of membrane potential. In in vivoimaging of cortical electrical stimulation, the optical response of the optimal QD–peptide–C60configuration exhibits temporal responsivity to electrical stimulation similar to that of VSDs. Notably, however, the QD–peptide–C60construct displays 20- to 40-foldgreater ΔF/F0than VSDs. The tractable nature of the QD–peptide–C60system offers the advantages of ease of assembly, large ΔF/F0, enhanced photostability, and high throughput without the need for complicated organic synthesis or genetic engineering, respectively, that is required of traditional VSDs and fluorescent protein constructs.

Background: Antibodies constitute an important drug development platform for drugs to treat several ophthalmic, oncologic, and immunologic conditions, but due to limitations inherent in antibody production and structure, a wide range of other protein binding scaffolds are being investigated. Designed ankyrin repeat proteins (DARPins) are simple to produce and offer a range of advantages over antibodies because of their stability, high binding affinity, and rigid structure. Objective: DARPins are being developed for a wide variety of medical applications, and the most studied molecule, abicipar pegol, is used to treat chorioretinal vascular diseases. This mini-review will discuss the current state of DARPin technology and will summarize drug development with a focus on abicipar. Methods: PubMed searches with keywords “DARPin” and “designed ankyrin repeat proteins” were performed and the reference lists of identified articles were examined for additional research material. Studies using DARPin molecules were identified at Clinicaltrials. gov. Non-peer reviewed data were found through Google searches of pertinent websites. Results: Abicipar prevents angiogenesis by binding all isoforms of vascular endothelial growth factor (VEGF)-A with single-digit picomolar affinity. Abicipar has a long intraocular half-life in rabbits and has produced promising results in pre-clinical studies. Pivotal phase III registration trials for the treatment of neovascular age-related macular degeneration are ongoing and a phase II/III trial for the treatment of diabetic macular edema has been announced. Conclusion: Abicipar pegol has the potential to effectively treat chorioretinal vascular conditions with an extended duration of action beyond those of currently used anti-VEGF drugs.

Prevention and management of postoperative ocular inflammation with corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) have been evaluated in several randomised controlled trials (RCTs). However, neither consensus regarding the efficacies of different regimens nor established guidelines are currently available. This has resulted in different practice patterns throughout the world. A systematic literature review found that for the management of postcataract inflammation nepafenac produced a positive outcome in three of three RCTs (3/3), as did ketorolac (1/1), bromfenac (7/7), loteprednol (3/3) and difluprednate (6/6), but not flurbiprofen (0/1). A single study found that betamethasone produced inconclusive results after retinal detachment (RD) surgery; ketorolac was effective (1/1) after vitrectomy, but triamcinolone was ineffective (0/1) after trabeculectomy. A two-round Delphi survey asked 28 international experts to rate both the inflammatory potential of different eye surgeries and their agreement with different treatment protocols. They rated trabeculectomy, RD surgery and combined phacovitrectomy as more inflammatory than cataract surgery. Vitrectomies for macular hole or epiretinal membrane were not deemed more inflammatory than cataract surgery. For trabeculectomy, they preferred to treat longer than for cataract surgery (NSAID + corticosteroid three times a day for 2 months vs 1 month). For vitrectomy alone, RD surgery and combined phacovitrectomy, the panel preferred the same treatment as for cataract surgery (NSAID + corticosteroid three times a day for 1 month). The discrepancy between preferred treatment and perception of the eye’s inflammatory status by the experts for RD and combined vitreoretinal surgeries highlights the need for RCTs to establish treatment guidelines.

AimTo report the short-term outcomes of eyes with choroidal neovascularisation (CNV) associated with causes other than age-related macular degeneration (AMD) after treatment with intravitreal ziv-aflibercept (IVZ) injections.MethodsThis retrospective study included eyes with non-AMD-related CNV that were treated with IVZ (1.25 mg/0.05 mL) on a pro re nata basis. The primary outcome measure is the mean change in best-corrected visual acuity (BCVA) and secondary outcome measures include the mean change in central macular thickness (CMT) and adverse events.Results23 eyes of 19 patients with CNV due to high myopia (9), macular telangiectasia (4), central serous chorioretinopathy (3), choroidal osteoma (2), choroiditis (2), Best's disease (2) and idiopathic (1) were treated. The mean follow-up period was 4±1.9 months. The median number of IVZ injections was 1 (range, 1–3) and the median treatment-free interval at the time of the final visit was 3 months (range, 1–8). The mean BCVA improved from 0.67 LogMAR to 0.58 LogMAR (p=0.0507). Nine of 23 (39%) eyes had BCVA gains of at least 0.1 LogMAR, 11 (48%) eyes had stable BCVA (within 0.1 LogMAR of baseline) and 3 (13%) eyes had a BCVA decline of at least 0.1 LogMAR at the final visit. The mean CMT improved significantly from baseline until the final visit (22 vs 174.5 μm; p=0.037). No ocular or systemic adverse events were noted.ConclusionsIVZ improves CMT in patients with CNV associated with causes other than AMD, but improvements in BCVA are modest.