Determining Risk Factors for Detachment After Endothelial Keratoplasties: Nine-Year Review of a Single Institution.

PURPOSE: To determine roles of patient history, donor tissue characteristics, tissue preparation methods, and surgeon technique for graft detachment requiring rebubbling after Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) procedures. METHODS: Retrospective analysis of all eyes undergoing first-time DSAEK or DMEK at the study institution between 2013 and 2022. Data were collected regarding recipients' history, donors' medical history, tissue preparation methods, intraoperative details, and postoperative clinical outcomes. Multivariate statistical analysis was conducted to identify risk factors for graft detachment necessitating rebubbling. RESULTS: Of 1240 eyes meeting inclusion criteria, 746 (60.2%) underwent DSAEK, and 494 (39.8%) underwent DMEK. DSAEK procedures had 12.5% rebubbling rate, whereas DMEK procedures had 18.4% rebubbling rate (P = 0.005). Sub50-DSAEK (<50 µm) grafts had 16.0% rebubble rate, whereas sub100-DSAEK (51-99 µm) and >100 µm DSAEKs had rebubble rate of 9.9% and 9.5%, respectively (P = 0.006). Significant risk factors for DSAEK graft detachment included history of retinal surgery (OR = 2.59), preloaded tissue (OR = 2.70), forceps insertion (OR = 2.33), use of sub50-DSAEK lenticules versus sub100-DSAEK (OR = 2.44) and >100 µm DSAEK (OR = 2.38) lenticules, and donor history of noninsulin-dependent diabetes mellitus (OR = 4.18). DMEK risk factors included recipient history of cancer (OR = 2.51) and use of higher SF6 gas concentration (OR = 1.09). Although rebubbled DMEK eyes had comparable refractive outcomes to nonrebubbled eyes (P >0.05), rebubbled DSAEK eyes had worse refractive outcomes at all time points (P < 0.05). CONCLUSIONS: Graft detachments in DSAEK and DMEK are influenced by various factors, including donor tissue characteristics, tissue preparation, and surgical technique. Identifying and understanding these factors can potentially improve postoperative outcomes.

Noninfectious Outcomes of Intravitreal Antibiotic Steroid Injection and Topical Nonsteroidal Antiinflammatory Drugs Versus Triple Drop Therapy After Cataract Surgery.

PURPOSE: To compare noninfectious outcomes of intravitreal antibiotic steroid (IVAS) injection (moxifloxacin-triamcinolone) and postoperative topical nonsteroidal antiinflammatory drugs (NSAID) with a standard 3-drop therapy (TDT) regimen (topical antibiotic, steroid, and NSAID) in patients after cataract surgery. DESIGN: Retrospective comparative clinical cohort study. METHODS: In 3 study centers in the United States, a total of 2143 eyes (N = 2143 patients) underwent cataract surgery with IVAS-NSAID or TDT between 2017 and 2022. Preoperative data were included, including patients' age, iris color, medical history, and ocular history. Postoperative data, including best-corrected visual acuity, intraocular pressure (IOP), and the need for IOP-lowering medications, were recorded at 1-week, 1-month, and 6-month time points. The primary outcome measures were postoperative complications, defined as persistent anterior chamber inflammation, persistent corneal edema (PCE), rebound inflammation, and cystoid macular edema, were compared between the 2 groups. RESULTS: There were 1079 eyes in the IVAS-NSAID group and 1064 eyes in the TDT group. Best-corrected visual acuity and IOP were similar between IVAS-NSAID and TDT eyes at all time points. A portion (11.6%) of TDT eyes experienced postoperative complications compared with 6.5% in IVAS-NSAID eyes (P < .001). Femtosecond laser-assisted cataract surgery was associated with increased rates of PCE in IVAS-NSAID eyes, and eyes with dark irides had a higher incidence of cystoid macular edema, PCE, and rebound inflammation in the IVAS-NSAID group. CONCLUSION: The IVAS-NSAID regimen overall had similar postoperative outcomes and fewer complications compared with the TDT regimen. IVAS-NSAID may be considered a safe alternative to topical regimens in non-femtosecond laser-assisted cataract surgery and patients with light irides.

Dry eye in the upper blepharoplasty patient: a study comparing orbicularis-sparing versus orbicularis-excising techniques.

PURPOSE: To compare subjective and objective dry eye syndrome (DES) metrics preoperatively and postoperatively in patients undergoing bilateral upper eyelid blepharoplasty (ULB) using orbicularis-sparing versus orbicularis-excising techniques. METHODS: A double-blind, randomized clinical trial was conducted on patients without prior DES or other severe conditions who presented to our institution between 2017 and 2019 for routine functional ULB. Patients were randomized into two treatment arms: bilateral ULB using the orbicularis-sparing technique or bilateral ULB using the orbicularis-excising technique. One subjective and seven objective DES assessments were performed on all patients preoperatively and 1 month and 1 year after surgery. RESULTS: A total of 63 patients were recruited for the study. Standard Patient Evaluation of Eye Dryness (SPEED) scores decreased in both treatment groups at 1 month and 1 year postoperatively. This change did not significantly vary based on surgical technique. Objective DES assessments were not significantly changed at both postoperative time points for either group. There was a correlation between the severity of preoperative DES symptoms and the subjective improvement of DES symptoms postoperatively in both groups. CONCLUSIONS: ULB with an orbicularis-sparing or orbicularis-excising technique does not worsen subjective or objective DES metrics and so, surgeons may confidently use either surgical technique. These findings may impact postoperative expectations for surgeons and patients alike.

Optimization of phospholipid chemistry for improved lipid nanoparticle (LNP) delivery of messenger RNA (mRNA).

Lipid nanoparticles (LNPs) have been established as an essential platform for nucleic acid delivery. Efforts have led to the development of vaccines that protect against SARS-CoV-2 infection using LNPs to deliver messenger RNA (mRNA) coding for the viral spike protein. Out of the four essential components that comprise LNPs, phospholipids represent an underappreciated opportunity for fundamental and translational study. We investigated this avenue by systematically modulating the identity of the phospholipid in LNPs with the goal of identifying specific moieties that directly enhance or hinder delivery efficacy. Results indicate that phospholipid chemistry can enhance mRNA delivery by increasing membrane fusion and enhancing endosomal escape. Phospholipids containing phosphoethanolamine (PE) head groups likely increase endosomal escape due to their fusogenic properties. Additionally, it was found that zwitterionic phospholipids mainly aided liver delivery, whereas negatively charged phospholipids changed the tropism of the LNPs from liver to spleen. These results demonstrate that the choice of phospholipid plays a role intracellularly by enhancing endosomal escape, while also driving organ tropism in vivo. These findings were then applied to Selective Organ Targeting (SORT) LNPs to manipulate and control spleen-specific delivery. Overall, selection of the phospholipid in LNPs provides an important handle to design and optimize LNPs for improved mRNA delivery and more effective therapeutics.

ELTD1, an effective anti-angiogenic target for gliomas: preclinical assessment in mouse GL261 and human G55 xenograft glioma models.

Background: Despite current therapies, glioblastoma is a devastating cancer, and validation of effective biomarkers for it will enable better diagnosis and therapeutic intervention for this disease. We recently discovered a new biomarker for high-grade gliomas, ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1) via bioinformatics, and validated that ELTD1 protein levels are significantly higher in human and rodent gliomas. The focus of this study was to assess the effect on tumor growth of an antibody against ELTD1 in orthotopic, GL261, and G55 xenograft glioma models. Methods: The effect of anti-ELTD1 antibody therapy was assessed by animal survival, MRI measured tumor volumes, MR angiography, MR perfusion imaging, and immunohistochemistry (IHC) characterization of microvessel density in mouse glioma models. Comparative treatments included anti-vascular endothelial growth factor (VEGF) and anti-c-Met antibody therapies, compared with untreated controls. Results: Tumor volume and survival data in this study show that antibodies against ELTD1 inhibit glioma growth just as effectively or even more so compared with other therapeutic targets studied, including anti-VEGF antibody therapy. Untreated GL261 or G55 tumors were found to have significantly higher ELTD1 levels (IHC) compared with contralateral normal brain. The anti-angiogenic effect of ELTD1 antibody therapy was observed in assessment of microvessel density, as well as from MR angiography and perfusion measurements, which indicated that anti-ELTD1 antibody therapy significantly decreased vascularization compared with untreated controls. Conclusions: Either as a single therapy or in conjunction with other therapeutic approaches, anti-ELTD1 antibodies could be a valuable new clinical anti-angiogenic therapeutic for high-grade gliomas.