Nanji KC, Roberto SA, Morley MG, Bayes J.
Preventing Adverse Events in Cataract Surgery: Recommendations From a Massachusetts Expert Panel. Anesth Analg 2018;126(5):1537-1547.
AbstractMassachusetts health care facilities reported a series of cataract surgery-related adverse events (AEs) to the state in recent years, including 5 globe perforations during eye blocks performed by 1 anesthesiologist in a single day. The Betsy Lehman Center for Patient Safety, a nonregulatory Massachusetts state agency, responded by convening an expert panel of frontline providers, patient safety experts, and patients to recommend strategies for mitigating patient harm during cataract surgery. The purpose of this article is to identify contributing factors to the cataract surgery AEs reported in Massachusetts and present the panel's recommended strategies to prevent them. Data from state-mandated serious reportable event reports were supplemented by online surveys of Massachusetts cataract surgery providers and semistructured interviews with key stakeholders and frontline staff. The panel identified 2 principal categories of contributing factors to the state's cataract surgery-related AEs: systems failures and choice of anesthesia technique. Systems failures included inadequate safety protocols (48.7% of contributing factors), communication challenges (18.4%), insufficient provider training (17.1%), and lack of standardization (15.8%). Choice of anesthesia technique involved the increased relative risk of needle-based eye blocks. The panel's surveys of Massachusetts cataract surgery providers show wide variation in anesthesia practices. While 45.5% of surgeons and 69.6% of facilities reported increased use of topical anesthesia compared to 10 years earlier, needle-based blocks were still used in 47.0% of cataract surgeries performed by surgeon respondents and 40.9% of those performed at respondent facilities. Using a modified Delphi approach, the panel recommended several strategies to prevent AEs during cataract surgery, including performing a distinct time-out with at least 2 care-team members before block administration; implementing standardized, facility-wide safety protocols, including a uniform site-marking policy; strengthening the credentialing and orientation of new, contracted and locum tenens anesthesia staff; ensuring adequate and documented training in block administration for any provider who is new to a facility, including at least 10 supervised blocks before practicing independently; using the least invasive form of anesthesia appropriate to the patient; and finally, adjusting anesthesia practices, including preferred techniques, as evidence-based best practices evolve. Future research should focus on evaluating the impact of these recommendations on patient outcomes.
Nelson DJ, Craig JP, Akpek EK, Azar DT, Belmonte C, Bron AJ, Clayton JA, Dogru M, Dua HS, Foulks GN, Gomes JAP, Hammitt KM, Holopainen J, Jones L, Joo C-K, Liu Z, Nichols JJ, Nichols KK, Novack GD, Sangwan V, Stapleton F, Tomlinson A, Tsubota K, Willcox MDP, Wolffsohn JS, Sullivan DA.
TFOS DEWS II Introduction. Ocul Surf 2017;15(3):269-275.
Nguyen HV, Jakobiec FA, Zakka FR, Yoon MK.
Bilateral Upper and Lower Eyelid Margin Swelling and Madarosis due to Lymphoma. Surv Ophthalmol 2017;
AbstractOver a 2 year period a 32-year-old woman developed swellings of all 4 eyelid margins accompanied by complete loss of eyelashes. An inflammatory dermatologic condition was considered the most likely cause. A full thickness right lower eyelid biopsy revealed a multinodular lymphoid tumor at the eyelid margin which immunophenotypically and genetically was diagnosed as an extranodal marginal zone lymphoma. The mode of presentation of the disease was considered to be most unusual, as was its B cell lineage, since the majority of primary cutaneous lymphomas are of T-cell origin. Systemic workup demonstrated bilateral involvement of the external auditory canals.
Nihalani BR, VanderVeen DK.
Benchmarks for outcome indicators in pediatric cataract surgery. Eye (Lond) 2017;31(3):417-421.
AbstractPurposeThe purpose of this study was to establish benchmarks for outcome indicators that may help ascertain the quality of pediatric cataract surgery with primary intraocular lens (IOL) implantation.Patients and methodsA retrospective chart review of patients older than 2 years undergoing cataract surgery with primary IOL implantation, by multiple surgeons in a tertiary-care center, from November 2005 to February 2016 was conducted. Patients with ocular comorbidities that would affect the outcomes were excluded. The outcome measures chosen were as follows: (1) final best corrected Snellen visual acuity (BCVA) in patients who had bilateral cataract surgery analyzed at the last clinic visit; (2) prediction error (PE)=expected refraction-actual refraction. Mean PE and mean absolute PE were assessed 1 month postoperatively, irrespective of age or laterality.ResultsMean age at surgery was 8.3±4.6 years and mean follow-up duration was 3.7±2.7 years. The results of outcome measures were as follows: (1) BCVA was 20/40 or better in 96% (n=124 eyes, mean patient age: 8.3±4.6 years). Remaining five eyes had amblyopia with two eyes having BCVA worse than 20/100 that did not respond to amblyopia treatment. (2) Mean PE was 0.3±1.1 D and mean absolute PE was 0.9±0.7 D. PE was within ±0.5 D in 43.0%, ±1.0 D in 66%, and ±2.0 D in 95% (n=235 eyes).ConclusionGood visual acuity after cataract surgery should be expected for children with bilateral cataracts, setting a high benchmark similar to that recommended in adult cataract surgery. Prediction error is greater in pediatric eyes than in adult eyes, setting a lower benchmark. This study establishes benchmark for outcome indicators in pediatric patients older than 2 years undergoing cataract surgery with primary IOL implantation.
Nocera AL, Miyake MM, Seifert P, Han X, Bleier BS.
Exosomes mediate interepithelial transfer of functional P-glycoprotein in chronic rhinosinusitis with nasal polyps. Laryngoscope 2017;127(9):E295-E300.
AbstractOBJECTIVE: P-glycoprotein (P-gp) drives type-2 helper T-cell inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) through unknown posttranslational mechanisms of overexpression. A recent randomized clinical trial demonstrated that inhibition of P-gp was as effective as oral steroids and biologics in treating CRSwNP. Exosomes are 30- to 150-nm vesicles capable of intercellular membrane protein transfer. The aims of this study were 1) to determine whether CRSwNP mucus exosomes are enriched with P-gp, and 2) whether exosomal P-gp can be functionally transferred to autologous epithelial cells as a putative mechanism for the proinflammatory overexpression of P-gp in CRSwNP. STUDY DESIGN: Institutional review board-approved study in CRSwNP and control patients (n = 10 per group). METHODS: P-gp content of purified mucus exosomes was characterized by transmission electron microscopy and enzyme-linked immunosorbent assay. Epithelial transfer of exosomal P-gp was determined by time-lapse fluorescent microscopy and calcein acetoxymethylester functional P-gp assay. RESULTS: CD63+/P-gp+ exosomes were detected in both groups. P-gp was significantly enriched in CRSwNP exosomes relative to control (median 198.5; interquartile range 123.6-270.5 vs. 74.4; 41.3-95.0 pcg P-gp/10(9) exosomes, P = 0.002). Exosomes were absorbed by epithelial cells within 10 minutes, resulting in a significant increase in P-gp activity in CRSwNP patients relative to control (P = 0.006). CONCLUSION: Here we demonstrate the presence and P-gp enrichment of mucus-derived exosomes, or rhinosomes, in CRSwNP. These rhinosomes are capable of rapid intercellular transfer of P-gp, leading to increased P-gp function within recipient cells. This represents a novel mechanism for maintaining P-gp overexpression in CRSwNP, and more generally for interepithelial transfer of other proteins between mucosal epithelial cells. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E295-E300, 2017.
Norsworthy MW, Bei F, Kawaguchi R, Wang Q, Tran NM, Li Y, Brommer B, Zhang Y, Wang C, Sanes JR, Coppola G, He Z.
Sox11 Expression Promotes Regeneration of Some Retinal Ganglion Cell Types but Kills Others. Neuron 2017;94(6):1112-1120.e4.
AbstractAt least 30 types of retinal ganglion cells (RGCs) send distinct messages through the optic nerve to the brain. Available strategies of promoting axon regeneration act on only some of these types. Here we tested the hypothesis that overexpressing developmentally important transcription factors in adult RGCs could reprogram them to a "youthful" growth-competent state and promote regeneration of other types. From a screen of transcription factors, we identified Sox11 as one that could induce substantial axon regeneration. Transcriptome profiling indicated that Sox11 activates genes involved in cytoskeletal remodeling and axon growth. Remarkably, α-RGCs, which preferentially regenerate following treatments such as Pten deletion, were killed by Sox11 overexpression. Thus, Sox11 promotes regeneration of non-α-RGCs, which are refractory to Pten deletion-induced regeneration. We conclude that Sox11 can reprogram adult RGCs to a growth-competent state, suggesting that different growth-promoting interventions promote regeneration in distinct neuronal types.
Novack GD, Asbell P, Barabino S, Bergamini MVW, Ciolino JB, Foulks GN, Goldstein M, Lemp MA, Schrader S, Woods C, Stapleton F.
TFOS DEWS II Clinical Trial Design Report. Ocul Surf 2017;15(3):629-649.
AbstractThe development of novel therapies for Dry Eye Disease (DED) is formidable, and relatively few treatments evaluated have been approved for marketing. In this report, the Subcommittee reviewed challenges in designing and conducting quality trials, with special reference to issues in trials in patients with DED and present the regulatory perspective on DED therapies. The Subcommittee reviewed the literature and while there are some observations about the possible reasons why so many trials have failed, there is no obvious single reason other than the lack of correlation between signs and symptoms in DED. Therefore the report advocates for conducting good quality studies, as described, going forward. A key recommendation for future studies is conduct consistent with Good Clinical Practice (GCP), including use of Good Manufacturing Practice (GMP) quality clinical trial material. The report also recommends that the design, treatments, and sample size be consistent with the investigational treatment, the objectives of the study, and the phase of development. Other recommendations for pivotal studies are a priori selection of the outcome measure, and an appropriate sample size.