Characterization of the resistome and predominant genetic lineages of Gram-positive bacteria causing keratitis.

Bacterial keratitis is a vision-threatening infection mainly caused by Gram-positive bacteria (GPB). Antimicrobial therapy is commonly empirical using broad-spectrum agents with efficacy increasingly compromised by the emergence of antimicrobial resistance. We used a combination of phenotypic tests and genome sequencing to identify the predominant lineages of GPB causing keratitis and to characterize their antimicrobial resistance patterns. A total of 161 isolates, including Staphylococcus aureus (n = 86), coagulase-negative staphylococci (CoNS; n = 34), Streptococcus spp. (n = 34), and Enterococcus faecalis (n = 7), were included. The population of S. aureus isolates consisted mainly of clonal complex 5 (CC5) (30.2%). Similarly, the population of Staphylococcus epidermidis was homogenous with most of them belonging to CC2 (78.3%). Conversely, the genetic population of Streptococcus pneumoniae was highly diverse. Resistance to first-line antibiotics was common among staphylococci, especially among CC5 S. aureus. Methicillin-resistant S. aureus was commonly resistant to fluoroquinolones and azithromycin (78.6%) and tobramycin (57%). One-third of the CoNS were resistant to fluoroquinolones and 53% to azithromycin. Macrolide resistance was commonly caused by erm genes in S. aureus, mphC and msrA in CoNS, and mefA and msr(D) in streptococci. Aminoglycoside resistance in staphylococci was mainly associated with genes commonly found in mobile genetic elements and that encode for nucleotidyltransferases like ant(4')-Ib and ant(9)-Ia. Fluroquinolone-resistant staphylococci carried from 1 to 4 quinolone resistance-determining region mutations, mainly in the gyrA and parC genes. We found that GPB causing keratitis are associated with strains commonly resistant to first-line topical therapies, especially staphylococcal isolates that are frequently multidrug-resistant and associated with major hospital-adapted epidemic lineages.

Evaluation and Optimization of Diabetic Retinopathy Screenings for Uninsured Latinx Patients in a Resource-Limited Student-Run Free Clinic.

Background: Diabetic retinopathy (DR) is a sight-threatening condition that causes progressive retina damage. Student-run free clinics represent a valuable opportunity to provide DR screenings to high-risk populations. We characterized the patient population, evaluated the performance, and conducted a needs assessment of DR screenings at the University of California, San Diego Student-Run Ophthalmology Free Clinic, which provides care to predominantly uninsured, Latino patients. Methods: Retrospective chart review was conducted of all patients seen at the free clinic since 2019 with a diagnosis of type II diabetes. Date and outcome of all DR-related screenings or visits from 2015 onward, demographics information, and DR risk factors such as A1c and insulin dependence were recorded. Predictors of diabetic retinopathy and frequency of DR screenings for each patient were analyzed using multiple logistic regression, t-test for equality of means, and Pearson's correlation. Results: Of 179 uninsured diabetic patients receiving care at the free clinic, 71% were female and average age was 59. 83% had hypertension, 93% had hyperlipidemia, and 79% had metabolic syndrome. Prevalence of non-proliferative DR was 34% and that of proliferative DR was 15% in diabetic patients. The free clinic capacity in recent years plateaued at just under 50% of patients seen for DR screening or visit per year, though average wait time was over 2 years between visits. Patients with higher no-show rates had less frequent DR screenings. Chronic kidney disease and poor glycemic control were the strongest predictors of DR. Conclusion: The student-run free ophthalmology clinic has been effective in providing screening and follow-up care for DR patients. Creation of a protocol to identify which patients are at highest risk of DR and should be seen more urgently, addressing no-shows, and implementation of a tele-retina program are potential avenues for improving clinic efficiency in a resource-limited setting for vulnerable populations.

Usability and Clinician Acceptance of a Deep Learning-Based Clinical Decision Support Tool for Predicting Glaucomatous Visual Field Progression.

PRCIS: We updated a clinical decision support tool integrating predicted visual field (VF) metrics from an artificial intelligence model and assessed clinician perceptions of the predicted VF metric in this usability study. PURPOSE: To evaluate clinician perceptions of a prototyped clinical decision support (CDS) tool that integrates visual field (VF) metric predictions from artificial intelligence (AI) models. METHODS: Ten ophthalmologists and optometrists from the University of California San Diego participated in 6 cases from 6 patients, consisting of 11 eyes, uploaded to a CDS tool ("GLANCE", designed to help clinicians "at a glance"). For each case, clinicians answered questions about management recommendations and attitudes towards GLANCE, particularly regarding the utility and trustworthiness of the AI-predicted VF metrics and willingness to decrease VF testing frequency. MAIN OUTCOMES AND MEASURES: Mean counts of management recommendations and mean Likert scale scores were calculated to assess overall management trends and attitudes towards the CDS tool for each case. In addition, system usability scale scores were calculated. RESULTS: The mean Likert scores for trust in and utility of the predicted VF metric and clinician willingness to decrease VF testing frequency were 3.27, 3.42, and 2.64, respectively (1=strongly disagree, 5=strongly agree). When stratified by glaucoma severity, all mean Likert scores decreased as severity increased. The system usability scale score across all responders was 66.1±16.0 (43rd percentile). CONCLUSIONS: A CDS tool can be designed to present AI model outputs in a useful, trustworthy manner that clinicians are generally willing to integrate into their clinical decision-making. Future work is needed to understand how to best develop explainable and trustworthy CDS tools integrating AI before clinical deployment.

Rates and Patterns of Diagnostic Conversion from Anatomical Narrow Angle to Primary Angle-Closure Glaucoma in the United States.

PURPOSE: To assess rates of diagnostic conversion from anatomical narrow angle (ANA) to primary angle-closure glaucoma (PACG) in the United States and identify factors associated with diagnostic conversion. DESIGN: Retrospective case-control study. PARTICIPANTS: Patients diagnosed with ANA between the years 2007 and 2019 were identified based on International Classification of Diseases (ICD) codes in the Optum Clinformatics Data Mart Database. Inclusion was limited to newly diagnosed ANA, defined as the following: (1) continuous enrollment during a 2-year look back period and 6-year study period from index (first) date of ANA diagnosis; (2) diagnosis by an ophthalmologist or optometrist and record of gonioscopy; and (3) no history of intraocular pressure (IOP)-lowering drops, laser peripheral iridotomy (LPI), or intraocular surgery. METHODS: Cox proportional hazards models were developed to assess factors associated with diagnostic conversion, defined as a change in ICD code from ANA to PACG. MAIN OUTCOME MEASURES: New diagnosis of PACG within the 6-year study period recorded after an index diagnosis of ANA. RESULTS: Among 3985 patients meeting inclusion criteria, 459 (11.52%) had detected diagnostic conversion to PACG within the study period. The conversion rate was stable at 3.54% per year after the first 6 months of ANA diagnosis. In the Cox proportional hazards model, age > 70 years and early (within 6 months of ANA diagnosis) need for LPI or IOP-lowering drops were positively associated with diagnostic conversion (hazard ratio [HR] > 1.59; P < 0.02). Cataract surgery at any time and late (after 6 months of ANA diagnosis) need for IOP-lowering drops appeared protective against diagnostic conversion (HR < 0.46; P < 0.004). CONCLUSIONS: Annual risk of diagnostic conversion from ANA to PACG is relatively low overall; elderly patients are at higher risk whereas patients receiving cataract surgery are at lower risk. The utility of long-term monitoring seems low for most patients with ANA, highlighting the need for improved clinical methods to identify patients at higher risk for PACG. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Structure and evolution of the squamate major histocompatibility complex as revealed by two Anolis lizard genomes.

The major histocompatibility complex (MHC) is an important genomic region for adaptive immunity and has long been studied in ecological and evolutionary contexts, such as disease resistance and mate and kin selection. The MHC has been investigated extensively in mammals and birds but far less so in squamate reptiles, the third major radiation of amniotes. We localized the core MHC genomic region in two squamate species, the green anole (Anolis carolinensis) and brown anole (A. sagrei), and provide the first detailed characterization of the squamate MHC, including the presence and ordering of known MHC genes in these species and comparative assessments of genomic structure and composition in MHC regions. We find that the Anolis MHC, located on chromosome 2 in both species, contains homologs of many previously-identified mammalian MHC genes in a single core MHC region. The repetitive element composition in anole MHC regions was similar to those observed in mammals but had important distinctions, such as higher proportions of DNA transposons. Moreover, longer introns and intergenic regions result in a much larger squamate MHC region (11.7 Mb and 24.6 Mb in the green and brown anole, respectively). Evolutionary analyses of MHC homologs of anoles and other representative amniotes uncovered generally monophyletic relationships between species-specific homologs and a loss of the peptide-binding domain exon 2 in one of two mhc2ß gene homologs of each anole species. Signals of diversifying selection in each anole species was evident across codons of mhc1, many of which appear functionally relevant given known structures of this protein from the green anole, chicken, and human. Altogether, our investigation fills a major gap in understanding of amniote MHC diversity and evolution and provides an important foundation for future squamate-specific or vertebrate-wide investigations of the MHC.

Detection of Nonglaucomatous Macula Findings With Ganglion Cell Analysis Printouts vs Full Macular Cube Scans.

Importance: Ganglion cell analysis (GCA) of ocular coherence tomography (OCT) imaging is routinely used to detect and monitor glaucomatous damage of the ganglion cell complex in the macula. The GCA printout provides qualitative and quantitative data about the macular ganglion cell-inner plexiform layer and a single B-scan of the retina through the fovea. However, the full macular cube scan, including all 128 B-scans, is available for review. The macular cube scan provides considerable information about nonglaucomatous ocular pathology that may be missed if clinicians review only the GCA printout. Objective: To determine the frequency and type of nonglaucomatous macular findings that are observable in the full macular cube scan but not the GCA printout. Design, Setting, and Participants: A retrospective cross-sectional analysis of GCA printouts and full macular cube scans to detect nonglaucomatous macular pathology at a tertiary care academic center. Consecutive patients undergoing ganglion cell complex imaging during routine glaucoma evaluations over a 1-week period in a multi-clinician glaucoma clinic. Main Outcomes and Measures: The prevalence and type of nonglaucomatous macular pathology visible on the GCA printout or macular cube scan. Results: Among 105 patients (mean (SD) age, 67 (15.46) years; 63 [60%] female and 42 [40%] male) 201 eyes were imaged (64 [31.7%] with suspected glaucoma, 126 [62.4%] with open-angle glaucoma, 6 [3.0%] with closed-angle glaucoma, and 6 [3.0%] with other glaucoma). GCA printouts and macular cube scans revealed nonglaucomatous macular pathology in 65 eyes (32.2%). Of these, 25 eyes (38.5%) included findings that were not visible on the GCA printout. Of the cases not visible on the printout, 16 eyes (64.0% ) included macular pathology that required further evaluation. Conclusions and Relevance: The findings indicate that nonglaucomatous macular pathology may be missed based on GCA printouts alone. While it may be beneficial to review the full macular cube to detect potentially vision-threatening disease and ensure proper patient care, this study cannot determine if this missed pathology affects clinical outcomes.

Comparison of the Effects of Latanoprostene Bunod and Timolol on Retinal Blood Vessel Density: A Randomized Clinical Trial.

PURPOSE: To compare the differences in retinal vessel density (VD) between topical administration of latanoprostene bunod (LBN) ophthalmic solution 0.024% and timolol maleate 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) and normal subjects. DESIGN: Randomized, single center, crossover clinical trial. METHODS: Eligible subjects were examined during 6 study visits over 12 weeks. All subjects were randomized in a 1:1 ratio to LBN dosed once daily or timolol dosed twice daily in both eyes (OU) for a duration of 4 weeks each, separated by a 2-week washout period. A comprehensive eye examination OU was performed at each visit. Testing was performed with optical coherence tomography and optical coherence tomography angiography (optic nerve and macula), as well as visual field examination, on the study eye at baseline and before and after each treatment. RESULTS: One eye from each of 50 patients was enrolled (10 healthy patients, 26 patients with OHT, and 14 patients with OAG). After administration of LBN there was significantly increased macular VD (0.76% [0.20%-1.33%], P = 0.009) and a trend in increasing peripapillary VD in patients with OAG and patients with OHT. In contrast, after administration of timolol, there were no differences in macular VD, and a decrease in peripapillary VD only was observed in the nasal inferior sector (-0.56% [-1.08% to -0.03%], P = .04) in patients with OAG and patients with OHT. No change in peripapillary or macular VD was observed in the normal subjects (P > .05 for all). CONCLUSIONS: Topical administration of LBN enhanced macular VD in patients with OAG or patients with OHT. In contrast, timolol administration did not have any effect on VD.

Population structure of ocular Streptococcus pneumoniae is highly diverse and formed by lineages that escape current vaccines.

Streptococcus pneumoniae is a leading cause of ocular infections including serious and sight-threatening conditions. The use of pneumococcal conjugate vaccines (PCV) has substantially reduced the incidence of pneumonia and invasive pneumococcal diseases, but has had limited impact on ocular infections. Additionally, widespread vaccine use has resulted in ongoing selective pressure and serotype replacement in carriage and disease. To gain insight into the population structure of pneumococcal isolates causing ocular infections in a post-PCV-13 time period, we investigated the genomic epidemiology of ocular S. pneumoniae isolates (n=45) collected at Massachusetts Eye and Ear between 2014 and 2017. By performing a series of molecular typing methods from draft genomes, we found that the population structure of ocular S. pneumoniae is highly diverse with 27 sequence types (grouped into 18 clonal complexes) and 17 serotypes being identified. Distribution of these lineages diverged according to the site of isolation, with conjunctivitis being commonly caused by isolates grouped in the Epidemic Conjunctivitis Cluster-ECC (60 %), and ST448 (53.3 %) being most frequently identified. Conversely, S. pneumoniae keratitis cases were caused by a highly diverse population of isolates grouping within 15 different clonal complexes. Serotyping inference demonstrated that 95.5 % of the isolates were non-PCV-13 vaccine types. Most of the conjunctivitis isolates (80 %) were unencapsulated, with the remaining belonging to serotypes 15B, 3 and 23B. On the other hand, S. pneumoniae causing keratitis were predominantly encapsulated (95.2 %) with 13 different serotypes identified, mostly being non-vaccine types. Carriage of macrolide resistance genes was common in our ocular S. pneumoniae population (42.2 %), and usually associated with the mefA +msrD genotype (n=15). These genes were located in the Macrolide Efflux Genetic Assembly cassette and were associated with low-level in vitro resistance to 14- and 15-membered macrolides. Less frequently, macrolide-resistant isolates carried an ermB gene (n=4), which was co-located with the tetM gene in a Tn-916-like transposon. Our study demonstrates that the population structure of ocular S. pneumoniae is highly diverse, mainly composed by isolates that escape the PCV-13 vaccine, with patterns of tissue/niche segregation, adaptation and specialization. These findings suggest that the population structure of ocular pneumococcus may be shaped by multiple factors including PCV-13 selective pressure, microbial-related and niche-specific host-associated features.

Dry Eye Symptom Severity and Visual Field Reliability Metrics.

PRCIS: Tracking failure frequency (TFF) increases with dry eye symptom severity and in the left eye. PURPOSE: Symptoms of dry eye disease are commonly encountered in glaucoma patients and can be exacerbated by topical glaucoma medications. Dry eye disease may influence the reliability of visual field (VF) tests and impact the accurate interpretation of the results. PATIENTS AND METHODS: Patients at the Veterans Administration Medical Center San Diego completed the 5-item Dry Eye Questionnaire before VF testing between December 2018 and February 2019. VF reliability metrics were recorded for each patient. Standard reliability metrics included fixation losses, false positive, and false negative rates. Gaze tracking (GT) metrics included percent of stimuli with gaze deviations between 1 and 2 degrees, 3 and 5 degrees, 6 degrees or greater, and percent of stimuli with tracking failure (TFF). The use of glaucoma medications and artificial tears was also recorded. RESULTS: A total of 494 patients completed the 5-item Dry Eye Questionnaire and VF testing. There was no association between dry eye symptom severity and standard reliability metrics or most GT metrics. However, TFF increased as dry eye symptom severity increased (P=0.015). TFF was also greater in the left eye, which was tested second (P=0.012); no other reliability metrics were related to laterality. Patients were more likely to use artificial tears with increased dry eye symptom severity (P<0.001), but there was no relationship between symptom severity and glaucoma medication use. DISCUSSION: Dry eye symptom severity may influence the acceptable range or threshold of TFF when using GT metrics to determine VF reliability. Likewise, the acceptable range or threshold for TFF may be different between eyes.

Racial and Sociodemographic Disparities in the Detection of Narrow Angles before Detection of Primary Angle-Closure Glaucoma in the United States.

PURPOSE: To assess the proportion of newly diagnosed cases of primary angle-closure glaucoma (PACG) with and without prior diagnosis of anatomical narrow angle (ANA) and to identify sociodemographic risk factors for late detection (PACG without prior ANA diagnosis). DESIGN: Retrospective cohort study. METHODS: One hundred two thousand six hundred seventeen patients with PACG were identified from the Optum Clinformatics Data Mart Database (2007-2019). Patients with newly diagnosed PACG met the following criteria: (1) diagnosis made by an ophthalmologist, (2) disease observable for at least 12 months before diagnosis, and (3) no history of treatment before diagnosis unless preceded by a diagnosis of ANA. Multivariate logistic regression modeling was performed to identify sociodemographic risk factors for late detection. MAIN OUTCOME MEASURES: Proportion of patients with newly diagnosed PACG without prior ANA diagnosis and sociodemographic factors associated with late detection. RESULTS: Thirty-one thousand forty-four patients were eligible. More than 70% of PACG cases were detected without prior ANA diagnosis, regardless of patient age, sex, or race. The odds of late detection were significantly higher (P < 0.001) among men (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.25-1.40), Black patients (OR, 1.25; 95% CI, 1.15-1.37), and patients 80 years of age or older (OR, 1.28; 95% CI, 1.11-1.47) or living in Southern (OR, 1.30; 95% CI, 1.22-1.40) or Pacific (OR, 1.27; 95% CI, 1.16-1.36) regions. Findings were similar for patients with PACG with a record of gonioscopy and treatment or with a 24-month lookback period. CONCLUSIONS: Most patients who receive a new diagnosis of PACG in the United States do not have a prior diagnosis of ANA. The elderly, men, and Black patients are at higher risk of late detection. A need exists for increased disease awareness among providers and more accessible tools to detect patients at risk of developing PACG.

Association of Visual Field Pattern Reversal with Paracentral Visual Field Loss.

PURPOSE: Visual field (VF) results that show more test points outside normal limits on the pattern deviation map than on the total deviation map have been assumed to be evidence of unreliable VF results. We propose the term pattern reversal to describe this VF finding and explore its association with paracentral loss. DESIGN: Retrospective cohort and case-control studies. PARTICIPANTS: Glaucoma and glaucoma suspect patients who completed VF testing in Veteran's Affairs ophthalmology or optometry clinics. METHODS: In the cohort study, VF results were included that demonstrated pattern reversal. The area of pattern reversal was categorized as peripheral, paracentral, or mixed (both peripheral and paracentral). In the case-control study, a group of patients with paracentral loss confirmed on 10-2 VF tests were compared with a control group whose VF results were without paracentral loss. MAIN OUTCOME MEASURES: In the cohort study, the calculated false-positive (FP) error rates were compared among groups categorized by area of pattern reversal. In the case-control study, the rates of pattern reversal were compared between patients with and without paracentral loss. RESULTS: Two hundred seventeen eyes of 145 patients were included in the cohort study. Visual field results with pattern reversal and mixed loss had significantly higher FP rates compared with those with paracentral or peripheral loss only (16.25% vs. 6.26% and 8.15%, respectively; P < 0.001). Fifty-five eyes of 41 patients were included in the case group and 55 eyes of 41 patients were included in the control group. Patients with paracentral loss were more likely to have history of pattern reversal compared with those without paracentral loss (58.2% vs. 29.1%; P = 0.004). Twelve eyes with paracentral loss had 24-2 VF results that showed defects on the pattern deviation map, but not on the total deviation map. CONCLUSIONS: Pattern reversal may be associated with paracentral VF loss and is not always associated with elevated FP rates.

Standard Reliability and Gaze Tracking Metrics in Glaucoma and Glaucoma Suspects.

PURPOSE: To compare standard reliability metrics and gaze tracking (GT) metrics on the Humphrey field analyzer (HFA). DESIGN: Retrospective cross-sectional study. METHODS: The study was performed at the VA Medical Center, San Diego, and included 494 glaucoma and glaucoma suspect patients who had an HFA 24-2 SITA Fast visual field (VF) performed in both eyes. Standard reliability metrics (fixation loss [FL], false-positive [FP], and false-negative [FN]) were compared to GT metrics (deviations of 1°-2° [M1], deviations of 3°-5° [M3], deviations >6° [M6], and tracking failure frequency [TFF]). The main outcome measures were Spearman rank-based correlation coefficient and area under the receiver operating characteristic (AUROC) curves between standard and GT reliability metrics. RESULTS: The 95th percentile limits for GT metrics were 66.7% for M1, 67.5% for M3, 49.5% for M6, and 79.8% for TFF. There were statistically significant correlations between standard and GT reliability metrics using the 95th percentile as a binary cutoff for GT metrics. However, low Spearman correlation values and AUROC calculations suggest little clinical significance of the associations. FN increased as VF severity worsened (P < .001). M6 was lower in eyes with mild compared to moderate and advanced VF loss (P = .012). CONCLUSIONS: GT metrics do not have a clinically significant association with standard reliability metrics. Both FN and M6 are influenced by VF severity. Aggregate GT metrics do not aid in reliability assessment. These findings suggest that GT metrics may provide an alternative or complementary measure of VF reliability.

Progressive Thinning of Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer in Glaucoma Eyes with Disc Hemorrhage.

PURPOSE: To evaluate the thinning of the circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) in primary open-angle glaucoma eyes with and without a history of disc hemorrhage (DH). DESIGN: Observational cohort study. PARTICIPANTS: Thirty-nine 39 eyes (34 participants) with DH and 117 eyes (104 participants) without DH from the Diagnostic Innovations in Glaucoma Study and the African Decent and Glaucoma Evaluation Study. METHODS: Participants had at least 1.5 years of follow-up, with a minimum of 3 visits with biannual spectral-domain OCT cpRNFL and mGCIPL thickness measurements and visual fields (VFs). The rates of cpRNFL and mGCIPL thinning were calculated using mixed-effects models. The dynamic range-based normalized rates of cpRNFL and mGCIPL thinning were calculated and compared between the DH and non-DH groups. MAIN OUTCOME MEASURES: Rates of cpRNFL and mGCIPL thinning. RESULTS: The rate of mGCIPL thinning was significantly faster in the DH group compared with the non-DH group (-0.62 µm/year vs. -0.38 µm/year; P = 0.024). The rate of cpRNFL thinning in the DH quadrant and rate of mGCIPL thinning in the inferotemporal sector in the DH group were faster than the corresponding regions in the non-DH group after adjusting for intraocular pressure (-1.33 µm/year vs. -0.58 µm/year; P = 0.053) and race (-0.82 µm/year vs. -0.44 µm/year; P = 0.048). In the DH group, percent rate of loss was significantly faster for the mGCIPL than the cpRNFL (-1.59 %/year vs. -1.31 %/year; P = 0.046). Rates of mGCIPL thinning were associated weakly with mean deviation slope, VF index slope, and guided progression analysis (GPA). The areas under the receiver operating characteristic curve for VF progression were 0.75 for mGCIPL and 0.56 for cpRNFL in the DH group. CONCLUSIONS: The rate of mGCIPL and cpRNFL thinning was faster in DH eyes than non-DH eyes. Compared with cpRNFL, mGCIPL showed higher proportional rates of thinning and greater association with functional progression. In addition to cpRNFL, clinicians should consider incorporating mGCIPL imaging to monitor glaucoma progression, especially in glaucoma eyes with DH.

Qualitative Evaluation of the 10-2 and 24-2 Visual Field Tests for Detecting Central Visual Field Abnormalities in Glaucoma.

PURPOSE: To examine whether glaucomatous central visual field abnormalities can be more effectively detected using a qualitative, expert evaluation of the 10-2 test compared with the topographically corresponding central 12 locations of the 24-2 test (C24-2). DESIGN: Cross-sectional study. METHODS: Eyes with a glaucomatous optic nerve appearance or ocular hypertension (n = 523) and healthy eyes (n = 107) were included as cases and control subjects, respectively. The 10-2 and C24-2 visual field results of all eyes were graded by 4 glaucoma specialists for the probability that central visual field abnormalities were present. RESULTS: The sensitivity of the 10-2 and C24-2 tests for detecting the cases at 95% specificity were not significantly different (e.g., 32.2% and 31.4%, respectively, for grader 1, P = .87; all graders P ≥ .25). At 95% specificity, the pattern standard deviation values from these tests had a similar sensitivity to the qualitative evaluation for the C24-2 test for all graders (P ≥ .083), but it had a significantly higher sensitivity than the qualitative evaluation for the 10-2 test for 3 graders (P ≤ .016). CONCLUSIONS: The similarity in performance of the 10-2 and C24-2 test suggests that the increased sampling density of the former does not significantly improve the detection of central visual field abnormalities, even when based on expert assessment. These findings should not be taken to mean that the 10-2 test is not useful, but it underscores the need for its utility to be clearly established before incorporating it as routine glaucoma standard of care.

Selecting Double Bond Positions with a Single Cation-Responsive Iridium Olefin Isomerization Catalyst.

The catalytic transposition of double bonds holds promise as an ideal route to alkenes of value as fragrances, commodity chemicals, and pharmaceuticals; yet, selective access to specific isomers is a challenge, normally requiring independent development of different catalysts for different products. In this work, a single cation-responsive iridium catalyst selectively produces either of two different internal alkene isomers. In the absence of salts, a single positional isomerization of 1-butene derivatives furnishes 2-alkenes with exceptional regioselectivity and stereoselectivity. The same catalyst, in the presence of Na+, mediates two positional isomerizations to produce 3-alkenes. The synthesis of new iridium pincer-crown ether catalysts based on an aza-18-crown-6 ether proved instrumental in achieving cation-controlled selectivity. Experimental and computational studies guided the development of a mechanistic model that explains the observed selectivity for various functionalized 1-butenes, providing insight into strategies for catalyst development based on noncovalent modifications.

A Compact Optical Pressure Measurement System for Acquiring Intraocular Pressure and Ocular Pulse.

Frequent and accurate monitoring of intraocular pressure is an important aspect of glaucoma management and is central to timely therapeutic intervention and treatment optimization. Intraocular pressure is known to fluctuate not only throughout the day, but also as a function of the heart rate. This pulsatory pressure change behavior is known as the ocular pulse. In this study, we report on the measurement of the ocular pulse profile using a miniaturized intraocular pressure sensor implanted in the eye of a New Zealand White rabbit. The pressure sensor is based on the principle of interferometry and does not require an internal power source. The ocular pulse variation has been measured up to 5 Hz with an accuracy of +/- 0.15 mmHg using both a DSLR reader and a handheld smartphone reader.

Rapid and Accurate Pressure Sensing Device for Direct Measurement of Intraocular Pressure.

Purpose: Intraocular pressure (IOP) is the primary modifiable risk factor for glaucoma. Current devices measure IOP via the dynamic response of the healthy cornea and do not provide the accurate IOP measurements for patients with altered corneal biomechanics. We seek to develop and test an accurate needle-based IOP measurement device that is not cornea dependent. Methods: Our device combines a high-resolution pressure microsensor with 30- and 33-gauge Luer lock needles to provide IOP measurements via a microcontroller and USB interface to a computer. The device was calibrated in a membrane chamber and then tested and validated in the anterior chamber and post-vitrectomy vitreous chamber of rabbit eyes. The results were compared to Tonopen readings across a pressure range of 0 to 100 mm Hg, imposed in increments of 10 mm Hg. Results: Both the needle based sensor device and the Tonopen demonstrated a linear relationship with changes in imposed pressure. The Tonopen was found to consistently underestimate the IOP both in the anterior and vitreous chambers. The Tonopen exhibited a significantly greater error than our needle-based sensor device. With increased pressure (>30 mm Hg), the error of the Tonopen increased, whereas the error of our device did not. The 30-gauge needle produces an insignificant improvement in accuracy over the 33-gauge needle. Conclusions: A needle-based sensor device enables accurate IOP measurements over a broad range of induced IOP. Translational Relevance: Direct measurement of IOP in the anterior chamber circumvents the influence of corneal parameters on IOP measurement.

A Randomized Controlled Trial Comparing Subconjunctival Injection to Direct Scleral Application of Mitomycin C in Trabeculectomy.

PURPOSE: To compare the efficacy of intraoperative scleral application with subconjunctival injection of mitomycin C (MMC) in trabeculectomy. DESIGN: Prospective, randomized, interventional study. METHODS: This study took place in a single clinical practice in an academic setting. Patients had medically uncontrolled glaucoma as indicated by high intraocular pressure (IOP), worsening visual field, or optic nerve head changes in whom primary trabeculectomy was indicated. Patients were older than 18 years with medically uncontrolled glaucoma and no history of incisional glaucoma surgery. Patients were randomized to MMC delivered by preoperative subconjunctival injection or by intraoperative direct scleral application using surgical sponges during trabeculectomy. Comprehensive eye examinations were conducted at 1 day, 1 week, 6 weeks, 3 months, and 6 months postoperatively. Subconjunctival 5-fluorouracil injections were given postoperatively, as needed. The primary outcome was the proportion of patients who demonstrated IOP of <21 mm Hg and ≥30% reduction in IOP from baseline. Secondary outcome measures included the number of IOP-lowering medications, bleb morphology using the Indiana Bleb Appearance Grading Scale, and complication rates. RESULTS: Participants (n = 100) were randomized into groups matched for baseline demographics, glaucoma status, and baseline IOP. At 6 months, there were no significant differences between the injection (n = 38) and sponge (n = 40) groups in surgical success (P = .357), mean IOP (P = .707), number of glaucoma medications (P = 1.000), bleb height (P = .625), bleb extension (P = .216), bleb vascularity (P = .672), or complications rates. CONCLUSION: Both techniques of MMC delivery (subconjunctival injection and direct scleral application) resulted in comparable surgical outcomes and bleb morphologies.

Promoting Quality Face-to-Face Communication during Ophthalmology Encounters in the Electronic Health Record Era.

OBJECTIVE: To evaluate informatics-enabled quality improvement (QI) strategies for promoting time spent on face-to-face communication between ophthalmologists and patients. METHODS: This prospective study involved deploying QI strategies during implementation of an enterprise-wide vendor electronic health record (EHR) in an outpatient academic ophthalmology department. Strategies included developing single sign-on capabilities, activating mobile- and tablet-based applications, EHR personalization training, creating novel workflows for team-based orders, and promoting problem-based charting to reduce documentation burden. Timing data were collected during 648 outpatient encounters. Outcomes included total time spent by the attending ophthalmologist on the patient, time spent on documentation, time spent on examination, and time spent talking with the patient. Metrics related to documentation efficiency, use of personalization features, use of team-based orders, and note length were also measured from the EHR efficiency portal and compared with averages for ophthalmologists nationwide using the same EHR. RESULTS: Time spent on exclusive face-to-face communication with patients initially decreased with EHR implementation (2.9 to 2.3 minutes, p = 0.005) but returned to the paper baseline by 6 months (2.8 minutes, p = 0.99). Observed participants outperformed national averages of ophthalmologists using the same vendor system on documentation time per appointment, number of customized note templates, number of customized order lists, utilization of team-based orders, note length, and time spent after-hours on EHR use. CONCLUSION: Informatics-enabled QI interventions can promote patient-centeredness and face-to-face communication in high-volume outpatient ophthalmology encounters. By employing an array of interventions, time spent exclusively talking with the patient returned to levels equivalent to paper charts by 6 months after EHR implementation. This was achieved without requiring EHR redesign, use of scribes, or excessive after-hours work. Documentation efficiency can be achieved using interventions promoting personalization and team-based workflows. Given their efficacy in preserving face-to-face physician-patient interactions, these strategies may help alleviate risk of physician burnout.

A Wireless Handheld Pressure Measurement System for In Vivo Monitoring of Intraocular Pressure in Rabbits.

Intraocular pressure (IOP) is the leading modifiable risk factor for preventing vision loss in glaucoma patients. Direct and frequent IOP measurements are highly desirable to assess adequacy of treatment and prevent further vision loss. In this study, we report on successful in vivo measurements of intraocular pressure in rabbits using an optical IOP measurement system. The sensor was implanted during cataract surgery in two New Zealand white (NZW) rabbits and tested in vivo for ten weeks. Prior to implantation, the sensors were characterized in vitro in the physiologically relevant pressure range of 0-60 mmHg. A portable wireless handheld reader consisting of an internal beam splitter, a monochromatic light source, and a digital single-lens reflex (DSLR) camera was also designed and implemented to capture interference patterns from the sensor. The sensitivity and accuracy of the sensor was 30 nm/mmHg and ±0.2 mmHg, respectively. Ten weeks post-implantation, the two NZW rabbits continued to respond well to the implant with no observable inflammation, signs of infection, or biofouling. All IOP measurements were obtained using the portable DSLR handheld reader. Successful in vivo studies demonstrate biocompatibility of the IOP sensor and prove feasibility of the IOP measurement system. The system has the potential to be used in both clinical and patient point-of-care (home) settings to frequently and accurately measure pressure.