Projection-Resolved Optical Coherence Tomography Angiography of Macular Retinal Circulation in Glaucoma.

PURPOSE: To detect macular perfusion defects in glaucoma using projection-resolved optical coherence tomography (OCT) angiography. DESIGN: Prospective observation study. PARTICIPANTS: A total of 30 perimetric glaucoma and 30 age-matched normal participants were included. METHODS: One eye of each participant was imaged using 6×6-mm macular OCT angiography (OCTA) scan pattern by 70-kHz 840-nm spectral-domain OCT. Flow signal was calculated by the split-spectrum amplitude-decorrelation angiography algorithm. A projection-resolved OCTA (PR-OCTA) algorithm was used to remove flow projection artifacts. Four en face OCTA slabs were analyzed: the superficial vascular complex (SVC), intermediate capillary plexus (ICP), deep capillary plexus (DCP), and all-plexus retina (SVC + ICP + DCP). The vessel density (VD), defined as the percentage area occupied by flow pixels, was calculated from en face OCTA. A novel algorithm was used to adjust the vessel density to compensate for local variations in OCT signal strength. MAIN OUTCOME MEASURES: Macular retinal VD, ganglion cell complex (GCC) thickness, and visual field (VF) sensitivity. RESULTS: Focal capillary dropout could be visualized in the SVC, but not the ICP and DVP, in glaucomatous eyes. In the glaucoma group, the SVC and all-plexus retinal VD (mean ± standard deviation: 47.2%±7.1% and 73.5%±6.6%) were lower than in the normal group (60.5%±4.0% and 83.2%±4.2%, both P < 0.001, t test). The ICP and DCP VD were not significantly lower in the glaucoma group. Among the overall macular VD parameters, the SVC VD had the best diagnostic accuracy as measured by the area under the receiver operating characteristic curve (AROC). The accuracy was even better when the worse hemisphere (inferior or superior) was used, achieving an AROC of 0.983 and a sensitivity of 96.7% at a specificity of 95%. Among the glaucoma participants, the hemispheric SVC VD values were highly correlated with the corresponding GCC thickness and VF sensitivity (P < 0.003). The reflectance compensation step in VD calculation significantly improved repeatability, normal population variation, and correlation with VF and GCC thickness. CONCLUSIONS: On the basis of PR-OCTA, glaucoma preferentially affects perfusion in the SVC in the macula more than the deeper plexuses. Reflectance-compensated SVC VD measurement by PR-OCTA detected glaucoma with high accuracy and could be useful in the clinical evaluation of glaucoma.

Optical coherence tomography angiography of optic disc perfusion in glaucoma.

PURPOSE: To compare optic disc perfusion between normal subjects and subjects with glaucoma using optical coherence tomography (OCT) angiography and to detect optic disc perfusion changes in glaucoma. DESIGN: Observational, cross-sectional study. PARTICIPANTS: Twenty-four normal subjects and 11 patients with glaucoma were included. METHODS: One eye of each subject was scanned by a high-speed 1050-nm-wavelength swept-source OCT instrument. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to compute 3-dimensional optic disc angiography. A disc flow index was computed from 4 registered scans. Confocal scanning laser ophthalmoscopy (cSLO) was used to measure disc rim area, and stereo photography was used to evaluate cup/disc (C/D) ratios. Wide-field OCT scans over the discs were used to measure retinal nerve fiber layer (NFL) thickness. MAIN OUTCOME MEASURES: Variability was assessed by coefficient of variation (CV). Diagnostic accuracy was assessed by sensitivity and specificity. Comparisons between glaucoma and normal groups were analyzed by Wilcoxon rank-sum test. Correlations among disc flow index, structural assessments, and visual field (VF) parameters were assessed by linear regression. RESULTS: In normal discs, a dense microvascular network was visible on OCT angiography. This network was visibly attenuated in subjects with glaucoma. The intra-visit repeatability, inter-visit reproducibility, and normal population variability of the optic disc flow index were 1.2%, 4.2%, and 5.0% CV, respectively. The disc flow index was reduced by 25% in the glaucoma group (P = 0.003). Sensitivity and specificity were both 100% using an optimized cutoff. The flow index was highly correlated with VF pattern standard deviation (R(2) = 0.752, P = 0.001). These correlations were significant even after accounting for age, C/D area ratio, NFL, and rim area. CONCLUSIONS: Optical coherence tomography angiography, generated by the new SSADA, repeatably measures optic disc perfusion and may be useful in the evaluation of glaucoma and glaucoma progression.

Oxidative degradation studies of an oxazolidinone-derived antibacterial agent, RWJ416457, in aqueous solutions.

The rates of oxidative degradation of a new antibacterial drug, RWJ416457, in aqueous solutions were investigated over the pH-range of 2 to 10. Two oxidative degradates were identified and the influences of pH, buffer concentration, metal ions, metal chelating agents, and temperatures were studied. The pH, metal chelating agents, and metal ions significantly changed the product distribution in addition to the degradation rate. Oxidative degradation is believed to follow a hydrogen abstraction (HAT) pathway. One degradate was the major product under acidic conditions and its predominance is attributed to a resonance-stabilized intermediate. The importance of the resonance structure was diminished under neutral and basic conditions. The product distribution changed and two degradates were formed in equal amounts. The study results guided the formulation development to minimize oxidation.

Vision loss after inadvertent corneal perforation during lid anesthesia.

A 68-year-old woman was referred for glaucoma management after inadvertent corneal perforation during eyelid anesthesia for upper eyelid blepharoplasty. A mixture of 50:50 2% lidocaine with 1:100,000 epinephrine and 0.5% bupivacaine buffered with sodium bicarbonate was injected intracamerally. Decreased vision and uncontrollable intraocular pressure resulted, despite prompt anterior chamber washout. Examination showed corneal edema, inflammation, and secondary angle closure. Intraocular pressure control with seton placement led to an improvement in vision; however, mild corneal haze remained, and specular microscopy showed endothelial cell loss, presumably secondary to local anesthetic toxicity. Inadvertent ocular penetration is a rare but serious complication of local eyelid anesthesia. Prompt recognition is essential to institute appropriate management and minimize subsequent vision loss.

Electron Beam Irradiated Corneal Versus Gamma-Irradiated Scleral Patch Graft Erosion Rates in Glaucoma Drainage Device Surgery.

INTRODUCTION: Patch graft erosion and implant exposure is a known complication of glaucoma drainage device (GDD) surgery. Recently, electron beam (e-beam) irradiated corneal tissue ha s become available; however, limited data exist on the rates of erosion for e-beam irradiated corneal grafts compared to traditional scleral grafts after GDD surgery. METHODS: This retrospective study examines the records of 253 eyes from 225 adult subjects who underwent GDD surgery with either e-beam irradiated corneal or scleral grafts at the Casey Eye Institute by five surgeons between April 22, 2014 and October 11, 2017. Surgical procedures and the occurrence of graft erosion were determined using billing codes and verified by manual review of electronic health records. RESULTS: The average age at the time of surgery was 61.3 ± 17.5 years (n = 200) and 60.8 ± 16.8 years (n = 53) for the e-beam irradiated cornea and sclera groups, respectively. The average follow-up time post-surgery was 416 ± 345 days and 495 ± 343 days for the e-beam irradiated cornea and sclera groups, respectively. There were no statistically significant differences in sex, age, follow-up time, and glaucoma diagnosis between the groups; however, the e-beam irradiated cornea group was statistically more likely to have an Ahmed implant as compared to the sclera group. No erosion events were noted in either group. CONCLUSION: e-Beam irradiated corneal grafts were used 3.8 times more frequently relative to scleral grafts, yet there were no cases of graft erosion in either group during the follow-up period.

Treatment of Epithelial Downgrowth Masquerading as Unilateral Hypopyon Uveitis in a HLA-B27+ Individual.

We report a case of an elderly woman with congenital rubella who presented with epithelial downgrowth (EDG) masquerading as hypopyon uveitis. We highlight the importance of endoscopy to completely identify all ingrowing epithelium with combined use of 5-fluorouracil to completely eradicate invading tissue.

Secondary use of electronic health record data for clinical workflow analysis.

Objective: Outpatient clinics lack guidance for tackling modern efficiency and productivity demands. Workflow studies require large amounts of timing data that are prohibitively expensive to collect through observation or tracking devices. Electronic health records (EHRs) contain a vast amount of timing data - timestamps collected during regular use - that can be mapped to workflow steps. This study validates using EHR timestamp data to predict outpatient ophthalmology clinic workflow timings at Oregon Health and Science University and demonstrates their usefulness in 3 different studies. Materials and Methods: Four outpatient ophthalmology clinics were observed to determine their workflows and to time each workflow step. EHR timestamps were mapped to the workflow steps and validated against the observed timings. Results: The EHR timestamp analysis produced times that were within 3 min of the observed times for >80% of the appointments. EHR use patterns affected the accuracy of using EHR timestamps to predict workflow times. Discussion: EHR timestamps provided a reasonable approximation of workflow and can be used for workflow studies. They can be used to create simulation models, analyze EHR use, and quantify the impact of trainees on workflow. Conclusion: The secondary use of EHR timestamp data is a valuable resource for clinical workflow studies. Sample timestamp data files and algorithms for processing them are provided and can be used as a template for more studies in other clinical specialties and settings.

Time Requirements for Electronic Health Record Use in an Academic Ophthalmology Center.

Importance: Electronic health record (EHR) systems have transformed the practice of medicine. However, physicians have raised concerns that EHR time requirements have negatively affected their productivity. Meanwhile, evolving approaches toward physician reimbursement will require additional documentation to measure quality and cost of care. To date, little quantitative analysis has rigorously studied these topics. Objective: To examine ophthalmologist time requirements for EHR use. Design, Setting, and Participants: A single-center cohort study was conducted between September 1, 2013, and December 31, 2016, among 27 stable departmental ophthalmologists (defined as attending ophthalmologists who worked at the study institution for ≥6 months before and after the study period). Ophthalmologists who did not have a standard clinical practice or who did not use the EHR were excluded. Exposures: Time stamps from the medical record and EHR audit log were analyzed to measure the length of time required by ophthalmologists for EHR use. Ophthalmologists underwent manual time-motion observation to measure the length of time spent directly with patients on the following 3 activities: EHR use, conversation, and examination. Main Outcomes and Measures: The study outcomes were time spent by ophthalmologists directly with patients on EHR use, conversation, and examination as well as total time required by ophthalmologists for EHR use. Results: Among the 27 ophthalmologists in this study (10 women and 17 men; mean [SD] age, 47.3 [10.7] years [median, 44; range, 34-73 years]) the mean (SD) total ophthalmologist examination time was 11.2 (6.3) minutes per patient, of which 3.0 (1.8) minutes (27% of the examination time) were spent on EHR use, 4.7 (4.2) minutes (42%) on conversation, and 3.5 (2.3) minutes (31%) on examination. Mean (SD) total ophthalmologist time spent using the EHR was 10.8 (5.0) minutes per encounter (range, 5.8-28.6 minutes). The typical ophthalmologist spent 3.7 hours using the EHR for a full day of clinic: 2.1 hours during examinations and 1.6 hours outside the clinic session. Linear mixed effects models showed a positive association between EHR use and billing level and a negative association between EHR use per encounter and clinic volume. Each additional encounter per clinic was associated with a decrease of 1.7 minutes (95% CI, -4.3 to 1.0) of EHR use time per encounter for ophthalmologists with high mean billing levels (adjusted R2 = 0.42; P = .01). Conclusions and Relevance: Ophthalmologists have limited time with patients during office visits, and EHR use requires a substantial portion of that time. There is variability in EHR use patterns among ophthalmologists.

Establishing a stability window for medium- and long-chain-triglyceride lipid-based total nutrient admixtures using USP standards.

PURPOSE: The stability window of medium-chain triglyceride (MCT) and long-chain-triglyceride (LCT) lipid-based total nutrient admixtures (TNAs) was studied. METHODS: Sixteen different admixtures were selected for study. Of these, eight base macronutrient concentrations representing low and high concentrations were selected, along with low and high concentrations of electrolytes. All TNAs studied contained 2 mg of elemental iron as part of the trace-element formulation, an amount previously shown to produce unstable TNAs with pure LCT-based lipid injectable emulsions. All admixtures were prepared in triplicate and analyzed over five time intervals: time 1 (immediately after preparation), time 2 (after four days of storage at 6 +/- 2 degrees C), and times 3, 4, and 5, corresponding to 6, 24, and 30 hours of storage at 25 +/- 2 degrees C, respectively, after time 2. Stability was measured by comparing results with USP standards for fat globule size in lipid injectable emulsions. RESULTS: A total of 48 admixtures were studied. Samples at each time interval showed an inconsistent but general increase in the number of globules with a diameter of >1.8 microm over time. All admixtures met both the proposed pharmacopoeial criteria for stability with respect to mean droplet size and volume-weighted proportion of fat globules with a diameter of >5 microm. CONCLUSION: A wide range of macronutrients and micronutrients were tested in a series of MCT-LCT-based TNAs and found to be stable. The use of MCTs and LCTs in lipid injectable emulsions confers greater stability to TNAs than has been achieved with pure LCT-based formulations.

Combined Glaucoma Tube Shunt (Ahmed) and Fluocinolone Acetonide (Retisert™) Implantation Compared to Ahmed Alone in Uveitic Glaucoma.

INTRODUCTION: Glaucoma is a known complication of uveitis, and may require glaucoma tube shunt implantation for intraocular pressure (IOP) control. The success of glaucoma tube shunt implantation in the setting of a local ocular steroid depot in uveitic glaucoma remains unknown. The purpose of this study was to determine whether patients who underwent combined glaucoma tube shunt (Ahmed) and fluocinolone acetonide (Retisert™, Bausch + Lomb, Bridgewater, NJ, USA) implantation have superior outcomes compared to patients with Ahmed implants only in the setting of uveitic glaucoma. METHODS: All participants were studied retrospectively and underwent Ahmed implantation alone or with existing/concurrent Retisert implantation (combined group) at a single academic institution. The main outcome measures were IOP, visual acuity (VA), number of IOP-lowering medications, and adverse events at 6 months after Ahmed implantation. Secondary outcome measures included adverse events and surgical success at 6 months after Ahmed implantation. RESULTS: Mean IOP at 6 months after Ahmed implantation was 15.3 ± 4.8 and 15.1 ± 4.9 mm Hg in the Ahmed only group (n = 17) and the combined group (n = 17), respectively (p = 0.89). The mean number of IOP-lowering medications at 6 months after Ahmed implantation was 1.7 ± 1.0 and 1.8 ± 1.0 in the Ahmed only group and the combined group, respectively (p = 0.86). Mean VA at 6 months after Ahmed implantation was 0.35 ± 0.29 and 0.42 ± 0.33 log mean angle of resolution in the Ahmed only group and the combined group, respectively (p = 0.50). No significant differences in surgical success or adverse events were noted between the two groups. CONCLUSION: At 6 months, no significant differences in mean IOP, mean number of IOP-lowering medications, VA, surgical success, or adverse events were noted between Ahmed implantation alone or combined Ahmed and Retisert implantation in patients with uveitic glaucoma.

Clinic Workflow Simulations using Secondary EHR Data.

Clinicians today face increased patient loads, decreased reimbursements and potential negative productivity impacts of using electronic health records (EHR), but have little guidance on how to improve clinic efficiency. Discrete event simulation models are powerful tools for evaluating clinical workflow and improving efficiency, particularly when they are built from secondary EHR timing data. The purpose of this study is to demonstrate that these simulation models can be used for resource allocation decision making as well as for evaluating novel scheduling strategies in outpatient ophthalmology clinics. Key findings from this study are that: 1) secondary use of EHR timestamp data in simulation models represents clinic workflow, 2) simulations provide insight into the best allocation of resources in a clinic, 3) simulations provide critical information for schedule creation and decision making by clinic managers, and 4) simulation models built from EHR data are potentially generalizable.

Physical compatibility of neonatal total parenteral nutrient admixtures containing organic calcium and inorganic phosphate salts.

PURPOSE: The compatibility of calcium and phosphate salts in total parenteral nutrient (TPN) admixtures at the highest concentrations recommended for preterm and term infants was studied. METHODS: Particulate matter from eight different macronutrient combinations was measured and counted (range, 1.8-50 mum) by a laser-based, single-particle optical sensing technique. Measurements were performed at four intervals after compounding the formulations under aseptic conditions (within 1 hour of preparation and at 6, 24, and 30 hours) at 23-27 degrees C. The number of particles measuring >or=5, >or=10, and >or=25 microm per milliliter of TPN admixture was recorded. Detailed visual inspections were also performed at these intervals, and pH was measured at the beginning (time 0) and end of the study (30 hours). Precipitated material was characterized by polarized microscopy and infrared spectroscopy. RESULTS: The TPN admixture with the lowest concentration of amino acids (0.5%), as well as the highest pH, resulted in significant growth of particulate matter over time. At 30 hours, the particle growth was accompanied by visible evidence of precipitation, which was confirmed to be dibasic calcium phosphate. Neither significant particle growth nor precipitation was noted in the remaining seven formulations, which had amino acid concentrations of 1-4%. CONCLUSION: Commonly used organic calcium and inorganic phosphate salts in cysteine-added, lipid-free TPN formulations at the highest recommended amounts for neonates were compatible when the amino acid concentration was between 1% and 4% and the dextrose concentration was 5% or 10%. The salts remained compatible for up to 30 hours at a room temperature of up to 27 degrees C. Precipitation of dibasic calcium phosphate occurred with lower amino acid concentrations and higher pH values.

Effects of period of gestation and position of fetal neck on nuchal translucency measurement.

OBJECTIVE: The aim of this study was to determine the effects of period of gestation and position of fetal neck on nuchal translucency measurement. MATERIALS AND METHODS: Nuchal translucency was measured in the mid-sagittal plane, with the fetal neck in the flexed, neutral, and extended positions in 100 pregnant women between 11 and 13(+6) weeks. Mean nuchal translucency measurements at different periods of gestation were compared. Differences between the extended and neutral positions (Δ extended nuchal translucency) and those between the flexed and neutral positions (Δ flexed nuchal translucency) were calculated. The repeatability coefficients for the measurements in all the three positions were computed. Statistical analysis was also done. RESULTS: Nuchal translucency values were 1.050 ± 0.282 mm in the 11th week, 1.243 ± 0.348 mm in the 12th week, and 1.823 ± 0.357 mm in the 13th week (r = 0.747, p < 0.0001). The mean Δ flexed value was 0.233 ± 0.133 mm lesser than the neutral value (p < 0.0001). The mean Δ extended nuchal translucency was 0.305 ± 0.155 mm greater than the neutral value (p < 0.0001). The repeatability coefficient was the lowest in the neutral position (0.17 mm in the neutral position, 0.28 in the flexed position and 0.41 mm in the extended position). CONCLUSION: We concluded that the period of gestation and fetal neck position can make a significant difference to nuchal translucency measurement. Repeatability of measurement is more accurate with the fetal neck in the neutral position. These findings have important implications for clinicians using nuchal translucency to screen the obstetric population for Down's syndrome.

Copper deposition in a variant of multiple myeloma: pathologic changes in the cornea and the lens capsule.

PURPOSE: To report the pathologic changes in the cornea and the lens capsule resulting from copper deposition in a variant of multiple myeloma. METHODS: Case report. RESULTS: Light microscopy of the cornea revealed endothelial cell attenuation with diffuse copper deposition in the central Descemet membrane, which showed thinning, whereas copper banding was seen in the midperipheral and peripheral cornea where the Descemet membrane was normal in thickness. Copper deposition was confirmed by x-ray microanalysis. The anterior lens capsule showed subepithelial copper deposits. Thickening, multilayering, and splitting of the lens capsule were also noted. CONCLUSIONS: We report the pattern of deposition of copper in the Descemet membrane of the cornea and the anterior lens capsule in multiple myeloma, associated with hypercupremia. Descemet membrane thinning and regional differences in copper deposition were noted. Also, thickening and splitting of the lens capsule are a novel observation.

Escalation of glaucoma therapy after deep lamellar endothelial keratoplasty.

PURPOSE: To determine the prevalence and risk factors for escalation of glaucoma therapy after deep lamellar endothelial keratoplasty (DLEK). METHODS: Retrospective review of every case of DLEK performed at a tertiary care facility between December 1, 2003 and January 31, 2006. RESULTS: Eighty eyes met the inclusion criteria. Escalation of glaucoma therapy occurred in 13 eyes (16.3%) during a mean follow-up period of 27.1 months. Ten eyes required additional topical medical therapy, and 3 eyes required surgical intervention. Glaucoma therapy escalation was significantly associated with preexisting glaucoma (42.9% vs. 10.6%; P = 0.008). CONCLUSION: Escalation of glaucoma therapy is not uncommon after DLEK, especially in eyes with preexisting glaucoma.

Time course of neuroanatomical and functional recovery after bilateral pudendal nerve injury in female rats.

The pudendal nerve innervates the external urethral sphincter (EUS) and is among the tissues injured during childbirth, which may lead to symptoms of stress urinary incontinence (SUI). To understand the mechanisms of injury and repair, urethral leak-point pressure (LPP) was measured 4 days, 2 wk, or 6 wk after bilateral pudendal nerve crush. Morphometric changes in the distal nerve and EUS were examined by light and electron microscopy. To determine whether recovery resulted from pudendal neuroregeneration, LPP was measured before and after pudendal nerve transection 2 wk after nerve crush. LPP was significantly decreased 4 days after pudendal nerve crush compared with sham-injured animals as well as 2 or 6 wk after nerve crush. LPP was not significantly different 2 or 6 wk after nerve crush compared with sham-injured animals, suggesting that urethral function had returned to normal. Four days after pudendal nerve crush, the EUS branch of the pudendal nerve distal to the injury site showed evidence of nerve degeneration and the EUS appeared disrupted. Two weeks after nerve crush, the distal nerve and EUS both showed evidence of both nerve degeneration and recovery. Two weeks after nerve crush, LPP was significantly decreased after nerve transection. Six weeks after nerve injury, evidence of neuroregeneration was observed in the pudendal nerve and the EUS. This study has demonstrated that functional recovery and neuroregeneration are significant 2 wk after nerve crush, although by anatomical assessment, recovery appears incomplete, suggesting that 2 wk represents an early time point of initial neuroregeneration.

Three dimensional virtual reality model of the normal female pelvic floor.

The anatomy of the pelvic floor is complex and difficult to visualize from conventional two-dimensional anatomy pictures. The goal of this project was to establish the methods necessary to develop a static three-dimensional virtual reality model of the normal female pelvic floor from high-resolution magnetic resonance imaging (MRI) scans. An asymptomatic nulliparous 23-year-old female with no urinary incontinence symptoms underwent a high-resolution pelvic floor MRI scan. Selected pelvic floor structures were manually segmented: bladder, urethra, vagina, uterus, cervix, levator ani, obturator externus, obturator internus, and pubic bone. With high-resolution scans, accurate segmentation of the structures was possible. The completed models were displayed on an ImmersaDesk Virtual Reality system and three clinicians verified their accuracy. Stereovision glasses were used to enhance the model while a receiver tracked head position. Three-dimensional virtual reality models of the female pelvic floor can enhance our understanding of anatomy and physiology of this complex part of the body. They can be used as tools for both research and teaching, facilitating improved treatment of pelvic floor pathologies.