Prognosticators of Visual Acuity After Indirect Traumatic Optic Neuropathy.

BACKGROUND: The purpose of this study is to determine whether there are radiographic and systemic clinical characteristics that can predict final visual outcomes in patients with indirect traumatic optic neuropathy (iTON). METHODS: This study is a retrospective, multicenter case series of adult patients with iTON treated initially at large, urban, and/or academic trauma centers with follow-up at an affiliated ophthalmology clinic. In addition to detailed cranial computed tomography characteristics, demographics, systemic comorbidities, coinjuries, blood products administered, and intracranial pressure, along with other factors, were gathered. LogMAR visual acuity (VA) at the initial presentation to the hospital and up to 12 months follow-up was collected. RESULTS: Twenty patients met inclusion criteria; 16 (80%) were men with a mean age of 40.9 years (±20.9). Mean initial VA was 1.61 logMAR (∼20/800, ± 0.95), and final VA was 1.31 logMAR (∼20/400, ± 1.06). Three patients (4 eyes) had no light perception (NLP) VA at presentation and remained NLP at final follow-up. Of the predictors analyzed, only the initial VA was found to be a significant predictor of visual outcome. The presence of orbital fractures, intraconal and/or extraconal hemorrhage, as well as systemic comorbidities, were not found to significantly affect visual outcome. CONCLUSIONS: After evaluating multiple factors, initial VA was the only factor associated with visual prognosis in iTON. This knowledge may better enable clinicians to predict visual prognosis and set reasonable expectations with patients and families at the time of injury.

Acute secondhand smoke-induced pulmonary inflammation is diminished in RAGE knockout mice.

The receptor for advanced glycation end-products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in proinflammatory signaling, and its role in irreversible pulmonary remodeling. The current research evaluated the in vivo effects of short-term secondhand smoke (SHS) exposure in RAGE knockout and control mice compared with identical animals exposed to room air only. Quantitative PCR, immunoblotting, and immunohistochemistry revealed elevated RAGE expression in controls after 4 wk of SHS exposure and an anticipated absence of RAGE expression in RAGE knockout mice regardless of smoke exposure. Ras activation, NF-κB activity, and cytokine elaboration were assessed to characterize the molecular basis of SHS-induced inflammation in the mouse lung. Furthermore, bronchoalveolar lavage fluid was procured from RAGE knockout and control animals for the assessment of inflammatory cells and molecules. As a general theme, inflammation coincident with leukocyte recruitment was induced by SHS exposure and significantly influenced by the availability of RAGE. These data reveal captivating information suggesting a role for RAGE signaling in lungs exposed to SHS. However, ongoing research is still warranted to fully explain roles for RAGE and other receptors in cells coping with involuntary smoke exposure for prolonged periods of time.

Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation.

BACKGROUND: Receptors for advanced glycation end-products (RAGE) are multiligand cell-surface receptors expressed abundantly by distal pulmonary epithelium. Our lab has discovered RAGE-mediated effects in the orchestration of lung inflammation induced by tobacco smoke and environmental pollutants; however, the specific contribution of RAGE to the progression of proximal airway inflammation is still inadequately characterized. METHODS AND RESULTS: We generated a Tet-inducible transgenic mouse that conditionally overexpressed RAGE using the club cell (Clara) secretory protein (CCSP) promoter expressed by club (Clara) cells localized to the proximal airway. RAGE was induced for 40 days from weaning (20 days of age) until sacrifice date at 60 days. Immunohistochemistry, immunoblotting, and qPCR revealed significant RAGE up-regulation when compared to non-transgenic controls; however, H&E staining revealed no detectible morphological abnormalities and apoptosis was not enhanced during the 40 days of augmentation. Freshly procured bronchoalveolar lavage fluid (BALF) from CCSP-RAGE TG mice had significantly more total leukocytes and PMNs compared to age-matched control littermates. Furthermore, CCSP-RAGE TG mice expressed significantly more tumor necrosis factor alpha (TNF-α), interleukin 7 (IL-7), and interleukin 14 (IL-14) in whole lung homogenates compared to controls. CONCLUSIONS: These data support the concept that RAGE up-regulation specifically in lung airways may function in the progression of proximal airway inflammation.

Antenatal exposure of maternal secondhand smoke (SHS) increases fetal lung expression of RAGE and induces RAGE-mediated pulmonary inflammation.

BACKGROUND: Receptors for advanced glycation end-products (RAGE) are immunoglobulin-like pattern recognition receptors abundantly localized to lung epithelium. Our research demonstrated that primary tobacco smoke exposure increases RAGE expression and that RAGE partly mediates pro-inflammatory signaling during exposure. However, the degree to which RAGE influences developing lungs when gestating mice are exposed to secondhand smoke (SHS) has not been determined to date. METHODS: Timed pregnant RAGE null and wild type control mice were exposed to 4 consecutive days of SHS from embryonic day (E) 14.5 through E18.5 using a state of the art nose-only smoke exposure system (Scireq, Montreal, Canada). RAGE expression was assessed using immunofluorescence, immunoblotting, and quantitative RT-PCR. TUNEL immunostaining and blotting for caspase-3 were performed to evaluate effects on cell turnover. Matrix abnormalities were discerned by quantifying collagen IV and MMP-9, a matrix metalloprotease capable of degrading basement membranes. Lastly, TNF-α and IL-1ß levels were assessed in order to determine inflammatory status in the developing lung. RESULTS: Pulmonary RAGE expression was elevated in both dams exposed to SHS and in fetuses gestating within mothers exposed to SHS. Fetal weight, a measure of organismal health, was decreased in SHS-exposed pups, but unchanged in SHS-exposed RAGE null mice. TUNEL assessments suggested a shift toward pulmonary cell apoptosis and matrix in SHS-exposed pups was diminished as revealed by decreased collagen IV and increased MMP-9 expression. Furthermore, SHS-exposed RAGE null mice expressed less TNF-α and IL-1ß when compared to SHS-exposed controls. CONCLUSIONS: RAGE augmentation in developing pups exposed to maternal SHS weakens matrix deposition and influences lung inflammation.

Conditional over-expression of RAGE by embryonic alveolar epithelium compromises the respiratory membrane and impairs endothelial cell differentiation.

BACKGROUND: Receptors for advanced glycation end-products (RAGE) are cell surface receptors prominently expressed by lung epithelium. Previous research demonstrated that over-expression of RAGE by murine alveolar epithelial cells during embryogenesis caused severe lung hypoplasia and neonatal lethality. However, the effects of RAGE over-expression on adjacent matrix and endothelial cells remained unknown. METHODS: RAGE transgenic (TG) mice were generated that conditionally over-expressed RAGE in alveolar type II cells when fed doxycycline (dox) from conception to E18.5. To evaluate effects on the basement membrane, immunostaining and immunoblotting were performed for collagen IV and MMP-9, a matrix metalloprotease capable of degrading basement membranes. To assess changes in vasculature, immunostaining, immunoblotting and qRT-PCR were performed for Pecam-1, a platelet endothelial cell adhesion marker also known as CD31. Lastly, to characterize potential regulatory mechanisms of endothelial cell differentiation, immunoblotting and qRT-PCR for FoxM1, a key endothelium-specific transcription factor of the Forkhead Box (Fox) family, were completed. RESULTS: Qualitative immunostaining for collagen IV was less in RAGE TG mice compared to controls and immunoblotting revealed decreased collagen IV in the RAGE TG mouse lung. Additionally, elevated MMP-9 detected via immunostaining and immunoblotting implicated MMP-9 as a possible down stream effector in matrix destabilization mediated by RAGE signaling. Lastly, Pecam-1 assessment revealed a decrease in the prevalence of microvascular endothelial cells coincident with FoxM1 abrogation in RAGE TG mice compared to controls. CONCLUSIONS: RAGE over-expression by alveolar epithelium weakened the basement membrane and associated matrix via increased MMP-9 activity. Furthermore, over-expression of RAGE inhibited FoxM1, suggesting that anomalous transcriptional control contributes to decreased endothelial cell prevalence in the TG mouse lung.

Postoperative Complications of True Dropless Cataract Surgery versus Standard Topical Drops.

Purpose Compare postoperative outcomes in cataract surgery between eyes with standard drop regimen versus dropless protocol by residents. Design Retrospective cohort study between April 1, 2018 and March 31, 2020. Methods The study was performed at Lyndon B. Johnson General Hospital in Houston, Harris County, Texas. A total of 547 eyes (234 dropless vs. 313 standard) with phacoemulsification cataract surgery and minimum of 1-month follow-up with best-corrected visual acuity (BCVA) were included. Dropless received 40 mg sub-Tenon's triamcinolone and intracameral moxifloxacin. Patients were followed at postoperative day 1 (POD1), week 1 (POW1), and month 1 (POM1). Postoperative rate of BCVA better than 20/40 (Good vision) and rate of complications were compared between groups. Results Good vision on POM1 in dropless (77.8%) was noninferior to standard (75.1%, p = 0.80). Complication rate in dropless (28.6%) was noninferior to standard (24.0%, p = 0.13). Intraocular pressure (IOP) elevation on POD1 ( p = 0.041) and anterior chamber (AC) cells on POW1 and POM1 ( p < 0.001) were more frequent in dropless. Mean spherical equivalent at POM1 was better in dropless (-0.37 D [±0.81 D]) compared with standard (-0.61D [±0.77 D], p = 0.001). Early posterior capsular opacification (early PCO) was more frequent in dropless ( p = 0.042). Conclusions Postoperative rate of BCVA better than 20/40 and rate of postoperative complications were noninferior, although dropless had higher rates of AC inflammation, IOP elevation, and early PCO.

Determining Risk Factors That Affect Progression in Patients with Nonproliferative Diabetic Retinopathy.

PURPOSE: To determine risk factors that affect nonproliferative diabetic retinopathy (NPDR) progression and establish a predictive model to estimate the probability of and time to progression in NPDR. Patients and Methods. Charts of diabetic patients who received an initial eye exam between 2010 and 2017 at our county hospital were included. Patients with proliferative diabetic retinopathy (PDR), fewer than 2 years of follow-up, or fewer than 3 clinic visits were excluded. Demographics and baseline systemic and ocular characteristics were recorded. Follow-up mean annual HbA1c and blood pressure, best-corrected visual acuity, and the number of antivascular endothelial growth factor treatments were recorded. Stage and date of progression were recorded. A 5-state nonhomogeneous continuous-time Markov chain with a backward elimination model was used to identify risk factors and estimate their effects on progression. RESULTS: Two hundred thirty patients were included. Initially, 65 eyes (28.3%) had no retinopathy; 73 (31.7%) mild NPDR; 60 (26.1%) moderate NPDR; and 32 (13.9%) severe NPDR. Patients were followed for a mean of 5.8 years (±2.0 years; range 2.1-9.4 years). 164 (71.3%) eyes progressed during the follow-up. Time-independent risk factors affecting progression rate were age (hazard ratio (HR) = 0.99, P=0.047), duration of diabetes (HR = 1.02, P=0.018), and Hispanic ethnicity (HR = 1.31, P=0.068). Mean sojourn times at mean age, duration of diabetes, and annual HbA1c for a non-Hispanic patient were estimated to be 3.03 (±0.97), 4.63 (±1.21), 6.18 (±1.45), and 4.85 (±1.25) years for no retinopathy, mild NPDR, moderate NPDR, and severe NPDR, respectively. Each 1% increase in HbA1c annually diminished sojourn times by 15%, 10%, 7%, and 10% for no retinopathy, mild NPDR, moderate NPDR, and severe NPDR, respectively. CONCLUSION: HbA1c level is a significant modifiable risk factor in controlling the progression of DR. The proposed model could be used to predict the time and rate of progression based on an individual's risk factors. A prospective multicenter study should be conducted to further validate our model.

Effects on phacoemulsification efficiency and chatter at variable longitudinal ultrasound settings when combined with constant torsional energy.

PURPOSE: To evaluate longitudinal power settings for optimally efficient lens fragment removal, using the Centurion machine. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, USA. DESIGN: Experimental study. METHODS: Porcine lens nuclei were cut into 2.0 mm cubes. Experiments were conducted at 100% torsional power; vacuum set at 500 mm Hg, aspiration 50 mL/min, and intraocular pressure 110 mm Hg. A 20-degree tip with a 30-degree bevel was used. Longitudinal power was tested between 20% and 100%. Efficiency (time for fragment removal) and chatter (the number of times the fragment bounced from the tip) were measured. RESULTS: A linear increase in efficiency was observed from 20% to 100% longitudinal power (R = 0.9281, slope = -0.0271). An efficiency slope change occurred at 60% power, with the largest incremental change in efficiency between 20% and 60% (R = 0.9756, slope = -0.0394) and a lesser change between 60% and 100% (R = 0.9827, slope = -0.0121). Chatter analysis showed minimal events at 20% to 60%, but a significant increase at >80% (P = .005). This increase appeared to be incremental (R = 0.8929). CONCLUSIONS: Increasing longitudinal power, with all other settings constant, increased efficiency. Greatest efficiency gains were observed between 20% and 60%. At 80% and 100%, chatter events increased significantly. With a goal of recommending optimally efficient settings while minimizing excess energy and chatter, adding 60% of longitudinal power to 100% torsional power was shown to be the best setting to increase efficiency and avoid repulsion in these vacuum and aspiration settings.

Optimum on-time duty cycle for a transversal ultrasound machine.

PURPOSE: To evaluate the optimum on-time setting for the most efficient removal of lens fragments using micropulse ultrasound (US) and Ellips FX transversal US in the Whitestar Signature Pro phacoemulsification machine. SETTING: John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Porcine lens nuclei were soaked in formalin for 2 hours and cut into 2.0 mm cubes. The US machine was used with a bent 0.9 mm phaco tip and a 30-degree bevel. The off time was set to 6 milliseconds (ms) and the on time varied from 4 to 10 ms in 1 ms increments. Efficiency (time for fragment removal) and chatter (number of times the fragment bounced from the tip) were measured. RESULTS: A linear incremental increase in efficiency was observed between 4 ms and 6 ms. The most statistically significant efficiency was achieved with an on time of 6 ms. On times shorter than 6 ms were significantly less efficient (P = .05). Greater on times (7 to 10 ms) did not result in a significant difference in efficiency (P = .72), but did appear to have more chatter events when comparing on-time settings of 7 to 10 ms with 4 to 6 ms (P = .02). CONCLUSIONS: With micropulse transversal US, 6 ms of on time was as efficient as longer on times. To maximize phacoemulsification efficiency and minimize chatter events, an on time of 6 ms is recommended.

Two single-piece acrylic intraocular lens choices and their effect on patient-reported driving habits.

PURPOSE: To determine whether intraocular lens (IOL) type affects patient driving habits 6 months to 5 years after cataract surgery, and to determine whether there were differences in self-reported driving habits between patients who received 1 of 2 IOLs. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Retrospective case series. METHODS: Patients completed a telephone-administered Driving Habits Questionnaire (DHQ) 6 months to 5 years after having bilateral cataract surgery with a single-piece hydrophobic acrylic IOL, SN60WF (Group 1) or ZCB00 IOL (Group 2), in both eyes. RESULTS: The study comprised 260 patients (130 in each IOL group). Of these, 117 in Group 1 and 114 in Group 2 were still active drivers. The DHQ response differences for each IOL group did not reach statistical significance, except for self-rated quality of driving and difficulties with driving at night. For these significant differences, contradictory results were found. CONCLUSIONS: Patients with either of the monofocal IOLs had similar self-reported driving habits after bilateral cataract surgery. The choice of IOL did not affect patients' postoperative driving habits.

Optimization of transversal phacoemulsification settings in peristaltic mode using a new transversal ultrasound machine.

PURPOSE: To determine the optimum bottle height, vacuum, aspiration rate, and power settings in the peristaltic mode of the Whitestar Signature Pro machine with Ellips FX tip action (transversal). SETTING: John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Porcine lens nuclei were hardened with formalin and cut into 2.0 mm cubes. Lens cubes were emulsified using transversal and fragment removal time (efficiency), and fragment bounces off the tip (chatter) were measured to determine optimum aspiration rate, bottle height, vacuum, and power settings in the peristaltic mode. RESULTS: Efficiency increased in a linear fashion with increasing bottle height and vacuum. The most efficient aspiration rate was 50 mL/min, with 60 mL/min statistically similar. Increasing power increased efficiency up to 90% with increased chatter at 100%. CONCLUSION: The most efficient values for the settings tested were bottle height at 100 cm, vacuum at 600 mm Hg, aspiration rate of 50 or 60 mL/min, and power at 90%.

The Effect of Pulsing on Transverse Ultrasound Efficiency and Chatter.

PURPOSE: To evaluate the effects of micropulse, long pulse, and continuous ultrasound on transverse ultrasound using Abbott Medical Optics' (AMO) WhiteStar Signature Pro with the Ellips FX handpiece. DESIGN: In vitro laboratory study. METHODS: This study was conducted at the John A. Moran Eye Center Laboratory, University of Utah, Salt Lake City, Utah, USA. Porcine lenses were hardened in formalin for 2 hours and equilibrated in basic salt solution (BSS) over a 24-hour period. The lenses were then cubed in 2.0 × 2.0-mm pieces. These pieces were stored in BSS until the time of experimentation. The AMO WhiteStar Signature Pro machine (Abbott Medical Optics) with the Ellips FX handpiece and a 0.9-mm bent Dewey tip with a 30-degree bevel (Microsurgical Technology Inc) were used for phacoemulsification. Three runs of 20 lenses each were performed, measuring efficiency and chatter. Transverse ultrasound varied in the 3 runs and included continuous, 6 ms on/off micropulse, and 50 ms on/off long pulse. RESULTS: Micropulse was more efficient than long pulse by 43% (P = .00003) and continuous by 42% (P = .000387). There were also less chatter events with micropulse than with long-pulse and continuous ultrasound. However, this difference did not reach significance. CONCLUSION: The 6 ms on and 6 ms off micropulse transverse 3-dimensional ultrasound is more efficient and produces fewer chatter events than both long-pulse and continuous ultrasound.

Effect of chamber stabilization software on efficiency and chatter in a porcine lens model.

PURPOSE: To evaluate the effects of the use of programmable chamber stabilization software (Chamber Stabilization Environment) settings on efficiency and chatter in a porcine lens model. SETTING: John A. Moran Eye Center Laboratory, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Porcine eyes were dissected and the lenses extracted. The lenses were then hardened and processed for the experiment. Phacoemulsification of the lens fragments was performed with the Whitestar Signature Pro with the Whitestar handpiece and a 0.9 mm straight Dewey tip with a 30-degree bevel. All arms of the study were run in peristaltic mode with 50 mL/minute aspiration, 100 cm bottle height, and on 100% power. The chamber stabilization software setting was used for each of the 4 study arms with a maximum vacuum of 500 mm Hg. Arm 1 included 20 runs with the up time set to 2000 milliseconds. Arm 2 was performed with similar settings but with an up time of 0 millisecond. Arms 3 and 4 were run with up times of 1000 milliseconds and 500 milliseconds, respectively. RESULTS: The mean efficiency time of each run was as follows: 0 millisecond = 1.4 seconds, 500 milliseconds = 0.95 seconds, 1000 milliseconds = 0.88 seconds, 2000 milliseconds = 0.93 seconds. When compared with 0 millisecond, each of the other arms were significantly faster. Chatter events were comparable between the study arms. CONCLUSION: The chamber stabilization software does not decrease efficiency when compared with full vacuum on if at least 500 milliseconds of up time is maintained.