Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis.

The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA's globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique "fingerprint" or "biomarker" vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.

Neuronal Epac1 mediates retinal neurodegeneration in mouse models of ocular hypertension.

Progressive loss of retinal ganglion cells (RGCs) leads to irreversible visual deficits in glaucoma. Here, we found that the level of cyclic AMP and the activity and expression of its mediator Epac1 were increased in retinas of two mouse models of ocular hypertension. Genetic depletion of Epac1 significantly attenuated ocular hypertension-induced detrimental effects in the retina, including vascular inflammation, neuronal apoptosis and necroptosis, thinning of ganglion cell complex layer, RGC loss, and retinal neuronal dysfunction. With bone marrow transplantation and various Epac1 conditional knockout mice, we further demonstrated that Epac1 in retinal neuronal cells (especially RGCs) was responsible for their death. Consistently, pharmacologic inhibition of Epac activity prevented RGC loss. Moreover, in vitro study on primary RGCs showed that Epac1 activation was sufficient to induce RGC death, which was mechanistically mediated by CaMKII activation. Taken together, these findings indicate that neuronal Epac1 plays a critical role in retinal neurodegeneration and suggest that Epac1 could be considered a target for neuroprotection in glaucoma.

Utilization of Portable Radios to Improve Ophthalmology Clinic Efficiency in an Academic Setting.

Improvement in clinic efficiency in the ambulatory setting is often looked at as an area for development of lean management strategies to deliver a higher quality of healthcare while reducing errors, costs, and delays. To examine the benefits of improving team communication and its impact on clinic flow and efficiency, we describe a time-motion study performed in an academic outpatient Ophthalmology clinic and its objective and subjective results. Compared to clinic encounters without the use of the portable radios, objective data demonstrated an overall significant decreases in mean workup time (15.18 vs. 13.10), room wait (13.10 vs. 10.47), and decreased the total time needed with an MD per encounter (9.45 vs. 6.63). Subjectively, significant improvements were seen in careprovider scores for patient flow (60.78 vs. 84.29), getting assistance (61.89 vs. 88.57), moving patient charts (54.44 vs. 85.71), teamwork (69.56 vs. 91.0), communications (62.33 vs. 90.43), providing quality patient care (76.22 vs. 89.57), and receiving input on the ability to see walk-in patients (80.11 vs. 90.43). For academic purposes, an improvement in engagement in patient care and learning opportunities was noted by the clinic resident-in-training during the pilot study. Portable radios in our pilot study were preferred over the previous method of communication and demonstrates significant improvements in certain areas of clinical efficiency, subjective perception of teamwork and communications, and academic learning.

Intraocular pressure and steep Trendelenburg during minimally invasive gynecologic surgery: is there a risk?

STUDY OBJECTIVE: Steep Trendelenburg position is frequently used during gynecologic minimally invasive surgery (MIS). However, little attention has been given to the potential impact of this nonphysiologic positioning on patients, specifically intraocular pressure (IOP). The purpose of our study was to evaluate IOP changes during laparoscopic or robotic hysterectomy conducted in the steep Trendelenburg position. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). SETTING: John Sealy Hospital at the University of Texas Medical Branch, Galveston, TX. PATIENTS: Female patients with no history of ocular pathology who underwent elective robotic or laparoscopic hysterectomy. INTERVENTIONS: The anesthesia protocol was standardized for all study patients. IOP and mean arterial pressure (MAP) were obtained before anesthesia, after general anesthesia and intubation were achieved, after 1 hour of steep Trendelenburg positioning, after 2 hours of steep Trendelenburg positioning, and after the patient was returned to the supine position. Ocular perfusion pressure (OPP) was calculated using the following equation: OPP = MAP - IOP. MAIN RESULTS: A total of 10 patients were included in this prospective study. A significant increase in IOP from baseline was observed after 1 hour and 2 hours of steep Trendelenburg positioning (p = .005 and .002, respectively). There was a statistically significant trend of increasing the IOP from baseline to the second hour of steep Trendelenburg positioning (p < .001). The IOP remained significantly elevated once the patient was returned to the supine position when compared with the baseline IOP (p = .006). OPP significantly decreased from baseline after 2 hours of steep Trendelenburg positioning (p = .03). CONCLUSIONS: IOP increases significantly when patients are placed in the steep Trendelenburg position. Although further studies are needed to better characterize this process, given the aging population of our MIS patients in whom risk for glaucoma is significant, preoperative ocular health assessment should be considered in certain cases.

Comparison of unenhanced and enhanced imaging protocols for angle measurements with anterior segment optical coherence tomography.

BACKGROUND AND OBJECTIVE: To compare the intraobserver and interobserver agreement of anterior chamber angle measurements using unenhanced and enhanced imaging protocols for anterior segment optical coherence tomography (AS-OCT). PATIENTS AND METHODS: Anterior segments of 30 eyes of 15 healthy subjects (mean age: 33.8 ± 13.0 years, 8 women) were imaged by a single examiner with AS-OCT using unenhanced and enhanced imaging protocol. Two masked observers analyzed each image independently on two separate occasions. The reproducibility of angle parameters was estimated by calculating coefficients of variation separately for each observer. Bland-Altman plots were constructed to assess the intraobserver and interobserver agreement. RESULTS: The intraobserver and interobserver reproducibility was similar between imaging protocols. Intra-observer and interobserver agreements were also similar for all parameters evaluated. The best estimate of scleral spur location was determined in all images by both observers. CONCLUSION: Measurement variability was similar with the unenhanced and enhanced imaging protocol in this series of eyes with open angles.

Cataract surgery and glaucoma.

PURPOSE OF REVIEW: To summarize the recent advances in the management of patients with coexisting cataract and glaucoma. RECENT FINDINGS: Although some evidence suggests that cataract surgery may be useful in the clinical management of eyes with angle closure glaucoma, recent studies show that the decrease in intraocular pressure (IOP) following cataract surgery alone in eyes with open angle glaucoma may be limited and transient. Combining cataract surgery with a trabeculectomy remains the preferred option. However, when IOP lowering is indicated, newer surgical techniques to lower IOP to be performed along with cataract extraction offer a promising alternative in patients with uncontrolled glaucoma and a visually significant cataract. SUMMARY: Cataract surgery alone or combined with trabeculectomy should be considered in the treatment of angle closure glaucoma. However, in eyes with open angle glaucoma, cataract surgery alone may be of limited clinical benefit in lowering IOP. Surgical alternatives to be combined with cataract extraction may be utilized to achieve a more significant IOP reduction. The appropriate treatment should be tailored based on patient's characteristics and the target IOP to be achieved.

Clinicians agreement in establishing glaucomatous progression using the Heidelberg retina tomograph.

PURPOSE: To assess the degree of concordance among clinicians reviewing 3 Heidelberg retina tomograph (HRT) printouts used to detect progression, the Moorfields regression analysis (MRA), the topographic change analysis (TCA), and trend analysis (TA), and to compare with progression identified by stereophotographs. DESIGN: Observational cohort study. PARTICIPANTS: We longitudinally followed 237 eyes of 168 patients (50 glaucomatous eyes, 187 glaucoma suspects) from the Diagnostic Innovation in Glaucoma Study (mean follow-up, 46.8+/-14.2 months), with a minimum of 4 HRT images (range, 4-8). METHODS: Three experienced observers judged the presence of progression using the HRT follow-up printouts available for each HRT method of analysis (MRA, TCA, TA). The overall assessment was based on majority rule, with >or=2 graders agreeing on the classification. MAIN OUTCOME MEASURES: Observers agreement in assessing HRT progression and agreement for progression or no progression between the HRT methods of analysis and the reference standard represented by masked stereophotograph assessment. The kappa test was used to assess the interobserver agreement. RESULTS: In general, agreement among clinicians for subjective assessment of progression based on HRT printouts was moderate to good; agreement (kappa) ranged from 0.52 to 0.71 for MRA, 0.61 to 0.63 for TCA, and 0.45 to 0.74 for TA. Of the 237 eyes, 16 (6.8%) were found to progress during follow-up based on masked stereophotograph assessment. Agreement for progression/no progression between the HRT methods and stereophotography was similar among MRA (84.8%, agreement on 5 progressing eyes and 196 nonprogressing eyes; kappa = 0.14), TCA, (82.3%, agreement on 8 progressing eyes and 187 nonprogressing eyes; kappa = 0.2), and TA (84%, agreement on 2 progressing eyes and 197 nonprogressing eyes; kappa = 0.01). CONCLUSIONS: Clinicians' agreement in identifying suspected glaucomatous progression using different HRT methods of analysis was moderate to good and was similar among all methods, including MRA, which is not designed to detect progression. Agreement between progression identified by HRT and masked stereophotograph assessment was poor. These results suggest that assessment of the HRT and stereophotography may be identifying different aspects of structural change. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.