Aqueous and Plasma Levels of Phosphorylated Tau 181 in Individuals with Normal Cognition.

Background: Plasma and cerebrospinal fluid (CSF) levels of p-tau181 have been associated with Alzheimer's disease (AD). The retina and vitreous have shown measurable quantities of phosphorylated tau 181 (p-tau181). The aqueous humor, which can be collected during cataract surgery, may have measurable concentrations of p-tau181. Objective: To determine whether p-tau181 is detectable in the aqueous humor and if so, whether it is associated with other measures that might be consistent with AD such as higher plasma p-tau181 concentration and lower Montreal Cognitive Assessment (MoCA-BLIND version 7.1) score. Methods: Aqueous humor samples, blood samples, and MoCA-BLIND scores were collected from patients who did not carry a clinical diagnosis of cognitive impairment at the time of cataract surgery. Aqueous p-tau181 concentrations and plasma p-tau181 concentrations were then measured using ultra-sensitive single-molecule assay ELISA technology. A rank-transformed mixed-effects multivariate regression model was used to determine associations between aqueous concentrations, plasma concentrations, and MoCA-BLIND scores. Results: 16 eyes of 16 participants were enrolled with an average age of 71.6. Average MoCA-BLIND score was 20.6/22, average aqueous p-tau181 concentration was 6.4 pg/mL, and average plasma p-tau181 concentration was 3.1 pg/mL. Higher plasma p-tau181 was significantly associated with higher aqueous p-tau181 (p = 0.02). Aqueous p-tau181 and plasma p-tau181 were negatively associated with MoCA-BLIND scores (p = 0.005 and p = 0.001 respectively) in these patients. Conclusions: Aqueous p-tau181 is positively correlated with plasma p-tau181 and is negatively correlated with MoCA-BLIND scores. Further study in individuals with mild cognitive impairment or AD characterized by cerebrospinal fluid and volumetric MRI metrics may yield further insights.

Resident involvement in cataract surgery at the Veterans Health Administration: complications, case complexity, and the role of experience.

PURPOSE: To characterize intraoperative complications, case complexity, and changes in complication rates with surgical experience for cataract surgeries involving residents at the Veterans Health Administration (VHA). SETTING: All VHA facilities where cataract surgery was performed. DESIGN: Multicenter, retrospective cohort study. METHODS: A retrospective review of all cataract surgeries within the VHA between July 2010 and June 2021 was conducted. Several parameters, including resident involvement, intraoperative complications, and case complexity as determined by Current Procedural Terminology codes, and use of pupil expansion or capsular support devices, were collected. Complication rates were compared between residents and attendings. RESULTS: Of 392 428 cataract surgeries completed across 108 VHA facilities, 90 504 were performed by attendings alone, while 301 924 involved a resident. Of these, 10 244 (11.3%) of attending cases were complex compared with 32 446 (10.7%) of resident cases. Pupil expansion devices were required in 8191 of attending cases (9.05%) and 31 659 (10.5%) of cases involving residents ( P < .001). Similarly, cases involving residents were more likely than attending-only cases to require a capsular support device (0.835% vs 0.586%, P < .001). Cases involving residents were more likely to have posterior capsular rupture (4.75% vs 2.58%, P < .001) and dropped nucleus (0.338% vs 0.198%, P < .001). Higher resident case volumes were associated with significantly lower complication rates for posterior capsular rupture, dropped nucleus, zonular loss, and suprachoroidal hemorrhage. CONCLUSIONS: Although residents had higher intraoperative complication rates than attendings, these rates were reduced with surgical experience. Residents were involved in a similar number of complex surgical cases as attendings.

Role of vasorin, an anti-apoptotic, anti-TGF-ß and hypoxia-induced glycoprotein in the trabecular meshwork cells and glaucoma.

Glaucoma, one of the leading causes of irreversible blindness, is commonly associated with elevated intraocular pressure due to impaired aqueous humour (AH) drainage through the trabecular meshwork. The aetiological mechanisms contributing to impaired AH outflow, however, are poorly understood. Here, we identified the secreted form of vasorin, a transmembrane glycoprotein, as a common constituent of human AH by mass spectrometry and immunoblotting analysis. ELISA assay revealed a significant but marginal decrease in vasorin levels in the AH of primary open-angle glaucoma patients compared to non-glaucoma cataract patients. Human trabecular meshwork (HTM) cells were confirmed to express vasorin, which has been shown to possess anti-apoptotic and anti-TGF-ß activities. Treatment of HTM cells with vasorin induced actin stress fibres and focal adhesions and suppressed TGF-ß2-induced SMAD2/3 activation in HTM cells. Additionally, cobalt chloride-induced hypoxia stimulated a robust elevation in vasorin expression, and vasorin suppressed TNF-α-induced cell death in HTM cells. Taken together, these findings reveal the importance of vasorin in maintenance of cell survival, inhibition of TGF-ß induced biological responses in TM cells, and the decreasing trend in vasorin levels in the AH of glaucoma patients suggests a plausible role for vasorin in the pathobiology of ocular hypertension and glaucoma.

Learning From the 2021 Ophthalmology Match: Virtual Residency Matching During the COVID-19 Pandemic.

Background: The effect of virtual interviews on residency match outcomes during the COVID-19 pandemic is unknown. Examining the ophthalmology match may help inform all specialties undergoing virtual interviews. Objective: To determine the impact of allopathic applicant match characteristics in the first year of the virtual residency Match process. Methods: Using the Association of University Professors of Ophthalmology match database, a retrospective review was conducted of all allopathic applicants to ophthalmology residency programs in the United States from the 2016 through the 2021 match cycles. Demographic information, interview numbers, and match outcomes were compared between the 2016-2020 (in-person) and 2021 (virtual) cycles. Results: A total of 3343 allopathic applicants were analyzed. Applicants in the 2021 Match applied to significantly more programs than 2016-2020 applicants did (78.7±23.6 vs 73.1±22.7, P<.001). Among matched and unmatched applicants, there was no significant difference in the number of interviews granted or completed. There was a significant reduction in the match rate between the 2016-2020 and 2021 Match cycles (81.3% vs 76.6%, P=.0009). A subanalysis of applicants who went to medical schools with ophthalmology residency programs (N=2308) found that the home institution match rate was significantly higher for the 2021 Match compared to the aggregate 2016-2020 Matches (26.1% vs 20.6%, respectively, P=.015). Conclusions: Significantly more applicants to ophthalmology residency programs matched at their home institutions in the 2021 virtual match cycle compared to the previous 5 years without influencing the interview numbers granted and attended.

Long-Term Decrease of Intraocular Pressure in Rats by Viral Delivery of miR-146a.

Purpose: To evaluate the effects of miR-146a in trabecular meshwork (TM) cells and on intraocular pressure (IOP) in vivo via viral delivery of miR-146a to the anterior chamber of rat eyes. Methods: Human TM cells were transfected with miR-146 mimic or inhibitor. Some cells from each group were then subjected to cyclic mechanical stress (CMS). Other cells from each group had no force applied. Gene expression was then analyzed by quantitative polymerase chain reaction (qPCR). Replication-deficient adenovirus and lentivirus expressing miR-146a were inoculated into the anterior segment of Brown Norway rat eyes. IOP was monitored by rebound tonometry, visual acuity was evaluated by optokinetic tracking (OKT), and inflammation markers in the anterior segment were examined by slit-lamp, qPCR, and semi-thin sections. Results: miR-146 affected the expression of genes potentially involved in outflow homeostasis at basal levels and under CMS. Both lentiviral and adenoviral vectors expressing miR-146a resulted in sustained decreases in IOP ranging from 2.6 to 4.4 mmHg. Long term follow-up of rats injected with lentiviral vectors showed a sustained effect on IOP of 4.4 ± 2.9 mmHg that lasted until rats were sacrificed more than 8 months later. Eyes showed no signs of inflammation, loss of visual acuity, or other visible abnormalities. Conclusions: Intracameral delivery of miR-146a can provide a long-term decrease of IOP in rats without signs of inflammation or other visible adverse effects. Transitional Relevance: The IOP-lowering effects of miR-146 observed in rats provides a necessary step toward the development of an effective gene therapy for glaucoma in humans.

Recurrent Tube Erosions with Anti-Vascular Endothelial Growth Factor Therapy in Patients with Age-Related Macular Degeneration.

PURPOSE: To determine the rates of primary and recurrent glaucoma tube shunt erosions in patients with age-related macular degeneration (AMD) receiving anti-vascular endothelial growth factor (VEGF) intravitreal injections. DESIGN: Retrospective case series. PARTICIPANTS: Patients with AMD who underwent tube revision for erosion at the Duke Eye Center from January 1, 1999, to January 1, 2019, were identified. Patients with and without anti-VEGF injections were compared. METHODS: Patient demographics, ocular diagnoses, glaucoma tube shunt types and locations, and dates of glaucoma surgeries and anti-VEGF injections were collected. Statistical analyses were performed with P < 0.05 as significant. MAIN OUTCOME MEASURES: Outcome measures included the number of tube erosions, time from anti-VEGF injection to tube erosion, and secondary complications after tube revisions. RESULTS: A total of 150 patients with AMD with anti-VEGF (309 tubes) and 262 patients with AMD without anti-VEGF (459 tubes) were identified. There was no statistically significant difference in the number of tube erosions in patients with anti-VEGF (15 tubes, 4.8%) versus without anti-VEGF (12 tubes, 2.6%) (P = 0.10). However, patients receiving anti-VEGF had on average a greater number of tube erosion events (2.1±0.7 events) compared with patients without anti-VEGF (1.3±0.7, P < 0.01). Ten patients (91%) received concurrent anti-VEGF injections at the time of tube erosion, and the average duration of prior anti-VEGF therapy was approximately 2 years. Tube erosion was noted 46.5±60.7 days from the preceding anti-VEGF injection. Secondary complications after tube revision in the anti-VEGF group included 5 explanted tubes for recurrent erosions. CONCLUSIONS: Our results suggest intravitreal anti-VEGF injections are linked to higher rates of recurrent glaucoma tube erosions in patients with AMD. The majority of patients received chronic and serial anti-VEGF injections. Thus, additional consideration should be given to glaucoma surgical planning in patients receiving anti-VEGF injections, especially in those with a primary tube erosion.

Factors Impacting Outcomes and the Time to Recovery From Malignant Glaucoma.

PURPOSE: To identify factors associated with the successful treatment of malignant glaucoma (MG). DESIGN: Retrospective case series. METHODS: Setting: single institution; study population: 64 eyes (55 subjects) with MG; observation procedure(s): chart review; main outcome measures: anatomy, intraocular pressure (IOP), best visual acuity (BVA). RESULTS: 87.5% (n=56/64) of eyes with MG required surgical intervention. Vitrectomy was more likely to be successful in eyes with a history of <3 incisional surgeries, <3 glaucoma drops, or IOP ≤30 mm Hg (P < .05). If vitrectomy was performed within 30 days, recovery of anatomy, BVA, and IOP occurred sooner (P < .05). IOP reduction was greater in subjects treated with oral carbonic anhydrase inhibitors (P = .016) or Nd:YAG laser hyaloidotomy (P = .007), and without a history of MG (P = .007). Time to maximal improvement was significantly longer for IOP and BVA than anatomy (P < .001). Treatment of MG with an oral carbonic anhydrase inhibitor hastened anatomic recovery (P = .01). Time to improvement in BVA was significantly faster in men and African Americans (P < .05). Time to maximal reduction in IOP occurred sooner in eyes that underwent anterior chamber reformation in clinic (P < .002). Trabeculectomy surgery prior to MG was associated with prolonged recovery of anatomy, BVA, and IOP (P < .05). CONCLUSIONS: Earlier vitrectomy may shorten recovery times for MG. Nd:YAG laser hyaloidotomy and oral carbonic anhydrase inhibitors may lead to greater IOP reduction. The time to maximal improvement in IOP and BVA may be longer than the time to anatomic resolution. Although trabeculectomy may impede time to recovery from MG, oral carbonic anhydrase inhibitors may shorten the time to anatomic recovery and anterior chamber reformation may hasten IOP recovery.

Role of the autotaxin-lysophosphatidic acid axis in glaucoma, aqueous humor drainage and fibrogenic activity.

Ocular hypertension due to impaired aqueous humor (AH) drainage through the trabecular meshwork (TM) is a major risk factor for glaucoma, a leading cause of irreversible blindness. However, the etiology of ocular hypertension remains unclear. Although autotaxin, a secreted lysophospholipase D and its catalytic product lysophosphatidic acid (LPA) have been shown to modulate AH drainage through TM, we do not have a complete understanding of their role and regulation in glaucoma patients, TM and AH outflow. This study reports a significant increase in the levels of autotaxin, lysophosphatidylcholine (LPC), LPA and connective tissue growth factor (CTGF) in the AH of Caucasian and African American open angle glaucoma patients relative to age-matched non-glaucoma patients. Treatment of human TM cells with dexamethasone, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) increased the levels of autotaxin protein, a response that was mitigated by inhibitors of glucocorticoid receptor, NF-kB and SMAD3. Dexamethasone, TNF-α, IL-1ß and LPC treatment of TM cells also led to an increase in the levels of CTGF, fibronectin and collagen type 1 in an autotaxin dependent manner. Additionally, in perfused enucleated mouse eyes, autotaxin and LPC were noted to decrease, while inhibition of autotaxin was increased aqueous outflow through the TM. Taken together, these results provide additional evidence for dysregulation of the autotaxin-LPA axis in the AH of glaucoma patients, reveal molecular insights into the regulation of autotaxin expression in TM cells and the consequences of autotaxin inhibitors in suppressing the fibrogenic response and resistance to AH outflow through the TM.

Treatment Outcomes Following Resident Performed Nonvalved (Baerveldt 350) Glaucoma Drainage Device Implantation.

PRECIS: When compared with outcomes by glaucoma specialists in several prospective studies, residents at the Durham Veterans Affairs Medical Center achieved comparable reductions in intraocular pressure (IOP) and failure rates during the year following Baerveldt drainage device implantation. PURPOSE: To review the outcomes of resident performed Baerveldt implantation through 1 year of postoperative management in a resident-run clinic. MATERIALS AND METHODS: The medical records of all veterans at the Durham Veterans Affairs Medical Center were searched to identify those with Baerveldt implantation by resident physicians from July 1, 2007 to June 30, 2017. Exclusion criteria include previous glaucoma tube or concurrent surgical intervention, including cataract extraction. All postoperative visits were reviewed and clinical data were collected. Failure was defined as 2 consecutive visits, starting at postoperative month (POM) 3, with IOP ≤5 mm Hg, or with IOP >21 mm Hg or <20% IOP reduction from baseline, reoperation for glaucoma, or loss of light perception. RESULTS: A total of 48 eyes were included with mean (SD) IOP and number of medications: baseline, 23.1 (6.7) mm Hg on 3.7 (1.0) medications; postoperative day 1, 20.5 (11.7) mm Hg on no medications; postoperative week 1, 14.3 (6.9) mm Hg and 1.9 (1.7) medications; POM1, 16.7 (6.4) mm Hg and 2.2 (1.5) medications; POM3, 15.1 (5.2) mm Hg and 2.1 (1.6) medications; POM6 12.8 (4.9) mm Hg and 2.8 (1.3) medications; POM12, 13.0 (4.0) mm Hg and 2.8 (1.4) medications. IOP decreased at all time intervals (P<0.01) but postoperative day 1 (P=0.15) while medication burden was reduced at every visit (P<0.01). Through 12 months, 8 patients (17%) failed with a time to failure of 9.2 (0.3) months. No patients underwent additional glaucoma surgical interventions or lost light perception. CONCLUSIONS: Residents can safely and efficaciously perform Baerveldt implantation, providing reassurance regarding the autonomy afforded residents in the operating room and clinic.

Prophylactic anterior vitrectomy during cataract surgery in eyes at increased risk for aqueous misdirection.

PURPOSE: Patients with chronic narrow angle glaucoma (CNAG) are at increased risk of developing aqueous misdirection (AM) following intraocular surgery. We present a retrospective case series on the use of posterior capsulorrhexis with core vitrectomy by an anterior approach (CAV) at the time of cataract extraction with or without glaucoma surgery as a prophylactic measure for the prevention of AM in CNAG. METHODS: Retrospective case series of six phakic eyes in four patients with CNAG and other risk factors for AM who underwent posterior capsulorrhexis and CAV at the time of cataract surgery with or without glaucoma surgery. The main outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP), and post-operative complications. RESULTS: Six eyes in four subjects underwent posterior capsulorrhexis with CAV at the time of cataract surgery. The case was combined with incisional glaucoma surgery in the five eyes with advanced visual field loss. The mean logMAR BCVA and IOP improved from 0.554 ±â€¯0.398 and 25.2 ±â€¯13 mmHg, respectively, at the pre-operative visit to 0.257 ±â€¯0.218 and 12.2 ±â€¯1.7 mmHg, respectively, at final follow-up. Both eyes with nanophthalmos developed non-appositional serous choroidals that resolved with atropine, but the left eye required additional treatment with synechiolysis, intraocular lens repositioning, limited AV and endocyclophotocoagulation. There were no permanent, vision-threatening complications. CONCLUSIONS AND IMPORTANCE: CAV can be safely combined with cataract surgery and glaucoma surgery, and it may be an effective intervention in eyes with CNAG and other risk factors for AM as a prophylactic measure against the development of AM.

Atypical Presentation of Acute Angle-Closure Glaucoma in Maroteaux-Lamy Mucopolysaccharidosis with Patent Prophylactic Laser Peripheral Iridotomy: A Case Report.

INTRODUCTION: Maroteaux-Lamy syndrome (MLS) is a rare progressive condition characterized by inflammation and scarring of multiple organs. Ocular complications caused by anterior segment abnormalities commonly cause visual impairment in MLS. Angle-closure glaucoma is one such complication, but there are limited data on presentation, workup, and management of this condition. CASE PRESENTATION: This case report describes an atypical presentation of acute angle-closure glaucoma in a patient with MLS despite a prior prophylactic laser peripheral iridotomy-which would typically prevent an acute angle-closure attack-that was patent and intact at the time of angle closure. DISCUSSION: Because of severe congenital anterior segment crowding, high axial hyperopia, and constant accommodative demand in patients with MLS, we recommend performing two prophylactic laser peripheral iridotomies simultaneously in the same eye instead of one. The mechanism for this indication differs from that in patients at risk of acute angle-closure glaucoma because of lens zonulopathy alone. We hope that this case report may help prevent vision loss and optimize quality of life in patients with MLS who may be wheelchair-bound but are typically high functioning with normal intelligence.

Four-dimensional microscope- integrated optical coherence tomography to enhance visualization in glaucoma surgeries.

We report the first use of swept-source microscope-integrated optical coherence tomography (SS-MIOCT) capable of live four-dimensional (4D) (three-dimensional across time) imaging intraoperatively to directly visualize tube shunt placement and trabeculectomy surgeries in two patients with severe open-angle glaucoma and elevated intraocular pressure (IOP) that was not adequately managed by medical intervention or prior surgery. We performed tube shunt placement and trabeculectomy surgery and used SS-MIOCT to visualize and record surgical steps that benefitted from the enhanced visualization. In the case of tube shunt placement, SS-MIOCT successfully visualized the scleral tunneling, tube shunt positioning in the anterior chamber, and tube shunt suturing. For the trabeculectomy, SS-MIOCT successfully visualized the scleral flap creation, sclerotomy, and iridectomy. Postoperatively, both patients did well, with IOPs decreasing to the target goal. We found the benefit of SS-MIOCT was greatest in surgical steps requiring depth-based assessments. This technology has the potential to improve clinical outcomes.

VEGF as a Paracrine Regulator of Conventional Outflow Facility.

Purpose: Vascular endothelial growth factor (VEGF) regulates microvascular endothelial permeability, and the permeability of Schlemm's canal (SC) endothelium influences conventional aqueous humor outflow. We hypothesize that VEGF signaling regulates outflow facility. Methods: We measured outflow facility (C) in enucleated mouse eyes perfused with VEGF-A164a, VEGF-A165b, VEGF-D, or inhibitors to VEGF receptor 2 (VEGFR-2). We monitored VEGF-A secretion from human trabecular meshwork (TM) cells by ELISA after 24 hours of static culture or cyclic stretch. We used immunofluorescence microscopy to localize VEGF-A protein within the TM of mice. Results: VEGF-A164a increased C in enucleated mouse eyes. Cyclic stretch increased VEGF-A secretion by human TM cells, which corresponded to VEGF-A localization in the TM of mice. Blockade of VEGFR-2 decreased C, using either of the inhibitors SU5416 or Ki8751 or the inactive splice variant VEGF-A165b. VEGF-D increased C, which could be blocked by Ki8751. Conclusions: VEGF is a paracrine regulator of conventional outflow facility that is secreted by TM cells in response to mechanical stress. VEGF affects facility via VEGFR-2 likely at the level of SC endothelium. Disruption of VEGF signaling in the TM may explain why anti-VEGF therapy is associated with decreased outflow facility and sustained ocular hypertension.

Intravitreal Anti-VEGF Injections Reduce Aqueous Outflow Facility in Patients With Neovascular Age-Related Macular Degeneration.

Purpose: We assess the effect of intravitreal anti-VEGF injections on tonographic outflow facility. Methods: Patients with age-related macular degeneration who had received unilateral intravitreal anti-VEGF injections were recruited into two groups, those with ≤10 and those with ≥20 total anti-VEGF injections. Intraocular pressure and tonographic outflow facility of injected and uninjected fellow eyes were measured and compared between groups. Risk factors for development of reduced outflow facility also were assessed. Results: Outflow facility was 12% lower in the injected eyes of patients who received ≥20 anti-VEGF injections, compared to contralateral uninjected eyes (P = 0.02). In contrast, there was no facility reduction for patients with ≤10 anti-VEGF injections (P = 0.4). In patients with ocular hypertension in the uninjected eye (IOP > 21 mm Hg, n = 5), the outflow facility of injected eyes was on average 46% lower (P = 0.01) than in the uninjected fellow eyes. This was significantly greater than the difference observed in patients with IOP ≤ 21 mm Hg in the uninjected eye (P = 2 × 10-4). In patients with ocular hypertension in the injected eye (n = 6) the differences in facility and IOP between contralateral eyes were significantly greater than in patients with IOP ≤ 21 mm Hg in the injected eye (P = 2 × 10-4 and P = 7 × 10-4, respectively). Conclusions: Chronic anti-VEGF injections significantly reduce outflow facility in patients with AMD. The greatest facility reduction is observed in patients with baseline ocular hypertension. Ophthalmologists who administer anti-VEGF injections should be aware of these findings and monitor patients closely for changes in IOP or evidence of glaucoma, especially in those with pre-existing ocular hypertension.

Simultaneous Implantation of an Ahmed and Baerveldt Glaucoma Drainage Device for Uncontrolled Intraocular Pressure in Advanced Glaucoma.

PURPOSE: To evaluate efficacy and safety of a novel technique, simultaneous implantation of Ahmed and Baerveldt shunts, for improved control of intraocular pressure (IOP) in advanced glaucoma with visual field defects threatening central fixation. PATIENTS AND METHODS: Retrospective case series; all patients receiving simultaneous Ahmed and Baerveldt implantation at a single institution between October 2004 and October 2009 were included. Records were reviewed preoperatively and at postoperative day 1, week 1, month 1, month 3, month 6, year 1, and yearly until year 5. Outcome measures included IOP, best-corrected visual acuity, visual field mean deviation, cup to disc ratio, number of glaucoma medications, and complications. RESULTS: Fifty-nine eyes were identified; mean (±SD) follow-up was 26±23 months. Primary open-angle glaucoma was most common (n=37, 63%). Forty-six eyes (78%) had prior incisional surgery. Mean preoperative IOP was 25.5±9.8 mm Hg. IOP was reduced 50% day 1 (P<0.001, mean 12.7±7.0 mm Hg), which persisted throughout follow-up. At year 1, cup to disc ratio and mean deviation were stable with decreased best-corrected visual acuity from logMAR 0.72±0.72(20/100) to 1.06±1.13(20/200) (P=0.007). The Kaplan-Meier survival analysis showed median and mean survival of 1205 and 829±91 days, respectively. Complication rate was 47%. CONCLUSIONS: IOP is markedly reduced postoperative day 1 following double glaucoma tube implantation with effects persisting over postoperative year 1 and up to year 5. Complications were higher than that seen in reports of single shunt implantation, which may be explained by patient complexity in this cohort. This technique may prove a promising novel approach for management of uncontrolled IOP in advanced glaucoma.

Rho kinase inhibitors for glaucoma treatment - Review / Inibidores da Rho-Quinase para o tratamento do glaucoma - Revisão

ABSTRACT Glaucoma is a progressive optic neuropathy characterized by the loss of ganglion cells and their axons. A major risk factor for glaucomatous visual field loss is elevated intraocular pressure (IOP), and several studies have shown that lowering IOP reduces the risk of glaucomatous progression. Currently, an increasing number of researches involve Rho kinase inhibitors, which are a new pharmacological class of hypotensive agents specifically targeting the diseased trabecular outflow pathway. Rho kinase inhibitors reduce IOP by increasing aqueous humor drainage through the primary outflow pathway in the eye, which is known as the trabecular meshwork. In addition to improving the outflow facility of the trabecular meshwork, Rho kinase inhibitors also enhance retinal ganglion cell survival after ischemic injury and increase ocular blood flow.

RESUMO Glaucoma é uma neuropatia óptica progressiva, caracterizada pela perda de células ganglionares e seus axônios. O principal fator de risco que leva à perda de campo visual relacionada ao glaucoma é a elevação da pressão intraocular (PIO) e vários estudos mostraram que a redução da pressão intraocular diminui o risco de progressão do glaucoma. Atualmente, uma nova classe de drogas hipotensoras foi desenvolvida e tem sido cada vez mais estudada, os inibidores da Rho-Kinase. Essas drogas reduzem a pressão intraocular aumentando a drenagem de humor aquoso através da via de drenagem primária do humor aquoso no olho, a malha trabecular. Além de aumentar o escoamento pela malha trabecular, inibidores da Rho-kinase também aumentam a sobrevivência das células ganglionares retinianas após isquemia e aumentam o fluxo ocular sanguíneo.

Human aqueous humor exosomes.

Aqueous humor (AH) is a dynamic intraocular fluid that supports the vitality of tissues that regulate intraocular pressure. We recently discovered that extracellular nanovesicles called exosomes are a major constituent of AH. Exosomes function in extracellular communication and contain proteins and small RNA. Our goal was to characterize the physical properties of AH exosomes and their exosomal RNA (esRNA) content. We isolated exosomes from human AH collected during cataract surgery from five patients using serial ultracentrifugation. We measured the size and concentration of AH exosomes in solution using nanoparticle tracking analysis. We found a single population of vesicles having a mean size of 121 ± 11 nm in the unprocessed AH. Data show that centrifugation does not significantly affect the mean particle size (121 ± 11 nm versus 124 ± 21 nm), but does impact the final number of exosomes in solution (87% loss from the unprocessed AH; n = 5). We extracted esRNA from the pooled human AH samples using miRCURY RNA isolation kit from Exiqon. The quality of extracted esRNA was evaluated using Agilent Bioanalyzer 2100 and was used to generate a sequencing library for small RNA sequencing with Illumina MiSeq sequencer. More than 10 different miRNAs were identified; abundant species included miR-486-5p, miR-204, and miR-184. We found that the majority of extracellular vesicles in the AH were in the exosome size range, suggesting that miRNAs housed within exosomes may function in communication between AH inflow and outflow tissues.

Physical Factors Affecting Outflow Facility Measurements in Mice.

PURPOSE: Mice are commonly used to study conventional outflow physiology. This study examined how physical factors (hydration, temperature, and anterior chamber [AC] deepening) influence ocular perfusion measurements in mice. METHODS: Outflow facility (C) and pressure-independent outflow (Fu) were assessed by multilevel constant pressure perfusion of enucleated eyes from C57BL/6 mice. To examine the effect of hydration, seven eyes were perfused at room temperature, either immersed to the limbus in saline and covered with wet tissue paper or exposed to room air. Temperature effects were examined in 12 eyes immersed in saline at 20 °C or 35 °C. Anterior chamber deepening was examined in 10 eyes with the cannula tip placed in the anterior versus posterior chamber (PC). Posterior bowing of the iris (AC deepening) was visualized by three-dimensional histology in perfusion-fixed C57BL/6 eyes and by spectral-domain optical coherence tomography in living CD1 mice. RESULTS: Exposure to room air did not significantly affect C, but led to a nonzero Fu that was significantly reduced upon immersion in saline. Increasing temperature from 20 °C to 35 °C increased C by 2.5-fold, more than could be explained by viscosity changes alone (1.4-fold). Perfusion via the AC, but not the PC, led to posterior iris bowing and increased outflow. CONCLUSIONS: Insufficient hydration contributes to the appearance of pressure-independent outflow in enucleated mouse eyes. Despite the large lens, AC deepening may artifactually increase outflow in mice. Temperature-dependent metabolic processes appear to influence conventional outflow regulation. Physical factors should be carefully controlled in any outflow studies involving mice.

Resident compliance with the american academy of ophthalmology preferred practice pattern guidelines for primary open-angle glaucoma.

PURPOSE: To examine resident adherence to preferred practice pattern (PPP) guidelines set up by the American Academy of Ophthalmology for follow-up care of primary open-angle glaucoma (POAG) patients. DESIGN: Retrospective chart review. PARTICIPANTS: One hundred three charts were selected for analysis from all patients with an International Classification of Diseases, Ninth Revision, code of open-angle glaucoma or its related entities who underwent a follow-up evaluation between July 2, 2003, and December 15, 2004, at the resident ophthalmology clinic in the Durham Veteran Affairs Medical Center. METHODS: Follow-up visits of POAG patients were evaluated for documentation of 19 elements in accordance to PPP guidelines. MAIN OUTCOME MEASURES: Compliance rates for the 19 elements of PPP guidelines first were averaged in all charts, and then were averaged per resident and were compared among 8 residents between their first and second years of residency. RESULTS: The overall mean compliance rate for all 19 elements was 82.6% for all charts (n = 103), 78.8% for first-year residents, and 81.7% for second-year residents. The increase from first to second year of residency was not significant (P>0.05). Documentation rates were high (>90%) for 14 elements, including all components of the physical examination and follow-up as well as most components of the examination history and management plan. Residents documented adjusting target intraocular pressure downward, local or systemic problems with medications, and impact of visual function on daily living approximately 50% to 80% of the time. Documentation rates for components of patient education were the lowest, between 5% and 16% in all charts. CONCLUSIONS: Residents' compliance with PPP guidelines for a POAG follow-up visit was very high for most elements, but documentation rates for components of patient education were poor. Adherence rates to PPP guidelines can be used as a tool to evaluate and improve resident performance during training. However, further studies are needed to establish the advantages of using PPP guidelines for resident education and to determine if such assessments can lead to improved patient care.