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Purpose: To report a case series of patients with uveitic glaucoma who were treated with micropulse transscleral cyclophotocoagulation (mpCPC)., Methods: This retrospective case series consists of patients from the University of Colorado Sue Anschutz-Rodgers Eye Center from 2015 to 2020 who were diagnosed with uveitic glaucoma. Information collected includes demographic data, type of uveitis, glaucoma severity, and prior glaucoma surgeries. Pre- and postoperative best corrected visual acuity, intraocular pressure (IOP), glaucoma medications, degree of inflammation, and uveitis therapies were included up to 36 months postoperatively. Surgical success was defined as an IOP reduction of 30% with achievement of IOP goal using the same number of glaucoma medications or less at 6 months or 1 year. Uveitis success was defined as the absence of persistent anterior uveitis at 3 months., Results: Six patients and seven eyes with uveitic glaucoma underwent mpCPC. Types of uveitis included idiopathic anterior uveitis, HLA-B27-associated anterior uveitis, varicella zoster virus anterior uveitis, juvenile idiopathic arthritis-associated chronic anterior uveitis, lichen planus-associated intermediate uveitis, and sarcoidosis-associated panuveitis. Two of six eyes (33.3%) at 6 months and three of five eyes (60%) at 1 year achieved surgical success. Around 6 months postoperatively, two out of seven eyes (28.6%) required Ahmed glaucoma valve placement (n = 1) or repeat mpCPC (n = 1). One eye (14.3%) required phacoemulsification with goniotomy followed by an Ahmed glaucoma valve 18 months after mpCPC. There were no cases of persistent anterior uveitis, hypotony, or phthisis after mpCPC in this cohort., Conclusions: Micropulse transscleral cyclophotocoagulation may safely reduce intraocular pressure in some patients with uveitic glaucoma without exacerbation of intraocular inflammation. Multiple treatments may be required to achieve longer-term success., (© 2024. The Author(s).)

Purpose: To determine differences in cataract surgery outcomes between English proficient (EP) and limited English proficiency (LEP) patients., Setting: Sue Anschutz-Rodgers Eye Center, Aurora, Colorado., Design: Retrospective., Methods: Patients who underwent phacoemulsification at the Sue Anschutz-Rogers Eye Center between January 2014 and February 2020 were included. Patients who self-identified as needing or preferring an interpreter in medical encounters were defined as LEP. Differences in surgical characteristics and outcomes including cataract maturity, surgical complexity, and surgical complications were analyzed., Results: 868 eyes (6.4%) were identified from LEP patients. LEP patients were more likely to have mature cataracts (5.1% vs 2.3%, P < .0001). LEP patients' surgeries were more likely to be considered complex (27.8% vs 15.3%, P < .0001) and use higher cumulative dissipated energy (mean of 9.5 [SD = 9.5] vs 7.2 [SD = 7.1], P < .0001). Preoperative visual acuity was worse in LEP patients (logMAR 0.566 [SD = 0.64] vs 0.366 [SD = 0.51], P < .0001) but showed greater improvement after surgery (logMAR 0.366 [SD = 0.54] vs 0.254 [SD = 0.41], P < .0001). There were no significant differences in operative time, intraoperative or postoperative complications. More LEP patients were on steroids 4 weeks postoperatively when compared with EP patients (14.6% vs 10.1%, P < .0002). LEP patients were less likely to undergo subsequent YAG capsulotomy (7.3% vs 12.8%, P < .0001)., Conclusions: Disparities in cataract outcomes between EP and LEP patients was demonstrated. Further research into ophthalmic health disparities for LEP patients is needed to understand the root causes and how they can be addressed., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Prcis: Glaucoma patients exhibit worse indices of sleep function by both objective and subjective metrics compared with controls., Purpose: The purpose of this study is to characterize the sleep parameters and physical activity levels of glaucoma patients compared with controls., Patients and Methods: A total of 102 patients with a diagnosis of glaucoma in at least 1 eye and 31 control subjects were enrolled in the study. Participants completed the Pittsburgh Sleep Quality Index (PSQI) during enrollment and then wore wrist actigraphs for 7 consecutive days to characterize circadian rhythm, sleep quality, and physical activity. The primary outcomes of the study were subjective and objective metrics of sleep quality using the PSQI and actigraphy devices, respectively. The secondary outcome was physical activity, measured by the actigraphy device., Results: From the PSQI survey, glaucoma patients had higher (worse) scores compared with controls for sleep latency, sleep duration, and subjective sleep quality, whereas scores for sleep efficiency were lower (better), suggesting more time spent in bed asleep. By actigraphy, time in bed was significantly higher in glaucoma patients as was time awake after sleep onset. Interdaily stability, quantifying the synchronization to the 24-hour light-dark cycle, was lower in glaucoma patients. There were no other significant differences between glaucoma and control patients with regard to rest-activity rhythms or physical activity metrics. In contrast to the survey data, findings from the actigraphy demonstrated that there were no significant associations between the study group and controls regarding sleep efficiency, onset latency, or total sleep time., Conclusions: In this study, patients with glaucoma demonstrated several subjective and objective differences in sleep function when compared with controls, whereas physical activity metrics were similar., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: To compare outcomes of phacoemulsification combined with endoscopic cyclophotocoagulation (phaco/ECP), first generation iStent implantation (phaco/iStent), or both (phaco/iStent/ECP) in patients with open-angle glaucoma., Methods: A retrospective chart review was performed on patients at the University of Colorado Department of Ophthalmology. Outcomes included intraocular pressure (IOP), medication use, best corrected visual acuity (BCVA), and surgical complications were analyzed. Success was defined as IOP reduction of ≥ 20% and/or reduction by at least one glaucoma medication., Results: A total of 394 eyes were included in the study. There were 170 eyes (43.1%) in the phaco/ECP group, 175 eyes (44.4%) in the phaco/iStent group, and 49 eyes (12.4%) in the phaco/iStent/ECP group. The mean pre-operative IOP was 15.9 mmHg for phaco/ECP, 15.8 mmHg for phaco/iStent, and 15.2 mmHg for phaco/iStent/ECP. At 24 months, the mean IOP was 13.7 mmHg (p < 0.0001), 14.2 mmHg (p = 0.0001), and 13.0 mmHg (p = 0.0007), respectively. The mean pre-operative number of glaucoma medications was 2.0 for phaco/ECP, 1.4 for phaco/iStent, and 2.2 for phaco/iStent/ECP and at 24 months post-surgery decreased to, 1.8 (p = 0.011), 0.9 (p < 0.0001), and 1.7 (p = 0.01), respectively. The success rate at 24 months was 54.4% for phaco/ECP, 75.3% for phaco/iStent, and 55.6% for phaco/iStent/ECP., Conclusion: Phacoemulsification when combined with ECP, iStent, or both, lowered IOP and glaucoma medication reliance at 24 months. The success rate for phaco/iStent was significantly higher than phaco/ECP. When iStent was added to phaco/ECP, the success rate was higher at earlier postoperative visits compared to the phaco/ECP alone., (© 2023. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Aim: To compare intraocular pressure (IOP) readings obtained with Perkins tonometry, iCare Home, iCare 200, and Tonopen to IOP readings obtained with the manometer of a perfusion system to assess the accuracy and reproducibility of each method of tonometry at set pressures., Methods: The IOP of human cadaveric eyes ( n =2) was measured using a manometer inserted into the eye through the optic nerve. IOP measurements were obtained using a Perkins tonometer, iCare Home, iCare 200, and Tonopen. These measurements were compared to set point IOP measurements of a manometer to determine accuracy and reproducibility of each device., Results: Mean IOP readings obtained with the Perkins tonometer compared to manometer readings demonstrated a difference of -1.0±5.0 mm Hg ( P =0.45), indicating a lower reading on average than manometery although not significant. Mean IOP difference between iCare 200 and manometer was 5.3±2.2 mm Hg ( P <0.0001). Mean difference in IOP between iCare Home and manometer was 3.5±2.4 mm Hg ( P =0.0004). Mean IOP difference compared to manometer was 4.6±4.0 mm Hg for the Tonopen ( P <0.0001). IOP measurements obtained with the Perkins tonometer demonstrated a standard deviation of 5.0 mm Hg while the Tonopen measurements demonstrated a 4.0 mm Hg standard deviation. In comparison, iCare 200 and iCare Home demonstrated 2.2 and 2.4 mm Hg standard deviation, respectively., Conclusion: Applanation tonometry produces more accurate IOP readings than rebound tonometry or Tonopen, however it demonstrates greater variability than the other forms of tonometry. Rebound tonometry is more reproducible but tends to over-estimate IOP., (International Journal of Ophthalmology Press.)

Prcis: Kahook Dual Blade (KDB) goniotomy can successfully lower intraocular pressure in some patients with uveitis-associated ocular hypertension or glaucoma., Purpose: The purpose of this study was to report a case series of patients that underwent KDB goniotomy at a single institution for uveitis-associated ocular hypertension or glaucoma with an open angle., Methods: We performed a retrospective chart review of all patients with uveitis-associated ocular hypertension or glaucoma who underwent KDB goniotomy with trabecular meshwork excision alone or in combination with phacoemulsification cataract surgery at a single center between August 2017 and February 2020. The case series included 45 eyes of 37 patients. All eyes developed ocular hypertension refractory to maximum-tolerated medical therapy and required surgical intervention. Two eyes were excluded as they were lost to follow-up before 5 months postoperatively. Surgical success was defined as reaching the goal intraocular pressure or lower for each patient, including ongoing medical therapy., Results: At most recent follow-up, 25 (55.6%) of 45 eyes had an intraocular pressure that was at goal. Mean follow-up time was 15.2±12.1 months ranging from 0.5 to 36 months postoperatively, considering that patients were eliminated from the data analysis once they required a second surgery. The mean number of preoperative medications, including oral carbonic anhydrase inhibitors was 3.7±1.2 medications. The mean number of postoperative medications through the last clinic visit was 2.5±1.9 medications for a mean reduction of 1.2±1.6 medications ( P -value <0.0001*)., Conclusions: This larger case series shows that some patients with uveitis-associated ocular hypertension or glaucoma with an open angle may have success with KDB goniotomy., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: To investigate the relationship between intraocular pressure (IOP)-lowering success of selective laser trabeculoplasty (SLT) and combined phacoemulsification/Kahook Dual Blade (phaco/KDB) goniotomy in eyes with mild to severe open angle glaucoma (OAG)., Methods: Eyes undergoing combined phaco/KDB goniotomy and that had previously undergone SLT were analyzed. Data collected included demographics, glaucoma type and severity, IOP, and topical IOP-lowering medications before and after both procedures. Eyes were divided into two groups based on success of SLT, defined as IOP reduction of at least 20% maintained on at least two consecutive follow-up visits without any subsequent medication additions or interventions. Phaco/KDB goniotomy success was defined as IOP reduction of at least 20% and/or reduction in the number of IOP-lowering medications of at least one up to 12 months of follow-up., Results: Overall, SLT was successful in 20 of 43 eyes (46.5%), of which 63.6% (7/11) had successful phaco/KDB goniotomy at 12 months follow-up. Among eyes with unsuccessful SLT, 60.0% (9/15) had successful phaco/KDB at 12 months follow-up. Phaco/KDB success rate was similar in patients regardless of their previous response to SLT at all postoperative time points up to 12 months follow-up (p = 0.87)., Conclusions: The presence or lack of IOP-lowering response to SLT did not influence the success rate of subsequent phaco/KDB goniotomy in eyes with mild to severe OAG. Patients who did not respond to SLT still benefited from phaco/KDB goniotomy at a later date., (© 2022. The Author(s).)

Intraocular implants, specifically those used in the treatment of glaucoma, are each associated with various implant related risks and complications of which surgeons placing these devices must be aware. Here we present a case of uveitis-glaucoma-hyphema (UGH) syndrome associated with the Hydrus Microstent., Competing Interests: The authors have no relevant conflicts of interest to disclose:CECY, DMS, MKE, MBP., (© 2022 The Authors. Published by Elsevier Inc.)

Objectives: The purpose of this study was to identify patients with glaucoma and corneal/ocular surface disease who have been fit with Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE; BostonSight, Needham, MA) devices and to understand the PROSE device fit experience in patients with glaucoma at Weill Cornell Medicine (WCM)., Methods: This is a retrospective chart review of patients older than 18 years who underwent PROSE device fitting at WCM. Records were reviewed for demographic information and ophthalmic variables. Descriptive statistics were performed., Results: Between 2011 and 2017, 281 patients underwent PROSE device fitting at WCM, of whom 24 patients (8.5%) had a glaucoma diagnosis and 17 patients (6.0%) were identified as glaucoma suspect. Ocular surface disease was the most common indication for PROSE device wear (58.3%). Five patients had a history of incisional glaucoma surgery in the eye undergoing PROSE device fitting: three valved glaucoma drainage implants and two trabeculectomies. Three of these eyes were successfully fit with PROSE devices., Conclusions: Patients fitted with Prosthetic Replacement of the Ocular Surface Ecosystem devices at WCM had a higher prevalence of glaucoma than in the general population. Among patients with incisional glaucoma surgery, PROSE device fitting was challenging, with a 40% failure rate., Competing Interests: S. H. Van Tassel serves as a consultant for New World Medical, makers of the Ahmed FP7 glaucoma drainage implant. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Contact Lens Association of Ophthalmologists.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Purpose: To assess whether iCare HOME rebound tonometry can detect therapy-related changes during self-monitoring of intraocular pressure (IOP)., Design: Prospective clinical trial., Participants: A total of 43 eyes (n = 27 subjects) with open-angle glaucoma or ocular hypertension were enrolled during standard-of-care clinic visits. Participants were grouped into control eyes managed on stable therapy (n = 18 eyes) or therapy change eyes undergoing selective laser trabeculoplasty (SLT, n = 8 eyes), initiating topical therapy (n = 8 eyes), or adding a second medication to existing monotherapy (n = 9 eyes)., Methods: Subjects recorded IOP 4 times daily for 1 week using iCare HOME tonometry. Upon tonometer return, subjects underwent SLT or new medication start; an additional week of iCare HOME measurements was collected after 4 to 6 weeks. Control subjects recorded an additional week of measurements after 6 weeks. Measurements were grouped into 4 time periods (5-10 am, 10 am to 3 pm, 3-8 pm, 8 pm to 1 am). Goldmann applanation tonometry (GAT) was performed at each study visit for comparison., Main Outcome Measures: Detection of therapy response defined as an IOP reduction of ≥20%., Results: For eyes that demonstrated a therapy response by GAT (n = 11), iCare HOME detected a therapy response in 90.9% of eyes in ≥1 time period and 45.5% of eyes in all 4 time periods. In eyes without a GAT-measured therapy response (n = 14), iCare HOME detected a response for 71.4% (n = 10) of eyes in ≥1 time period and for 7.1% of eyes (n = 1) at all 4 time periods. In treatment eyes, intraday and interday average minimum and maximum IOP, as well as interday IOP range, were significantly reduced after therapy without a significant change in intraday IOP range. Control group eyes did not demonstrate a significant change in average IOP minimum, maximum, or range between study weeks., Conclusions: Home tonometry with iCare HOME reliably detects therapy-related IOP changes in patients with glaucoma and ocular hypertension. Treatment responses correlated well with in-office GAT and may detect treatment responses missed by GAT. Intraocular pressure measurements via home tonometry provide additional clinical information regarding intraday and interday IOP fluctuation beyond standard of care in office GAT measurements. The iCare HOME is a valuable tool to monitor therapeutic efficacy in patients with glaucoma., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Glaucoma drainage implants have been used with increasing frequency for the management of glaucoma. Patients who are candidates for glaucoma drainage devices often have more severe disease and are at risk of vision loss with post-operative elevations in intraocular pressure (IOP). One post-operative complication that can result in IOP elevation after glaucoma drainage device implantation is occlusion of the tube lumen., Case Presentation: Here, we present a novel case of tube occlusion by the anterior capsule in a patient who underwent combined phacoemulsification and Ahmed glaucoma valve implantation. The tube occlusion was successfully managed with Nd:YAG capsulotomy with immediate IOP lowering., Conclusions: While there have been previous reports of occlusion of the tube lumen by vitreous, iris, blood and fibrin, to our knowledge this is the first report of tube occlusion by the anterior lens capsule and the first report to describe its successful management.

Glaucoma, a leading cause of irreversible blindness, affects more than 64 million people worldwide and is expected to grow in number due to the aging global population and enhanced methods of detection. Although topical therapies are often effective when used as prescribed, the drawbacks of current medical management methods include poor patient adherence, local and systemic side effects, and in some cases, limited therapeutic efficacy. Novel ocular drug delivery platforms promise to deliver differentiated drug formulations with targeted delivery leveraging patient-independent administration. Several platforms are in various stages of development with promising pre-clinical and clinical data. The Bimatoprost Sustained Release (SR) intracameral implant was approved in the United States in March of 2020, making it the first long-term injectable therapy available for the treatment of glaucoma. This review aims to provide an update on novel sustained release drug delivery systems that are available today as well as those that might be commercialized in coming years., (International Journal of Ophthalmology Press.)

Purpose of Review: The field of teleglaucoma has expanded rapidly in recent years with several large-scale teleglaucoma screening programs in existence throughout the world. Additionally, teleglaucoma programs for use in disease management are under study. The limited access to care that resulted from the COVID-19 pandemic highlighted the need for expansion of such programs. This article reviews the literature on teleglaucoma for screening and management of glaucoma, discussing considerations for incorporating teleglaucoma into clinical practice., Recent Findings: Teleglaucoma screening reduces the rate of false-positive referrals and can accurately screen at-risk populations with accuracy similar to in-person screening. The use of teleglaucoma for the management of glaucoma shows promise for low-risk patients with early disease. Furthermore, teleglaucoma is cost-effective and reduces travel burden for patients resulting in high patient satisfaction., Summary: Teleglaucoma offers potential for improving access to glaucoma care, reducing the burden on patients and health care systems., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Aim and Objective: The goal of this study was to measure acute ocular effects in patients undergoing routine sphenopalatine ganglion (SPG) nerve block for headache. Projections from the SPG influence blood flow to the eye which may influence intraocular pressure (IOP). There are limited animal and human studies investigating the relationship between the SPG and its effect on the eye., Materials and Methods: This was a single-site, investigator-initiated, single-visit, prospective study. Participants were aged 18-85 years old who had consented to SPG nerve block for headache. The primary outcome measures were change in near visual acuity (NVA) and IOP pre-procedure to immediately post-procedure. Additional data collected included pupil diameter and presence of any ocular or visual complaints., Results: A total of 13 patients were enrolled in the study. Average pre-procedure IOP was 14.2 mm Hg [standard deviation (SD) 3.8] in the right eye and 13.7 mm Hg (SD 3.2) in the left eye. Average post-procedure IOP was 14.8 mm Hg (SD 3.8) in the right eye and 14.2 mm Hg (SD 2.9) in the left eye. Neither the right nor left eye experienced a statistically significant change in IOP after SPG block. There were no statistically significant changes in average NVA or pupil diameter in either eye. There were no adverse events., Conclusion and Clinical Significance: This pilot study suggests no significant acute changes in IOP or other ocular parameters after SPG block for headache disorders and supports the fact that the procedure is safe as it relates to ocular health. The ocular effects of SPG blockade merit further study in a larger cohort of patients., How to Cite This Article: Siegel DT, Ertel MK, Patnaik JL, et al. Acute Ocular Effects of Sphenopalatine Ganglion Nerve Block. J Curr Glaucoma Pract 2020;14(2):57-60., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.)

There are seven conserved CTCF binding domains in the herpes simplex virus 1 (HSV-1) genome. These binding sites individually flank the latency-associated transcript (LAT) and the immediate early (IE) gene regions, suggesting that CTCF insulators differentially control transcriptional domains in HSV-1 latency. In this work, we show that two CTCF binding motifs in HSV-1 display enhancer blocking in a cell-type-specific manner. We found that CTCF binding to the latent HSV-1 genome was LAT dependent and that the quantity of bound CTCF was site specific. Following reactivation, CTCF eviction was dynamic, suggesting that each CTCF site was independently regulated. We explored whether CTCF sites recruit the polycomb-repressive complex 2 (PRC2) to establish repressive domains through a CTCF-Suz12 interaction and found that Suz12 colocalized to the CTCF insulators flanking the ICP0 and ICP4 regions and, conversely, was removed at early times postreactivation. Collectively, these data support the idea that CTCF sites in HSV-1 are independently regulated and may contribute to lytic-latent HSV-1 control in a site-specific manner. IMPORTANCE The role of chromatin insulators in DNA viruses is an area of interest. It has been shown in several beta- and gammaherpesviruses that insulators likely control the lytic transcriptional profile through protein recruitment and through the formation of three-dimensional (3D) chromatin loops. The ability of insulators to regulate alphaherpesviruses has been understudied to date. The alphaherpesvirus HSV-1 has seven conserved insulator binding motifs that flank regions of the genome known to contribute to the establishment of latency. Our work presented here contributes to the understanding of how insulators control transcription of HSV-1., (Copyright © 2018 American Society for Microbiology.)

Unlabelled: Following infection of epithelial tissues, herpes simplex virus 1 (HSV-1) virions travel via axonal transport to sensory ganglia and establish a lifelong latent infection within neurons. Recent studies have revealed that, following intraganglionic or intrathecal injection, recombinant adeno-associated virus (rAAV) vectors can also infect sensory neurons and are capable of stable, long-term transgene expression. We sought to determine if application of rAAV to peripheral nerve termini at the epithelial surface would allow rAAV to traffic to sensory ganglia in a manner similar to that seen with HSV. We hypothesized that footpad or ocular inoculation with rAAV8 would result in transduction of dorsal root ganglia (DRG) or trigeminal ganglia (TG), respectively. To test this, we inoculated the footpads of mice with various amounts of rAAV as well as rAAV capsid mutants. We demonstrated that this method of inoculation can achieve a transduction rate of >90% of the sensory neurons in the DRG that innervate the footpad. Similarly, we showed that corneal inoculation with rAAV vectors in the rabbit efficiently transduced >70% of the TG neurons in the optic tract. Finally, we demonstrated that coinfection of mouse footpads or rabbit eyes with rAAV vectors and HSV-1 resulted in colocalization in nearly all of the HSV-1-positive neurons. These results suggest that rAAV is a useful tool for the study of HSV-1 infection and may provide a means to deliver therapeutic cargos for the treatment of HSV infections or of dysfunctions of sensory ganglia., Importance: Adeno-associated virus (AAV) has been shown to transduce dorsal root ganglion sensory neurons following direct intraganglionic sciatic nerve injection and intraperitoneal and intravenous injection as well as intrathecal injection. We sought to determine if rAAV vectors would be delivered to the same sensory neurons that herpes simplex virus (HSV-1) infects when applied peripherally at an epithelial surface that had been treated to expose the underlying sensory nerve termini. For this study, we chose two well-established HSV-1 infection models: mouse footpad infection and rabbit ocular infection. The results presented here provide the first description of AAV vectors transducing neurons following delivery at the skin/epithelium/eye. The ability of AAV to cotransduce HSV-1-infected neurons in both the mouse and the rabbit provides an opportunity to experimentally explore and disrupt host and viral proteins that are integral to the establishment of HSV-1 latency, to the maintenance of latency, and to reactivation from latency in vivo., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

In herpes simplex virus 1 (HSV-1), binding clusters enriched in CTCF during latency have been previously identified. We hypothesized that CTCF binding to CTCF clusters in HSV-1 would be disrupted in a reactivation event. To investigate, CTCF occupation of three CTCF binding clusters in HSV-1 was analyzed following sodium butyrate (NaB)- and explant-induced reactivation in the mouse. Our data show that the CTCF domains positioned within the HSV-1 genome, specifically around the latency-associated transcript (LAT) and ICP0 and ICP4 regions of the genome, lose CTCF occupancy following the application of reactivation stimuli in wild-type virus. We also found that CTCF binding clusters upstream of the ICP0 and ICP4 promoters both function as classical insulators capable of acting as enhancer blockers of the LAT enhancer. Finally, our results suggest that CTCF occupation of domains in HSV-1 may be differentially regulated both during latency and at early times following reactivation by the presence of lytic transcripts and further implicate epigenetic regulation of HSV-1 as a critical component of the latency-reactivation transition.

Purpose: To examine the effects of neuroprotectin D1 (NPD1), a stereospecific derivative of docosahexaenoic acid, on choroidal neovascularization (CNV) in a laser-induced mouse model. Specifically, this was assessed by clinically grading laser-induced lesions, measuring leakage area, and volumetrically quantifying vascular endothelial cell proliferation., Methods: C57Bl/6 mice were treated with vehicle control or NPD1, and choroidal neovascularization was induced by laser rupture of Bruch's membrane; treatment was administered throughout the first week of recovery. One and two weeks after CNV induction, fundus fluorescein angiography was performed. Angiograms were clinically graded to assess leakage severity, while leakage area was measured by image analysis of angiograms. Proliferation of vascular endothelial cells was evaluated volumetrically by three-dimensional laser confocal immunofluorescent microscopy of cytoskeletal, nuclear, and endothelial cell markers., Results: At seven days after CNV induction, NPD1-treated mice had 60% fewer clinically relevant lesions than controls, dropping to 80% fewer by 14 days. NPD1 mice exhibited 25% smaller leakage area than controls at 7 days and 44% smaller area at 14 days. Volumetric immunofluorescence revealed 46% less vascular endothelial cell volume in 7-day NPD1-treated mice than in 7-day controls, and by 14 days NPD1 treatment was 68% lower than controls. Furthermore, comparison of 7- and 14-day volumes of NPD1-treated mice revealed a 50% reduction at 14 days., Conclusions: NPD1 significantly inhibits choroidal neovascularization. There are at least two possible mechanisms that could explain the neuroprotective action of NPD1. Ultimately, nuclear factor-kappaB could be inhibited with a reduction in cyclooxygenase-2 (COX-2) to reduce vascular endothelial growth factor (VEGF) expression, and/or activation of the resolution phase of the inflammatory response/survival pathways could be upregulated. Moreover, NPD1 continues to be effective after treatment is concluded, suggesting sustained protection and highlighting the potential applicability of this lipid mediator in preventing or ameliorating endothelial cell growth in pathoangiogenesis.