Rotational extraction of incarcerated iris (REII): a slit lamp technique to reduce incarcerated iris after nonpenetrating deep sclerectomy for glaucoma.

PURPOSE: Iris incarceration is a complication of glaucoma filtering surgery that often requires surgery. We describe a technique for reduction of incarcerated iris at the slit lamp, dubbed rotational extraction of incarcerated iris (REII). A retrospective analysis of visual function and intraocular pressure (IOP) was done in patients treated with REII after nonpenetrating deep sclerectomy. METHODS: We retrospectively evaluated a cohort of patients who received REII for iris incarceration after nonpenetrating deep sclerectomy for glaucoma. IOP (applanation) and visual acuity (VA) were measured day-of, and 1, 3, 6, and 12 months post-REII. Adverse events were recorded. Kaplan-Meier survival analysis was done with definitions of IOP control at 15, 18, and 21 mmHg. RESULTS: Forty-one eyes of 41 patients were treated with REII. Median time to iris incarceration from glaucoma surgery was 50 days (range 1-1906). Mean pre-REII IOP ± SD was 33.7 ± 14.1 mmHg, which reduced to 11.5 ± 6.1 mmHg day-of. LogMAR VA was 0.72 ± 0.8 log units at baseline and was unchanged at 12 months (P = 0.53). Survival analysis demonstrated varying efficacy depending on the definition of success. 79.0 to 92.2% of eyes achieved IOP control immediately after REII, 39.5 to 71.1% at 1 month, 26.3 to 52.6% at 3 months, 21.1 to 44.3% at 6 months, and 10.5 to 38.0% at 12 months. Nearly half (47.4%) of eyes required a tube shunt by 12 months. CONCLUSION: REII may be a safe, minimally invasive slit lamp procedure that can reduce incarcerated iris and delay more invasive intervention for 3-6 months in most eyes.

Altered expression of aquaporin 1 and aquaporin 5 in the cornea after primary blast exposure.

Purpose: Our study aimed to determine whether the altered expression of biomarkers linked to corneal injuries, such as the edema-regulating proteins aquaporin-1 and aquaporin-5 (AQP1 and AQP5), occurred following primary blast exposure. Methods: Adult male Dutch Belted rabbits were anesthetized and exposed to blast waves with peak overpressures of 142.5-164.1 kPa (20.4-23.4 psi). These exposure groups experienced peak blast overpressure-specific impulses (impulse per unit surface area) of 199.6-228.5 kPa-ms. Unexposed rabbits were included as controls. The animals were euthanized at 48 h post-exposure. Corneas obtained from the euthanized blast-exposed and control rabbits were processed for quantitative PCR and western blot to quantify mRNA and the protein expression of AQP1 and AQP5. Immunohistochemical analysis was conducted to determine the cellular localization of AQP1 and AQP5. Results: Corneal thickness increased up to 18% with the peak blast overpressure-specific impulses of 199.6-228.5 kPa-ms at 48 h after blast exposure. mRNA levels of AQP1 and AQP5 increased in the whole cornea lysates of blast-exposed rabbits relative to those of the controls. Western blot analyses of whole cornea lysates revealed that the expression levels of AQP1 and AQP5 were approximately 2- and 1.5-fold higher, respectively, in blast-exposed rabbits compared to controls. The extent of AQP1 immunostaining (AQP1-IS) increased in the epithelial cell layer after blast exposure. The AQP5-IS pattern changed from a mixed membrane and cytoplasmic expression in the controls to predominantly cytoplasmic expression in the basally located cornea epithelial cells of blast-exposed rabbits. Conclusions: Primary blast exposure resulted in edema-related changes in the cornea manifested by the altered expression of the edema-regulating proteins AQP1 and AQP5 with blast overpressure-specific impulses. These findings support potential acute corneal injury mechanisms in which the altered regulation of water permeability is caused by primary blast exposure.

Efficacy of a Novel Retrobulbar Extension Shunt to Rescue Eyes with Fibrotic Encapsulated Blebs and Uncontrolled Ocular Hypertension.

PURPOSE: Retrobulbar glaucoma shunts are large-bore fenestrated silicone stents that redirect aqueous humor into the retrobulbar space. They were designed to rescue failed standard tube shunts with fibrotic encapsulation in patients with intractable ocular hypertension. This article evaluates longer-term outcomes of a larger population undergoing retrobulbar aqueous redirection. METHODS: Outcomes of all retrobulbar shunts were placed among this progressive-entry surgical population over an 8-year interval. Implants were produced by New World Medical (NWM) in Rancho Cucamonga, California, and AJL in Bilbao, Spain. Mean and percentage IOP reduction and medications required were evaluated at annual intervals, along with pre-operative and final visual acuity. Significance of change was assessed by two-tailed paired t-test. Failure was designated as any eye requiring placement of another shunt or diode-cyclophotocoagulation. All data are included in this analysis regardless of outcome. RESULTS: Thirty-five retrobulbar shunts were implanted (18M, 17F; mean 54.3 years; mean follow-up 32.5 months). Short-term AJL shunt performance was comparable to that of the 26 NWM shunts, for which there was longer-term follow-up. Three shunts (9%) failed: Two eyes required diode at 6 months, one another standard shunt after > 2 years. Preoperative medications averaged 2.6, reduced to 0.4-0.75 medications at each annual assessment (P < 0.0001). IOP was substantially reduced (by 53-57% from mean baseline 29.9-32.5 mmHg to 16.4-18.4 mmHg; P < 0.0008) at every annual follow-up. Visual acuity remained stable (baseline mean VA 0.27, final VA 0.30; P = 0.68). CONCLUSION: Retrobulbar extension shunts can convert tube shunt failures, with high success rate, to eyes with IOP control comparable to successful primary filtration surgery.

The consequences of avian ocular trauma: histopathological evidence and implications of acute and chronic disease.

OBJECTIVE: To present a description and categorization of the histopathological lesions in avian ocular trauma. ANIMAL STUDIED: Seventy-five birds diagnosed with ocular trauma at to the Comparative Ocular Pathology Laboratory of Wisconsin. PROCEDURES: Histological slides were reviewed, and the type of trauma was classified by cause into either (i) blunt trauma or (ii) penetrating trauma and by duration into (i) acute or (ii) chronic. RESULTS: Blunt trauma was the most common source of trauma, and the most frequent lesions were observed in the retina (91%), with 71% of retinas having a tear or detachment and 46% of retinas showing chronic degenerative changes. Damage to the iris/ciliary body was present in 77% of cases. Corneal (17%) and lens (31%) lesions were relatively low. Acute traumatic events had a higher prevalence of readily identifiable discrete retinal tears/detachments (64%). Nearly all cases of chronic trauma exhibited chronic retinal lesions (93.7%), as well as a greater percentage of cartilage/bone lesions (71.4%), irido/cyclodialysis (51.9%), lenticular lesions (72.7%), and corneal damage (83.3%). However, the incidence of iridocyclodialysis was roughly equivalent for acute and chronic blunt trauma. CONCLUSIONS: Ocular trauma can lead to profound acute and chronic lesions within the eye. Here, we provide insight into understanding ocular damage caused by trauma, which may help future studies suggest new therapeutic options and provide insight regarding the releasability of avian wildlife.

Prospective Comparison of VisuALL Virtual Reality Perimetry and Humphrey Automated Perimetry in Glaucoma.

Aim and background: Automated perimetry plays an important role in the diagnosis and monitoring of glaucoma patients. The purpose of this study is to prospectively determine parity between Humphrey visual field analyzer (HVFA) perimetry (the current gold standard) and the VisuALL virtual reality perimeter (VRP). Materials and methods: In this prospective fully paired diagnostic accuracy study, patients with stable, long-term HVFA visual fields (horizontal dots for ≥4 consecutive visits on progression analysis) with preperimetric, mild, moderate, or severe visual field loss were familiarized with the VRP and then tested using its proprietary software. These results were used for point-by-point comparison with a contemporaneous HVFA test. This study was approved by the Institutional Review Board (IRB) of the University of the Incarnate Word, San Antonio, Texas, United States of America (IRB approval #20-06-002). Results: The prospective study analyzed 43 eyes of 24 glaucoma patients. Spearman's correlation of mean deviation (MD) revealed a strong correlation between HVFA and VRP with rs(41) = 0.871, p < 0.001. The overall mean difference in locus-locus sensitivity between the devices was -0.4 ± 1.5 dB but varied for different visual field locations and glaucoma severity. Conclusion: The parity between the VRP and HVFA was remarkably strong for mild and moderate glaucoma. Given its portability, ease of use, space efficiency, and low cost, the VRP presents a viable alternative. Clinical significance: Automated perimetry, specifically the HVFA, has been the gold standard for visual field assessment since its introduction. The recent COVID-19 pandemic has illuminated the advantages of the VRP, allowing for safer visual assessment for both patient and clinician alike. Our study hopes to establish parity between these systems, allowing for the efficient integration of a novel head-mounted perimetry system that can safely diagnose and monitor glaucomatous progression in clinical practice. Precis: Investigation of parity between Olleyes VisuALL virtual reality perimetry (VRP) and existing standard HVFA perimetry is essential to the diagnosis and management of glaucoma. Linear correlations between the two were established from 43 glaucomatous eyes. Parity was strong for mild and moderate glaucoma, presenting VRP as a viable alternative. How to cite this article: Griffin JM, Slagle GT, Vu TA, et al. Prospective Comparison of VisuALL Virtual Reality Perimetry and Humphrey Automated Perimetry in Glaucoma. J Curr Glaucoma Pract 2024;18(1):4-9.

Association of OCT angle recess width with IOP response after intravitreal triamcinolone injection.

PURPOSE: A circumferential pretrabecular anatomical structure, the angle recess (AR), can be imaged with anterior segment ocular coherence tomography. AR's utility to predict ocular hypertension after intravitreal triamcinolone injection was assessed. METHODS: All intravitreal triamcinolone injection recipients from 2002 to 2005 with high-resolution anterior segment ocular coherence tomography images had AR width (between the anteriormost prominence of the iris root and posterior cornea) measured by masked physicians using the caliper function of Stratus ocular coherence tomography. Intraocular pressures (IOPs) from 1 month before to 6 months after the injection were compiled for IOP rise (Δ) and maximal IOP (max), categorized as "minimal" (IOPmax < 21 mmHg and/or IOPΔ ≤ 5 mmHg), "moderate" (IOPmax 21-29 mmHg and/or IOPΔ 6-14 mmHg), or "severe" (IOPmax ≥ 30 mmHg and/or IOPΔ ≥ 15 mmHg). Linear regression and analyses of variance were applied. RESULTS: Twenty-six eyes satisfied the entry criteria, with 11 (42%) eyes demonstrating minimal, 11 (42%) moderate, and 4 (15%) severe IOP responses. The corresponding (mean ± SEM) AR widths were: 326 ± 31.5 µm, 281 ± 22.0 µm, and 138 ± 20.3 µm, respectively. Highly significant AR width differences existed between moderate and severe responders and between minimal and severe responders (both P < 0.004); 5 of 6 patients with IOP ≥ 29 mmHg had AR < 200 µm. CONCLUSION: These findings indicate that a potentially clinically useful relationship exists between AR width and IOP elevation accompanying intravitreal triamcinolone injection. Anterior segment screening could become a beneficial extension of ocular coherence tomography for retinal practices.

Digital Ocular Compressions Reduce Intraocular Pressure in Eyes With Tube Shunts.

PRCIS: Digital ocular compressions (DOCs) decrease intraocular pressure in eyes with tube shunts by significantly greater magnitude and duration when compared with fellow eyes without filtering surgery. PURPOSE: DOCs are commonly used by glaucoma surgeons to reduce intraocular pressure (IOP) in the early postoperative period. Little is known, however, about the effects of DOC in eyes with tube shunts. We therefore examined these effects in eyes with long-established, functional glaucoma tube shunts. METHODS: In this masked prospective study, adult subjects with primary open angle glaucoma and an Ahmed tube shunt in only 1 eye were recruited. After obtaining baseline IOP with Goldmann applanation tonometry a single transpalpebral DOC was applied to each eye (in random order). Postcompression IOP was measured after 10, 20, 30, 60, 90, 120, 150, 180, 210, and 240 minutes or until the measured IOP returned to baseline. The fellow (nonsurgical) eye was a control. Magnitude and duration of IOP reduction were evaluated using Kaplan-Meier analysis. The pressure applied to eyes in each cohort was standardized through the use of a force sensitive resistor and impulse was analyzed for differences. RESULTS: Twenty-two eyes of 11 patients underwent DOC. There was no significant difference in the impulse applied to eyes in each cohort (P=0.6). A mean initial IOP reduction of 5.36 mm Hg occurred in tube shunt eyes and 2.55 in control eyes (P=0.014). Log-rank analysis demonstrated longer survival in the tube shunt group (P=0.049). CONCLUSIONS: DOC is an effective method for transiently reducing IOP in eyes with long-established, patent tube shunts for about an hour. To maintain this decrease in pressure, compressions will have to be performed on a scheduled basis.

Nonpenetrating Deep Sclerectomy for Progressive Glaucoma: Long-term (5-year) Follow-up of Intraocular Pressure Control and Visual Field Survival.

PURPOSE: To monitor 5-year outcomes of nonpenetrating deep sclerectomy (NPDS) with mitomycin C (MMC) in a new consecutive patient cohort. MATERIALS AND METHODS: All eyes undergoing NPDS surgery between 1/08 and 6/12 were monitored for intraocular pressure (IOP), number of antiglaucoma medications (meds), and visual field indices [mean deviation (MD) and corrected pattern standard deviation (CPSD)], relative to the preoperative baseline using the two-tailed paired Student's t test. RESULTS: Of 106 eyes undergoing NPDS with MMC, mean IOP was 19.7 ± 0.5 [sem] mm Hg preoperatively, 11.9 ± 0.5 at 3 months, 12.5 ± 0.6 at 6 months, 12.4 ± 0.5 at 12 months, 12.6 ± 0.6 at 18 months, 11.1 ± 0.6 at 2 years, 11.8 ± 0.5 at 2.5 years, 11.0 ± 0.5 at 3 years, 11.7 ± 0.5 at 3.5 years, 10.7 ± 0.7 at 4 years, 11.6 ± 0.5 at 4.5 years, and 12.4 ± 0.7 at 5 years (average IOP reduction of 7.8 mm Hg or 37%; p < 10-6) at 5 years. About 92% of eyes had stable IOP ≥5 and ≤21 mm Hg at 5 years. Mean preoperative meds 2.7 ± 0.1 was reduced to 0.40 ±0.09 at 3 months, 0.51 ± 0.1 at 6 months, 0.38 ± 0.08 at 12 months, 0.49 ± 0.09 at 18 months, 0.41 ± 0.09 at 2 years, 0.39 ± 0.09 at 2.5 years, 0.49 ± 0.1 at 3 years, 0.58 ± 0.1 at 3.5 years, 0.49 ± 0.1 at 4 years, 0.64 ± 0.1 at 4.5 years, and 0.52 ± 0.1 at 5 years, corresponding to mean reduction of 2.2 meds (81%; p < 10-22) at 5 years. Mean deviation and CPSD were stable relative to baseline at all time intervals (R = 0.83-0.94; p < 0.0001). CONCLUSION: With appropriate postoperative management, eyes undergoing NPDS can maintain excellent IOP control with minimal medication use and maintain very stable visual fields over an extended time frame. HOW TO CITE THIS ARTICLE: Slagle G, Groth SL, Montelongo M, et al. Nonpenetrating Deep Sclerectomy for Progressive Glaucoma: Long-term (5-year) Follow-up of Intraocular Pressure Control and Visual Field Survival. J Curr Glaucoma Pract 2020;14(1):3-9.

Repeatability of Goldmann tonometry performed by optometry students on glaucoma patients.

BACKGROUND: The purpose of this study was to evaluate the repeatability of masked Goldmann tonometry performed by optometry students on patients with glaucoma. METHODS: Subjects were recruited from among patients scheduled to undergo selective laser trabeculoplasty at the Rosenberg School of Optometry clinic. Each subject had masked Goldmann tonometry performed by three examiners at each office visit: two fourth professional-year optometry interns and an attending optometrist. Each examiner performed three sequential masked tonometry measurements on each eye. RESULTS: Twenty-eight interns and two optometrists performed masked Goldmann tonometry on 12 glaucoma patients. The co-efficient of variation was 9.1 per cent for the right eye and 12.1 per cent for the left eye for interns compared with 6.4 per cent right eye and 6.6 per cent left eye for optometrists. There was significant interaction between intern and patient on co-efficient of variation (two-factor analysis of variance, p = 0.005), indicating co-efficient of variation was influenced by both intern and patient factors. No such interaction was found for optometrist-performed measurements (p = 0.96). Mean interobserver difference for interns ranged between 0.9 and 3.1 mmHg, with 95 per cent limits of agreement that were proportional to mean intraocular pressure. Mean interobserver difference for optometrists ranged between 0.6 and 1.8 mmHg without proportionality bias. At higher pressure levels intern measurements became more variable and tended to overestimate optometrist measurements. CONCLUSIONS: Both intraobserver and interobserver repeatability of masked tonometry was lower for interns than experienced optometrists. Intern performance differed from optometrists in that intern measurements became more variable at higher intraocular pressure levels and were significantly influenced by patient factors. The present results support the need for trainee exposure to patients with abnormally elevated intraocular pressure. Research into factors that influence trainee Goldmann tonometry repeatability is needed.

Association of Diopsys® Short-duration Transient Visual Evoked Potential Latency with Visual Field Progression in Chronic Glaucoma.

AIM: To determine the association of Diopsys® NOVA-LX amplitude and latency abnormality scores with perimetric staging of chronic glaucoma, and to explore potential single-visit short-duration transient visual evoked potential (SD-tVEP) trend detection ability utilizing Humphrey 30-2 field progression data. MATERIALS AND METHODS: Setting: Glaucoma subspecialty clinic. Participants: Treated adult chronic glaucoma patients undergoing SD-tVEP evaluation. Main outcome measures: (1) Proportion of eyes designated as suspect or abnormal by the NOVA-LX multifactorial algorithm were determined as a function of glaucoma severity using the most recent Humphrey visual field analyzer (HVFA) 30-2 field. (2) Association between long-term HVFA-guided progression analysis (GPA) annual slopes and SD-tVEP abnormality was assessed to determine whether a single VEP test might help to identify eyes more prone to progressive visual field (VF) loss. RESULTS: One hundred and thirty-three eyes of 84 patients (mean age 68 years) were analyzed. The SD-tVEP abnormality increased proportionately with severity of VF loss under high-contrast (Hc) test conditions for both latency (p = 0.001) and amplitude (p < 0.01). The HVFA progression analysis printouts existed for 91 eyes (mean 12.3 fields per eye/range 5-18). Nearly three-quarters (72.5%) of eyes with mean annual HVFA progression >0.7 dB/year (n = 29) had single-visit VEP latency abnormalities. Fewer than half (46.7%) of the remainder (n = 62) showed latency abnormality. Mean progression for eyes with abnormal vs normal VEP latency was -0.87 ± 0.3 dB/year vs -0.32 ± 0.4 dB/year. CONCLUSION: Diopsys NOVA-LX Hc latency abnormality shows strong association with VF loss among a diverse population of clinical patients undergoing active treatment for chronic glaucoma, and appears likely to afford clinically useful trend-detecting test. CLINICAL SIGNIFICANCE: The SD-tVEP has the potential to serve as a single-visit clinical indicator to identify glaucoma patients at high risk for VF progression.How to cite this article: Trevino R, Sponsel WE, Majcher CE, Allen J, Rabin J. Association of Diopsys® Short-duration Transient Visual Evoked Potential Latency with Visual Field Progression in Chronic Glaucoma. J Curr Glaucoma Pract 2018;12(1):29-35.

Visual evoked potential repeatability using the Diopsys NOVA LX fixed protocol in normal older adults.

PURPOSE: The purpose of this study was to evaluate the intrasession and intersession repeatability of visual evoked potentials in normal adults over 40 years of age as recorded using the Diopsys NOVA LX fixed protocol. METHODS: Inclusion criteria were adults aged over 40 years with best corrected distance acuity of 20/40 or better in each eye. Subjects underwent three consecutive visual evoked potential examinations using the Diopsys NOVA LX fixed protocol. All examination procedures were carried out in accordance with the manufacturer recommendations. To assess intersession repeatability, nine subjects returned in 2-6 weeks for repeat examination. RESULTS: A total of 46 subjects were recruited. Mean ± SD age: 53±9 years (range: 40-84 years); 69% of subjects were female and 80% were non-white. Coefficients of variation (CVs) and intra-class correlation coefficients (ICCs) revealed greater repeatability for P100 latency (CV: 3%-7%; ICC: 0.39-0.76) than for P100 amplitude (CV: 21%-33%; ICC: 0.34-0.69) and greater repeatability for recordings made with high contrast stimuli (amplitude CV: 21%-23%; latency CV: 3%-7%) than low contrast stimuli (amplitude CV: 24%-33%; latency CV: 6%-7%). Minimum detectable change values ranged between 4.50 and 9.95 µv for amplitude and 8.16-15.26 ms for latency. Repeatability was not influenced by age, sex, or race. CONCLUSION: The Diopsys NOVA LX fixed protocol demonstrated clinically acceptable intrasession and intersession repeatability in these healthy older adults, with latency being more repeatable than amplitude and examinations employing high contrast stimuli being more repeatable than those using low contrast stimuli.

Dronabinol and retinal hemodynamics in humans.

PURPOSE: To investigate the effects of oral cannabinoids on retinal hemodynamics assessed by video fluorescein angiography in healthy subjects. DESIGN: Interventional study. METHODS: In a self-experiment, the cannabinoid dronabinol (delta-9-tetrahydrocannabinol [THC]) was administered orally to eight healthy medical doctors (7.5 mg Marinol; Unimed Pharmaceuticals, Chicago, Illinois, USA). At baseline and two hours after dronabinol intake, intraocular pressure (IOP) was measured and retinal hemodynamics were assessed by fluorescein angiography. The retinal arteriovenous passage time was determined on the basis of dye dilution curves by means of digital image analysis in a masked fashion. RESULTS: Dronabinol resulted in a significant IOP reduction from 13.2 +/- 1.9 mm Hg to 11.8 +/- 2.0 mm Hg (P = .038). The retinal arteriovenous passage time decreased from 1.77 +/- 0.35 seconds to 1.57 +/- 0.31 seconds (P = .028). Systemic blood pressure and heart rate were not statistically significantly altered. CONCLUSIONS: Cannabinoids, already known for their ability to reduce IOP, may result in increased retinal hemodynamics. This may be beneficial in ocular circulatory disorders, including glaucoma.

Racial Differences in Selective Laser Trabeculoplasty Efficacy.

AIM: Sub-Saharan Africa has a population of 1 billion, with one ophthalmologist per million people. Basic ophthalmic support services are virtually absent for all but a few urban populations. Minimally invasive laser treatment may help. This study reports our initial experience using selective laser trabeculoplasty (SLT) in a mixed-racial population of adult glaucoma patients in Durban, South Africa. STUDY DESIGN: Institution Review Board approved the 5-year chart review. MATERIALS AND METHODS: Consecutive glaucomatous adults underwent SLT (Lumenis Selecta) on one or both eyes applying 360° treatment of 120 to 140 closely spaced burns (400 urn spot size for 3 ns; range 1.1-1.4 mJ). Significance of change in intraocuar pressure (IOP) from baseline at 1, 3, 6, and 12 months was assessed by two-tailed paired t-test. RESULTS: Among 148 eyes of 84 patients (60 African, 21 Indian, 3 Caucasian), 69 had already undergone glaucoma therapy, and 15 untreated (de novo). Among all eyes, mean IOP was reduced by >32% with mean IOP < 15 mm Hg from baseline at all four study intervals (p < 0.0001). A 20% reduction in IOP was sustained at 12 months in 90% of African eyes but in only 50% of Indian eyes. CONCLUSION: Selective laser trabeculoplasty was effective in producing clinically significant IOP reduction among South African adults with or without prior medical or surgical anti-glaucoma therapy. Socioeconomically comparable individuals of Indian ancestry showed good therapeutic responses, but significantly less efficacious than those observed among Black subjects. Programs to provide first-line SLT management of glaucoma in Africa, where 90% of patients are unable to sustain prescribed medical therapy, appear to be a very appropriate option. HOW TO CITE THIS ARTICLE: Goosen E, Coleman K, Visser L, Sponsel WE. Racial Differences in Selective Laser Trabeculoplasty Efficacy. J Curr Glaucoma Pract 2017;11(1):22-27.

Making Basic Science Studies in Glaucoma More Clinically Relevant: The Need for a Consensus.

Glaucoma is a chronic, progressive, and debilitating optic neuropathy that causes retinal damage and visual defects. The pathophysiologic mechanisms of glaucoma remain ill-defined, and there is an indisputable need for contributions from basic science researchers in defining pathways for translational research. However, glaucoma researchers today face significant challenges due to the lack of a map of integrated pathways from bench to bedside and the lack of consensus statements to guide in choosing the right research questions, techniques, and model systems. Here, we present the case for the development of such maps and consensus statements, which are critical for faster development of the most efficacious glaucoma therapy. We underscore that interrogating the preclinical path of both successful and unsuccessful clinical programs is essential to defining future research. One aspect of this is evaluation of available preclinical research tools. To begin this process, we highlight the utility of currently available animal models for glaucoma and emphasize that there is a particular need for models of glaucoma with normal intraocular pressure. In addition, we outline a series of discoveries from cell-based, animal, and translational research that begin to reveal a map of glaucoma from cell biology to physiology to disease pathology. Completion of these maps requires input and consensus from the global glaucoma research community. This article sets the stage by outlining various approaches to such a consensus. Together, these efforts will help accelerate basic science research, leading to discoveries with significant clinical impact for people with glaucoma.

Pattern Electroretinography and Visual Evoked Potentials Provide Clinical Evidence of CNS Modulation of High- and Low-Contrast VEP Latency in Glaucoma.

PURPOSE: Both pattern electroretinography (PERG) and visual evoked potentials (VEP) can be performed using low- (15%; Lc) and high- (85%; Hc) contrast gratings that may preferentially stimulate the magno- and parvocellular pathways. We observed that among glaucomatous patients showing only one VEP latency deficit per eye, there appeared to be a very strong tendency for an Hc delay in one eye and an Lc delay in the other. METHODS: Diopsys NOVA-LX system was used to measure VEP Hc and Lc latency among a clinical glaucoma population to find all individuals with either a single Hc or Lc latency abnormality in each eye (group 1), or with greater than 0 and less than 4 Hc or Lc VEP latency abnormalities in the two eyes (group 2) to determine whether a significant inverse correlation existed for these values in either group. Hc and Lc PERG data were also evaluated to assess associated retinal ganglion cell responses. RESULTS: A strong inverse correlation (P = 0.0000003) was observed between the Hc and Lc VEP latency values among the 64 eyes in group 1. Group 2 provided a comparable result (n = 143; 286 eyes; P = 0.0005). PERG (n = 81; 162 eyes) also showed strong bilateral symmetry for magnitude values (P < 0.0001 for both Lc and Hc in groups 1 and 2). CONCLUSIONS: Bilateral retention of both low-resolution/high-speed and high-resolution/low-speed function may persist with both eyes open despite symmetrically pathologic retinal ganglion cell PERG waveform asynchrony for Hc and Lc stimuli in the paired eyes. TRANSLATIONAL RELEVANCE: Clinical electrophysiology strongly suggests binocular compensation for dynamic dysfunction operates under central nervous system (CNS) control in glaucoma.

Low-Level Primary Blast Causes Acute Ocular Trauma in Rabbits.

The objective of this study was to determine whether clinically significant ocular trauma can be induced by a survivable isolated primary blast using a live animal model. Both eyes of 18 Dutch Belted rabbits were exposed to various survivable low-level blast overpressures in a large-scale shock tube simulating a primary blast similar to an improvised explosive device. Eyes of the blast-exposed rabbits (as well as five control rabbits) were thoroughly examined before and after blast to detect changes. Clinically significant changes in corneal thickness arose immediately after blast and were sustained through 48 h, suggesting possible disruption of endothelial function. Retinal thickness (RT) increased with increasing specific impulse immediately after exposure. Intraocular pressure (IOP) was inversely correlated with the specific impulse of the blast wave. These findings clearly indicate that survivable primary blast causes ocular injuries with likely visual functional sequelae of clinical and military relevance.

Simulations of Porcine Eye Exposure to Primary Blast Insult.

PURPOSE: A computational model of the porcine eye was developed to simulate primary blast exposure. This model facilitates understanding of blast-induced injury mechanisms. METHODS: A computational model of the porcine eye was used to simulate the effects of primary blast loading for comparison with experimental findings from shock tube experiments. The eye model was exposed to overpressure-time histories measured during physical experiments. Deformations and mechanical stresses within various ocular tissues were then examined for correlation with pathological findings in the experiments. RESULTS: Stresses and strains experienced in the eye during a primary blast event increase as the severity of the blast exposure increases. Peak stresses in the model occurred in locations in which damage was most often observed in the physical experiments. CONCLUSIONS: Blast injuries to the anterior chamber may be due to inertial displacement of the lens and ciliary body while posterior damage may arise due to contrecoup interactions of the vitreous and retina. Correlation of modeling predictions with physical experiments lends confidence that the model accurately represents the conditions found in the physical experiments. TRANSLATIONAL RELEVANCE: This computational model offers insights into the mechanisms of ocular injuries arising due to primary blast and may be used to simulate the effects of new protective eyewear designs.

Comparative effects of latanoprost (Xalatan) and unoprostone (Rescula) in patients with open-angle glaucoma and suspected glaucoma.

PURPOSE: To compare, in paired eyes of open-angle glaucoma patients and glaucoma suspects, hydrodynamic and visual changes after 1 month of topical latanoprost in one eye and unoprostone in the other. DESIGN: Single-center, institutional randomized clinical trial. METHODS: After completing a washout period off all topical medication, 25 adults (mean age 54 +/- SEM 2 years) with bilateral open-angle glaucoma or glaucoma suspect status underwent morning (8 to 10 AM) and afternoon (1 to 3 PM) measurements of intraocular pressure (IOP), pulsatile ocular blood flow (POBF), contrast, sensitivity, frequency doubling technology, and Humphrey 10-2 perimetry (HVFA II) in both eyes. Each then started unoprostone 0.15% (Rescula) in one randomly assigned eye and latanoprost 0.005% (Xalatan) in the other. Unoprostone was administered at 8 AM and 8 PM and latanoprost at 8 PM with placebo at 8 AM, both from masked bottles. After 28 days, differences were determined for each measured variable by two-tailed paired t test. RESULTS: Starting from similar baseline IOP levels, after 1 month of treatment, the mean morning IOP values differed according to the topical agent received (16.2 +/- SEM 0.6 mm Hg for latanoprost vs 17.9 +/- 0.7 mm Hg for unoprostone; P =.001). These morning pressures were 2.6 mm Hg lower than baseline in the eyes receiving latanoprost (P <.0001), and 1.6 mm Hg lower in unoprostone-treated eyes (P =.02). Afternoon values were 3.1 +/- SEM 0.6 lower than corresponding baseline in eyes receiving latanoprost, and 2.4 +/- SEM 0.6 mm Hg in unoprostone-treated eyes (P <.0001 from baseline for both medications; interdrug mean IOP difference; P =.04). Eyes receiving unoprostone showed a 1.7-db improvement in frequency doubling mean deviation (P =.03), the only significant visual function change observed. Pulsatile ocular blood flow increased 30% relative to baseline in eyes receiving latanoprost, (P <.0001) and 16% in eyes receiving unoprostone (P =.05) by the morning of day 28. That afternoon, mean POBF had increased 30% (P <.0001) relative to afternoon baseline values among eyes receiving latanoprost and 18% (P =.03) among those receiving unoprostone (interdrug change difference, P =.05). Humphrey perimetry and contrast sensitivity remained stable with both prostanoids. CONCLUSIONS: Both latanoprost and unoprostone produced significant reductions in IOP and increases in POBF, with stable central and perimacular visual function. Latanoprost once daily produced IOP reduction and POBF increases nearly twofold greater than those obtained with unoprostone twice daily. These differences in IOP and POBF change between unoprostone and latanoprost were statistically significant.

Latanoprost and brimonidine: therapeutic and physiologic assessment before and after oral nonsteroidal anti-inflammatory therapy.

PURPOSE: To assess, before and during oral nonsteroidal anti-inflammatory drug coadministration, latanoprost's and brimonidine's hypotensive action in eyes at risk of glaucomatous progression, assessing the effect of each drug on ocular perfusion and visual function. METHODS: Twenty consenting adults with open-angle glaucoma or ocular hypertension underwent a double-masked, bilateral, randomized prospective study. Treatment started with either latanoprost 0.005% in the morning and placebo in the evening, or brimonidine 0.2% twice daily in one eye; after 1 week starting the other in the fellow eye. After another week, oral indomethacin 25 mg four times a day, commenced for 2 more weeks. Intraocular pressure, ocular circulation, and visual function were monitored pretreatment, after unilateral monotherapy (day 7), bilateral ocular therapy (day 14), and coadministered oral indomethacin (day 28). Intrasubject differences (interocular and intraocular relative to baseline) were determined by two-tailed paired t test. RESULTS: A loss of the significance of intraocular pressure reduction with brimonidine was noted after oral indomethacin coadministration (-14%; P =.004 for brimonidine alone versus -11%; P =.3 with indomethacin). Significant intraocular pressure reduction with latanoprost persisted despite indomethacin (-25%; P <.0001 for latanoprost alone versus -30%; P <.0001 with indomethacin). Pulsatile ocular blood flow increased 40% with latanoprost, but was unchanged with brimonidine (interdrug difference, P =.004). Midperipheral retinal microcirculation increased 23% (P =.03) with latanoprost. Humphrey perimetry and contrast sensitivity remained consistently at or above baseline with both latanoprost and brimonidine. Indomethacin had no significant effect on ocular perfusion or visual function measures. CONCLUSIONS: Circulatory and hydrodynamic findings differed substantially for the two drugs. The loss of significance of intraocular pressure reduction with brimonidine during indomethacin treatment may be clinically important.