Peripheral visual field loss and activities of daily living.

PURPOSE OF REVIEW: Peripheral visual field (VF) loss affects 13% of the population over 65. Its effect on activities of daily living and higher order visual processing is as important as it is inadequately understood. The purpose of this review is to summarize available literature on the impact of peripheral vision loss on driving, reading, face recognition, scene recognition and scene navigation. RECENT FINDINGS: In this review, glaucoma and retrochiasmal cortical damage are utilized as examples of peripheral field loss which typically spare central vision and have patterns respecting the horizontal and vertical meridians, respectively. In both glaucoma and retrochiasmal damage, peripheral field loss causes driving difficulty - especially with lane maintenance - leading to driving cessation, loss of independence, and depression. Likewise, peripheral field loss can lead to slower reading speeds and decreased enjoyment from reading, and anxiety. In glaucoma and retrochiasmal field loss, face processing is impaired which impacts social functioning. Finally, scene recognition and navigation are also adversely affected, impacting wayfinding and hazard detection leading to decreased independence as well as more frequent injury. SUMMARY: Peripheral VF loss is an under-recognized cause of patient distress and disability. All peripheral field loss is not the same, differential patterns of loss affect parameters of activities of daily living (ADL) and visual processing in particular ways. Future research should aim to further characterize patterns of deranged ADL and visual processing, their correlation with types of field loss, and associated mechanisms.

Pragmatic adjunctive usage of netarsudil: A retrospective chart review from a tertiary care center.

Purpose: This retrospective chart review of netarsudil (Rhopressa) characterizes intra-ocular pressure (IOP) reduction, drug tolerance, drug cost, and compliance in a tertiary university Midwest clinic in a variety of glaucoma diagnoses on patients prescribed netarsudil 01/2017 to 5/2020. Methods: Patient demographics, primary diagnosis, indication for medication, prescription date, prescription fill status, duration of use, discontinuation reason, and number of IOP-lowering medications were noted. Confounding medication changes were excluded from IOP analysis. The IOP difference between the first visit after starting netarsudil and the baseline (mean before starting netarsudil on the stable medication regimen) was calculated. Results: A total of 133 patients were prescribed netarsudil (age 69 ± 20 years, 59% females, 79% white, 86% primary glaucoma) as adjunct glaucoma medication (mean medications 3.2 ± 0.9). Indications were lowering IOP (mean baseline IOP 20.0 ± 6 mmHg) and drug regimen simplification. Prescription was not filled by 22/133 subjects because of the cost (68%) and the need for surgery (23%). No demographic factors were associated with prescription fill status. A total of 101 eyes of 76 patients were used for IOP analysis. The mean change in IOP was -0.8 ± 6.4 mmHg, (IOP decrease in 67%, increase or no change in 33% eyes). Netarsudil was discontinued in 52% (50/96) patients; the reasons include surgery for IOP control (42%), allergies (30%), cost (14%), and paradoxical rise in IOP (12%). Conclusion: Netarsudil was used as adjunct third or fourth line medication at a glaucoma practice in Midwestern USA. 17% of prescriptions went unfilled; netarsudil was discontinued in 52% of patients. IOP response was variable in this population with severe complex glaucoma.

What do patients with glaucoma see: a novel iPad app to improve glaucoma patient awareness of visual field loss.

PURPOSE: Glaucoma patients with peripheral vision loss have in the past subjectively described their field loss as 'blurred' or 'no vision compromise'. We developed an iPad app for patients to self-characterise perception within areas of glaucomatous visual field loss. METHODS: Twelve glaucoma patients with visual acuity ≥20/40 in each eye, stable and reliable Humphrey Visual Field (HVF) over 2 years were enrolled. An iPad app (held at 33 cm) allowed subjects to modify 'blur' or 'dimness' to match their perception of a 2×2 m wall-mounted poster at 1 m distance. Subjects fixated at the centre of the poster (spanning 45° of field from centre). The output was degree of blur/dim: normal, mild and severe noted on the iPad image at the 54 retinal loci tested by the HVF 24-2 and was compared to threshold sensitivity values at these loci. Monocular (Right eye (OD), left eye (OS)) HVF responses were used to calculate an integrated binocular (OU) visual field index (VFI). All three data sets were analysed separately. RESULTS: 36 HVF and iPad responses from 12 subjects (mean age 71±8.2y) were analysed. The mean VFI was 77% OD, 76% OS, 83% OU. The most common iPad response reported was normal followed by blur. No subject reported dim response. The mean HVF sensitivity threshold was significantly associated with the iPad response at the corresponding retinal loci (For OD, OS and OU, respectively (dB): normal: 23, 25, 27; mild blur: 18, 16, 22; severe blur: 9, 9, 11). On receiver operative characteristic (ROC) curve analysis, the HVF retinal sensitivity cut-off at which subjects reported blur was 23.4 OD, 23 OS and 23.3 OU (dB). CONCLUSIONS: Glaucoma subjects self-pictorialised their field defects as blur; never dim or black. Our innovation allows translation of HVF data to quantitatively characterise visual perception in patients with glaucomatous field defects.

A Hydrogel Ionic Circuit Based High-Intensity Iontophoresis Device for Intraocular Macromolecule and Nanoparticle Delivery.

Iontophoresis is an electrical-current-based, noninvasive drug-delivery technology, which is particularly suitable for intraocular drug delivery. Current ocular iontophoresis devices use low current intensities that significantly limit macromolecule and nanoparticle (NP) delivery efficiency. Increasing current intensity leads to ocular tissue damage. Here, an iontophoresis device based on a hydrogel ionic circuit (HIC), for high-efficiency intraocular macromolecule and NP delivery, is described. The HIC-based device is capable of minimizing Joule heating, effectively buffering electrochemical (EC) reaction-generated pH changes, and absorbing electrode overpotential-induced heating. As a result, the device allows safe application of high current intensities (up to 87 mA cm-2 , more than 10 times higher than current ocular iontophoresis devices) to the eye with minimal ocular cell death and tissue damage. The high-intensity iontophoresis significantly enhances macromolecule and NP delivery to both the anterior and posterior segments by up to 300 times compared to the conventional iontophoresis. Therapeutically effective concentrations of bevacizumab and dexamethasone are delivered to target tissue compartments within 10-20 min of iontophoresis application. This study highlights the significant safety enhancement enabled by an HIC-based device design and the potential of the device to deliver therapeutic doses of macromolecule and NP ophthalmic drugs within a clinically relevant time frame.

Effects of Acute Intracranial Pressure Changes on Optic Nerve Head Morphology in Humans and Pig Model.

PURPOSE: The lamina cribrosa (LC) is a layer of fenestrated connective tissue tethered to the posterior sclera across the scleral canal in the optic nerve head (ONH). It is located at the interface of intracranial and intraocular compartments and is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) or Cerebrospinal fluid (CSF) pressure (CSFP) posteriorly. We hypothesize that the pressure difference across LC will determine LC position and meridional diameter of scleral canal (also called Bruch's membrane opening diameter; BMOD). METHODS: We enrolled 19 human subjects undergoing a medically necessary lumbar puncture (LP) to lower CSFP and 6 anesthetized pigs, whose ICP was increased in 5 mm Hg increments using a lumbar catheter. We imaged ONH using optical coherence tomography and measured IOP and CSFP/ICP at baseline and after each intervention. Radial tomographic ONH scans were analyzed by two independent graders using ImageJ, an open-source software. The following ONH morphological parameters were obtained: BMOD, anterior LC depth and retinal thickness. We modeled effects of acute CSFP/ICP changes on ONH morphological parameters using ANOVA (human study) and generalized linear model (pig study). RESULTS: For 19 human subjects, CSFP ranged from 5 to 42 mm Hg before LP and 2 to 19.4 mm Hg after LP. For the six pigs, baseline ICP ranged from 1.5 to 9 mm Hg and maximum stable ICP ranged from 18 to 40 mm Hg. Our models showed that acute CSFP/ICP changes had no significant effect on ONH morphological parameters in both humans and pigs. CONCLUSION: We conclude that ONH does not show measurable morphological changes in response to acute changes of CSFP/ICP. Proposed mechanisms include compensatory and opposing changes in IOP and CSFP/ICP and nonlinear or nonmonotonic effects of IOP and CSFP/ICP across LC.

Vision, attention, and driving.

Safe driving demands the coordination of multiple sensory and cognitive functions, such as vision and attention. Patients with neurologic or ophthalmic disease are exposed to selective pathophysiologic insults to driving-critical systems, placing them at a higher risk for unsafe driving and restricted driving privileges. Here, we evaluate how vision and attention contribute to unsafe driving across different patient populations. In ophthalmic disease, we focus on macular degeneration, glaucoma, diabetic retinopathy, and cataract; in neurologic disease, we focus on Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Unsafe driving is generally associated with impaired vision and attention in ophthalmic and neurologic patients, respectively. Furthermore, patients with ophthalmic disease experience some degree of impairment in attention. Similarly, patients with neurologic disease experience some degree of impairment in vision. While numerous studies have demonstrated a relationship between impaired vision and unsafe driving in neurologic disease, there remains a dearth of knowledge regarding the relationship between impaired attention and unsafe driving in ophthalmic disease. In summary, this chapter confirms-and offers opportunities for future research into-the contribution of vision and attention to safe driving.

Predictors of Intraocular Pressure Lowering after Phacoemulsification and iStent Implantation.

PURPOSE: To explore the demographic and clinical variables associated with intraocular pressure (IOP) lowering after cataract extraction (CE) alone or CE in combination with the iStent (Glaukos Corporation) placement (CE+IS). DESIGN: Retrospective data extraction and survival analysis of consecutive patients identified over a 2-year period. PARTICIPANTS: Patients with mild to moderate glaucoma who underwent CE (48 eyes of 32 patients) or CE+IS (61 eyes of 37 patients) were analyzed. METHODS: Inability to reduce the number of medications or the IOP by at least 20% compared with baseline on 2 consecutive visits was considered surgical failure. Using Cox proportional hazards models, survival analysis was performed, and demographic and clinical variables were evaluated as risk factors. MAIN OUTCOME MEASURES: Time to failure after surgical procedure. RESULTS: CE+IS had lower odds of failure than CE alone (hazard ratio [HR], 2.01; P = 0.047). In White patients, CE+IS showed greater odds of success compared with CE alone (HR, 2.86; P = 0.007). For non-White patients, no difference was found in the outcomes for the 2 procedures (HR, 0.59; P = 0.48). In the multivariate analysis, non-White race (HR, 8.75; P = 0.0002) and longer axial length (HR, 1.61; P = 0.03) were associated with greater hazard of failure after CE+IS. In the CE group, greater odds of failure were associated with steeper corneal curvature (HR, 1.74; P = 0.008), shallower anterior chamber (HR, 0.22; P = 0.008), and longer axial length (HR, 1.58; P = 0.01). CONCLUSIONS: Addition of the iStent to CE improved the duration of IOP lowering in White patients, but not in non-White patients. Associations between IOP lowering after CE and biometric parameters may allow for leveraging these clinical parameters for better case selection for these procedures.

The Effects of Acute Intracranial Pressure Changes on the Episcleral Venous Pressure, Retinal Vein Diameter and Intraocular Pressure in a Pig Model.

PURPOSE: Orbital veins such as the retinal veins and episcleral veins drain into the cavernous sinus, an intracranial venous structure. We studied the effects of acute intracranial pressure (ICP) elevation on episcleral venous pressure, intraocular pressure and retinal vein diameter in an established non-survival pig model. METHODS: In six adult female domestic pigs, we increased ICP in 5 mm Hg increments using saline infusion through a lumbar drain. We measured ICP (using parenchymal pressure monitor), intraocular pressure (using pneumatonometer), episcleral venous pressure (using venomanometer), retinal vein diameter (using OCT images) and arterial blood pressure at each stable ICP increment. The average baseline ICP was 5.4 mm Hg (range 1.5-9 mm Hg) and the maximum stable ICP ranged from 18 to 40 mm Hg. Linear mixed models with random intercepts were used to evaluate the effect of acute ICP increase on outcome variables. RESULTS: With acute ICP elevation, we found loss of retinal venous pulsation and increased episcleral venous pressure, intraocular pressure and retinal vein pressure in all animals. Specifically, acute ICP increase was significantly associated with episcleral venous pressure (ß = 0.31; 95% CI 0.14-0.48, p < .001), intraocular pressure (ß = 0.37, 95%CI 0.24-0.50; p < .001) and retinal vein diameter (ß = 11.29, 95%CI 1.57-21.00; p = .03) after controlling for the effects of arterial blood pressure. CONCLUSION: We believe that the ophthalmic effects of acute ICP elevation are mediated by increased intracranial venous pressure producing upstream pressure changes within the orbital and retinal veins. These results offer exciting possibilities for the development of non-invasive ophthalmic biomarkers to estimate acute ICP elevations following significant neuro-trauma.

Glaucomatous visual fields and neurocognitive function are independently associated with poor lane maintenance during driving simulation.

BACKGROUND: Driving simulators are a safe alternative to on-road vehicles for studying driving behavior in glaucoma drivers. Visual field (VF) loss severity is associated with higher driving simulator crash risk, though mechanisms explaining this relationship remain unknown. Furthermore, associations between driving behavior and neurocognitive performance in glaucoma are unexplored. Here, we evaluated the hypothesis that VF loss severity and neurocognitive performance interact to influence simulated vehicle control in glaucoma drivers. METHODS: Glaucoma patients (n = 25) and suspects (n = 18) were recruited into the study. All had > 20/40 corrected visual acuity in each eye and were experienced field takers with at least three stable (reliability > 20%) fields over the last 2 years. Diagnosis of neurological disorder or cognitive impairment were exclusion criteria. Binocular VFs were derived from monocular Humphrey VFs to estimate a binocular VF index (OU-VFI). Montreal Cognitive Assessment (MoCA) was administered to assess global and sub-domain neurocognitive performance. National Eye Institute Visual Function Questionnaire (NEI-VFQ) was administered to assess peripheral vision and driving difficulties sub-scores. Driving performance was evaluated using a driving simulator with a 290° panoramic field of view constructed around a full-sized automotive cab. Vehicle control metrics, such as lateral acceleration variability and steering wheel variability, were calculated from vehicle sensor data while patients drove on a straight two-lane rural road. Linear mixed models were constructed to evaluate associations between driving performance and clinical characteristics. RESULTS: Patients were 9.5 years older than suspects (p = 0.015). OU-VFI in the glaucoma group ranged from 24 to 98% (85.6 ± 18.3; M ± SD). OU-VFI (p = .0066) was associated with MoCA total (p = .0066) and visuo-spatial and executive function sub-domain scores (p = .012). During driving simulation, patients showed greater steering wheel variability (p = 0.0001) and lateral acceleration variability (p < .0001) relative to suspects. Greater steering wheel variability was independently associated with OU-VFI (p = .0069), MoCA total scores (p = 0.028), and VFQ driving sub-scores (p = 0.0087), but not age (p = 0.61). CONCLUSIONS: Poor vehicle control was independently associated with greater VF loss and worse neurocognitive performance, suggesting both factors contribute to information processing models of driving performance in glaucoma. Future research must demonstrate the external validity of current findings to on-road performance in glaucoma.

Surgical interventions for primary congenital glaucoma.

BACKGROUND: Primary congenital glaucoma (PCG) is an optic neuropathy with high intraocular pressure (IOP) that manifests within the first few years of a child's life and is not associated with other systemic or ocular abnormalities. PCG results in considerable morbidity even in high-income countries. OBJECTIVES: To compare the effectiveness and safety of different surgical techniques for PCG. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2020, Issue 4); Ovid MEDLINE; Embase.com; PubMed; metaRegister of Controlled Trials (mRCT) (last searched 23 June 2014); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 27 April 2020. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs comparing different surgical interventions in children under five years of age with PCG. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included 16 trials (13 RCTs and three quasi-RCTs) with 587 eyes in 446 children. Eleven (69%) trials were conducted in Egypt and the Middle East, three in India, and two in the USA. All included trials involved children younger than five years of age, with follow-up ranging from six to 80 months. The interventions compared varied across trials. Three trials (on 68 children) compared combined trabeculotomy and trabeculectomy (CTT) with trabeculotomy. Meta-analysis of these trials suggests there may be little to no evidence of a difference between groups in mean IOP (mean difference (MD) 0.27 mmHg, 95% confidence interval (CI) -0.74 to 1.29; 88 eyes; 2 studies) and surgical success (risk ratio (RR) 1.01, 95% CI 0.90 to 1.14; 102 eyes; 3 studies) at one year postoperatively. We assessed the certainty of evidence as very low for these outcomes, downgrading for risk of bias (-1) and imprecision (-2). Hyphema was the most common adverse outcome in both groups (no meta-analysis due to considerable heterogeneity; I2 = 83%). Two trials (on 39 children) compared viscotrabeculotomy to conventional trabeculotomy. Meta-analysis of 42 eyes suggests there is no evidence of between groups difference in mean IOP (MD -1.64, 95% CI -5.94 to 2.66) and surgical success (RR 1.11, 95% CI 0.70 to 1.78) at six months postoperatively. We assessed the certainty of evidence as very low, downgrading for risk of bias and imprecision due to small sample size. Hyphema was the most common adverse outcome (38% in viscotrabeculotomy and 28% in conventional trabeculotomy), with no evidence of difference difference (RR 1.33, 95% CI 0.63 to 2.83). Two trials (on 95 children) compared microcatheter-assisted 360-degree circumferential trabeculotomy to conventional trabeculotomy. Meta-analysis of two trials suggests that mean IOP may be lower in the microcatheter group at six months (MD -2.44, 95% CI -3.69 to -1.19; 100 eyes) and at 12 months (MD -1.77, 95% CI -2.92 to -0.63; 99 eyes); and surgical success was more likely to be achieved in the microcatheter group compared to the conventional trabeculotomy group (RR 1.59, 95% CI 1.14 to 2.21; 60 eyes; 1 trial at 6 months; RR 1.54, 95% CI 1.20 to 1.97; 99 eyes; 2 trials at 12 months). We assessed the certainty of evidence for these outcomes as moderate due to small sample size. Hyphema was the most common adverse outcome (40% in the microcatheter group and 17% in the conventional trabeculotomy group), with greater likelihood of occurring in the microcatheter group (RR 2.25, 95% CI 1.25 to 4.04); the evidence was of moderate certainty due to small sample size (-1). Of the nine remaining trials, no two trials compared the same two surgical interventions: one trial compared CTT versus CTT with sclerectomy; three trials compared various suturing techniques and adjuvant use including mitomycin C, collagen implant in CTT; one trial compared CTT versus Ahmed valve implant in previously failed surgeries; one trial compared CTT with trabeculectomy; one trial compared trabeculotomy to goniotomy; and two trials compared different types of goniotomy. No trials reported quality of life or economic data. Many of the included trials had limitations in study design, implementation, and reporting, therefore the reliability and applicability of the evidence remains unclear. AUTHORS' CONCLUSIONS: The evidence suggests that there may be little to no evidence of difference between CTT and routine conventional trabeculotomy, or between viscotrabeculotomy and routine conventional trabeculotomy. A 360-degree circumferential trabeculotomy may show greater surgical success than conventional trabeculotomy. Considering the rarity of the disease, future research would benefit from a multicenter, possibly international trial, involving parents of children with PCG and with a follow-up of at least one year.

Effect of Near Work on Intraocular Pressure in Emmetropes.

OBJECTIVE: To determine whether accommodation induced by reading alters intraocular pressure (IOP) in healthy, young, emmetropic adults and to document the duration and magnitude of this effect. DESIGN: Cross-sectional study. Participants. Fifteen healthy, emmetropic young adults. METHODS: Subjects performed 20 minutes of near work (reading at 33 cm) followed by 20 minutes of far work (reading at 520 cm) while IOP was measured using an iCare tonometer at baseline and every 5 minutes thereafter. Statistical analysis was performed using repeated measures ANOVA. Main Outcome Measures. Intraocular pressure. RESULTS: IOP decreased significantly compared to baseline IOP after 10 minutes of near work (average change of -1.60 ± 2.2 (SD) mm Hg, p < 0.05). IOP remained lower than baseline IOP throughout all subsequent near and far work. The difference in IOP at the end of experimentation compared to baseline IOP was -1.87 ± 1.81 mm Hg (p < 0.05). IOP remained lower than baseline IOP throughout all subsequent near and far work. The difference in IOP at the end of experimentation compared to baseline IOP was -1.87 ± 1.81 mm Hg (. CONCLUSIONS: Near work decreases IOP in healthy emmetropes, and this effect is sustained for at least 20 minutes after discontinuing prolonged near work. Providers may need to consider this effect when measuring IOP in clinical practice.

Pneumotonometer Accuracy Using Manometric Measurements after Radial Keratotomy, Clear Corneal Incisions and Lamellar Dissection in Porcine Eyes.

Purpose/Aim of the study: Measured intraocular pressure (IOP) after corneal incisions may not be reflective of the true IOP because of changes in corneal biomechanical properties. The purpose of this study is to investigate the effect of various corneal incisions on pneumotonometer accuracy in enucleated porcine eyes.Materials and Methods: A pneumotonometer was used to measure IOP (IOPp) at manometrically controlled pressure levels of 10, 20, 30 and 40 mmHg in enucleated porcine eyes. IOP measurements at each level were repeated after one of the following corneal incisions: radial keratotomy (8 eyes), lamellar dissection (10 eyes), clear cornea standard phacoemulsification incisions (10 eyes). The pneumotonometer error, defined as the difference between IOPp and manometric pressure (IOPm), was calculated for each pressure level. The error before the corneal incisions was compared to the error after the corneal incisions to assess the accuracy of the pneumotonometer.Results: The pneumotonometer underestimates true IOP at all pressure levels, both before and after the corneal procedures. There was a statistically significant greater underestimation of IOP after radial keratotomy incisions at pressure levels of 20, 30 and 40 mmHg (p = .013, 0.004, and 0.002, respectively). There was no statistically significant difference in the amount of pneumotonometer underestimation error after lamellar dissection or standard cataract incisions.Conclusion: The pneumotonometer underestimates true IOP in enucleated porcine eyes at all pressure levels between 10-40 mmHg. Radial keratotomy incisions caused a statistically significant greater underestimation error in pneumotonometry measurements at pressures of 20-40 mmHg. Lamellar dissection and clear corneal cataract incisions did not cause an additional error in pneumotonometry measurements in enucleated porcine eyes.

Early-Stage Ocular Hypertension Alters Retinal Ganglion Cell Synaptic Transmission in the Visual Thalamus.

Axonopathy is a hallmark of many neurodegenerative diseases including glaucoma, where elevated intraocular pressure (ocular hypertension, OHT) stresses retinal ganglion cell (RGC) axons as they exit the eye and form the optic nerve. OHT causes early changes in the optic nerve such as axon atrophy, transport inhibition, and gliosis. Importantly, many of these changes appear to occur prior to irreversible neuronal loss, making them promising points for early diagnosis of glaucoma. It is unknown whether OHT has similarly early effects on the function of RGC output to the brain. To test this possibility, we elevated eye pressure in mice by anterior chamber injection of polystyrene microbeads. Five weeks post-injection, bead-injected eyes showed a modest RGC loss in the peripheral retina, as evidenced by RBPMS antibody staining. Additionally, we observed reduced dendritic complexity and lower spontaneous spike rate of On-αRGCs, targeted for patch clamp recording and dye filling using a Opn4-Cre reporter mouse line. To determine the influence of OHT on retinal projections to the brain, we expressed Channelrhodopsin-2 (ChR2) in melanopsin-expressing RGCs by crossing the Opn4-Cre mouse line with a ChR2-reporter mouse line and recorded post-synaptic responses in thalamocortical relay neurons in the dorsal lateral geniculate nucleus (dLGN) of the thalamus evoked by stimulation with 460 nm light. The use of a Opn4-Cre reporter system allowed for expression of ChR2 in a narrow subset of RGCs responsible for image-forming vision in mice. Five weeks following OHT induction, paired pulse and high-frequency stimulus train experiments revealed that presynaptic vesicle release probability at retinogeniculate synapses was elevated. Additionally, miniature synaptic current frequency was slightly reduced in brain slices from OHT mice and proximal dendrites of post-synaptic dLGN relay neurons, assessed using a Sholl analysis, showed a reduced complexity. Strikingly, these changes occurred prior to major loss of RGCs labeled with the Opn4-Cre mouse, as indicated by immunofluorescence staining of ChR2-expressing retinal neurons. Thus, OHT leads to pre- and post-synaptic functional and structural changes at retinogeniculate synapses. Along with RGC dendritic remodeling and optic nerve transport changes, these retinogeniculate synaptic changes are among the earliest signs of glaucoma.

Indirect Traumatic Optic Neuropathy Induced by Primary Blast: A Fluid-Structure Interaction Study.

Current knowledge of traumatic ocular injury is still limited as most studies have focused on the ocular injuries that happened at the anterior part of the eye, whereas the damage to the optic nerve known as traumatic optic neuropathy (TON) is poorly understood. The goal of this study is to understand the mechanism of the TON following the primary blast through a fluid-structure interaction model. An axisymmetric three-dimensional (3D) eye model with detailed orbital components was developed to capture the dynamics of the eye under the blast wave. Our numerical results demonstrated a transient pressure elevation in both vitreous and cerebrospinal fluid (CSF). A high strain rate over 100 s-1 was observed throughout the optic nerve during the blast with the most vulnerable part located at the intracanalicular region. The optic nerve deforming at such a high strain rate may account for the axonal damage and vision loss in patients subjected to the primary blast. The results from this work would enhance the understanding of indirect TON and provide guidance in the design of protective eyewear against such injury.

Relative Contributions of Intracranial Pressure and Intraocular Pressure on Lamina Cribrosa Behavior.

PURPOSE: To characterize the relative contributions of intraocular pressure (IOP) and intracranial pressure (ICP) on lamina cribrosa (LC) behavior, specifically LC depth (LCD) and LC peak strain. METHODS: An axially symmetric finite element model of the posterior eye was constructed with an elongated optic nerve and retro-orbital subarachnoid space ensheathed by pia and dura mater. The mechanical environment in LC was evaluated with ICP ranging from 5 to 15 mmHg and IOP from 10 to 45 mmHg. LCD and LC peak strains at various ICP and IOP levels were estimated using full factorial experiments. Multiple linear regression analyses were then applied to estimate LCD and LC peak strain using ICP and IOP as independent variables. RESULTS: Both increased ICP and decreased IOP led to a smaller LCD and LC peak strain. The regression correlation coefficient for LCD was -1.047 for ICP and 1.049 for IOP, and the ratio of the two regression coefficients was -1.0. The regression correlation coefficient for LC peak strain was -0.025 for ICP and 0.106 for IOP, and the ratio of the two regression coefficients was -0.24. A stiffer sclera increased LCD but decreased LC peak strain; besides, it increased the relative contribution of ICP on the LCD but decreased that on the LC peak strain. CONCLUSIONS: ICP and IOP have opposing effects on LCD and LC peak strain. While their effects on LCD are equivalent, the effect of IOP on LC peak strain is 3 times larger than that of ICP. The influences of these pressure are dependent on sclera material properties, which might explain the pathogenesis of ocular hypertension and normal-tension glaucoma.

The Water-Drinking Test Revisited: An Analysis of Test Results in Subjects with Glaucoma.

PURPOSE: The Water-Drinking Test (WDT) has been shown to predict the diurnal IOP change. This study evaluates the factors that may affect the WDT results. METHODS: This study was conducted on 203 glaucoma patients who had undergone trabeculectomy (53) or tube surgery (31), or had a medically controlled open-angle (82) or closed-angle (37) glaucoma. IOP was measured at baseline and then every 15 minutes over a one-hour period after drinking water. The main outcome measures were IOP change (increase in IOP from baseline) at all measurement time points, IOP peak (highest IOP after drinking water), IOP fluctuation (difference between IOP peak and baseline), and assessing the association of these IOPs with a patient's demographic and management modalities. RESULTS: The mean age of the participants was 54±18 years, and 113 (56%) were male. Female patients showed greater IOP fluctuation than males (7.28 vs. 5.92 mm Hg; P=0.016), and a greater IOP peak (22.7 vs. 20.1 mm Hg; P=0.001). The observed associations between gender and IOP changes were only significant in <50 years. IOP at 60 minutes was greater in tube than trabeculectomy (5.6 vs. 3.1 mm Hg; P=0.007). The number of topical medications showed a direct independent association with IOP changes (P<0.001). Compared to other classes of topical medications, latanoprost showed lower WDT-IOP profile (P=0.0003). CONCLUSIONS: WDT-IOP change was diminished in subjects on latanoprost, and was greater in females <50 years, and those on greater number of medications.

Intracranial Pressure Influences the Behavior of the Optic Nerve Head.

In this work, the biomechanical responses of the optic nerve head (ONH) to acute elevations in intracranial pressure (ICP) were systematically investigated through numerical modeling. An orthogonal experimental design was developed to quantify the influence of ten input factors that govern the anatomy and material properties of the ONH on the peak maximum principal strain (MPS) in the lamina cribrosa (LC) and postlaminar neural tissue (PLNT). Results showed that the sensitivity of ONH responses to various input factors was region-specific. In the LC, the peak MPS was most strongly dependent on the sclera thickness, LC modulus, and scleral canal size, whereas in the PLNT, the peak MPS was more sensitive to the scleral canal size, neural tissue modulus, and pia mater modulus. The enforcement of clinically relevant ICP in the retro-orbital subarachnoid space influenced the sensitivity analysis. It also induced much larger strains in the PLNT than in the LC. Moreover, acute elevation of ICP leads to dramatic strain distribution changes in the PLNT, but had minimal impact on the LC. This work could help to better understand patient-specific responses, to provide guidance on biomechanical factors resulting in optic nerve diseases, such as glaucoma, papilledema, and ischemic optic neuropathy, and to illuminate the possibilities for exploiting their potential to treat and prevent ONH diseases.

Optic nerve morphology as marker for disease severity in cerebral palsy of perinatal origin.

BACKGROUND: It is difficult to predict the neurologic outcome and ambulatory status in children with perinatal neurologic insult until 2-5years age. This study aims to correlate clinical optic nerve head (ONH) findings-cupping, pallor and hypoplasia, with gestational period and neurologic (motor) outcomes in patients with cerebral palsy (CP) from perinatal insults. METHODS: 54 consecutive patients with CP from perinatal insults were enrolled. Patients with intraocular disease, retinopathy of prematurity and hydrocephalus were excluded. ONH was labeled as pale, hypoplastic or large cup (cup/disc ratio≥0.5) if 2 ophthalmologists independently agreed after an ophthalmoscopic examination. Inter-rater reliability was excellent. RESULTS: Mean age at examination was 10.98±6.49years; mean gestational period was 33.26±4.78weeks. Abnormal ONH (pallor, cupping or hypoplasia) was seen in 38/54 (70%) patients. Of patients with pallor (n=17), 88% were quadriplegic and 82% non-ambulatory. Mean cup/disc ratio was 0.45±0.22; 50% patients had large cup. Multivariate logistic regression models showed that disc pallor was associated with non-ambulatory status (OR: 21.7; p=0.003) and quadriplegia (OR: 12.8; p=0.03). Large cup was associated with age at examination (OR 1.15; p=0.03). Cup/disc ratio showed positive correlation with age at examination (Pearson's r=0.39; p=0.003). There was no significant association of ONH parameters with gestational age. CONCLUSION: Clinically observed ONH changes (pallor, cupping and hypoplasia) are common in CP. Presence of ONH pallor serves as an indicator for poor motor outcome in patients who develop CP from perinatal causes and should prompt early referral for rehabilitation.