Anxiety in visual field testing.

BACKGROUND: To determine if Humphrey visual field (HVF) testing induces anxiety and how anxiety relates to visual field parameters of reliability and severity. DESIGN: A prospective cohort study at a university affiliated private ophthalmic practice. PARTICIPANTS: 137 consecutive age-matched and gender-matched patients with glaucoma undergoing either HVF testing only (n=102) or Heidelberg retinal tomography (HRT) only (n=35) were enrolled. METHODS: Prior to testing, participants completed the State-Trait Anxiety Inventory questionnaire. A 5-point Likert scale was used to grade pretest anxiety and was repeated after testing to grade intratest anxiety. Subjective discomfort parameters were also recorded. MAIN OUTCOME MEASURES: Anxiety scores were used to make non-parametrical comparisons and correlations between cohorts and also against visual field reliability and severity indices. RESULTS: Trait anxiety (p=0.838) and pretest anxiety (p=0.802) were not significantly different between test groups. Within the HVF group, intratest anxiety was 1.2 times higher than pretest anxiety (p=0.0001), but was not significantly different in the HRT group (p=0.145). Pretest anxiety was correlated with test unreliability (Spearman's r=0.273, p=0.006), which was predictive of worse test severity (p=0.0027). Subjects who had undergone more than 10 visual field tests had significantly lower pretest and intratest anxiety levels than those who had not (p=0.0030 and p=0.0004, respectively). CONCLUSIONS: HVF testing induces more anxiety than HRT. Increased pretest anxiety may reduce HVF test reliability. Increased test experience or interventions aimed at reducing pretest anxiety may result in improved test reliability and accuracy.

Retinal and optic nerve changes in glaucoma: From animal study to clinical implication.

Animal models of experimental glaucoma provide the ability to longitudinally characterize changes in the optic nerve head and surrounding retinal nerve fiber layer with various imaging modalities and compare them to histomorphometric changes. Analysis of the optic nerve head surface by confocal scanning laser tomography and structures deep to this by spectral domain optical coherence tomography allow for the detection of the earliest structural changes seen in glaucoma. Algorithms utilizing these parameters along with retinal nerve fiber layer measurement are likely to play an important role in the future of glaucoma progression monitoring.

Response of retinal Connexin43 to optic nerve injury.

PURPOSE: To characterize the spatial and temporal expression of Connexin43 (Cx43) after partial optic nerve transection and evaluate its relationship to retinal ganglion cell (RGC) loss and retinal glial response. METHODS: Partial, unilateral, superior optic nerve transection was performed in 150 Wistar rats. The retinas were evaluated at 8 and 24 hours and 3, 7, 14, 28, and 56 days after injury. Immunohistochemical analysis identified changes in several markers including Cx43 immunoreactivity (ir), RGC counts (Brn3a), and retinal astrocytes (GFAP). RESULTS: After injury, superior retinal Cx43-ir peaked at 3 days (192.1% of control; P = 0.0002) and 28 days (212.1% of control; P < 0.0001) and troughed at 14 days (73.8% of control; P = 0.0028) and 56 days (72.5% of control; P = 0.0232). Inferior retinal Cx43-ir was elevated at only 28 days (127.4% increase; P = 0.0481). Superior RGC loss began at 3 days (84.0% of control; P = 0.0454) and continued to decline by 56 days (18.8% of control; P < 0.0001). Inferior RGC loss began at 28 days (73.4% of control; P = 0.0021). An increase in GFAP-ir occurred in the superior retina from day 3 (153.7% of control; P = 0.0017) and from day 28 (186.7% of control; P = 0.0013) in the inferior retina, persisting in both the superior and inferior retina to 56 days (P = 0.0027). CONCLUSIONS: A biphasic upregulation of retinal Cx43 protein occurs in the superior retina with peaks at 3 and 28 days after injury, but at only 28 days in the inferior retina. There is an associated loss of RGCs and a retinal astrocytic inflammatory response.

Acute primary angle closure attack does not cause an increased cup-to-disc ratio.

PURPOSE: To determine if an increased cup-to-disc ratio (CDR) and retinal nerve fiber layer (RNFL) loss occur after acute primary angle closure (APAC). DESIGN: Prospective, observational case series. PARTICIPANTS: Twenty participants with unilateral APAC provided 20 affected eyes and 20 fellow eyes (controls) for analysis. METHODS: After initial presentation, participants attended 3 further assessments over a 12-month period (visit 2, within 2 weeks; visit 3, 2-3 months; and visit 4, 6-12 months), in which they underwent the following investigations: Heidelberg Retinal Tomography (Heidelberg Engineering, Dossenheim, Germany), optical coherence tomography of the RNFL and macula, and automated perimetry. MAIN OUTCOME MEASURES: Cup-to-disc ratio, optic cup area, neuroretinal rim area, RNFL thickness, macular thickness, and volume. RESULTS: There was no change from visits 2 to 4 in CDR (0.46 ± 0.17 vs. 0.47 ± 0.20; P = 0.94), neuroretinal rim area (1.64 ± 0.55 vs. 1.64 ± 0.57; P = 0.96), or other optic nerve head parameters analyzed in eyes with APAC. The mean overall RNFL thickness decreased from 106.6 ± 17.9 µm to 92.9 ± 18.3 µm between visits 2 and 3 (P<0.01) in affected eyes. The superior quadrant RNFL thickness decreased from 134.8 ± 25.9 µm to 113 ± 25.7 µm (P<0.01), and the inferior quadrant RNFL thickness decreased from 139.1 ± 28.4 µm to 115.6 ± 24.9 µm (P<0.01). There was no significant change in macular thickness or volume. CONCLUSIONS: This study demonstrated that an increase in CDR does not occur after APAC that is treated promptly, although RNFL loss does occur.

Role of connexin43 in central nervous system injury.

Gap junctions are specialized cell-to-cell contacts that provide direct intercellular communication. In the central nervous system (CNS), gap junction coupling occurs between both neurons and glial cells. One of the most abundant gap junction proteins in the CNS is connexin43 (Cx43). The functional syncytium formed by astrocytes via Cx43 gap junction intercellular communication has, for example, been implicated in maintaining the homeostasis of the extracellular milieu of neurons. In particular, astrocytes are involved in the spatial buffering of many ions, signalling molecules and energy sources. In this review, the role of Cx43 following CNS injury is examined by combining evidence surrounding the response of Cx43 to CNS injury and the effects of Cx43 gap junction blockade on neuronal survival in various models of injury. Combined evidence suggests that transient blockade targeting the window of initial Cx43 upregulation observed following injury is potentially therapeutic.

Retinal nerve fiber layer loss in glaucoma patients with a relative afferent pupillary defect.

PURPOSE: To assess the amount of structural loss (retinal nerve fiber layer [RNFL] thickness loss, macular thickness [MT] and volume [MV] measured by optical coherence tomography [OCT]) and functional loss (visual acuity [VA], visual field mean deviation [MD], brightness sensitivity, and red perception) necessary for a relative afferent pupillary defect (RAPD) to manifest in patients with glaucoma. METHODS: In this case-control study, 50 glaucoma patients were prospectively enrolled: 25 with RAPD and 25 without. The presence of an RAPD was determined and quantified using the swinging-flashlight test, with neutral-density filters. A separate examiner, masked to the pupillary findings, assessed participants for brightness sense, red perception, VA, MD, RNFL thickness, MT, and MV. RESULTS: Differences in RNFL thickness (P < 0.0001), brightness sense (P = 0.0007), red perception (P = 0.030), and MD (P < 0.0001) were found between control and RAPD patients, but not in visual acuity or macular OCT parameters. An absolute difference in RNFL thickness of 14.6 µm or greater, intereye difference of 9.5 dB or greater, and brightness of less than 64% in the weaker eye, were all associated with 100% specificity of RAPD presence. When RNFL thickness was reduced to 83% of the less advanced eye, the sensitivity and specificity of RAPD presence were 72% (95% confidence interval [CI], 0.51-0.88) and 100% (95% CI, 0.86-1.00), respectively. CONCLUSIONS: An RAPD was clinically detected in all participants in whom RNFL thickness decreased to 83% of that in the less advanced eye. Subjective brightness is the most accurate clinical surrogate for detecting an RAPD in patients with primary open-angle glaucoma.