High rate of conversion from ocular hypertension to glaucoma in subjects with uveitis.

AIMS: To examine presentation, management and long-term sequelae of ocular hypertension and uveitic glaucoma. METHODS: Retrospective observational study of all subjects with uveitic glaucoma or ocular hypertension seen in Auckland uveitis clinics over the last 10 years. RESULTS: A total of 188 eyes of 139 subjects with uveitic glaucoma or ocular hypertension were included for analysis. Total follow-up was 1854.5 eye years (mean 9.9 years). The mean age at uveitis diagnosis was 49.3 years. 52.5% of subjects were male. The most common diagnoses were idiopathic uveitis (29.3%), sarcoidosis (13.3%), herpes zoster (6.9%), HLA-B27 uveitis (6.9%), tuberculosis (5.9%) and Posner-Schlossmann or cytomegalovirus (CMV) uveitis (5.3%). Median intraocular pressure (IOP) at diagnosis was 35 mm Hg (IQR 29-45). 144 eyes (77.0%) developed glaucoma during the follow-up period, of whom 41 lost some central vision due to glaucoma. Oral acetazolamide was required for IOP control in 64.5%, 50 eyes underwent trabeculectomy, 18 eyes required a tube and 6 underwent minimally invasive glaucoma surgery. CONCLUSION: Rapid progression was observed from ocular hypertension to uveitic glaucoma. Uveitic glaucoma is aggressive, with high likelihood of requiring surgical management and high risk of central vision loss. Close collaboration between uveitis and glaucoma specialists is required to maximise outcomes for these patients.

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.

Patient satisfaction with topical ocular hypotensives.

BACKGROUND: The aim of this study is to assess patient satisfaction, convenience of use, ease of administration, side effects and treatment burden of topical ocular hypotensives. DESIGN: Prospective, observational cohort. PARTICIPANTS: Two thousand five hundred and forty-one patients with glaucoma or ocular hypertension. METHODS: The Treatment Impact Patient Satisfaction Scale (TIPSS) was administered by mail to all patients with glaucoma or ocular hypertension registered with Glaucoma New Zealand during a 3-month study period. The questionnaire assessed patient demographics; topical ocular hypotensive use including number of medications, frequency of administration, ease of use, class of medication, and presence/severity of side effects; impact on quality of life; and patient satisfaction. Univariate and multivariate analyses were performed to identify determinants of patient satisfaction. MAIN OUTCOME MEASURES: Patient satisfaction. RESULTS: Almost 80% of respondents were either 'very satisfied' or 'satisfied' with topical ocular hypotensives. Factors that were predictive of patient satisfaction included satisfaction with frequency of eye drop use {odds ratio (OR) 2.4 (95% confidence interval [CI] 1.8-3.1); P < 0.001}, subjective convenience (OR 2.6 [95% CI 2.0-3.4]; P < 0.001) and ease of administration (OR 2.5 [95% CI 2.0-3.3]; P < 0.001). Male gender was associated with lower satisfaction (OR 0.6 [95% CI 0.5-0.9]; P = 0.01). Factors that were not predictive of patient satisfaction included age, duration of eye drop use, class of medication and the presence of side effects. CONCLUSIONS: Patients with glaucoma and ocular hypotension are satisfied with topical ocular hypotensives. Efforts to improve patient satisfaction should focus on convenience and ease of administration.

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.

Non-arteritic anterior ischaemic optic neuropathy: a review and update.

Non-arteritic anterior ischaemic optic neuropathy (NAION) is the most common acute optic neuropathy in people aged 50 years and older. The condition is caused by infarction of the laminar or retrolaminar portion of the optic nerve head supplied by the short posterior ciliary arteries (SPCAs). The underlying aetiology and pathophysiology is poorly elucidated. Factors that have been implicated include nocturnal hypotension, impaired autoregulation of the microvascular supply, vasculopathic occlusion, and venous insufficiency. These factors are thought to result in axonal oedema causing a compartment syndrome in a structurally crowded optic disc leading to axonal degeneration and loss of retinal ganglion cells via apoptosis. Clinically NAION is characterised by sudden, usually painless, loss of vision in one or both eyes. Examination findings include decreased visual acuity, a visual field defect, decreased colour vision, a relative afferent pupillary defect, and optic disc swelling. Despite significant research, treatment options for NAION remain limited.

Publication and citation analysis of the Australian and New Zealand Journal of Ophthalmology and Clinical and Experimental Ophthalmology over a 10-year period: the evolution of an ophthalmology journal.

PURPOSE: To analyse the pattern of change in publication content and citations generated by a mid-ranking ophthalmology journal as it evolved from the Australian and New Zealand Journal of Ophthalmology (ANZJO) to its successor, Clinical 0mp; Experimental Ophthalmology (CEO). METHODS: The Science Citation Index was used to analyse the publications of ANZJO and CEO over two 10-year periods (1990-1999 and 2000-2009, respectively). Publication and citation patterns were analysed in terms of source authors, institutions and countries. As a secondary measure, journal impact factors (JIFs) were retrieved from the Journal Citation Reports at the end of each period. RESULTS: Over the specified periods, 859 articles published in ANZJO were cited 1210 times, and 1529 articles published in CEO were cited 5374 times. Australia was the largest contributing country to both journals; however, the proportional contributions from other countries including New Zealand, UK, USA, India and China increased significantly in CEO. Articles were cited by authors from 793 institutions in 60 countries for ANZJO and 2997 institutions in 95 countries for CEO. The contribution by key authors (identified as the top 10 most-published authors) towards total journal publications was 24% in ANZJO, but only 16% in CEO; however, these publications were responsible for 26.6% and 28.8% of the total citations, respectively. With respect to the most recent JIFs, ANZJO was 0.433 in 1999 (ranked 33 of 43 journals) and CEO was 1.35 in 2008 (ranked 27 of 48 journals). CONCLUSION: CEO has substantially increased the number of publications, citation counts and international sources compared with its well-established predecessor, ANZJO, over the assessed periods. CEO also appears to have a higher international profile with increasing citations counts from more countries. This evolution from a regional, to a more international, journal has been substantial and is reflected by a significant increment in JIF, and a modest increase in overall JIF-ranking, for CEO.