Testing an aetiological model of visual hallucinations in Parkinson's disease.

The exact pathogenesis of visual hallucinations in Parkinson's disease is not known but an integrated model has been proposed that includes impaired visual input and central visual processing, impaired brainstem regulation of sleep-wake cycle with fluctuating vigilance, intrusion of rapid eye movement dream imagery into wakefulness and emergence of internally generated imagery, cognitive dysfunction and influence of dopaminergic drugs. In a clinical study, we assessed motor and non-motor function, including sleep, mood, autonomic and global, frontal and visuoperceptive cognitive function in patients with and without visual hallucinations. A subgroup of patients underwent detailed ophthalmological assessment. In a separate pathological study, histological specimens were obtained from cases of pathologically proven Parkinson's disease and a retrospective case notes review was made for reporting of persistent formed visual hallucinations. An assessment of Lewy body and Lewy neurite pathology was carried out in five cortical regions as recommended by diagnostic criteria for dementia with Lewy Bodies and in brainstem nuclei. Ninety-four patients (mean age 67.5 ± 9.5 years) participated in the clinical study of whom 32% experienced visual hallucinations. When corrected for multiple comparisons, patients with visual hallucinations had significantly greater disease duration, treatment duration, motor severity and complications, sleep disturbances, in particular excessive daytime somnolence and rapid eye movement sleep behavioural disorder, disorders of mood, autonomic dysfunction and global, frontal and visuoperceptive cognitive dysfunction. Of the 94 patients, 50 (53%) underwent ophthalmological assessment. There were no differences in ocular pathology between the visual hallucination and non-visual hallucination groups. In a logistic regression model the four independent determinants of visual hallucinations were rapid eye movement sleep behavioural disorder (P = 0.026), autonomic function (P = 0.004), frontal cognitive function (P = 0.020) and a test of visuoperceptive function (object decision; P = 0.031). In a separate study, post-mortem analysis was performed in 91 subjects (mean age at death 75.5 ± 8.0 years) and persistent visual hallucinations were documented in 63%. Patients in the visual hallucinations group had similar disease duration but had significantly higher Lewy body densities in the middle frontal (P = 0.002) and middle temporal gyri (P = 0.033) and transentorhinal (P = 0.005) and anterior cingulate (P = 0.020) cortices but not parietal cortex (P = 0.22). Using a comprehensive assessment of the clinical, demographic and ophthalmological correlates of visual hallucinations in Parkinson's disease, the combined data support the hypothesized model of impaired visual processing, sleep-wake dysregulation and brainstem dysfunction, and cognitive, particularly frontal, impairment all independently contributing to the pathogenesis of visual hallucinations in Parkinson's disease. These clinical data are supported by the pathological study, in which higher overall cortical Lewy body counts, and in particular areas implicated in visuoperception and executive function, were associated with visual hallucinations.

Incidence of Glaucoma Progression and Rate of Visual Field Deterioration in a Cohort of Urban Ghanaians.

PRCIS: The annual incidence of glaucoma progression (9.7%) and rates of visual field mean deviation (MD) change in progressors (-1.02±0.06 dB/y) are high in a small cohort of urban Ghanaians. PURPOSE: To report the incidence of glaucoma progression and the rate of visual field deterioration in a small cohort of Ghanaians. METHODS: One hundred ten subjects (204 eyes) diagnosed with glaucoma at a baseline population-based screening examination were re-examined a mean of 8.3±0.8 years later. Eyes were classified as having progressed if the optic disc alone, visual field alone or both showed significant glaucomatous changes on follow-up. Visual field MD was used to calculate the rate of visual field progression. RESULTS: Progression was observed in 89 (80.9%, 9.7%/year) subjects (130 eyes). Progression occurred in 32 (31.7%, 3.8%/year) subjects by optic disc alone (46 eyes), 38 (44.7%, 5.4%/year) subjects by visual field alone (58 eyes), and 19 (25.0%, 3.0%/year) subjects by both modalities (26 eyes). The average rate of change in MD differed significantly between progressors (-1.02±1.06 dB/y) and nonprogressors (+0.089±0.49 dB/y), P =0.001. The rate of visual field worsening was greater among those who were classified as having progressed by both structure and function (-1.29±0.68 dB/y) and by function alone (-1.21±1.20 dB/y) than by structure alone (-0.55±0.76 dB/y). Progression was significantly associated with older age [odds ratio (OR), 1.42; P <0.001] and higher baseline intraocular pressure (OR, 1.18; P =0.002). Factors associated with rate of MD change were baseline older age (OR, 1.66; P =0.003), higher intraocular pressure (OR, 2.81; P =0.007), better visual field MD (OR, 1.41; P =0.004), and systemic hypertension (OR, 1.15; P =0.029). CONCLUSION: The incidence and rate of visual field progression are high in this longitudinal study of Ghanaian subjects with glaucoma. The findings may have important clinical and public health policy ramifications.

Visual function and fitness to drive.

INTRODUCTION: Driving is recognized to be a visually intensive task and accordingly there is a legal minimum standard of vision required for all motorists. The purpose of this paper is to review the current United Kingdom (UK) visual requirements for driving and discuss the evidence base behind these legal rules. The role of newer, alternative tests of visual function that may be better indicators of driving safety will also be considered. Finally, the implications of ageing on driving ability are discussed. SOURCES OF DATA: A search of Medline and PubMed databases was performed using the following keywords: driving, vision, visual function, fitness to drive and ageing. In addition, papers from the Department of Transport website and UK Royal College of Ophthalmologists guidelines were studied. AREAS OF AGREEMENT, AREAS OF CONTROVERSY, GROWING POINTS, AREAS TIMELY FOR DEVELOPING RESEARCH: Current UK visual standards for driving are based upon historical concepts, but recent advances in technology have brought about more sophisticated methods for assessing the status of the binocular visual field and examining visual attention. These tests appear to be better predictors of driving performance. Further work is required to establish whether these newer tests should be incorporated in the current UK visual standards when examining an individual's fitness to drive.

Chronic anterior uveitis following bacille Calmette-Guérin vaccination: molecular mimicry in action?

A 13-year-old girl developed bilateral chronic anterior uveitis following bacille Calmette-Guérin (BCG) vaccination. HLA testing was negative for B27 but positive for DRB1 *0404, a variant of DR4 often associated with rheumatoid arthritis. The authors propose her HLA repertoire allowed for a BCG-induced abnormal autoimmune response by the mechanism of molecular mimicry.

Longitudinal Change in Central Corneal Thickness in the Tema Eye Survey.

PURPOSE: To determine the change and rate of change in central corneal thickness (CCT) and their determinants. DESIGN: Longitudinal observational population-based study. METHODS: A total of 758 normal and 58 glaucomatous subjects underwent complete eye examination, with CCT measurements at 2 separate visits. Change and rate of change in CCT were determined. Univariate and multivariate linear regression analyses were performed to determine the factors associated with change and rate of change. RESULTS: The mean follow-up duration was 8.4 ± 0.7 years. The overall change was -8.9 ± 16.7 µm in OD and -9.8 ± 16.2 µm in OS, both P < .0001. Changes in glaucomatous and normal subjects were -14.1 ± 2.2 µm vs -8.6 ± 0.6 µm in OD (P = .02) and -14.5 ± 2.2 µm vs -9.5 ± 0.6 µm in OS (P = .03), respectively. The overall rate of thinning was -1.1 µm/year (OD) and -1.2 µm/year (OS). Rates in glaucomatous and normal eyes were -1.7 ± 0.3 µm/year vs -1.0 ± 0.1 µm/year in OD (P = .02) and -1.7 ± 0.3 µm/year vs -1.1 ± 0.1 µm/year in OS (P = .03), respectively. Change and rate of change were associated with baseline CCT (ß = -0.1 to -0.09 and -0.011, respectively, all P < .001) and glaucoma (ß = -6.8 to -5.6, P ≤ .009, and -0.75 to -0.69, P ≤ .007, respectively). CONCLUSION: CCT decreased significantly over time. The change and rate of change were greater in glaucomatous than normal eyes, and were greater than described in cross-sectional studies.

Treatment of Recalcitrant Cyclitic Neovascular Pupillary Membranes.

PURPOSE: To describe a new approach for the treatment of cyclitic vascularized pupillary membranes. PATIENTS AND METHODS: A retrospective interventional case series describing 3 patients undergoing a novel interventional treatment at a single institutional center. RESULTS: This technique allows successful completion of laser membranectomy to create a pupillary aperture. This aperture resulted in improved vision and an enhanced ability to examine for and treat ischemic retinal disease. CONCLUSIONS: This technique describes a new use for bevacizumab that enables the surgeon to treat recalcitrant and recurrent cyclitic vascularized pupillary membranes.

Intravitreal bevacizumab in refractory neovascular glaucoma: a prospective, observational case series.

OBJECTIVE: To examine the efficacy of intravitreal bevacizumab for pain relief in eyes with refractory neovascular glaucoma. METHODS: In this prospective case series, 52 eyes with neovascular glaucoma were administered intravitreal bevacizumab, 1.25 mg, and monitored for 6 months. The primary outcome measure was change in subjective pain score. Intraocular pressure and iris neovascularization were evaluated at each visit. Surgical intervention for control of intraocular pressure was performed according to clinical need. RESULTS: Forty-two patients (44 eyes) completed the 6-month follow-up. Subjective pain score was reduced significantly 1 week after intravitreal bevacizumab injection and lasted throughout the follow-up period (median [interquartile range]: baseline, 3 [0-6]; week 1, 1 [0-3]; month 1, 0 [0-1]; month 3, 0 [0-1]; and month 6, 0 [0-0]; Kruskal-Wallis χ(2) 31.03; P < .001). A rapid, yet relatively transient, reduction in iris neovascularization was also noted (iris neovascularization grade at baseline, 4.0 [3-4]; week 1, 2.5 [1-4]; month 1, 2.0 [1-4]; month 3, 3.0 [2-4]; and month 6, 3.0 [2-4], χ(2) 23.33; P < .001). Four eyes (8%) required more than 1 injection to facilitate further intraocular surgery. CONCLUSIONS: Intravitreal bevacizumab is a useful adjunct in the management of refractory neovascular glaucoma, producing rapid relief of pain. However, we found no evidence to suggest that intravitreal bevacizumab lowers intraocular pressure in eyes with angle closure; conventional medical, laser, and surgical treatment are still needed in these eyes.

The relationship between diurnal variations in intraocular pressure measurements and central corneal thickness and corneal hysteresis.

PURPOSE: To examine the relationship between office-hour changes in IOP, measured with the Goldmann applanation tonometer (GAT) and dynamic contour tonometer (DCT), and the corneal characteristics central corneal thickness (CCT) and corneal hysteresis (CH). METHODS: Sixty-two eyes of 62 untreated normal subjects and patients with untreated glaucoma had IOP measurements performed with the GAT (mm Hg) and DCT (mm Hg) over an 8-hour period at 2-hour intervals beginning at 9 AM. CCT (micrometers) was measured using a noncontact optical low-coherence reflectometry (OLCR) pachymeter, and CH (mm Hg) was measured with an ocular response analyzer (ORA). The associations between IOP measurements and corneal characteristics for each patient over the measurement period were assessed by using multilevel modeling. RESULTS: GAT and DCT IOP and CCT changed significantly during office hours (ANOVA; GAT: F = 19.9, P < 0.001; DCT: F = 4.6, P = 0.001; CCT: F = 16.4; P < 0.001). No significant changes were observed in CH (ANOVA; F = 1.8, P = 0.13). Multilevel modeling analysis of the interrelationships between CCT, CH, and age on IOP measurements revealed that both CCT and CH changes were significantly associated with GAT IOP changes (GAT IOP/CCT slope, 0.04 mm Hg/microm; 95% confidence intervals [CIs], 0.02-0.06; GAT IOP/CH slope, 0.20 mm Hg/mm Hg; 95% CI, 0.01-0.39). CCT, but not CH, changes were significantly associated with DCT IOP changes (DCT IOP/CCT slope, 0.03 mm Hg/microm; 95% CI, 0.00-0.05). However, although the association between CCT and GAT IOP was relatively uniform between subjects, association between CCT and DCT IOP showed greater intersubject variability. Age had no effect on the diurnal variation of IOP measured with either device. CONCLUSIONS: Measured IOP and corneal characteristics covary during office hours. Changes in CCT and CH are associated with changes in GAT IOP and, less consistently, with DCT IOP. The data suggest that variations in corneal characteristics explain a small proportion of the change in IOP measurements made with the GAT during office hours.

Optic disc and visual field changes after trabeculectomy.

PURPOSE: To assess the changes in optic nerve head (ONH) structure and visual field (VF) sensitivity over time in a cohort of patients with glaucoma after trabeculectomy. METHODS: The MoreFlow Medical Research Council 5-Fluorouracil (5-FU) study was an 80-month prospective randomized controlled trial of per-operative 5-FU versus placebo on the outcomes of primary trabeculectomy. Before surgery, patients had ONH imaging with a retinal tomograph and full-threshold visual field testing. After surgery, ONH imaging was performed annually and VF testing at 4-month intervals. This analysis included only patients with a minimum of 3 years' postoperative ONH and VF data. ONH images were analyzed by linear regression of sector rim area (RA) over time with change defined as a significant slope >1% of baseline RA per year in any sector. VFs were analyzed with point-wise linear regression analysis (PLRA) techniques with the stringent three-omitting criteria used. Eyes were classed as progressing or not based on analysis with either technique. Patients' median IOP level, intervisit IOP fluctuation, and percentage reduction in IOP over the follow-up period were also determined. RESULTS: Two hundred fifty eyes of 250 patients were suitable for analysis. Of these, 70 (28%) eyes were deemed to show glaucoma progression approximately 5 years after surgery: 20 eyes by ONH alone, 35 by VF alone, and 15 by both methods. Of the 15 shown to be progressing by both ONH and VF analysis, only 7 (3% total cohort) showed congruity in the location of change. Eyes showing changes in both ONH and VF sensitivity had slightly higher median follow-up IOP (median IOP [interquartile range; IQR] nonprogressors 14.0 mm Hg [11.8-16.0 mm Hg], progressors 15.1 mm Hg [12.7-17.0 mm Hg]; Mann-Whitney U test [MWU]; P = 0.03) and lower degrees of IOP reduction from baseline (percentage IOP reduction [IQR]: nonprogressors -38.4% [-51.8% to -26.4%]; progressors -31.4% [-43.1% to -21.5%]; MWU P = 0.01) compared with eyes showing no progression. CONCLUSIONS: The study demonstrates that approximately one third of eyes continued to show progression of glaucoma at five years after trabeculectomy, as determined by trend-based analysis of ONH structural changes and VF sensitivity over time. The study suggests that the degree of IOP reduction after trabeculectomy may play an important role in the progression of glaucoma as detected by both functional and structural methods.

Predicting visual field loss in ocular hypertensive patients using wavelet-fourier analysis of GDx scanning laser polarimetry.

PURPOSE: To predict which ocular hypertensive (OHT) patients later develop a visual field loss by applying shape-based analysis (wavelet-Fourier analysis, WFA) to retinal nerve fiber layer (RNFL) thickness estimates. METHODS: Visual field information and scanning laser polarimetry (SLP) RNFL estimates were obtained from both eyes of 122 patients (73 glaucoma and 49 OHT) and 102 healthy individuals. WFA was applied to RNFL temporal, superior nasal, inferior, and temporal (TSNIT) curves (28 points) of the glaucoma and healthy eyes to obtain a classifier. Without modification, the classifier was then applied to the OHT eyes (16 OHTconverters and 33 OHTnonconverters). The visual fields of the OHT patients (6-month follow-up for a mean period of 4 years) were analyzed using the Advanced Glaucoma Intervention Study (AGIS) criteria to identify eyes which developed subsequent field loss in this period of time (OHT converters) and those that did not (OHT nonconverters). For the OHT converters, the classifier was applied to scans from each of three points in time before the initial visual field damage. For the OHT nonconverters, the last available scan was used. The accuracy of the WFA metric in predicting conversion of OHT eyes was assessed by calculating area under the receiver operating characteristic (ROC) curve (area under the ROC curve, AUC), sensitivity at 80% specificity, and likelihood ratio. RESULTS: The performance (AUC) of WFA in predicting conversion of the OHT eyes from scans taken just before visual field loss was 0.83 with a sensitivity (SD)/specificity (SD) of 0.76 +/- 0.11/0.80 +/- 0.07 and likelihood ratio (+LR +/- SD) of 3.8 +/- 1.4. Performance for scans obtained 6 months before the first signs of visual field defects was 0.77 (AUC), 0.71 +/- 0.11/0.80 +/- 0.07 (sensitivity/specificity), and 3.5 +/- 1.4 (+LR +/- SD). Performance was 0.73 (AUC), 0.59 +/- 0.12/0.8 +/- 0.07 (sensitivity/specificity), and 3.0 +/- 0.12 (+LR +/- SD) using the earliest available RNFL estimates. CONCLUSION: The WFA method of temporal, superior nasal, inferior, and temporal shape analysis offers a means of predicting progression in OHT patients before visual field loss.