Comparing 2-dimensional macular pigment optical density with objective and subjective perimetry and visual acuity in age-related macular degeneration.

PURPOSE: To compare diagnostic power for different severities of age-related macular degeneration (AMD) of two-dimensional macular pigment optical densities (2D-MPOD) and spatially matched objective perimetry, with standard perimetry and best-corrected visual acuity (BCVA). METHODS: The ObjectiveField Analyser (OFA) provided objective perimetry, and a Heidelberg Spectralis optical coherence tomography (OCT) measured 2D-MPOD in AMD patients, both completed twice over 0.99 ± 0.16 years. From each 2D-MPOD image, we extracted 20 regions/macula, matched to the 20 OFA stimuli/macula. For each region, we calculated 7 measures from the 2D-MPOD pixel values and correlated those with OFA sensitivities and delays. We quantified 2D-MPOD changes, the ability of 2D-MPOD and OFA to discriminate AMD stages, and the discriminatory power of Matrix perimetry and BCVA using percentage area under receiver operator characteristic plots (%AUROC). RESULTS: In 58 eyes of 29 subjects (71.6 ± 6.3 years, 22 females), we found significant correlations between 2D-MPOD and OFA sensitivities for Age-Related Eye Disease Studies (AREDS)-3 and AREDS-4 severities. Delays showed significant correlations with AREDS-2. For AREDS-4, correlations extended across all eccentricities. Regression associated with the Bland-Altman plots showed significant changes in 2D-MPOD over the study period, especially variability measures. MPOD per-region medians discriminated AREDS-1 from AREDS-3 eyes at a %AUROC of 80.0 ± 6.3%, outperforming OFA, Matrix perimetry, and BCVA. CONCLUSIONS: MPOD changes correlated with central functional changes and significant correlations extended peripherally in later-stage AMD. Good diagnostic power for earlier-stage AMD and significant change over the study suggest that 2D-MPOD and OFA may provide effective biomarkers.

The structure-function relationship between multifocal pupil perimetry and retinal nerve fibre layer in glaucoma.

BACKGROUND: Multifocal pupillographic objective perimetry (mfPOP) is a novel method for assessing functional change in diseases like glaucoma. Previous research has suggested that, in contrast to the pretectally-mediated melanopsin response of intrinsically photosensitive retinal ganglion cells, mfPOP responses to transient onset stimuli involve the extrastriate cortex, and thus the main visual pathway. We therefore investigate the correlation between peripapillary retinal nerve fibre layer (pRNFL) thickness and glaucomatous visual field changes detected using mfPOP. Parallel analyses are undertaken using white on white standard automated perimetry (SAP) for comparison. METHODS: Twenty-five glaucoma patients and 24 normal subjects were tested using SAP, 3 mfPOP variants, and optical coherence tomography (OCT). Arcuate clusters of the SAP and mfPOP deviations were weighted according to their contribution to published arcuate divisions of the retinal nerve fibre layer. Structure-function correlation coefficients (r) were computed between pRNFL clock-hour sector thickness measurements, and the local visual field sensitivities from both SAP and mfPOP. RESULTS: The strongest correlation was observed in the superior-superotemporal disc sector in patients with worst eye SAP MD < -12 dB: r = 0.93 for the mfPOP LumBal test (p < 0.001). Correlations across all disc-sectors were strongest in these same patients in both SAP and mfPOP: SAP r = 0.54, mfPOP LumBal r = 0.55 (p < 0.001). In patients with SAP MD ≥ -6 dB in both eyes, SAP correlations across all sectors were higher than mfPOP; mfPOP correlations however, were higher than SAP in more advanced disease, and in normal subjects. CONCLUSIONS: For both methods the largest correlations with pRNFL thickness corresponded to the inferior nasal field of more severely damaged eyes. Head-to-head comparison of mfPOP and SAP showed similar structure-function relationships. This agrees with our recent reports that mfPOP primarily stimulates the cortical drive to the pupils.

Rapid, non-contact multifocal visual assessment in multiple sclerosis.

OBJECTIVE: Previous work on temporally sparse multifocal methods suggests that the results are correlated with disability and progression in people with multiple sclerosis (PwMS). Here, we assess the diagnostic power of three cortically mediated sparse multifocal pupillographic objective perimetry (mfPOP) methods that quantified response-delay and light-sensitivity at up to 44 regions of both visual fields concurrently. METHODS: One high-spatial-resolution mfPOP method, P129, and two rapid medium-resolution methods, W12 and W20, were tested on 44 PwMS and controls. W12 and W20 took 82 s to test both visual fields concurrently, providing response delay and sensitivity at each field location, while P129 took 7 min. Diagnostic power was assessed using areas under the receiver operating characteristic (AUROC) curves and effect-size (Hedges' g). Linear models examined significance. Concurrent testing of both eyes permitted assessment of between-eye asymmetries. RESULTS: Per-region response delays and asymmetries achieved AUROCs of 86.6% ± 4.72% (mean ± SE) in relapsing-remitting MS, and 96.5% ± 2.30% in progressive MS. Performance increased with increasing disability scores, with even moderate EDSS 2 to 4.5 PwMS producing AUROCs of 82.1 to 89.8%, Hedge's g values up to 2.06, and p = 4.0e - 13. All tests performed well regardless of any history of optic neuritis. W12 and W20 performed as well or better than P129. CONCLUSION: Overall, the 82-s tests (W12 and W20) performed better than P129. The results suggest that mfPOP assesses a correlate of disease severity rather than a history of inflammation, and that it may be useful in the clinical management of PwMS.

A Review of the Categorizations of Mild, Moderate, and Severe Bacterial Keratitis Ulcers and Day-1 Treatment Regimen When Using the Topical Fluoroquinolones 0.3% Ciprofloxacin and 0.3% Ofloxacin.

Background: There are published suggestions that bacterial keratitis (BK) can be classified as mild, moderate, or severe and that the day-1 antibiotic drop regimen may differ for each category using the topical second-generation fluoroquinolones 0.3% ciprofloxacin and 0.3% ofloxacin (2FQ). The classification criteria are not consistently defined and the suggested regimens are often unreferenced and so here, the evidence base for applying such regimens in clinical practice is examined. Objective: To examine the evidence base regarding the categorization criteria used for BK and determine whether any evidence exists to support suggestions that different day-1 treatment regimen using the 2FQ may be applied based on any assigned categorization. Methods: The literature on BK treatment was reviewed, as were the clinical studies involving the commercially available 2FQ. All statements pertaining to classification and treatment paradigms involving BK were then collated and reviewed, as were the methodologies employed in the 2FQ clinical studies. Results: There have been no clinical trials using the 2FQ, or indeed any other topical antibiotics, which have used different day-1 drop regimen depending on the size, depth, and location of the ulcer or for ulcers classified as mild, moderate, or severe. Thus, there is no evidence to support the suggestion that a lower number of drops on day 1 is as effective as a higher number on categorized BK ulcers. Conclusions: No standardized method of categorizing BK was found, and there is no evidence to support the contention that mild, moderate, or smaller BK ulcers should be treated any differently to larger or severe ulcers on day 1. The manufacturers of 2FQ do not supply different treatment regimens for different ulcer sizes and severity categories. When using the 2FQ, all BK ulcers should be treated equally in line with the manufacturers' recommended day-1 treatment regimen.

Severity of age-related macular degeneration at first presentation in Bhutan: a 3-year national study.

BACKGROUND: Medical services are still developing in Bhutan. There is no published national report on age-related macular degeneration (AMD). We therefore aim to determine the demographic characteristics and severity of AMD at first presentation among Bhutanese patients attending their recently inaugurated vitreoretinal (VR) clinics over a 3-year national survey, and to inform national health policy to develop suitable health program to prevent AMD-related blindness and visual impairment. METHODS: A retrospective cross-sectional consecutive case series study was conducted on all new AMD cases in Bhutan. If a patient presented with asymmetrical AMD, the eye with more severe AMD was considered. If both the eyes had the same severity one eye was chosen randomly. Collection of demographic data and clinical details including diagnostic testing (fundus photography, OCT and fluorescent angiography) and clinical staging were performed. RESULTS: Of 521 new AMD patients aged 71.9 ± 11.3 years, 306/521 (58.7%) were males (p = 0.005). At their first presentation, 234/521 patients (44.9%) already had late-stage AMD. Importantly, 69/234 patients (29.5%), that is half of total neovascular AMD (nAMD) patients, had disciform scars (DS) which were beyond treatment, and 7/234 patients (3.0%) had geographic atrophy (GA). Seven patients had retinal pigment epithelium tear at presentation. Fourteen of nineteen polypoidal choroidal vasculopathy (PCV) patients were younger than 50 years. CONCLUSIONS: Half of nAMD cases presented as DS not amenable to the treatment. Many potentially treatable nAMD patients had already lost central vision and were legally blind. Young people with PCV losing vision early in life with longer morbidity-affected life and socio-economic burden was concerning. GA and DS cases need visual rehabilitation to improve their QoL. Incorporating a screening program for AMD with effective health education, and maintaining a national AMD Registry, would potentially lower AMD-related blindness and visual impairment.

Multifocal pupillographic objective perimetry for assessment of early diabetic retinopathy and generalised diabetes-related tissue injury in persons with type 1 diabetes.

BACKGROUND: To examine the potential utility of five multifocal pupillographic objective perimetry (mfPOP) protocols, in the assessment of early diabetic retinopathy (DR) and generalised diabetes-related tissue injury in subjects with type 1 diabetes (T1D). METHODS: Twenty-five T1D subjects (age 41.8 ± 12.1 (SD) years, 13 male) with either no DR (n = 13) or non-proliferative DR (n = 12), and 23 age and gender-matched control subjects (age 39.7 ± 12.9 years, 9 male) were examined by mfPOP using five different stimulus methods differing in visual field eccentricity (central 30° and 60°), and colour (blue, yellow or green test-stimuli presented on, respectively, a blue, yellow or red background), each assessing 44 test-locations per eye. In the T1D subjects, we assessed 16 metabolic status and diabetes complications variables. These were summarised as three principal component analysis (PCA) factors. DR severity was assessed using Early Treatment of Diabetic Retinopathy Study (ETDRS) scores. Area under the curve (AUC) from receiver operator characteristic analyses quantified the diagnostic power of mfPOP response sensitivity and delay deviations for differentiating: (i) T1D subjects from control subjects, (ii) T1D subjects according to three levels of the identified PCA-factors from control subjects, and (iii) TID subjects with from those without non-proliferative DR. RESULTS: The two largest PCA-factors describing the T1D subjects were associated with metabolic variables (e.g. body mass index, HbA1c), and tissue-injury variables (e.g. serum creatinine, vibration perception). Linear models showed that mfPOP per-region response delays were more strongly associated than sensitivities with the metabolic PCA-factor and ETDRS scores. Combined mfPOP amplitude and delay measures produced AUCs of 90.4 ± 8.9% (mean ± SE) for discriminating T1D subjects with DR from control subjects, and T1D subjects with DR from those without of 85.9 ± 8.8%. The yellow and green stimuli performed better than blue on most measures. CONCLUSIONS/INTERPRETATION: In T1D subjects, mfPOP testing was able to identify localised visual field functional abnormalities (retinal/neural reflex) in the absence or presence of mild DR. mfPOP responses were also associated with T1D metabolic status, but less so with early stages of non-ophthalmic diabetes complications.

Assessing migraine patients with multifocal pupillographic objective perimetry.

BACKGROUND: To establish the effects of stimulating intrinsically-photosensitive retinal ganglion cells (ipRGCs) on migraine severity, and to determine if migraine produces objectively-measured visual field defects. METHODS: A randomized, open labelled, crossover study tested migraineurs and normal controls using multifocal pupillographic objective perimetry (mfPOP) with 44 test-regions/eye. A slow blue protocol (BP) stimulated ipRGCs, and a fast yellow protocol (YP) stimulated luminance channels. Migraine diaries assessed migraine severity. Per-region responses were analyzed according to response amplitude and time-to-peak. RESULTS: Thirty-eight migraineurs (42.0 ± 16.5 years, 23 females) and 24 normal controls (39.2 ± 15.2 years, 14 females) were tested. The proportion of subjects developing a migraine did not differ after either protocol, either during the 1st day (odds ratio 1.0; 95% confidence interval 0.2-4.4, p = 0.48) or during the first 3 days after testing (odds ratio 0.8; 95% confidence interval 0.3-2.1, p = 0.68). Migraine days/week did not increase following testing with either protocol in comparison to the baseline week (1.4 ± 1.6 pre-testing (mean ± SD), 1.3 ± 1.4 post-BP, and 1.3 ± 1.2 post-YP; p = 0.96), neither did other measures of severity. Migraine occurring up to 2 weeks before testing significantly lowered amplitudes, - 0.64 ± 0.14 dB (mean ± SE), while triptan use increased amplitudes by 0.45 ± 0.10 dB, both at p < 0.001. CONCLUSIONS: Stimulating ipRGCs did not affect migraine occurrence or severity. Pupillary response characteristics were influenced by the occurrence of a recent migraine attack and a history of triptan use.

Rural-urban differences in myopia prevalence among myopes presenting to Bhutanese retinal clinical services: a 3-year national study.

PURPOSE: To determine the prevalence and demographic characteristics of myopia among patients presenting to the national vitreo-retinal (VR) services in Bhutan. METHODS: The records of the VR clinic at the apex national referral centre, providing the only VR services in the country, were reviewed to identify all new myopia patients over three years. Thus, we surveyed all referrals nationally. The patients were categorised into urban and rural females and males. We assessed myopia prevalence in each group by occupational and educational categories. We examined univariate prevalence data and a multivariate logistic regression (MLR) identified independent factors. RESULTS: Of 2913 cases 1544 (53.0%) were males. Females presented earlier (mean ±SD): overall 45.7 ± 21.9 cf. 48.6 ± 21.6 years, p = 0.003, and among myopes 23.9 ± 13.5 cf. 27.6 ± 18.6 years, p = 0.032. Myopia constituted 92.1% of refractive error, an overall prevalence of 12.3%. Myopia was more common among females (p = 0.01) and urbanites (p = 0.02). Myopia prevalence was highest among urban females (20.9%), followed by urban males (11.9%), rural females (6.8%), and rural males (5.2%). Logistic regression revealed that the odds of having myopia were increased by being a student (4.96 ×) or professional (1.96 ×), and decreased by rural living (1.75 ×), all p ≤ 0.038. CONCLUSIONS: This is the first study on myopia in Bhutan. As observed throughout East and Southeast Asia, the prevalence of myopia was higher in females and urbanites and positively associated with formal education. Given known risk factors, these prevalences may be driven by educational pressures and reduced time spent outdoors.

Relationships between retinal structure and function and vision-related quality of life measures in advanced age-related macular degeneration.

PURPOSE: To evaluate the association between ophthalmic structure/function measures and five standardized quality of life (QoL) instruments, in patients with advanced age-related macular degeneration (AMD). METHODS: We examined 20 AMD patients (ages 66-93 years) recruited from the Canberra Hospital Ophthalmology Department. Visual function measures included low and high contrast visual acuity (LCVA and HCVA) and measures from 10-2 Matrix visual fields (VF). Optical coherence tomography (OCT) quantified central retinal thickness (CRT), average macular thickness (AT), and retinal nerve fibre layer thickness (RNFL). The QoL instruments were the macular degeneration-related quality of life (MacDQoL), the National Eye Institute Visual Functioning Questionnaire (VFQ), its two face-recognition questions (A6 and 11), and the Geriatric Depression Scale (GDS). Pearson correlations, Canonical Correlation Analysis (CCA), and cross-validated stepwise-regression were used to examine the relationships between structure/function measures and the QoL instruments. RESULTS: The selected models for the five instruments had R2 ranging from 0.65 ± 0.12 to 0.90 ± 0.05 (mean ± SD) and median F-statistics > 188. HCVA was strongly associated with all QoL except the GDS, for which CRT, AT and RNFL figured highly. RNFL was most important for MacDQoL, and 2nd for VFQ question-A6. Centrally weighted VF measures were rarely selected but global VF measures were common, especially for the overall NEI-VFQ questionnaire. CCA revealed that the structure/function measures and QoL instruments contained 2 statistically independent mechanisms. CONCLUSIONS: In patients with advanced AMD, CRT and HCVA were strong determinants of QoL instruments in AMD patients.

Insights for mfVEPs from perimetry using large spatial frequency-doubling and near frequency-doubling stimuli in glaucoma.

PURPOSE: To compare two forms of perimetry that use large contrast-modulated grating stimuli in terms of: their relative diagnostic power, their independent diagnostic information about glaucoma and their utility for mfVEPs. We evaluated a contrast-threshold mfVEP in normal controls using the same stimuli as one of the tests. METHODS: We measured psychophysical contrast thresholds in one eye of 16 control subjects and 19 patients aged 67.8 ± 5.65 and 71.9 ± 7.15, respectively, (mean ± SD). Patients ranged in disease severity from suspects to severe glaucoma. We used the 17-region FDT-perimeter C20-threshold program and a custom 9-region test (R9) with similar visual field coverage. The R9 stimuli scaled their spatial frequencies with eccentricity and were modulated at lower temporal frequencies than C20 and thus did not display a clear spatial frequency-doubling (FD) appearance. Based on the overlapping areas of the stimuli, we transformed the C20 results to 9 measures for direct comparison with R9. We also compared mfVEP-based and psychophysical contrast thresholds in 26 younger (26.6 ± 7.3 y, mean ± SD) and 20 older normal control subjects (66.5 ± 7.3 y) control subjects using the R9 stimuli. RESULTS: The best intraclass correlations between R9/C20 thresholds were for the central and outer regions: 0.82 ± 0.05 (mean ± SD, p ≤ 0.0001). The areas under receiver operator characteristic plots for C20 and R9 were as high as 0.99 ± 0.012 (mean ± SE). Canonical correlation analysis (CCA) showed significant correlation (r = 0.638, p = 0.029) with 1 dimension of the C20 and R9 data, suggesting that the lower and higher temporal frequency tests probed the same neural mechanism(s). Low signal quality made the contrast-threshold mfVEPs non-viable. The resulting mfVEP thresholds were limited by noise to artificially high contrasts, which unlike the psychophysical versions, were not correlated with age. CONCLUSION: The lower temporal frequency R9 stimuli had similar diagnostic power to the FDT-C20 stimuli. CCA indicated the both stimuli drove similar neural mechanisms, possibly suggesting no advantage of FD stimuli for mfVEPs. Given that the contrast-threshold mfVEPs were non-viable, we used the present and published results to make recommendations for future mfVEP tests.

Recovery dynamics of multifocal pupillographic objective perimetry from tropicamide dilation.

PURPOSE: To study the pupillary system by combining mydriasis and multifocal pupillographic objective perimetry (mfPOP). In particular, we explored how the dynamics of recovery differ for concurrently measured direct and consensual sensitivity, response delay, and signal-to-noise ratios (SNRs) for binocular mydriasis. METHODS: We recruited 26 normal participants, all with brown irides. The dichoptic mfPOP stimuli concurrently assessed 44-region/eye and both pupils. Two pre-dilation tests were followed by pairs of repeated tests at 1, 2, 4, 6, 8, 12, 24, and 48 h following dilation of both pupils with 1% tropicamide. Three subjects were retested with only the right pupil dilated. Linear models determined the independent effects of mydriasis upon the per-region and pupil measures over time. RESULTS: Post-dilation, the per-region delays initially decreased by 16.3 ± 6.02 ms (mean ± SE) (p < 0.0001, cf. baseline of 471.1 ± 4.36 ms), then increased to slower than baseline by 17.42 ± 5.57 ms after 4 h (p < 0.002), recovering to baseline at 8 h. By comparison, per-region sensitivities (constriction amplitudes) were still reduced by - 6.20 ± 0.70 µm at 8 h (p < 0.0001, cf. baseline of 21.1 ± 0.55 µm), recovered at 24 h, but rebounded at 48 h (p = 0.005). The SNRs for sensitivities and delays both recovered by 8-12 h. Across all the data, sensitivities reduced by 2.67 ± 0.25 µm/decade of age, and delay increased by 15.4 ± 1.98 ms/decade (both p < 0.00001). Data from 3 of the 26 subjects who repeated the testing for monocular dilation found that consensual response sensitivities were larger than direct for 8 h (p < 0.018). CONCLUSIONS: The per-region sensitivities were affected for longer than SNRs or delays. Strong early SNRs indicated proportionately lower pupil noise for larger pupil diameters. Following mydriasis with tropicamide 1%, the constriction amplitude measurements with mfPOP should be considered only after 48 h, but time-to-peak can be measured after 8-12 h.

Pattern of vitreo-retinal diseases at the national referral hospital in Bhutan: a retrospective, hospital-based study.

BACKGROUND: Knowing the pattern and presentation of the diseases is critical for management strategies. To inform eye-care policy we quantified the pattern of vitreo-retinal (VR) diseases presenting at the national referral hospital in Bhutan. METHODS: We reviewed all new patients over three years from the retinal clinic of the Jigme Dorji Wangchuck National Referral Hospital. Demographic data, presenting complaints and duration, treatment history, associated systemic diseases, diagnostic procedures performed, and final diagnoses were quantified. Comparisons of the expected and observed frequency of gender used Chi-squared tests. We applied a sampling with replacement based bootstrap analysis (10,000 cycles) to estimate the population means and the standard errors of the means and standard error of the 10th, 25th, 50th, 75th and 90th percentiles of the ages of the males and females within 20-year cohorts. We then applied t-tests employing the estimated means and standard errors. The 2913 subjects insured that the bootstrap estimates were statistically conservative. RESULTS: The 2913 new cases were aged 47.2 ± 21.8 years. 1544 (53.0%) were males. Housewives (953, 32.7%) and farmers (648, 22.2%) were the commonest occupations. Poor vision (41.9%), screening for diabetic and hypertensive retinopathy (13.1%), referral (9.7%), sudden vision loss (9.3%), and trauma (8.0%) were the commonest presenting symptoms. Coexistent diabetes and hypertension were the most common associated systemic diseases. Haematological tests (blood sugar, HbA1c and lipid profile, 31.8%), OCT (27.4%), refraction (9.9%), B-scan (8.7%), fundus photography (8.0%) were the most commonly performed diagnostic tests. Hypertensive retinopathy (18.9%) was the commonest VR disease, followed by refractive errors referred for retinal evaluation (16.7%), diabetic retinopathy with macular oedema (15.8%), and AMD (11.0%). Retinal detachment was more prevalent in females (83 vs. 41, p = 0.007). Rare vision-threatening diseases like seasonal hyper-acute pan-uveitis also presented. CONCLUSIONS: The developing VR service in Bhutan is challenged by the spectrum of diseases, limited human resources (e.g. one retinal surgeon during the study), and accessibility to tertiary eye-care services, all amidst difficult terrain. Sustained effort and robust coordination among the eye-care professionals, government and non-governmental organisations are critical for optimising VR services, especially as rates of diseases such as diabetes and hypertension grow.

Retinal laser services in Bhutan: a 3-year national survey.

BACKGROUND: We conducted this study to report on the indications and types of retinal laser therapy (RLT) performed in Bhutan, knowing which is critical for proper planning and successful delivery of the services. METHODS: We reviewed the laser registers maintained in the laser rooms and vitreoretinal (VR) operating theatres (including paediatric cases managed under anaesthesia) over three years at the national and the two regional referral hospitals (RRHs). Intraoperative laser treatments (endolaser) were excluded. Patient demography, indications and types of RLT were recorded and quantified. Comparisons of the expected and observed frequencies used Chi-squared tests. RESULTS: A total of 685 patients, including 8 cases of bilateral retinopathy of prematurity (ROP) received RLT. The majority of patients (411 cases, 60.0%, p < 0.0001) were males. The mean age was 54.1 ± 14.1 years, median 56 years. The most common indications for RLT were diabetic retinopathy (DR) and diabetic macular oedema (DMO) (542 cases, 66.0%), followed by retinal vein occlusion (RVO) (91 cases, 13.3%). Pan-retinal photocoagulation was the most common type of RLT performed (337 cases, 49.2%), followed by modified grid laser (207 cases, 30.2%), sectoral laser (41 cases, 6.0%), and prophylactic laser photocoagulation (33 cases, 4.8%). CONCLUSIONS: The majority of patients were within working-age. Common indications for RLT were preventable such as DR, DMO and RVO, indicating need to control systemic diseases such as diabetes, hypertension, and dyslipidaemia. Currently, regular RLT is provided only at the national referral hospital in Thimphu, and periodically in the eastern and central RRHs when the retinal specialist visits. There is need to extend the retinal services to the eastern and central RRHs to improve accessibility and patient coverage in these regions challenged with difficult terrain and poor public transport system.

Caricaturing can improve facial expression recognition in low-resolution images and age-related macular degeneration.

Previous studies of age-related macular degeneration (AMD) report impaired facial expression recognition even with enlarged face images. Here, we test potential benefits of caricaturing (exaggerating how the expression's shape differs from neutral) as an image enhancement procedure targeted at mid- to high-level cortical vision. Experiment 1 provides proof-of-concept using normal vision observers shown blurred images as a partial simulation of AMD. Caricaturing significantly improved expression recognition (happy, sad, anger, disgust, fear, surprise) by ∼4%-5% across young adults and older adults (mean age 73 years); two different severities of blur; high, medium, and low intensity of the original expression; and all intermediate accuracy levels (impaired but still above chance). Experiment 2 tested AMD patients, running 19 eyes monocularly (from 12 patients, 67-94 years) covering a wide range of vision loss (acuities 6/7.5 to poorer than 6/360). With faces pre-enlarged, recognition approached ceiling and was only slightly worse than matched controls for high- and medium-intensity expressions. For low-intensity expressions, recognition of veridical expressions remained impaired and was significantly improved with caricaturing across all levels of vision loss by 5.8%. Overall, caricaturing benefits emerged when improvement was most needed, that is, when initial recognition of uncaricatured expressions was impaired.

Characterisation and functional mapping of surface potentials in the rat dorsal column nuclei.

KEY POINTS: The brainstem dorsal column nuclei (DCN) process sensory information arising from the body before it reaches the brain and becomes conscious. Despite significant investigations into sensory coding in peripheral nerves and the somatosensory cortex, little is known about how sensory information arising from the periphery is represented in the DCN. Following stimulation of hind-limb nerves, we mapped and characterised the evoked electrical signatures across the DCN surface. We show that evoked responses recorded from the DCN surface are highly reproducible and are unique to nerves carrying specific sensory information. ABSTRACT: The brainstem dorsal column nuclei (DCN) play a role in early processing of somatosensory information arising from a variety of functionally distinct peripheral structures, before being transmitted to the cortex via the thalamus. To improve our understanding of how sensory information is represented by the DCN, we characterised and mapped low- (<200 Hz) and high-frequency (550-3300 Hz) components of nerve-evoked DCN surface potentials. DCN surface potentials were evoked by electrical stimulation of the left and right nerves innervating cutaneous structures (sural nerve), or a mix of cutaneous and deep structures (peroneal nerve), in 8-week-old urethane-anaesthetised male Wistar rats. Peroneal nerve-evoked DCN responses demonstrated low-frequency events with significantly longer durations, more high-frequency events and larger magnitudes compared to responses evoked from sural nerve stimulation. Hotspots of low- and high-frequency DCN activity were found ipsilateral to stimulated nerves but were not symmetrically organised. In conclusion, we find that sensory inputs from peripheral nerves evoke unique and characteristic DCN activity patterns that are highly reproducible both within and across animals.

Inter-visit Test-Retest Variability of OCT in Glaucoma.

PURPOSE: To determine the inter-visit test-retest variability (TRV) of a spectral domain optical coherence tomograph, the Topcon 3D OCT-2000, in the measurement of optic nerve head topography, peripapillary retinal nerve fiber layer (pRNFL), and macular ganglion cell complex (GCC) parameters in glaucoma patients. We also examine whether TRV with this instrument varies with the extent of glaucomatous damage. METHODS: Twenty-four subjects with varying degrees of glaucoma severity provided 41 eyes with usable results for the study. 3D Disc Retinal Nerve Fiber Layer Analysis and Macula V (GCC) scans were repeated 1 week apart, at the same time of day, to determine the inter-visit TRV. TRV was determined using Bland-Altman limits of agreement (LoA) and the resulting coefficients of repeatability (CR). RESULTS: The overall horizontal and vertical cup/disc ratio CRs were 0.05 and 0.07, respectively. The GCC CR was 2.9 µm. In contrast, average pRNFL TRV expanded with increasing damage, with the LoA being well fitted by ±(34.67 - 0.294(d)), where d is the pRNFL thickness. A more complex model, with constant LoA of ±5.61 µm at d >82 µm, and linearly expanding TRV below that, achieved marginal significance (P < .06). CONCLUSIONS: The repeatability of GCC measurements with this instrument was excellent. The determination of statistically significant change in average pRNFL should take into account average pRNFL thickness.

Retest Variability in the Medmont M700 Automated Perimeter.

PURPOSE: To investigate the level of test-retest variability in the Medmont M700 automated perimeter. We compare the retest variability of the outer 20° test points of one test method to test points in the inner 10° of two test methods to determine whether test points from different tests and regions exhibit different retest variability. We also generate some clinically applicable coefficient of repeatability (CoR) values for M700 Overall Defect (OD) and Pattern Defect (PD) indices. METHODS: Twenty-four glaucoma patients with varying degrees of field loss were enrolled, and 21 patients (40 eyes) had usable results. The Central (30°) test and the Macula (10°) test were performed on each eye on the same day. To determine retest variability, the tests were repeated 1 week later at the same time of day. RESULTS: Test points from 5 to 20 dB in the outer 20° of the 30° test showed lower retest variance than points of equal decibel value in the central 10° of the same test. For the 30° test, the OD CoR was 2.4 dB. The PD retest CoR varied with glaucoma severity, ranging from 1.24 dB for PD less than or equal to 2.8 to 3.1 dB for PD more than 5.7. The 10° test CoR for OD was 2.1 dB, and PD retest CoR ranged from 1.58 for PD less than or equal to 2.8 to 2.4 for PD more than 5.7. CONCLUSIONS: In glaucoma patients, retest variance for some decibel values does not seem to increase with increasing eccentricity in the M700. The OD values as graded by the M700 do not appear to correspond well with the amount of visual field loss and are not directly comparable to mean deviation results reported by other perimeters. Pattern defect values in the M700 seem to correlate well with the degree of field loss.

Visual evoked potential and psychophysical contrast thresholds in glaucoma.

PURPOSE: We compared the diagnostic power of electrophysiologically and psychophysically measured contrast thresholds for the diagnosis of glaucoma. Additionally, we investigated whether combining results from the two methods improved diagnostic power. METHODS: Seven-eight subjects between 40 and 88 years formed the main study group: 21 normal controls (9 males) and 57 glaucoma patients (30 males) were tested. Twenty-two younger control subjects were also tested. Contrast thresholds were determined for a 1 cpd sinusoidal grating, subtending 41° × 52° modulated at 14.3 rps. The thresholds were based on the same staircase method applied to visual evoked potential (VEP) and psychophysical responses (Psyc). Diagnostic power was assessed by the percent area under the curve (%AUC) of receiver operating characteristic plots. RESULTS: Psyc showed significant age dependence, -0.10 ± 0.02 dB, while VEPs did not. Diagnostic performance for moderate and severe eyes combined was modest: Psyc 74 ± 9.0 % and VEP 72 ± 9.1 %, but improved significantly (p < 0.05) for a simple combined method, up to 90 ± 6.0 % for moderate disease. The combined method improved %AUC for all severities on average (p < 0.03). Canonical correlation analysis indicated that the four threshold measures contained independent information and that these independent dimensions were each correlated with glaucoma severity (p < 0.0015). CONCLUSION: Combining the VEP and Psyc thresholds appeared to improve diagnostic power. Canonical correlation analysis indicated that they measured statistically independent aspects of glaucoma possibly related to disease severity. Adding the 20-s psychophysical test to a VEP test produced a significant benefit for a small time cost.