The ChromaTest, a digital color contrast sensitivity analyzer, for diabetic maculopathy: a pilot study

BACKGROUND: To assess the ability of the Chromatest in investigating diabetic maculopathy. METHOD: Patients with Type 2 diabetes and no concurrent ocular pathology or previous laser photocoagulation were recruited. Visual acuities were assessed followed by colour contrast sensitivity testing of each eye using Chromatest. Dilated fundoscopy with slit lamp biomicroscopy with 78 D lens was then performed to confirm the stage of diabetic retinopathy according to the Early Treatment Diabetic Retinopathy Study. RESULTS: 150 eyes in 150 patients were recruited into this study. 35 eyes with no previous laser photocoagulation were shown to have clinically significant macular oedema (CSMO) and 115 eyes with untreated non-proliferative diabetic retinopathy (NPDR) on fundus biomicroscopy. Statistical significant difference was found between CSMO and NPDR eyes for protan colour contrast threshold (p = 0.01). Statistical significance was found between CSMO and NPDR eyes for tritan colour contrast threshold (p = 0.0002). Sensitivity and specificity for screening of CSMO using pass-fail criterion for age matched TCCT results achieved 71% (95% confidence interval: 53-85%) and 70% (95% confidence interval: 60-78%), respectively. However, threshold levels were derived using the same data set for both training and testing the effectiveness since this was the first study of NPDR using the Chromatest CONCLUSION: The ChromaTest is a simple, cheap, easy to use, and quick test for colour contrast sensitivity. This study did not achieve results to justify use of the Chromatest for screening, but it reinforced the changes seen in tritan colour vision in diabetic retinopathy

Where Are All the Mycobacterium avium Subspecies paratuberculosis in Patients with Crohn's Disease?

Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic granulomatous inflammation of the intestines, Johne's disease, in dairy cows and every other species of mammal in which it has been identified. MAP has been identified in the mucosal layer and deeper bowel wall in patients with Crohn's disease by methods other than light microscopy, and by direct visualization in small numbers by light microscopy. MAP has not been accepted as the cause of Crohn's disease in part because it has not been seen under the microscope in large numbers in the intestines of patients with Crohn's disease. An analysis of the literature on the pathology of Crohn's disease and on possible MAP infection in Crohn's patients suggests that MAP might directly infect endothelial cells and adipocytes and cause them to proliferate, causing focal obstruction within already existing vessels (including granuloma formation), the development of new vessels (neoangiogenesis and lymphangiogenesis), and the “creeping fat” of the mesentery that is unique in human pathology to Crohn's disease but also occurs in bovine Johne's disease. Large numbers of MAP might therefore be found in the mesentery attached to segments of intestine affected by Crohn's disease rather than in the bowel wall, the blood and lymphatic vessels running through the mesentery, or the mesenteric fat itself. The walls of fistulas might result from the neoangiogenesis or lymphangiogenesis that occurs in the bowel wall in Crohn's disease and therefore are also possible sites of large numbers of MAP. The direct visualization of large numbers of MAP organisms in the tissues of patients with Crohn's disease will help establish that MAP causes Crohn's disease

Quantification of Visual Field Loss in Age-Related Macular Degeneration

Background An evaluation of standard automated perimetry (SAP) and short wavelength automated perimetry (SWAP) for the central 10–2 visual field test procedure in patients with age-related macular degeneration (AMD) is presented in order to determine methods of quantifying the central sensitivity loss in patients at various stages of AMD. Methods 10–2 SAP and SWAP Humphrey visual fields and stereoscopic fundus photographs were collected in 27 eyes of 27 patients with AMD and 22 eyes of 22 normal subjects. Results Mean Deviation and Pattern Standard Deviation (PSD) varied significantly with stage of disease in SAP (both p<0.001) and SWAP (both p<0.001), but post hoc analysis revealed overlap of functional values among stages. In SWAP, indices of focal loss were more sensitive to detecting differences in AMD from normal. SWAP defects were greater in depth and area than those in SAP. Central sensitivity (within 1°) changed by −3.9 and −4.9 dB per stage in SAP and SWAP, respectively. Based on defect maps, an AMD Severity Index was derived. Conclusions Global indices of focal loss were more sensitive to detecting early stage AMD from normal. The SWAP sensitivity decline with advancing stage of AMD was greater than in SAP. A new AMD Severity Index quantifies visual field defects on a continuous scale. Although not all patients are suitable for SWAP examinations, it is of value as a tool in research studies of visual loss in AMD

Morphological and Functional Changes in the Retina after Chronic Oxygen-Induced Retinopathy

The mouse model of oxygen-induced retinopathy (OIR) has been widely used for studies of retinopathy of prematurity (ROP). This disorder, characterized by abnormal vascularization of the retina, tends to occur in low birth weight neonates after exposure to high supplemental oxygen. Currently, the incidence of ROP is increasing because of increased survival of these infants due to medical progress. However, little is known about changes in the chronic phase after ROP. Therefore, in this study, we examined morphological and functional changes in the retina using a chronic OIR model. Both the a- and b-waves in the OIR model recovered in a time-dependent manner at 4 weeks (w), 6 w, and 8 w, but the oscillatory potential (OP) amplitudes remained depressed following a return to normoxic conditions. Furthermore, decrease in the thicknesses of the inner plexiform layer (IPL) and inner nuclear layer (INL) at postnatal day (P) 17, 4 w, and 8 w and hyperpermeability of blood vessels were observed in conjunction with the decrease in the expression of claudin-5 and occludin at 8 w. The chronic OIR model revealed the following: (1) a decrease in OP amplitudes, (2) morphological abnormalities in the retinal cells (limited to the IPL and INL) and blood vessels, and (3) an increase in retinal vascular permeability via the impairment of the tight junction proteins. These findings suggest that the experimental animal model used in this study is suitable for elucidating the pathogenesis of ROP and may lead to the development of potential therapeutic agents for ROP treatment

Physiological Effects of Superoxide Dismutase on Altered Visual Function of Retinal Ganglion Cells in db/db Mice

Background: The C57BLKS/J db/db (db/db) mouse is a widely used type 2 diabetic animal model, and this model develops early inner retinal neuronal dysfunction beginning at 24 weeks. The neural mechanisms that mediate early stage retinal dysfunction in this model are unknown. We evaluated visual response properties of retinal ganglion cells (RGCs) during the early stage of diabetic insult (8, 12, and 20 wk) in db/db mice and determined if increased oxidative stress plays a role in impaired visual functions of RGCs in 20 wk old db/db mice. Methodology/Principal Findings: In vitro extracellular single-unit recordings from RGCs in wholemount retinas were performed. The receptive field size, luminance threshold, and contrast gain of the RGCs were investigated. Although ONand OFF-RGCs showed a different time course of RF size reduction, by 20 wk, the RF of ON- and OFF-RGCs were similarly affected. The LT of ON-RGCs was significantly elevated in 12 and 20 wk db/db mice compared to the LT of OFF-RGCs. The diabetic injury also affected contrast gains of ON- and OFF-RGCs differently. The generation of reactive oxidative species (ROS) in fresh retina was estimated by dihydroethidium. Superoxide dismutase (SOD) (300 unit/ml) was applied in Ames medium to the retina, and visual responses of RGCs were recorded for five hours. ROS generation in the retinas of db/db mice increased at 8wk and continued to progress at 20 wk of ages. In vitro application of SOD improved visual functions in 20 wk db/db mice but the SOD treatment affected ON- and OFF-RGCs differently in db/m retina

Enhanced text spacing improves reading performance in individuals with macular disease

The search by many investigators for a solution to the reading problems encountered by individuals with no central vision has been long and, to date, not very fruitful. Most textual manipulations, including font size, have led to only modest gains in reading speed. Previous work on spatial integrative properties of peripheral retina suggests that 'visual crowding' may be a major factor contributing to inefficient reading. Crowding refers to the fact that juxtaposed targets viewed eccentrically may be difficult to identify. The purpose of this study was to assess the combined effects of line spacing and word spacing on the ability of individuals with age-related macular degeneration (ARMD) to read short passages of text that were printed with either high (87.5%) or low contrast (17.5%) letters. Low contrast text was used to avoid potential ceiling effects and to mimic a possible reduction in letter contrast with light scatter from media opacities. For both low and high contrast text, the fastest reading speeds we measured were for passages of text with double line and double word spacing. In comparison with standard single spacing, double word/line spacing increased reading speed by approximately 26% with high contrast text (p < 0.001), and by 46% with low contrast text (p < 0.001). In addition, double line/word spacing more than halved the number of reading errors obtained with single spaced text. We compare our results with previous reading studies on ARMD patients, and conclude that crowding is detrimental to reading and that its effects can be reduced with enhanced text spacing. Spacing is particularly important when the contrast of the text is reduced, as may occur with intraocular light scatter or poor viewing conditions. We recommend that macular disease patients should employ double line spacing and double-character word spacing to maximize their reading efficiency. © 2013 Blackmore-Wright et al

No evidence for loss of short-wavelength sensitive cone photoreceptors in normal ageing of the primate retina

In old world primates including humans, cone photoreceptors are classified according to their maximal sensitivity at either short (S, blue), middle (M, green) or long (L, red) wavelengths. Colour discrimination studies show that the S-cone pathway is selectively affected by age and disease, and psychophysical models implicate their loss. Photoreceptors have high metabolic demand and are susceptible to age or disease-related losses in oxygen and nutrient supply. Hence 30% of rods are lost over life. While comparable losses are not seen in cones, S-cones comprise less than 10% of the cone population, so significant loss would be undetected in total counts. Here we examine young and aged primate retinae stained to distinguish S from M/L-cones. We show there is no age-related cone loss in either cone type and that S-cones are as regularly distributed in old as young primates. We propose that S-cone metabolism is less flexible than in their M/L counterparts, making them more susceptible to deficits in normal cellular function. Hypoxia is a feature of the ageing retina as extracellular debris accumulates between photoreceptors and their blood supply which likely impacts S-cone function. However, that these cells remain in the ageing retina suggests the potential for functional restoration