Functional loss in early age-related maculopathy: the ischaemia postreceptoral hypothesis.

We review proposed models and psychophysical and electrophysiological tests performed in many studies for early age-related maculopathy (ARM). We suggest that ischaemia is the trigger for impaired retinal pigment epithelium function causing imbalance of secretion of vascular growth factors, reduced disc degradation capability and reduced metabolic activity and possible inflammatory response. This results in increased deposition of cell debris, such as drusen and thickens Bruch's membrane causing even more ischaemia of the overlying neurosensory retina. The photoreceptors are more resistant to ischaemia given their proximity to the choroid. Furthermore, being 'upstream' from the inner retinal layers, they act as an oxygen sink depriving retinal layers further from the choroid. Postreceptoral cell layers and especially parts of the inner nuclear layer that are located in the watershed zone between two sources of blood supply are preferentially vulnerable to ischaemia. Based on psychophysical and electrophysiological findings we propose that most of the function impairment in early ARM starts postreceptorally.

Postreceptoral adaptation abnormalities in early age-related maculopathy.

Age-related maculopathy (ARM) has become the major cause of blindness in the Western World. Currently its pathogenesis and primary site of functional damage is not fully understood but ischemia is believed to play a major role. Early detection and precise monitoring of progression of ARM are main goals of current research due to lack of sufficient treatment options, especially in the dry, atrophic form of this disease. We applied the multifocal electroretinogram (mfERG) that can detect any local functional deficit objectively in the central retina. We recorded two paradigms in early ARM patients, the fast flicker and the slow flash paradigm which both represent fast adaptation processes of the proximal retina but under differing photopic conditions and stimulation rates. By subtracting the waveform responses we extracted a late component in the difference waveform that was significantly reduced in the early ARM group compared to a healthy control group (p < or = 0.05). We propose that this multifocal nonlinear analysis permits the detection of adaptative deficits and provides topographic mapping of retinal dysfunction in early ARM. The difference waveform component we extracted with this novel approach might indicate early functional loss in ARM caused by ischemia in postreceptoral layers such as bipolar cells and inner plexiform regions.

Monitoring retinal function in early age-related maculopathy: visual performance after 1 year.

PURPOSE: To monitor visual performance in early age-related maculopathy (ARM). METHODS: We measured monocular visual function-high-contrast visual acuity (HC-VA), central visual fields (mean sensitivity, MS), colour vision (desaturated Panel D-15), Pelli-Robson (P-R), and cone- and rod-mediated multifocal electroretinograms (mfERG) in 13 ARM subjects and 13 age-matched control subjects with normal fundi at baseline and after 1 year. All had visual acuity of 6/12 or better. The mfERG data were compared to templates derived from the control group at baseline. We analysed the mfERG results by averaging the central and peripheral fields and the superior and inferior fields (CP and SI methods) and by calculating the local responses. RESULTS: The mean rod-mediated responses were significantly delayed in the ARM group for the CP (P=0.04) and the SI methods (P=0.03) at baseline compared to the control group. This did not change significantly after 1 year, whereas the mean cone-mediated responses were within the normal range at both times. Although the local analysis revealed lower amplitudes for the cone- and rod-mediated responses at baseline this was not found after 1 year and only the local rod-mediated latencies were delayed at both times (P<0.01). HC-VA, desaturated Panel D-15 and P-R were significantly worse in the ARM group (P< or =0.01) at baseline but did not show further significant deterioration. Progressive fundus changes were found in only two subjects (18%). CONCLUSION: Although there was significant impairment of retinal function in early ARM at baseline no further deterioration was evident after 1 year.

Cone- and rod-mediated multifocal electroretinogram in early age-related maculopathy.

PURPOSE: To investigate the cone- and rod-mediated multifocal electroretinograms (mfERG) in early age-related maculopathy (early ARM). METHODS AND SUBJECTS: We investigated the cone- and rod-mediated mfERG in 17 eyes of 17 subjects with early ARM and 16 eyes of 16 age-matched control subjects with normal fundi. All subjects had a visual acuity of 6/12 or better. We divided the ARM subjects into two groups based on drusen size and retinal pigment epithelium abnormalities-a less advanced (ARM1) and a more advanced (ARM2) group. The mfERG data were compared to templates derived from the control group. We analysed the mfERG results for the central and peripheral fields (CP method) and the superior and inferior fields (SI method). RESULTS: While the mean cone results showed no statistically significant difference between the groups, the rods showed significantly delayed responses in the ARM1 group for the CP and the SI methods, but not in the ARM2 group, although there was a trend of longer latencies compared to the control group. CONCLUSION: Our results show a functional impairment of the rods in early ARM subjects. As there is histopathological evidence showing earlier rod than cone impairment in early ARM, following the rod function with the mfERG might be helpful in diagnosis or for monitoring the progression of early ARM.

Role of strain and ligand effects in the modification of the electronic and chemical properties of bimetallic surfaces.

Periodic density functional calculations are used to illustrate how the combination of strain and ligand effects modify the electronic and surface chemical properties of Ni, Pd, and Pt monolayers supported on other transition metals. Strain and the ligand effects are shown to change the width of the surface d band, which subsequently moves up or down in energy to maintain a constant band filling. Chemical properties such as the dissociative adsorption energy of hydrogen are controlled by changes induced in the average energy of the d band by modification of the d-band width.

Modification of the surface electronic and chemical properties of Pt(111) by subsurface 3d transition metals.

The modification of the electronic and chemical properties of Pt(111) surfaces by subsurface 3d transition metals was studied using density-functional theory. In each case investigated, the Pt surface d-band was broadened and lowered in energy by interactions with the subsurface 3d metals, resulting in weaker dissociative adsorption energies of hydrogen and oxygen on these surfaces. The magnitude of the decrease in adsorption energy was largest for the early 3d transition metals and smallest for the late 3d transition metals. In some cases, dissociative adsorption was calculated to be endothermic. The surfaces investigated in this study had no lateral strain in them, demonstrating that strain is not a necessary factor in the modification of bimetallic surface properties. The implications of these findings are discussed in the context of catalyst design, particularly for fuel cell electrocatalysts.

Measurements of preferred walking speed in subjects with central and peripheral vision loss.

BACKGROUND: Previous mobility studies have used Preferred Walking Speed (PWS) in order to determine the walking efficiency in terms of the Percent Preferred Walking Speed (PPWS) of visually impaired adults. PWS has been measured in previous studies using the sighted guide (SG) and non-sighted guide (NSG) techniques. This study compared the NSG, SG and string (ST) (subjects walked by holding on lightly to a cardboard tube attached to a piece of string) techniques of measuring PWS in visually impaired subjects. METHODS: Forty visually impaired subjects with central and peripheral vision loss were recruited. PWS was measured using the NSG, SG and ST techniques. For each technique, PWS was determined by recording the time taken for a subject to walk an unobstructed, straight 20-m corridor. RESULTS: There were no significant differences in PWS using the SG, NSG and ST techniques. CONCLUSION: For assessing walking efficiency, either the SG, NSG or ST technique could be employed when measuring PWS in visually impaired subjects.

Does mobility performance of visually impaired adults improve immediately after orientation and mobility training?

BACKGROUND: Previous studies that have attempted to determine the effect of orientation and mobility training on mobility performance of visually impaired adults have had a number of limitations. With the inclusion of a control group of subjects, this study investigated the effect of orientation and mobility training on mobility performance of a group of visually impaired adults. METHODS: Vision was measured binocularly as high- and low-contrast visual acuity, letter and edge contrast sensitivity, and Humphrey kinetic visual fields. The subjects' mobility performance was assessed as percentage preferred walking speed (PPWS) and error score before and after mobility training. RESULTS: Orientation and mobility training did not enhance mobility performance compared with the control group, who did not receive training, when performance was measured immediately after training. PPWS improved for both groups with short-term practice only, but there was no improvement in error score due to either practice or training. CONCLUSIONS: There was no immediate improvement in mobility performance of visually impaired adults after orientation and mobility training. Familiarity with the route may play an important role in measured improvement of mobility performance after orientation and mobility training.

Eye movements and reading with large print and optical magnifiers in macular disease.

PURPOSE: Reading rate has been the main performance measure in studies that have compared reading with large print and optical magnifiers; eye movement characteristics have not been considered. We compared both eye movement characteristics and reading rates for subjects with macular disease reading without and with a range of low-vision devices. METHODS: Silent reading rate and eye movement characteristics for text passages at critical print size of 21 subjects aged 14 to 88 years with macular disease were measured with and without their preferred low-vision device. Saccadic frequency was determined from a sequencing task comprising five letters each separated by 5 degrees. Eye movements were recorded using an infrared limbal reflection system. RESULTS: There were no significant differences in reading rate, fixation durations, saccade numbers per word, or percent retrace time when using a low-vision device compared with reading without a low-vision device. The percentage of regressions was, however, lower with the low-vision device. Saccadic frequency in the sequencing task was predictive of reading performance with and without a low-vision device. CONCLUSIONS: When reading at critical print size, in terms of reading rate or saccades per word, there was no advantage to using large print over an optical low-vision device.

Oral and silent reading performance with macular degeneration.

Previous studies have shown that reading rate for very large print (6 degrees, 1.86 logMAR character size) is a strong predictor of oral reading rate with low vision devices (LVDs). We investigated whether this would apply using large print sizes more readily available in clinical situations (e.g. 2 degrees, 1.4 logMAR), for subjects with macular degeneration. We assessed rauding rates--reading for understanding. A combination of near word visual acuity and large print reading rate (without LVDs) provided the best prediction of oral rauding rates (with LVDs). However, near word visual acuity alone was almost as good. Similarly, silent rauding rate was predicted best by near word visual acuity alone. We give near visual acuity limits as a clinical guide to expected oral and silent reading performance with LVDs for patients with macular degeneration.

Repeatability and intercorrelations of standard vision tests as a function of age.

PURPOSE: We assessed repeatability and intercorrelations of five standard vision tests in subjects with normal vision. METHODS: Seventy-eight subjects (aged 21 to 68 years) completed five measurements each of high- and low-contrast visual acuity, near visual acuity and contrast sensitivity (Pelli-Robson chart). RESULTS: Except for correlations between high- and low-contrast visual acuity (r = 0.78), intercorrelations between tests were low to moderate (r < 0.5). For each measure, variability for the group was about one line on the chart (one triplet for the Pelli-Robson chart) and the minimum variability for an individual subject was about one third of this. On average, 1 to 2 lines can be expected to be lost over the normal lifespan on each test. Variability in responses did not increase significantly with age for any test. CONCLUSIONS: The criterion for judging change on commonly used clinical vision tests is about one line for subjects over a wide age range.

[A simplified screening test for the identification of individuals with diminished vision in developing countries]. / Prueba de tamizaje simplificada para identificar a personas con visión disminuida en países en desarrollo.

Simple but effective tests have been produced for screening subjects with low vision in developing countries. These tests of distance and near vision, based on the E test, were evaluated and validated in trials with people aged 4-90 years, and have been field tested in the health, education and rehabilitation services in 32 developing countries. Their sensitivity and specificity as screening tools for low vision have been calculated: sensitivity of 85% and specificity of 96% for the distance vision test, and sensitivity of 100% and specificity of 84% for the near vision test. The content and format of the tests have been demonstrated to be appropriate for developing countries, and their effectiveness for screening for low vision has been confirmed.

Prueba de tamizaje simplificada para identificar a personas con visión disminuida en países en desarrollo / A simplified screening test for identifying people with low vision in developing countries

Se han creado pruebas sencillas pero útiles para el tamizaje de personas con visión disminuida en países en desarrollo. Estas pruebas, que miden la visión de lejos y de cerca y que se basan en el uso de una figura en E, fueron evaluadas y respaldadas mediante ensayos en que participaron personas de 4 a 90 años de edad, y se han puesto a prueba en los servicios de salud, educación y rehabilitación de 32 países en desarrollo. Se han calculado su sensibilidad y especificidad como instrumentos para la detección de la visión disminuída: en la prueba de visión a distancia, la sensibilidad es de 85 por ciento y la especificidad, de 96 por ciento; en la prueba de visión cercana, la sensibilidad es de 100 por ciento y la especificidad, de 84 por ciento. Se ha demostrado que el contenido y el formato de las pruebas son adecuados para países en desarrollo y se ha comprobado la utilidad de las mismas para el tamizaje de la visión disminuida

Simple but effective tests have been produced for screening subjects with low vision in developing countries. These tests of distance and near vision, based on the E test, were evaluated and validated in trials with people aged 4­90 years, and have been field tested in the health, education and rehabilitation services in 32 developing countries. Their sensitivity and specificity as screening tools for low vision have been calculated: sensitivity of 85% and specificity of 96% for the distance vision test, and sensitivity of 100% and specificity of 84% for the near vision test. The content and format of the tests have been demonstrated to be appropriate for developing countries, and their effectiveness for screening for low vision has been confirmed.

Prueba de tamizaje simplificada para identificar a personas con visión disminuida en países en desarrollo / A simplified screening test for identifying people with low vision in developing countries

Se han creado pruebas sencillas pero útiles para el tamizaje de personas con visión disminuida en países en desarrollo. Estas pruebas, que miden la visión de lejos y de cerca y que se basan en el uso de una figura en E, fueron evaluadas y respaldadas mediante ensayos en que participaron personas de 4 a 90 años de edad, y se han puesto a prueba en los servicios de salud, educación y rehabilitación de 32 países en desarrollo. Se han calculado su sensibilidad y especificidad como instrumentos para la detección de la visión disminuída: en la prueba de visión a distancia, la sensibilidad es de 85 por ciento y la especificidad, de 96 por ciento; en la prueba de visión cercana, la sensibilidad es de 100 por ciento y la especificidad, de 84 por ciento. Se ha demostrado que el contenido y el formato de las pruebas son adecuados para países en desarrollo y se ha comprobado la utilidad de las mismas para el tamizaje de la visión disminuida

Rediscovering mycophenolic acid: a review of its mechanism, side effects, and potential uses.

Oral mycophenolic acid (MPA) therapy has been investigated in the treatment of moderate to severe psoriasis since the early 1970s and has been found to be both safe and effective. By inhibiting de novo purine biosynthesis, it functions as an antifungal, antibacterial, antiviral, and immunosuppressive agent. The recent availability of mycophenolate mofetil (MMF), a morpholinoester of MPA, has created renewed interest in the antipsoriatic properties of MPA. MMF is currently indicated for the prevention of organ rejection in transplant recipients and is used concomitantly with cyclosporine and corticosteroids. This review focuses on the pharmacology of MPA and MMF, studies of MPA in the treatment of psoriasis, and therapy with MMF. There is a potential application of MMF in the treatment of severe psoriasis and other inflammatory dermatoses, as well as topical MPA for the treatment of psoriasis.

Referral to low vision services by ophthalmologists.

PURPOSE: People in need of low vision rehabilitation services often experience delays in referral to services. This study investigates referral criteria of Australian ophthalmologists, the frequency of referral of their patients with low vision and their perceptions of low vision services. METHODS: A survey was sent to a representative, random sample of 200 ophthalmologists. They were asked about criteria used for the referral of their patients with low vision. The survey included questions on the frequency with which they prescribed low vision devices (LVD) and referral of their patients to low vision and rehabilitation services and peer support groups. Perceptions of the quality and availability of low vision services were also investigated. RESULTS: The response rate was 82%. Approximately 11% of ophthalmologists' patients have low vision. It is uncommon for ophthalmologists to prescribe LVD but 67% refer most of their patients with low vision. It is less common for them to refer to rehabilitation services (29%) or peer support services (18%). The perceived local availability of services influences the rate of referral. Ophthalmologists who used the criteria of moderate low vision (< 6/21 to < 6/60) are more likely to refer more of their patients than those who use the criteria of severe low vision. CONCLUSIONS: Australian ophthalmologists refer most of their visually impaired patients to low vision services, but infrequently to rehabilitation services or peer support groups. Differences in perceived need for low vision services indicated by the criteria used for referral, and the perceived availability, influence the rate at which ophthalmologists refer their patients for services. Ophthalmologists are encouraged to refer patients with permanent visual loss to low vision services earlier.

A simplified screening test for identifying people with low vision in developing countries.

Simple but effective tests have been produced for screening subjects with low vision in developing countries. These tests of distance and near vision, based on the E test, were evaluated and validated in trials with people aged 4-90 years, and have been field tested in the health, education and rehabilitation services in 32 developing countries. Their sensitivity and specificity as screening tools for low vision have been calculated; sensitivity of 85% and specificity of 96% for the distance vision test, and sensitivity of 100% and specificity of 84% for the near vision test. The content and format of the tests have been demonstrated to be appropriate for developing countries, and their effectiveness for screening for low vision has been confirmed.