Early local functional changes in the human diabetic retina : a global flash multifocal electroretinogram study

Purpose: To investigate early functional changes of local retinal defects in type II diabetic patients using the global flash multifocal electroretinogram (MOFO mfERG). Methods: Thirty-eight diabetic patients and 14 age-matched controls were recruited. Nine of the diabetics were free from diabetic retinopathy (DR), while the remainder had mild to moderate non-proliferative diabetic retinopathy. The MOFO mfERG was performed at high (98%) and low (46%) contrast levels. MfERG responses were grouped into 35 regions for comparison with DR classification at those locations. Z-scores of the regional mfERG responses were compared across different types of DR defects. Results: The mfERG waveform consisted of the direct component (DC) and the induced component (IC). Local reduction in DC and IC amplitudes were found in diabetic patients with and without DR. With increasing severity of retinopathy, there was a further deterioration in amplitude of both components. Under MOFO mfERG paradigm, amplitude was a useful screening parameter. Conclusion: The MOFO mfERG can help in detecting early functional anomalies before the appearance of visible signs, and may assist in monitoring further functional deterioration in diabetic patients.

Global flash multifocal electroretinogram : early detection of local functional changes and its correlations with optical coherence tomography and visual field loss in diabetic eyes

Purpose: To investigate the correlations of the global flash multifocal electroretinogram (MOFO mfERG) with common clinical visual assessments – Humphrey perimetry and Stratus circumpapillary retinal nerve fiber layer (RNFL) thickness measurement in type II diabetic patients. Methods: Forty-two diabetic patients participated in the study: ten were free from diabetic retinopathy (DR) while the remainder suffered from mild to moderate non-proliferative diabetic retinopathy (NPDR). Fourteen age-matched controls were recruited for comparison. MOFO mfERG measurements were made under high and low contrast conditions. Humphrey central 30-2 perimetry and Stratus OCT circumpapillary RNFL thickness measurements were also performed. Correlations between local values of implicit time and amplitude of the mfERG components (direct component (DC) and induced component (IC)), and perimetric sensitivity and RNFL thickness were evaluated by mapping the localized responses for the three subject groups. Results: MOFO mfERG was superior to perimetry and RNFL assessments in showing differences between the diabetic groups (with and without DR) and the controls. All the MOFO mfERG amplitudes (except IC amplitude at high contrast) correlated better with perimetry findings (Pearson’s r ranged from 0.23 to 0.36, p<0.01) than did the mfERG implicit time at both high and low contrasts across all subject groups. No consistent correlation was found between the mfERG and RNFL assessments for any group or contrast conditions. The responses of the local MOFO mfERG correlated with local perimetric sensitivity but not with RNFL thickness. Conclusion: Early functional changes in the diabetic retina seem to occur before morphological changes in the RNFL.

Multifocal electroretinogram responses in Nepalese diabetic patients without retinopathy

Purpose To determine neuroretinal function with multifocal electroretinogram (mfERG) in diabetic subjects without retinopathy. Methods Multifocal electroretinogram (mfERG) was performed in 18 eyes of 18 diabetic subjects without retinopathy and 17 eyes of 17 age and gender-matched healthy control participants. Among 18 diabetic subjects, two had type 1 and 16 had type 2 diabetes. MfERG responses were averaged by the retinal areas of six concentric rings and four quadrants, and 103 retinal locations; N1–P1 amplitude and P1-implicit time were analysed. Results Average mfERG N1–P1 amplitude (in nv/deg2) of 103 retinal locations was 56.3 ± 17.2 (mean ± SD) in type 1 diabetic subjects, 47.2 ± 9.3 in type 2 diabetic subjects and 71.5 ± 12.7 in controls. Average P1-implicit time (in ms) was 43.0 ± 1.3 in type 1 diabetic subjects, 43.9 ± 2.3 in type 2 diabetic subjects and 41.9 ± 2.1 in controls. There was significant reduction in average N1–P1 amplitude and delay in P1-implicit time in type 2 diabetic subjects in comparison to controls. mfERG amplitude did not show any significant correlation with diabetes duration and blood sugar level. However, implicit time showed a positive correlation with diabetes duration in type 2 diabetic subjects with diabetes duration ≥5 years. Conclusions This is the first study in a Nepalese population with diabetes using multifocal electroretinography. We present novel findings that mfERG N1–P1 amplitude is markedly reduced along with delay in P1-implicit time in type 2 diabetic subjects without retinopathy. These findings indicate that there might be significant dysfunction of inner retina before the development of diabetic retinopathy in the study population, which have higher prevalence of diabetes than the global estimate and uncontrolled blood sugar level.

Effect of accommodation on peripheral ocular aberrations

Changes in peripheral aberrations, particularly higher-order aberrations, as a function of accommodation have received little attention. Wavefront aberrations were measured for the right eyes of 9 young adult emmetropes at 38 field positions in the central 42 x 32 degrees of the visual field. Subjects accommodated monocularly to targets at vergences of either 0.3 or 4.0 D. Wavefront data for a 5 mm diameter pupil were analyzed either in terms of the vector components of refraction or Zernike coefficients and total RMS wavefront aberrations. Relative peripheral refractive error (RPRE) was myopic at both accommodation demands and showed only a slight, not statistically significant, hypermetropic shift in the vertical meridian with the higher accommodation demand. There was little change in the astigmatic components of refraction or the higher-order Zernike coefficients, apart from fourth-order spherical aberration which became more negative (by 0.10 µm) at all field locations. Although it has been suggested that nearwork and the state of peripheral refraction may play some role in myopia development, for most of our adult emmetropes any changes with accommodation in RPRE and aberration were small. Hence it seems unlikely that such changes can be of importance to late-onset myopisation.

The effect of incipient presbyopia on the correspondence between accommodation and vergence

Purpose: To investigate the accommodation-convergence relationship during the incipient phase of presbyopia. The study aimed to differentiate between the current theories of presbyopia and to explore the mechanisms by which the oculomotor system compensates for the change in the accommodation-convergence relationship contingent on a declining amplitude of accommodation. Methods: Using a Canon R-1 open-view autorefractor and a haploscope device, measurements were made of the stimulus and response accommodative convergence/accommodation ratios and the convergence accommodation/convergence ratio of 28 subjects aged 35-45 years at the commencement of the study. Amplitude of accommodation was assessed using a push-down technique. The measurements were repeated at 4-monthly intervals over a 2-year period. Results: The results showed that with the decline in the amplitude of accommodation there is an increase in the accommodative convergence response per unit of accommodative response and a decrease in the convergence accommodation response per unit of convergence. Conclusions: The results of this study fail to support the Hess-Gullstrand theory of presbyopia in that the ciliary muscle effort required to produce a unit change in accommodation increases, rather than stays constant, with age. Data show that the near vision response is limited to the maximum vergence response that can be tolerated and, despite being within the amplitude of accommodation, a stimulus may still appear blurred because the vergence component determines the proportion of available accommodation utilised during near vision.

Myopia: structural and functional correlates

Ocular dimensions are widely recognised as key variants of refractive error. Previously, accurate depiction of eye shape in vivo was largely restricted by limitations in the imaging techniques available. This thesis describes unique applications of the recently introduced 3-dimensional magnetic resonance imaging (MRI) approach to evaluate human eye shape in a group of young adult subjects (n=76) with a range of ametropia (MSE= -19.76 to +4.38D). Specific MRI derived parameters of ocular shape are then correlated with measures of visual function. Key findings include the significant homogeneity of ocular volume in the anterior eye for a range of refractive errors, whilst significant volume changes occur in the posterior eye as a function of ametropia. Anterior vs. posterior eye differences have also been shown through evaluations of equivalent spherical radius; the posterior 25% cap of the eye was shown to be relatively steeper in myopes compared to emmetropes. Further analyses showed differences in retinal quadrant profiles; assessments of the maximum distance from the retinal surface to the presumed visual axes showed exaggerated growth of the temporal quadrant in myopic eyes. Comparisons of retinal contour values derived from transformation of peripheral refraction data were made with MRI; flatter retinal curvature values were noted when using the MRI technique. A distinctive feature of this work is the evaluation of the relationship between ocular structure and visual function. Multiple aspects of visual function were evaluated through several vehicles: multifocal electroretinogram testing, visual field sensitivity testing, and the use of psychophysical methods to determine ganglion cell density. The results show that many quadrantic structural and functional variations exist. In general, the data could not demonstrate a significant correlation between visual function and associated measures of ocular conformation either within or between myopic and emmetropic groups.

Accommodation in young adults wearing multifocal soft contact lenses under long- and short- wavelength lighting

Purpose: Several studies have suggested accommodative lags may serve as a stimulus for myopic growth, and while a blurred foveal image is believed to the main stimulus for accommodation, spectral composition of the retinal image is also believed to influence accommodative accuracy. Of particular interest is how altering spectral lighting conditions influences accommodation in the presence of soft multifocal contact lenses, which are currently being used off-label for myopia control. Methods: Accommodative responses were assessed using a Grand Seiko WAM-5500 autorefractor for four target distances: 25, 33, 50, and 100cm for 30 young adult subjects (14 myopic, 16 emmetropic; mean refractive errors (±SD, D) -4.22±2.04 and -0.15±0.67 respectively). Measurements were obtained with four different soft contact lenses, Single vision distance (SVD), Single vision near (SVN), Centre-Near (CN) and Centre-Distance (CD) (+1.50 add), and three different lighting conditions: red (peak λ 632nm), blue (peak λ 460nm), and white (peak λ 560nm). Corrections for chromatic differences in refraction were made prior to calculating accommodative errors. Results: The size of accommodative errors was significantly affected by lens design (p<0.001), lighting (p=0.027), and target distance (p=0.009). Mean accommodative errors were significantly larger with the SV lenses compared to the CD and CN designs (p<0.001). Errors were also significantly larger under blue light compared to white (p=0.004) and a significant interaction noted between lens design and lighting (p<0.001). Blue light generally decreased accommodative lags and increased accommodative leads relative to white and red light, the opposite was true of red light (p≤0.001). Lens design also significantly influenced direction of accommodative error (i.e. lag or lead) (p<0.001). Interactions with or between refractive groups were not found to be statistically significant for either the magnitude or direction of accommodative error (p>0.05 for all). Conclusions: Accuracy of accommodation is affected by both lens design and by wavelength of lighting. These accommodative lag data lend some support to recent speculation about the potential therapeutic value of lighting with a spectral bias towards blue during near work for myopia, although such treatment effects are likely to be more subtle under broad compared to the narrow spectrum lighting conditions used here.

Variability of the accommodation response in early onset myopia

Purpose. Hyperopic retinal defocus (blur) is thought to be a cause of myopia. If the retinal image of an object is not clearly focused, the resulting blur is thought to cause the continuing lengthening of the eyeball during development causing a permanent refractive error. Both lag of accommodation, especially for near targets, and greater variability in the accommodative response, have been suggested as causes of increased hyperopic retinal blur. Previous studies of lag of accommodation show variable findings. In comparison, greater variability in the accommodative response has been demonstrated in adults with late onset myopia but has not been tested in children. This study looked at the lag and variability of accommodation in children with early onset myopia. Methods. Twenty-one myopic and 18 emmetropic children were tested. Dynamic measures of accommodation and pupil size were made using eccentric photorefraction (Power Refractor) while children viewed targets set at three different accommodative demands (0.25, 2, and 4 D). Results. We found no difference in accommodative lag between groups. However, the accommodative response was more variable in the myopes than emmetropes when viewing both the near (4 D) and far (0.25 D) targets. Since pupil size and variability also varied, we analyzed the data to determine whether this could account for the inter-group differences in accommodation variability. Variation in these factors was not found to be sufficient to explain these differences. Changes in the accommodative response variability with target distance were similar to patterns reported previously in adult emmetropes and late onset myopes. Conclusions. Children with early onset myopia demonstrate greater accommodative variability than emmetropic children, and have similar patterns of response to adult late onset myopes. This increased variability could result in an increase in retinal blur for both near and far targets. The role of accommodative variability in the etiology of myopia is discussed.

Changes in intraocular pressure and ocular pulse amplitude with accommodation

Aims: To investigate the change that occurs in intraocular pressure (IOP) and ocular pulse amplitude (OPA) with accommodation in young adult myopes and emmetropes. Methods: Fifteen progressing myopic and 17 emmetropic young adult subjects had their IOP and OPA measured using the Pascal dynamic contour tonometer. Measurements were taken initially with accommodation relaxed, and then following 2 min of near fixation (accommodative demand 3 D). Baseline measurements of axial length and corneal thickness were also collected prior to the IOP measures. Results: IOP significantly decreased with accommodation in both the myopic and emmetropic subjects (mean change 1.861.1 mm Hg, p<0.0001). There was no significant difference (p>0.05) between myopes and emmetropes in terms of baseline IOP or the magnitude of change in IOP with accommodation. OPA also decreased significantly with accommodation (mean change for all subjects 0.560.5, p<0.0001). The myopic subjects (baseline OPA 2.060.7 mm Hg) exhibited a significantly lower baseline OPA (p¼0.004) than the emmetropes (baseline OPA 3.261.3 mm Hg),and a significantly lower magnitude of change in OPA with accommodation. Conclusion: IOP decreases significantly with accommodation, and changes similarly in progressing myopic and emmetropic subjects. However, differences found between progressing myopes and emmetropes in the mean OPA levels and the decrease in OPA associated with accommodation suggested some changes in IOP dynamics associated with myopia.

Regional changes in choroidal thickness associated with accommodation

Purpose. To characterize the changes occurring in choroidal thickness (ChT) across the posterior pole during accommodation using enhanced-depth imaging optical coherence tomography (OCT). Methods. Forty participants (mean age 21 ± 2 years) had measures of ChT and ocular biometry taken during accommodation to 0, 3, and 6 diopter (D) stimuli, with the Spectralis OCT and Lenstar biometer. A Badal optometer and cold mirror system was mounted on both instruments, allowing measurement collection while subjects viewed an external fixation target at varying accommodative demands. Results. The choroid exhibited significant thinning during accommodation to the 6 D stimulus in both subfoveal (mean change, −5 ± 7 μm) and parafoveal regions (P < 0.001). The magnitude of these changes varied by parafoveal meridian, with the largest changes seen in the temporal (−9 ± 12 μm) and inferotemporal (−8 ± 8 μm) meridians (P < 0.001). Axial length increased with accommodation (mean change, +5 ± 11 μm at 3 D, +14 ± 13 μm at 6 D), and these changes were weakly negatively associated with the choroidal changes (r2 = 0.114, P < 0.05). Conclusions. A small, but significant thinning of the choroid was observed at the 6 D accommodation demand, which was greatest in the temporal and inferotemporal parafoveal choroid, and increased with increasing eccentricity from the fovea. The regional variation in the parafoveal thinning corresponds to the distribution of the nonvascular smooth muscle within the uvea, which may implicate these cells as the potential mechanism by which the choroid thins during accommodation.

Evidence for an "epidemic" of myopia.

INTRODUCTION:

It has been widely suggested that the prevalence of myopia is growing worldwide, and that the increases observed in East Asia, in particular, are sufficiently severe as to warrant the term "epidemic". Data in favour of a cohort effect in myopia prevalence are reviewed, with attention to significant shortcomings in the quality of available evidence. Additional factors contributing to myopia prevalence, including near work, genetics and socioeconomic status, are detailed.

MATERIALS AND METHODS:

Medline search of articles regarding myopia prevalence, trends and mechanisms.

RESULTS:

Age-related changes in myopia prevalence (increase during childhood, and regression in the fifth and sixth decades) are discussed as an alternative explanation for cross-sectional patterns in myopia prevalence. There have only been a handful of studies that have examined the relative contribution of longitudinal changes in refraction over life and birth cohort differences on age-specific myopia prevalence as measured in cross-sectional studies. Available data suggest that both longitudinal changes and cohort effects may be present, and that their relative contribution may differ in different racial groups.

CONCLUSIONS:

In view of the relatively weak evidence in favour of a large cohort effect for myopia in East Asia, and the even greater lack of evidence for increased prevalence of secondary ocular pathology, there appears to be inadequate support for large-scale interventions to prevent or delay myopia at the present time.

Myopia, spectacle wear, and risk of bicycle accidents among rural Chinese secondary school students: the Xichang Pediatric Refractive Error Study report no. 7.

OBJECTIVE: To study the effect of myopia and spectacle wear on bicycle-related injuries in rural Chinese students. Myopia is common among Chinese students but few studies have examined its effect on daily activities. METHODS: Data on visual acuity, refractive error, current spectacle wear, and history of bicycle use and accidents during the past 3 years were sought from 1891 students undergoing eye examinations in rural Guangdong province. RESULTS: Refractive and accident data were available for 1539 participants (81.3%), among whom the mean age was 14.6 years, 52.5% were girls, 26.8% wore glasses, and 12.9% had myopia of less than -4 diopters in both eyes. More than 90% relied on bicycles to get to school daily. A total of 2931 accidents were reported by 423 participants, with 68 requiring medical attention. Male sex (odds ratio, 1.55; P < .001) and spectacle wear (odds ratio, 1.38; P = .04) were associated with a higher risk of accident, but habitual visual acuity and myopia were unassociated with the crash risk, after adjusting for age, sex, time spent riding, and risky riding behaviors. CONCLUSION: These results may be consistent with data on motor vehicle accidents implicating peripheral vision (potentially compromised by spectacle wear) more strongly than central visual acuity in mediating crash risk.

Fator de correção para indivíduos com capacidade acomodativa baseado no uso do refrator automático

OBJETIVO: Pesquisar um fator de correção para avaliação do erro refrativo sem a utilização da cicloplegia. MÉTODOS: Foram estudados 623 pacientes (1.246 olhos), de ambos os sexos, com idade entre 3 e 40 anos. As refratometrias estática e dinâmica foram obtidas usando-se o refrator automático Shin-Nippon Accuref-K 9001. A cicloplegia foi obtida com a instilação de uma gota de colírio ciclopentolato a 1%, com refratometria estática 30 minutos após. Os dados foram submetidos à análise estatística usando a técnica do modelo de regressão linear e modelo de regressão múltipla do valor dióptrico com e sem cicloplegia, em função da idade. RESULTADOS: A correlação entre valores dióptricos sem e com cicloplegia quanto ao erro astigmático variou de 81,52% a 92,27%. Quanto ao valor dióptrico esférico, a correlação foi menor (53,57% a 87,78%). O mesmo se observou em relação ao eixo do astigmatismo (28,86% a 58,80%). O modelo de regressão múltipla em função da idade mostrou coeficiente de determinação múltiplo maior para a miopia (86,38%) e astigmatismo (79,79%). O menor coeficiente foi observado para o eixo do astigmatismo (17,70%). CONCLUSÃO: Avaliando-se os erros refrativos com e sem cicloplegia, observou-se alta correlação nas ametropias cilíndricas. Foram desenvolvidas equações matemáticas como fator de correção para refratometrias dos pacientes sem cicloplegia, portadores de ametropias cilíndricas e esféricas.

The Effect of nutritional supplementation on subjective and objective measures of visual and retinal function:a random controlled trial

In industrialised countries age-related macular disease (ARMD) is the leading cause of visual loss in older people. Because oxidative stress is purported to be associated with an increased risk of disease development the role of antioxidant supplementation is of interest. Lutein is a carotenoid antioxidant that accumulates within the retina and is thought to filter blue light. Increased levels of lutein have been associated with reduced risk of developing ARMD and improvements in visual and retinal function in eyes with ARMD. The aim of this randomised controlled trial (RCT) was to investigate the effect of a lutein-based nutritional supplement on subjective and objective measures of visual function in healthy eyes and in eyes with age-related maculopathy (ARM) – an early form of ARMD. Supplement withdrawal effects were also investigated. A sample size of 66 healthy older (HO), healthy younger (HY), and ARM eyes were randomly allocated to receive a lutein-based supplement or no treatment for 40 weeks. The supplemented group then stopped supplementation to look at the effects of withdrawal over a further 20 weeks. The primary outcome measure was multifocal electroretinogram (mfERG) N1P1 amplitude. Secondary outcome measures were mfERG N1, P1 and N2 latency, contrast sensitivity (CS), Visual acuity (VA) and macular pigment optical density (MPOD). Sample sizes were sufficient for the RCT to have an 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures when the healthy eye groups were combined, and CS, VA and mfERG in the ARM group. This RCT demonstrates significant improvements in MPOD in HY and HO supplemented eyes. When HY and HO supplemented groups were combined, MPOD improvements were maintained, and mfERG ring 2 P1 latency became shorter. On withdrawal of the supplement mfERG ring 1 N1P1 amplitude reduced in HO eyes. When HO and HY groups were combined, mfERG ring 1 and ring 2 N1P1 amplitudes were reduced. In ARM eyes, ring 3 N2 latency and ring 4 P1 latency became longer. These statistically significant changes may not be clinically significant. The finding that a lutein-based supplement increases MPOD in healthy eyes, but does not increase mfERG amplitudes contrasts with the CARMIS study and contributes to the debate on the use of nutritional supplementation in ARM.