Structure and function in age-related maculopathy

Purpose. Age-related maculopathy (ARM) is the leading cause of severe vision impairment and irreversible vision loss in developed countries. Visual functional changes, such as visual acuity deficits, increased crowding and the decrease of contrast sensitivity have been studied for years in patients with different stages of ARM. Optical coherence tomography (OCT) and Confocal Scanning Laser Ophthalmoscopy (CSLO) are two newly developed non-contact and non-invasive clinical imaging techniques which have been used increasingly in clinical investigation and research of ocular diseases such as ARM. OCT gives high resolution, cross-sectional images showing the microstructure of the intraocular tissue such as retinal thickness changes while CSLO provides large field, high resolution topographic images of the retina. Both techniques provide more detailed information of the retina in ARM than conventional instruments such as fundus photography. The first purpose of the present study was to investigate the relationship between retinal anatomical changes measured by OCT and CSLO and sensory functional changes measured from the same predetermined retinal areas in patients with early ARM. The second purpose was to document and study these functional and structural changes in early ARM and to develop protocols that might be used in a larger scale study.;Results. Among all the functional measurements, mixed ANOVA showed a significant difference between controls and ARM subjects for low spatial frequency static contrast sensitivity (SCS) (p=0.05). Visual acuity (un-crowded VA and crowded VA) and the crowding effect showed a borderline effect (p=0.072, p=0.084 and p=0.595 respectively). Compared to controls, there was no evidence of increased contour interaction effects in early ARM and no consistent deficits were found in other functional measures. There was no difference in alternating contrast sensitivity between the two groups (p=0.586). Overall OCT retinal thickness showed no significant difference between controls and ARM subjects (p=0.466). Neither did the OCT RPE-choriocapillaris complex (RPE-CC) measurements. However, the OCT RPE-CC measurements tended to be more variable, either thicker or thinner in the ARM group. Pearson correlation coefficients between structural and functional measures for 9 retinal locations showed significant correlation at several locations between OCT RPE-CC thickness and changes of VA and ACS at p = 0.005 level. There were some significant correlations between OCT RPE-CC thickness and the measures of SCS and ACS for averaged functional and structural measurements. OCT RPE-CC thickest correlated with SCS (p=0.028) and OCT RPE-CC thinnest correlated with SCS and ACS (p=0.022 and 0.04 respectively). There were also several significant correlations between functional measures i.e. several functional measures tended to correlate with each other as would be expected. There was no correlation between fundus grade and functional measurements and no correlation between CSLO grade and functional measurements. The agreement between fundus and CSLO grade was 71% for 9 retinal locations, but there was high correlation between fundus grade and OSLO grade (r = 0.822, p = 0.007) for grades averaged across the nine locations.;Conclusions. There was no simple relationship between structural and functional measures in this group of people with early atrophic ARM. The subjects with very early ARM showed significant loss of low spatial frequency SCS before the loss of VA compared to controls and this indicates that SCS may be one of the earliest functional losses in ARM. Alternating CS, crowded and un-crowded visual acuity did not reach significance for difference between the two groups. Compared to controls, there was no evidence of increased contour interaction effects in early ARM. The RPE-CC thickness showed a trend of being more variable in thickness (thicker or thinner) in early atrophic ARM which could be an early sign of loss of function of the RPE cells. There was no significant association between functional measures and fundus grade and CSLO grade in early atrophic ARM.;Methods. Ten early ARM participants aged 55 and up with good visual acuity and 10 age-matched controls were recruited and all the measurements were obtained from the same eye of each participant at 9 predetermined retinal locations. Crowded and un-crowded visual acuity was measured at 9 predetermined retinal locations without dilation using computer-generated single and crowded Landolt Cs with a psychophysical modified method of constant stimuli. Static contrast sensitivity (SCS) and alternating contrast sensitivity (ACS) was measured without dilation at the same retinal location using the Morphonome 3.2 computer program and a psychophysical method of limits. Spatial frequency was 0.4 cpd for the contrast sensitivity measurements and the flicker rate was 7.5 Hz for the alternating grating. The grating for the measurements was a sine-wave grating in a 3° field and was presented with short duration (274 msecs for SCS, 200 msecs for ACS). Structural measurements were performed with dilation in the same eye of each participant and at the same retinal locations. A Humphrey-Zeiss Optical Coherence Tomography (OCT2) (wavelength 843 nm, near-infrared light) was used to take high resolution, cross-sectional images with a horizontal scan of length 1.13mm. A non-commercial confocal scanning laser ophthalmoscopy (CSLO) (HeNe laser, wavelength 632.8nm) was used to take high resolution images of the entire posterior pole of the retina. Fundus photography was used as a reference for structural measurements and was graded using the Wisconsin Age-related Maculopathy Grading System (WARMGS) (12). The complete CSLO image was combined in Microsoft PowerPoint and was graded using the same grading rule as for fundus photography. All the data were collected from predetermined retinal areas in 10 subjects with early ARM and 10 control subjects. Mixed ANOVA was used to find the differences between ARM and control groups, the Pearson and Spearman correlation coefficients were used to determine any association between structural and functional measures and the F test for equivalence of two variances was used to find out the variability of the data.