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Importance This study demonstrates that increasing quintiles of baseline high-sensitivity C-reactive protein (hsCRP) level may be associated with higher risk of incident clinically significant macular edema, the leading cause of vision loss in working-aged individuals in North America. Objective To determine whether baseline levels of hsCRP and intercellular adhesion molecule 1 (ICAM-1) predict development and progression of diabetic retinopathy (DR), clinically significant macular edema (CSME), retinal hard exudates, and proliferative DR in the Diabetes Control and Complications Trial (DCCT) cohort. Design The DCCT was a large multicenter randomized controlled clinical trial. Setting Twenty-nine medical centers in the United States and Canada. Participants The DCCT population consisted of 1441 subjects with type 1 diabetes mellitus aged 13 to 39 years at study entry. Intervention We measured levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 in stored baseline blood samples. Main Outcome Measures We assessed the association of levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 with incident DR end points ascertained from grading of standardized 7-field stereoscopic retinal color photographs taken at baseline and every 6 months during follow-up. Results After adjustment for randomized treatment assignment and other factors, we observed a statistically significant association between hsCRP and risk of CSME, with a relative risk (RR) for the top vs bottom quintile of 1.83 (95% CI, 0.94-3.55; P for trend = .01). Similarly, for the development of retinal hard exudates, the RR for the top vs bottom quintile of hsCRP level was 1.78 (95% CI, 0.98-3.25; P for trend = .004), whereas for ICAM-1 level, the RR comparing the top vs bottom quintiles was 1.50 (95% CI, 0.84-2.68; P for trend = .05). There were no statistically significant associations between baseline VCAM-1 or tumor necrosis factor α receptor 1 levels and risk of any of the DR end points. Conclusions and Relevance After adjusting for known risk factors, increasing quintiles of baseline hsCRP level may be associated with higher risk of incident CSME and macular hard exudate in the DCCT cohort. Circulating levels of ICAM-1 may also be associated with the development of retinal hard exudates.

Within a duration of 20 ms humans can compare the orientations of two test lines so as to encode and place in memory their mean orientation and orientation difference while ignoring noise lines in the space between the test lines. Furthermore, performance is not impaired by randomly varying the location of each test line from trial-to-trial. We conclude that the two test lines are not compared by shifting eye fixation or attention from one to the other, nor by attending to two spatial locations. This evidence is consistent with the proposal that the human visual system contains second-stage long-distance comparators, any one of which responds to simultaneous stimulation of two conventional first-stage spatial filters located some distance apart and is insensitive to stimuli that fall between these two first-stage filters. We suggest that our observers performed discriminations by attending to the outputs of the proposed second-stage long-distance comparators rather than by attending to two spatial locations. In addition to their mean orientation and orientation difference, humans can simultaneously encode and place in memory the separation and mean location of the two test lines while ignoring stimuli in the space between the lines. We suggest that, following each of the eye's exploratory saccades, the proposed second-stage long-distance comparators, in effect, take a snapshot of an object's retinal image that ignores the object's surface texture while encoding the shape of its boundary.

The psychophysical data reported here bear on how the boundaries of an object’s retinal image are processed in early vision. We propose that the visual system contains a mechanism sensitive to four relationships between two local stimuli some distance apart and that the output of this hypothetical mechanism encodes and labels orthogonally the four relationships. We measured the just-noticeable difference in the orientation difference between two test lines as well as the just-noticeable differences in their mean orientation, mean location, and separation. A pair of noise lines was located between the two test lines. By arranging that trial-to-trial variations in the orientation difference, mean orientation, mean location and separation of the test lines had zero correlation with each other and with trial-to-trial variations in the corresponding variables for the two noise lines we could demonstrate that psychophysical responses were based on the task-relevant variable and that, for each of the four task-relevant variables, all task-irrelevant variables were ignored. The finding that responses to the test lines were unaffected by the noise lines implies that discriminations were not influenced by first–stage spatial filters with strictly local receptive fields that responded to both test lines. Because these findings held for a presentation duration of 20 ms we can exclude the possibility that observers compared the two test lines by shifting either fixation or attention. We propose that, rather than by attending to two different locations, the test lines were selected by attending to the output of the long-distance comparator whose ‘separation’ label signaled the largest magnitude. The above proposals can account for several previously reported phenomena. More generally, an array of the proposed long-distance comparators constitutes a system that may be capable of specifying the shape, size, location and implicit orientation of an object’s retinal image.