Retinal mid-peripheral capillary free zones are enlarged in cognitively unimpaired older adults at high risk for Alzheimer's disease.

BACKGROUND: Compared to standard neuro-diagnostic techniques, retinal biomarkers provide a probable low-cost and non-invasive alternative for early Alzheimer's disease (AD) risk screening. We have previously quantified the periarteriole and perivenule capillary free zones (mid-peripheral CFZs) in cognitively unimpaired (CU) young and older adults as novel metrics of retinal tissue oxygenation. There is a breakdown of the inner retinal blood barrier, pericyte loss, and capillary non-perfusion or dropout in AD leading to potential enlargement of the mid-peripheral CFZs. We hypothesized the mid-peripheral CFZs will be enlarged in CU older adults at high risk for AD compared to low-risk individuals. METHODS: 20 × 20° optical coherence tomography angiography images consisting of 512 b-scans, 512 A-scans per b-scan, 12-µm spacing between b-scans, and 5 frames averaged per each b-scan location of the central fovea and of paired major arterioles and venules with their surrounding capillaries inferior to the fovea of 57 eyes of 37 CU low-risk (mean age: 66 years) and 50 eyes of 38 CU high-risk older adults (mean age: 64 years; p = 0.24) were involved in this study. High-risk participants were defined as having at least one APOE e4 allele and a positive first-degree family history of AD while low-risk participants had neither of the two criteria. All participants had Montreal Cognitive Assessment scores ≥ 26. The mid-peripheral CFZs were computed in MATLAB and compared between the two groups. RESULTS: The periarteriole CFZ of the high-risk group (75.8 ± 9.19 µm) was significantly larger than that of the low-risk group (71.3 ± 7.07 µm), p = 0.005, Cohen's d = 0.55. The perivenule CFZ of the high-risk group (60.4 ± 8.55 µm) was also significantly larger than that of the low-risk group (57.3 ± 6.40 µm), p = 0.034, Cohen's d = 0.42. There were no significant differences in foveal avascular zone (FAZ) size, FAZ effective diameter, and vessel density between the two groups, all p > 0.05. CONCLUSIONS: Our results show larger mid-peripheral CFZs in CU older adults at high risk for AD, with the potential for the periarteriole CFZ to serve as a novel retinal vascular biomarker for early AD risk detection.

The retinal and perceived locus of fixation in the human visual system.

Due to the dramatic difference in spatial resolution between the central fovea and the surrounding retinal regions, accurate fixation on important objects is critical for humans. It is known that the preferred retinal location (PRL) for fixation of healthy human observers rarely coincides with the retinal location with the highest cone density. It is not currently known, however, whether the PRL is consistent within an observer or is subject to fluctuations and, moreover, whether observers' subjective fixation location coincides with the PRL. We studied whether the PRL changes between days. We used an adaptive optics scanning laser ophthalmoscope to project a Maltese cross fixation target on an observer's retina and continuously imaged the exact retinal location of the target. We found that observers consistently use the same PRL across days, regardless of how much the PRL is displaced from the cone density peak location. We then showed observers small stimuli near the visual field location on which they fixated, and the observers judged whether or not the stimuli appeared in fixation. Observers' precision in this task approached that of fixation itself. Observers based their judgment on both the visual scene coordinates and the retinal location of the stimuli. We conclude that the PRL in a normally functioning visual system is fixed, and observers use it as a reference point in judging stimulus locations.

Comparing habitual and i. Scription refractions.

BACKGROUND: Many patients voice concerns regarding poor night vision, even when they see 20/20 or better in the exam room. During mesopic and scotopic conditions the pupil size increases, increasing the effects on visual performance of uncorrected (residual) refractive errors. The i.Scription refraction method claims to optimize traditional refractions for mesopic and scotopic conditions, by using the information that the Zeiss i.Profilerplus gathers of ocular aberrations (low and high order). The aim of this study was to investigate any differences between habitual and i.Scription refractions and their relationship to night vision complaints. METHODS: Habitual, subjective, and i.Scription refractions were obtained from both eyes of eighteen subjects. Low and high order aberrations of the subjects were recorded with the Zeiss i.Profilerplus. The root mean square (RMS) metric was calculated for small (3 mm) and maximum pupil sizes. Subjects rated their difficulty with driving at night on a scale of 1-10. RESULTS: There was a statistically significant difference between the habitual and i.Scription refractions on both the sphere and cylinder values [(t = 3.12, p < 0.01), (t = 5.39, p < 0.01)]. The same was found when comparing the subjective and i.Scription refractions [(t = 2.31, p = 0.03), (t = 2.54, p = 0.02)]. There were no significant differences found when comparing the sphere and cylinder values between the habitual and subjective refractions or on any combination of spherical equivalent refraction. The maximum pupil size of the subject population on this study, measured with the i.Profilerplus, was 4.8 ± 1.04 mm. Ten out of the eighteen subjects had discomfort at night with an average magnitude of 4 ± 2.7. Ratings of difficulty with night vision correlated with the change in spherical equivalent correction between the habitual and i.Scription refractions (p = 0.01). A sub-analysis of myopic subjects (n = 15) showed an increase in the significance of this relationship (p = 0.002). CONCLUSIONS: The i.Scription method improves night vision by correcting the sphere and cylinder more precisely. There was a correlation between the amount of change in the cylinder value between habitual and i.Scription prescriptions and the magnitude of the reported visual discomfort at night.

The corneal nerve density in the sub-basal plexus decreases with increasing myopia: a pilot study.

PURPOSE: Myopia can cause many changes in the health of the eye. As it becomes more prevalent worldwide, more patients seek correction in the form of glasses, contact lenses and refractive surgery. In this study we explore the impact that high myopia has on central corneal nerve density by comparing sub basal nerve plexus density measured by confocal microscopy in a variety of refractive errors. METHODS: Seventy healthy adult subjects between the ages of 21-50 years participated in this study. The study took place in two phases with no overlapping subjects (n = 30 phase 1 and n = 40 phase 2). In both phases an autorefraction, keratometry reading, corneal thickness measure and confocal corneal scan of the sub basal nerve plexus were performed for both eyes. There were 11 hyperopes (+0.50 to +3.50DS), six emmetropes (-0.25 to +0.50DS), 30 low myopes (-5.50 to -0.50DS), and 23 high myopes (-5.50DS and above). In the second phase of the study additional tests were performed including an axial length, additional corneal scans, and a questionnaire that asked about age of first refractive correction and contact lens wear. Corneal nerves were imaged over the central cornea with a Nidek CS4 confocal microscope (460 × 345 µm field). Nerves were evaluated using the NeuronJ program for density calculation. One eye was selected for inclusion based on image quality and higher refractive error (more myopic or hyperopic). RESULTS: As myopia increased, nerve density decreased (t1  = 3.86, p < 0.001). We also note a decrease in data scatter above -7 D. The relationship between axial length values and nerve density was also significant and the slope was not as robust as refractive error (t1  = 2.4, p < 0.04). As expected there was a significant difference between the four groups in axial length (F3  = 19.9, p < 0.001) and age of first refractive correction of the myopic groups (14.9 vs 11.5 years; t46  = 2.99 p < 0.01). There was no difference in keratometry readings or corneal thickness between the groups (F3  = 0.6, p = 0.66 and F3  = 1.2, p = 0.33 respectively). CONCLUSION: Corneal nerve density in the sub-basal plexus decreased with increasing myopia. This could have implications for corneal surgery and contact lens wear in this patient population.

Modeling the foveal cone mosaic imaged with adaptive optics scanning laser ophthalmoscopy.

To better understand the limitations of high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO), we describe an imaging model that examines the smallest cone photoreceptors in the fovea of normal human subjects and analyze how different factors contribute to their resolution. The model includes basic optical factors such as wavelength and pupil size, and defines limits caused by source coherence which are specific to the AOSLO imaging modality as well as foveal cone structure. The details of the model, its implications for imaging, and potential techniques to circumvent the limitations are discussed in this paper.

The locus of fixation and the foveal cone mosaic.

High-resolution retinal imaging with adaptive optics was used to record the position of a light stimulus on the cone mosaic, with an error at least five times smaller than the diameter of the smallest foveal cones. We discuss the factors that limit the accuracy with which absolute retinal position can be determined. In five subjects, the standard deviation of fixation positions measured in discrete trials ranged from 2.1 to 6.3 arcmin, with an average of 3.4 arcmin (about 17 microm), in agreement with previous studies (R. W. Ditchburn, 1973; R. M. Steinman, G. M. Haddad, A. A. Skavenski, & D. Wyman, 1973). The center of fixation, based on the mean retinal position for each of three subjects, was displaced from the location of highest foveal cone density by an average of about 10 arcmin (about 50 microm), indicating that cone density alone does not drive the location on the retina selected for fixation. This method can be used in psychophysical studies or medical applications requiring submicron registration of stimuli with respect to the retina or in delivering light to retinal features as small as single cells.