Spatial lipidomics of coronary atherosclerotic plaque development in a familial hypercholesterolemia swine model.

Coronary atherosclerosis is caused by plaque build-up, with lipids playing a pivotal role in its progression. However, lipid composition and distribution within coronary atherosclerosis remain unknown. This study aims to characterize lipids and investigate differences in lipid composition across disease stages to aid in the understanding of disease progression. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize lipid distributions in coronary artery sections (n = 17) from hypercholesterolemic swine. We performed histology on consecutive sections to classify the artery segments and to investigate colocalization between lipids and histological regions of interest in advanced plaque, including necrotic core and inflammatory cells. Segments were classified as healthy (n = 6), mild (n = 6), and advanced disease (n = 5) artery segments. Multivariate data analysis was employed to find differences in lipid composition between the segment types, and the lipids' spatial distribution was investigated using non-negative matrix factorization (NMF). Through this process, MALDI-MSI detected 473 lipid-related features. NMF clustering described three components in positive ionization mode: triacylglycerides (TAG), phosphatidylcholines (PC), and cholesterol species. In negative ionization mode, two components were identified: one driven by phosphatidylinositol(PI)(38:4), and one driven by ceramide-phosphoethanolamine(36:1). Multivariate data analysis showed the association between advanced disease and specific lipid signatures like PC(O-40:5) and cholesterylester(CE)(18:2). Ether-linked phospholipids and LysoPC species were found to colocalize with necrotic core, and mostly CE, ceramide, and PI species colocalized with inflammatory cells. This study, therefore, uncovers distinct lipid signatures correlated with plaque development and their colocalization with necrotic core and inflammatory cells, enhancing our understanding of coronary atherosclerosis progression.

The association between human blood clot analogue computed tomography imaging, composition, contraction, and mechanical characteristics.

BACKGROUND: Clot composition, contraction, and mechanical properties are likely determinants of endovascular thrombectomy success. A pre-interventional estimation of these properties is hypothesized to aid in selecting the most suitable treatment for different types of thrombi. Here we determined the association between the aforementioned properties and computed tomography (CT) characteristics using human blood clot analogues. METHODS: Clot analogues were prepared from the blood of 4 healthy human donors with 5 red blood cell (RBC) volume suspensions: 0%, 20%, 40%, 60% and 80% RBCs. Contraction was measured as the weight of the contracted clots as a percentage of the original suspension. The clots were imaged using CT with and without contrast to quantify clot density and density increase. Unconfined compression was performed to determine the high strain compressive stiffness. The RBC content was analysed using H&E staining. RESULTS: The 5 RBC suspensions formed only two groups of clots, fibrin-rich (0% RBCs) and RBC-rich (>90% RBCs), as determined by histology. The density of the fibrin-rich clots was significantly lower (31-38HU) compared to the RBC-rich clots (72-89HU), and the density increase of the fibrin-rich clots was significantly higher (82-127HU) compared to the RBC-rich clots (3-17HU). The compressive stiffness of the fibrin-rich clots was higher (178-1624 kPa) than the stiffness of the RBC-rich clots (6-526 kPa). Additionally, the degree of clot contraction was higher for the fibrin-rich clots (89-96%) compared to the RBC-rich clots (11-77%). CONCLUSIONS: CT imaging clearly reflects clot RBC content and seems to be related to the clot contraction and stiffness. CT imaging might be a useful tool in predicting the thrombus characteristics. However, future studies should confirm these findings by analysing clots with intermediate RBC and platelet content.

Identifying lipid traces of atherogenic mechanisms in human carotid plaque.

BACKGROUND AND AIMS: Lipids play an important role in atherosclerotic plaque development and are interesting candidate predictive biomarkers. However, the link between circulating lipids, accumulating lipids in the vessel wall, and plaque destabilization processes in humans remains largely unknown. This study aims to provide new insights into the role of lipids in atherosclerosis using lipidomics and mass spectrometry imaging to investigate lipid signatures in advanced human carotid plaque and plasma samples. METHODS: We used lipidomics and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to investigate lipid signatures of advanced human carotid plaque and plasma obtained from patients who underwent carotid endarterectomy (n = 14 out of 17 whose plaque samples were analyzed by DESI-MSI). Multivariate data analysis and unsupervised clustering were applied to identify lipids that were the most discriminative species between different patterns in plaque and plasma. These patterns were interpreted by quantitative comparison with conventional histology. RESULTS: Lipidomics detected more than 300 lipid species in plasma and plaque, with markedly different relative abundances. DESI-MSI visualized the spatial distribution of 611 lipid-related m/z features in plaques, of which 330 m/z features could be assigned based on exact mass, comparison to the lipidomic data, and high mass resolution MSI. Matching spatial lipid patterns to histological areas of interest revealed several molecular species that were colocalized with pertinent disease processes in plaque including specific sphingomyelin and ceramide species with calcification, phospholipids and free fatty acids with inflammation, and triacylglycerols and phosphatidylinositols with fibrin-rich areas. CONCLUSIONS: By comparing lipid species in plaque and plasma, we identified those circulating species that were also prominently present in plaque. Quantitative comparison of lipid spectral patterns with histology revealed the presence of specific lipid species in destabilized plaque areas, corroborating previous in vitro and animal studies.

Tensile and Compressive Mechanical Behaviour of Human Blood Clot Analogues.

Endovascular thrombectomy procedures are significantly influenced by the mechanical response of thrombi to the multi-axial loading imposed during retrieval. Compression tests are commonly used to determine compressive ex vivo thrombus and clot analogue stiffness. However, there is a shortage of data in tension. This study compares the tensile and compressive response of clot analogues made from the blood of healthy human donors in a range of compositions. Citrated whole blood was collected from six healthy human donors. Contracted and non-contracted fibrin clots, whole blood clots and clots reconstructed with a range of red blood cell (RBC) volumetric concentrations (5-80%) were prepared under static conditions. Both uniaxial tension and unconfined compression tests were performed using custom-built setups. Approximately linear nominal stress-strain profiles were found under tension, while strong strain-stiffening profiles were observed under compression. Low- and high-strain stiffness values were acquired by applying a linear fit to the initial and final 10% of the nominal stress-strain curves. Tensile stiffness values were approximately 15 times higher than low-strain compressive stiffness and 40 times lower than high-strain compressive stiffness values. Tensile stiffness decreased with an increasing RBC volume in the blood mixture. In contrast, high-strain compressive stiffness values increased from 0 to 10%, followed by a decrease from 20 to 80% RBC volumes. Furthermore, inter-donor differences were observed with up to 50% variation in the stiffness of whole blood clot analogues prepared in the same manner between healthy human donors.

Label-free analytic histology of carotid atherosclerosis by mid-infrared optoacoustic microscopy.

Background and aims: Analysis of atherosclerotic plaque composition is a vital tool for unraveling the pathological metabolic processes that contribute to plaque growth. Methods: We visualize the constitution of human carotid plaques by mid-infrared optoacoustic microscopy (MiROM), a method for label-free analytic histology that requires minimal tissue preparation, rapidly yielding large field-of-view en-face images with a resolution of a few micrometers. We imaged endarterectomy specimens (n = 3, 12 sections total) at specific vibrational modes, targeting carbohydrates, lipids and proteins. Additionally, we recorded spectra at selected tissue locations. We identified correlations in the variability in this high-dimensional data set using non-negative matrix factorization (NMF). Results: We visualized high-risk plaque features with molecular assignment. Consistent NMF components relate to different dominant tissue constituents, dominated by lipids, proteins, and cholesterol and carbohydrates respectively. Conclusions: These results introduce MiROM as an innovative, stain-free, analytic histology technology for the biochemical characterization of complex human vascular pathology.

Autoradiographical assessment of inflammation-targeting radioligands for atherosclerosis imaging: potential for plaque phenotype identification.

PURPOSE: Many radioligands have been developed for the visualization of atherosclerosis by targeting inflammation. However, interpretation of in vivo signals is often limited to plaque identification. We evaluated binding of some promising radioligands in an in vitro approach in atherosclerotic plaques with different phenotypes. METHODS: Tissue sections of carotid endarterectomy tissue were characterized as early plaque, fibro-calcific plaque, or phenotypically vulnerable plaque. In vitro binding assays for the radioligands [111In]In-DOTATATE; [111In]In-DOTA-JR11; [67Ga]Ga-Pentixafor; [111In]In-DANBIRT; and [111In]In-EC0800 were conducted, the expression of the radioligand targets was assessed via immunohistochemistry. Radioligand binding and expression of radioligand targets was investigated and compared. RESULTS: In sections characterized as vulnerable plaque, binding was highest for [111In]In-EC0800; followed by [111In]In-DANBIRT; [67Ga]Ga-Pentixafor; [111In]In-DOTA-JR11; and [111In]In-DOTATATE (0.064 ± 0.036; 0.052 ± 0.029; 0.011 ± 0.003; 0.0066 ± 0.0021; 0.00064 ± 0.00014 %Added activity/mm2, respectively). Binding of [111In]In-DANBIRT and [111In]In-EC0800 was highest across plaque phenotypes, binding of [111In]In-DOTA-JR11 and [67Ga]Ga-Pentixafor differed most between plaque phenotypes. Binding of [111In]In-DOTATATE was the lowest across plaque phenotypes. The areas positive for cells expressing the radioligand's target differed between plaque phenotypes for all targets, with lowest percentage area of expression in early plaque sections and highest in phenotypically vulnerable plaque sections. CONCLUSIONS: Radioligands targeting inflammatory cell markers showed different levels of binding in atherosclerotic plaques and among plaque phenotypes. Different radioligands might be used for plaque detection and discerning early from vulnerable plaque. [111In]In-EC0800 and [111In]In-DANBIRT appear most suitable for plaque detection, while [67Ga]Ga-Pentixafor and [111In]In-DOTA-JR11 might be best suited for differentiation between plaque phenotypes.

Lipid signature of advanced human carotid atherosclerosis assessed by mass spectrometry imaging.

Carotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes of mortality and disability worldwide. The disease is characterized by plaques, heterogeneous deposits of lipids, and necrotic debris in the vascular wall, which grow gradually and may remain asymptomatic for decades. However, at some point a plaque can evolve to a high-risk plaque phenotype, which may trigger a cerebrovascular event. Lipids play a key role in the development and progression of atherosclerosis, but the nature of their involvement is not fully understood. Using matrix-assisted laser desorption/ionization mass spectrometry imaging, we visualized the distribution of approximately 200 different lipid signals, originating of >90 uniquely assigned species, in 106 tissue sections of 12 human carotid atherosclerotic plaques. We performed unsupervised classification of the mass spectrometry dataset, as well as a histology-directed multivariate analysis. These data allowed us to extract the spatial lipid patterns associated with morphological plaque features in advanced plaques from a symptomatic population, revealing spatial lipid patterns in atherosclerosis and their relation to histological tissue type. The abundances of sphingomyelin and oxidized cholesteryl ester species were elevated specifically in necrotic intima areas, whereas diacylglycerols and triacylglycerols were spatially correlated to areas containing the coagulation protein fibrin. These results demonstrate a clear colocalization between plaque features and specific lipid classes, as well as individual lipid species in high-risk atherosclerotic plaques.

Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach.

PURPOSE: Atherosclerotic plaque development and progression signifies a complex inflammatory disease mediated by a multitude of proinflammatory leukocyte subsets. Using single photon emission computed tomography (SPECT) coupled with computed tomography (CT), this study tested a new dual-isotope acquisition protocol to assess each radiotracer's capability to identify plaque phenotype and inflammation levels pertaining to leukocytes expressing leukocyte function-associated antigen-1 (LFA-1) and the leukocyte subset of proinflammatory macrophages expressing somatostatin receptor subtype-2 (SST2). Individual radiotracer uptake was quantified and the presence of corresponding immunohistological cell markers was assessed. METHODS: Human symptomatic carotid plaque segments were obtained from endarterectomy. Segments were incubated in dual-isotope radiotracers [111In]In-DOTA-butylamino-NorBIRT ([111In]In-Danbirt) and [99mTc]Tc-[N0-14,Asp0,Tyr3]-octreotate ([99mTc]Tc-Demotate 2) before scanning with SPECT/CT. Plaque phenotype was classified as pathological intimal thickening, fibrous cap atheroma or fibrocalcific using histology sections based on distinct morphological characteristics. Plaque segments were subsequently immuno-stained with LFA-1 and SST2 and quantified in terms of positive area fraction and compared against the corresponding SPECT images. RESULTS: Focal uptake of co-localising dual-radiotracers identified the heterogeneous distribution of inflamed regions in the plaques which co-localised with positive immuno-stained regions of LFA-1 and SST2. [111In]In-Danbirt and [99mTc]Tc-Demotate 2 uptake demonstrated a significant positive correlation (r = 0.651; p = 0.001). Fibrous cap atheroma plaque phenotype correlated with the highest [111In]In-Danbirt and [99mTc]Tc-Demotate 2 uptake compared with fibrocalcific plaques and pathological intimal thickening phenotypes, in line with the immunohistological analyses. CONCLUSION: A dual-isotope acquisition protocol permits the imaging of multiple leukocyte subsets and the pro-inflammatory macrophages simultaneously in atherosclerotic plaque tissue. [111In]In-Danbirt may have added value for assessing the total inflammation levels in atherosclerotic plaques in addition to classifying plaque phenotype.

Variation in Coronary Atherosclerosis Severity Related to a Distinct LDL (Low-Density Lipoprotein) Profile: Findings From a Familial Hypercholesterolemia Pig Model.

OBJECTIVE: In an adult porcine model of familial hypercholesterolemia (FH), coronary plaque development was characterized. To elucidate the underlying mechanisms of the observed inter-individual variation in disease severity, detailed lipoprotein profiles were determined. Approach and Results: FH pigs (3 years old, homozygous LDLR R84C mutation) received an atherogenic diet for 12 months. Coronary atherosclerosis development was monitored using serial invasive imaging and histology. A pronounced difference was observed between mildly diseased pigs which exclusively developed early lesions (maximal plaque burden, 25% [23%-34%]; n=5) and advanced-diseased pigs (n=5) which developed human-like, lumen intruding plaques (maximal plaque burden, 69% [57%-77%]) with large necrotic cores, intraplaque hemorrhage, and calcifications. Advanced-diseased pigs and mildly diseased pigs displayed no differences in conventional risk factors. Additional plasma lipoprotein profiling by size-exclusion chromatography revealed 2 different LDL (low-density lipoprotein) subtypes: regular and larger LDL. Cholesterol, sphingosine-1-phosphate, ceramide, and sphingomyelin levels were determined in these LDL-subfractions using standard laboratory techniques and high-pressure liquid chromatography mass-spectrometry analyses, respectively. At 3 months of diet, regular LDL of advanced-diseased pigs contained relatively more cholesterol (LDL-C; regular/larger LDL-C ratio 1.7 [1.3-1.9] versus 0.8 [0.6-0.9]; P=0.008) than mildly diseased pigs, while larger LDL contained more sphingosine-1-phosphate, ceramides, and sphingomyelins. Larger and regular LDL was also found in plasma of 3 patients with homozygous FH with varying LDL-C ratios. CONCLUSIONS: In our adult FH pig model, inter-individual differences in atherosclerotic disease severity were directly related to the distribution of cholesterol and sphingolipids over a distinct LDL profile with regular and larger LDL shortly after the diet start. A similar LDL profile was detected in patients with homozygous FH.

Automated segmentation of atherosclerotic histology based on pattern classification.

BACKGROUND: Histology sections provide accurate information on atherosclerotic plaque composition, and are used in various applications. To our knowledge, no automated systems for plaque component segmentation in histology sections currently exist. MATERIALS AND METHODS: We perform pixel-wise classification of fibrous, lipid, and necrotic tissue in Elastica Von Gieson-stained histology sections, using features based on color channel intensity and local image texture and structure. We compare an approach where we train on independent data to an approach where we train on one or two sections per specimen in order to segment the remaining sections. We evaluate the results on segmentation accuracy in histology, and we use the obtained histology segmentations to train plaque component classification methods in ex vivo Magnetic resonance imaging (MRI) and in vivo MRI and computed tomography (CT). RESULTS: In leave-one-specimen-out experiments on 176 histology slices of 13 plaques, a pixel-wise accuracy of 75.7 ± 6.8% was obtained. This increased to 77.6 ± 6.5% when two manually annotated slices of the specimen to be segmented were used for training. Rank correlations of relative component volumes with manually annotated volumes were high in this situation (P = 0.82-0.98). Using the obtained histology segmentations to train plaque component classification methods in ex vivo MRI and in vivo MRI and CT resulted in similar image segmentations for training on the automated histology segmentations as for training on a fully manual ground truth. The size of the lipid-rich necrotic core was significantly smaller when training on fully automated histology segmentations than when manually annotated histology sections were used. This difference was reduced and not statistically significant when one or two slices per section were manually annotated for histology segmentation. CONCLUSIONS: Good histology segmentations can be obtained by automated segmentation, which show good correlations with ground truth volumes. In addition, these can be used to develop segmentation methods in other imaging modalities. Accuracy increases when one or two sections of the same specimen are used for training, which requires a limited amount of user interaction in practice.

Transglutaminase activity regulates atherosclerotic plaque composition at locations exposed to oscillatory shear stress.

OBJECTIVE: Atherosclerosis preferentially develops at sites of disturbed blood flow. We tested the hypothesis that transglutaminase activity plays a role in plaque development at these locations. METHODS AND RESULTS: Exposure of endothelial cells to steady flow (7 dynes/cm(2)) was associated with relatively low transglutaminase activity, whereas under low oscillatory flow (1.3 ± 2.6 dynes/cm(2)) endothelial cells showed a >4-fold higher level of transglutaminase activity. Under oscillatory flow, transglutaminase activity increased the expression of the chemokine MCP-1 (CCL2). In vivo, oscillatory flow was induced by placement of a tapered perivascular cast around the carotid artery of type 2 transglutaminase (TGM2) knockout mice and WT counterparts. After 2 days, significantly less monocytes adhered to the endothelium in TGM2 knockout mice as compared to WT. In a more chronic setting, ApoE knockout mice that were equipped with the flow-modifying cast developed lesions proximal to the cast (low shear stress), and distal to the cast (oscillatory shear stress). Inhibition of transglutaminase induced a marked reduction in macrophage and fat content in distal lesions only. In addition, lesion size was increased in this area, which was attributed to an increase in smooth muscle content. CONCLUSION: Oscillatory shear stress increases endothelial transglutaminase activity. In turn, transglutaminase activity affects the expression of MCP-1 in vitro and monocyte recruitment in vivo. In a mouse model of atherosclerosis, transglutaminase activity has a major effect on plaque composition under oscillatory shear stress.

Comparison of Optical Performance in Eyes Implanted with Aspheric Foldable, Spherical Foldable, and Rigid PMMA IOLs.

PURPOSE: To compare the optical performance of rigid spherical polymethylmethacrylate (PMMA), foldable spherical, and foldable aspheric intraocular lenses (IOLs). METHODS: Measurements were obtained monocularly from pseudophakic patients with a PMMA IOL (Ophtec PC265y or Rayner 105U), spherical AcrySof MA30 IOL (Alcon Laboratories Inc), or aspheric Tecnis ZA9003 IOL (Abbott Medical Optics). Contrast sensitivity was measured using the Holladay automated contrast sensitivity test with 5.0-mm artificial pupil at 3 and 6 cycles per degree at optimal focus and at several defocus levels. The myopic shift (shift of the optimal focus toward more myopic values at lower spatial frequencies) and depth of focus were determined. Wavefront aberrations were assessed with a Hartmann-Shack wavefront analyzer; straylight was measured using the C-Quant meter (Oculus Optikgeräte GmbH). RESULTS: Nine patients with a spherical rigid PMMA IOL, 19 patients with a spherical foldable IOL, and 24 patients with an aspheric foldable IOL met the inclusion criteria. Eyes with an aspheric IOL showed less spherical aberration than eyes with other IOLs; no differences were found in overall higher order aberrations. No differences in contrast sensitivity at optimal focus and in straylight were found among the IOLs. Eyes with a PMMA IOL showed a larger depth of focus compared to eyes with an aspheric IOL. Eyes with an aspheric IOL had a smaller myopic shift than eyes with other IOLs. CONCLUSIONS: Optical performance differences among the IOLs in this study are small, concurring with similar higher order aberrations found in the three groups. Reduction in myopic shift appears to be the most obvious effect of aspheric IOLs.

Three-dimensional registration of histology of human atherosclerotic carotid plaques to in-vivo imaging.

An accurate spatial relationship between 3D in-vivo carotid plaque and lumen imaging and histological cross sections is required to study the relationship between biomechanical parameters and atherosclerotic plaque components. We present and evaluate a fully three-dimensional approach for this registration problem, which accounts for deformations that occur during the processing of the specimens. By using additional imaging steps during tissue processing and semi-automated non-linear registration techniques, a 3D-reconstruction of the histology is obtained. The methodology was evaluated on five specimens obtained from patients, operated for severe atherosclerosis in the carotid bifurcation. In more than 80% of the histology slices, the quality of the semi-automated registration with computed tomography angiography (CTA) was equal to or better than the manual registration. The inter-observer variability was between one and two in-vivo CT voxels and was equal to the manual inter-observer variability. Our technique showed that the angles between the normals of the registered histology slices and the in-vivo CTA scan direction ranged 6-56 degrees , indicating that proper 3D-registration is crucial for establishing a correct spatial relation with in-vivo imaging modalities. This new 3D-reconstruction technique of atherosclerotic plaque tissue opens new avenues in the field of biomechanics as well as in the field of image processing, where it can be used for validation purposes of segmentation algorithms.

Straylight measurements in pseudophakic eyes with natural and dilated pupils: one-year follow-up.

PURPOSE: To compare the amount of straylight in natural pupils and dilated pupils in pseudophakic eyes 6 weeks and 1 year after cataract extraction. SETTING: Laboratory of Experimental Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. METHODS: This study evaluated patients with bilateral age-related cataract who had cataract surgery with implantation of an aspheric Tecnis ZA9003 or spherical Sensar AR40e intraocular lens (IOL). Straylight measurements were performed with a C-Quant straylight meter 6 weeks after surgery (with natural pupils) and 1 year after surgery (with natural and dilated pupils) in a randomly chosen eye. Retroillumination photographs of dilated pupils were taken to document posterior capsule opacification. The main outcome variable for straylight measurements was the logarithmic straylight parameter, log(s). RESULTS: Twenty-two patients were evaluated. There was a statistically significant decrease in straylight in a natural pupil between 6 weeks (mean 1.44 log[s]) and 1 year (mean 1.30 log[s]) postoperatively (P = .012). The straylight parameter was greater after dilation (mean 1.48 log[s]) than with a natural pupil (1.29 log[s]) at 1 year (P = .012). This difference was greater when more anterior capsule was visible in the pupillary area (P = .031). CONCLUSIONS: Straylight decreased significantly in the first year after cataract surgery. Furthermore, it increased with increasing pupil size, which was associated with a capsulorhexis smaller than the pupil. This indicates the capsulorhexis should be as large as possible to prevent straylight, especially under low-luminance conditions when the pupil is large.

Clinical comparison of the optical performance of aspheric and spherical intraocular lenses.

PURPOSE: To compare the optical performance of aspheric Tecnis ZA9003 and spherical Sensar AR40e intraocular lenses (IOLs). SETTING: Laboratory of Experimental Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. METHODS: An aspheric IOL was implanted in 1 eye and a spherical IOL in the other eye of patients with bilateral age-related cataract. Contrast sensitivity was measured using 2 computerized tests (vertical sine-modulated gratings and circular sine-modulated patterns) with cycloplegia and a 5.0 mm artificial pupil under photopic conditions at optimum refractive correction and at several defocus levels. The depth of focus and the myopic shift (shift of optimum focus toward more myopic values at lower spatial frequencies) were determined. Higher-order aberrations were assessed using a Hartmann-Shack wavefront analyzer; straylight was measured with a straylight meter. RESULTS: In the 60 eyes evaluated, there were no statistically significant differences in contrast sensitivity measured at optimum focus, depth of focus, or straylight between the 2 IOLs. The mean spherical aberration was significantly lower with the aspheric IOL (-0.036 microm) than with the spherical IOL (0.064 microm) (P<.001) and the mean myopic shift, statistically significantly smaller (0.05 diopter [D] and -0.47 D, respectively) (P<.001). CONCLUSIONS: Eyes with the aspheric IOL had lower spherical aberration than eyes with the spherical IOL and, related to that, a smaller myopic shift. No significant differences were found between the 2 IOLs in contrast sensitivity measured at optimum focus, depth of focus, or straylight. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Relationship between contrast sensitivity and spherical aberration: comparison of 7 contrast sensitivity tests with natural and artificial pupils in healthy eyes.

PURPOSE: To find a contrast sensitivity test that can be used clinically to evaluate interventions aimed at minimizing spherical aberration and determine the circumstances under which these tests should be performed. SETTING: Laboratory of Experimental Ophthalmology, University of Groningen, Groningen, The Netherlands. METHODS: Contrast sensitivity tests were performed using 2 experimental designs. Design 1 was with a natural pupil under mesopic and photopic conditions. Design 2 was with a 5.0 mm artificial pupil after cycloplegia under photopic conditions only. Two computerized tests (vertical sine-modulated gratings [VSG] and Holladay circular sine-modulated patterns [HACSS]) and 5 chart tests (Pelli-Robson, acuity-measuring letter charts at low contrast [2.5% and 10%], VectorVision, and edge contrast sensitivity) were used. Spherical aberration was assessed with a Hartmann-Shack wavefront analyzer. RESULTS: Forty-nine healthy subjects aged 20 to 35 years (n = 24) and 55 to 70 years (n = 25) participated. Design 2 showed a significant relationship between contrast sensitivity and spherical aberration with the HACSS at 3 cycles per degree (cpd) (P = .03) and 6 cpd (P = .01) and with the VSG at 6 cpd (P = .01). Design 1 yielded no significant relationships. CONCLUSIONS: Using an artificial pupil, a relationship between contrast sensitivity and spherical aberration was established with the VSG and HACSS tests but not with the chart tests. No test showed a relationship using natural pupils under either lighting condition. Chart tests are unsuitable for uncovering contrast sensitivity differences related to differences in spherical aberration, as typically found in healthy phakic eyes.