scholarly journals INFLUENCE OF THE SCLERAL LENS AND FLUID RESERVOIR THICKNESSES ON RESIDUAL ASTIGMATISM

2021 ◽  
Vol 5 (1) ◽  
pp. e1-e8
Author(s):  
Langis Michaud ◽  
Gabriella Courey
Keyword(s):  
Visual Acuity ◽  
Prospective Study ◽  
Refractive Error ◽  
Slit Lamp ◽  
Logmar Acuity ◽  
Clinically Significant ◽  
Lens Wear ◽  
High Order Aberrations ◽  
Fluid Reservoir

PurposeThis study aims to determine if lens or tear fluid reservoir thicknesses (LT/FRT) may influence the presence of residual astigmatism and participant’s visual acuity. MethodsThe study was a randomized, non-dispensing, prospective study. Empirically and randomly chosen participants were fitted with 4 combinations (350 and 250 um LT fitted with 250 and 350 um FRT) of 16 mm diameter scleral lenses, designed using a corneo-scleral profiler software (sMap 3D, Visionary Optics, US). Lenses haptics were kept spherical for all lenses. They were evaluated under a slit lamp, anterior segement OCT (objective fluid reservoir and lens thicknesses), topography over lenses and aberrometry, after 30 minutes of lens wear. Spherico-cylindrical refraction and logMar acuity were also assessed. ResultsStudy population was composed of 24 participants aged 24.2 + 4.7 years old. Baseline refractive error was -2.3 + 1.6 D with -0.48 + 0.26 D of astigmatism. In vivo (OCT) lens A was 344.1 ± 15.4 um thick, fitted with a vault of 213.6 ± 42.4 um; Lens B was 346.2 ± 12.5/327.2 ± 44.8; Lens C was 260.3 ± 17.7/214.0 ± 40.6 um and Lens D was 262.2 ±13.2/330.8 ± 52.0 respectively. All lenses were found similarly decentered inferiorly by 0.10 to 0.15 um. BCVA was −0.32 + 0.08 (A), −0.21 + 0.10 (B), −0.28 + 0.08 (C), and −0.14 + 0.10 (D), compared to −0.25 + 0.08 (A), −0.11 + 0.10 (B), −0.23 + 0.06 (C), and −0.05 + 0.12 (D) when sphere only was compensated. Residual refractive astigmatism (RA = -0.50 to -0.75D) is found significantly higher based on the FRT (F=9.560; p=0.037) and not LT(F=0.429; p=0.522). There is no correlation be-tween RA and over-k readings (Lens A r=-0.078, p=0.773; Lens B r=−0.073, p=0.788; Lens C r=−0.345, p=0.171; Lend D r=0.019, p=0.944). Higher order aberrations, mostly vertical coma, were found clinically significant but not statistically different between lenses (A= 0.350 + 0.032; B=0.382 + 0.053, C=0.329 + 0.044 and D=0.385+ 0.062; p=0.776) ConclusionThis study proves that low level of RA may be found when scleral lenses are fitted on normal corneas. Its occurrence is related to the presence of high-order aberrations and less likely to lens flexure.

scholarly journals Thickness profiles of the corneal epithelium along the steep and flat meridians of astigmatic corneas after orthokeratology

2020 ◽  
Author(s):  
Jiaqi Zhou ◽  
Feng Xue ◽  
Xingtao Zhou ◽  
Rajeev Krishnan Naidu ◽  
Yishan Qian
Keyword(s):  
Optical Coherence Tomography ◽  
Visual Acuity ◽  
Prospective Study ◽  
Corneal Epithelium ◽  
Fourier Domain ◽  
Corneal Epithelial ◽  
Epithelial Thickness ◽  
Corneal Epithelial Thickness ◽  
A Prospective Study ◽  
Lens Wear

Abstract Background: To investigate the changes in corneal epithelial thickness along the principle meridians of astigmatic corneas after six months of overnight spherical myopic orthokeratology (OK) lens wear. Methods: A prospective study. Fifty-seven subjects with up to 1.50 diopters (D) of corneal toricity wore spherical OK lenses for 6 months. Evaluations of OK lens fit, visual acuity, refractions and corneal toricity (CT) were performed. Fourier-domain optical coherence tomography (FD-OCT) was conducted to measure the corneal epithelial thickness (ET) along the principle meridians of corneal toricity over a diameter of 6mm. The means of △ET of the same diameter at individual meridians (△ETSm and △ETFm) were calculated and compared. Results: Visual acuity and refraction improved significantly after OK lens wear. △ETFm (-4.2±3.4μm) thinned more than △ETSm (-3.4±4.0μm, P=0.027) at 1.5mm in radius. △ETSm thickened more than △ETFm at 2.5mm (△ETSm: 4.1±5.1μm, △ETFm: 2.8±4.2μm, P=0.019) and 3.0mm (△ETSm: 5.0±5.0μm, △ETFm: 3.7±4.9μm, P=0.036).∣△ETSm - △ETFm∣ were significantly correlated with the baseline central CT at 2.0mm, 2.5mm and 3.0mm (2.0mm: r=0.285, P=0.032; 2.5mm: r=0.422, P=0.001; 3.0mm: r=0.239, P=0.027). ∣△ETSm - △ETFm∣was significantly correlated with the baseline peripheral CT at 2.5mm (r=0.299, P=0.028). Conclusions: Overnight wear of spherical OK lenses resulted in differential changes in the thickness profiles of the corneal epithelium between the steep and flat meridians in eyes with corneal toricity.

scholarly journals Clinical Performance of a Novel Daily Disposable Soft Contact Lens

2020 ◽  
Vol 4 (1) ◽  
pp. e23-e30
Author(s):  
Stacie Cummings ◽  
Bradley Giedd ◽  
Christopher Pearson
Keyword(s):  
Visual Acuity ◽  
Contact Lens ◽  
Contact Lenses ◽  
Corneal Edema ◽  
Slit Lamp ◽  
Subjective Ratings ◽  
Soft Contact ◽  
Slit Lamp Examination ◽  
Soft Contact Lens ◽  
Lens Wear

Background and Objective: Verofilcon A (PRECISION1®; Alcon) silicone hydrogel daily disposable contact lenses were designed to address clinical issues associated with new wearer discontinuation, including vision quality, sustained comfort, and ease of handling. The present study assessed the objective and subjective performance of verofilcon A contact lenses in subjects needing optical correction for refractive ametropia. Material and Methods: Subjects aged 18 years and older with non-diseased eyes, a history of successful soft contact lens wear for distance correction in both eyes during the previous 3 months, and a best spectacle-corrected visual acuity of 20/25 or better with a manifest cylinder of ≤ 0.75 diopters in each eye were recruited. The primary endpoint was distance visual acuity. Secondary endpoints included subjective ratings of overall vision, comfort, and handling, and safety endpoints included adverse events and biomicroscopy/slit lamp examination findings. Results: This study recruited 70 subjects (140 eyes), aged 20–48 years, who were predominantly white (93%), non-Hispanic/Latino (94%), and female (73%); one subject discontinued due to a change in residence. Of the 140 eyes, 132 (94.3%) had 20/20 or better vision with their habitual contact lenses. Similarly, of the 138 eyes that completed the study, 136 (98.6%) had 20/20 or better vision at dispensation of verofilcon A lenses and 132 (95.7%) had 20/20 or better vision at 3 months. Mean ± SD subjective ratings of overall vision, overall comfort, and overall handling, each on a 10-point scale, were 9.4 ± 0.8, 9.4 ± 0.8, and 9.2 ± 1.3, respectively, at lens dispensing, and 9.4 ± 0.9, 9.5 ± 0.8, and 9.2 ± 1.0, respectively, at 3 months. Mean ± SD daily wear times at 1 week and 3 months were 14.71 ± 1.85 and 15.05 ± 1.27 hours, respectively, with 68.1% at 1 week and 73.9% at 3 months wearing verofilcon A lenses for 14–18 hours per day. None of the subjects experienced a serious adverse event or discontinued lens wear, with biomicroscopy/slit lamp examination showing no evidence of corneal edema or chemosis. Conclusion: Subjects wearing verofilcon A lenses had visual acuity similar to that when wearing their habitual lens. Verofilcon A lenses were highly rated for vision quality, comfort, and handling. Verofilcon A lenses may be an option for subjects with refractive ametropia who desire lenses that can be worn for >14 hours per day and are easy to handle.

scholarly journals Prevalence of Refractive Error and Need for Corrective Lenses in Medically Underserved Residents of Tijuana, Mexico

2019 ◽  
Author(s):  
John L. Ubels ◽  
Jonathan M. Ismond ◽  
Micah A. Timmermans ◽  
Arlene J. Hoogewerf
Keyword(s):  
Visual Acuity ◽  
Refractive Error ◽  
Access To Health Care ◽  
Refractive Errors ◽  
Eye Care ◽  
Source Program ◽  
Reading Glasses ◽  
Clinically Significant ◽  
Eye Exams ◽  
Uncorrected Refractive Error

AbstractPurposeThe population of Tijuana, Mexico is growing rapidly, with a current official population estimate of 1.7 million. Nearly 80,000 people migrate to Tijuana each year, resulting in the rise of neighborhoods with substandard housing, lack of services and inadequate access to health care, including eye care. This study describes refractive errors and the need for corrective lenses among participants attending free clinics in these neighborhoods where they received free eye exams and glasses during January 2016. Methods: This is a retrospective observational chart review of de-identified data collected from intake forms that were filled out for each participant at the clinics. Subjects were self-selected in response to announcements in the neighborhoods where clinics were conducted. Subjects with presenting uncorrected visual acuity 20/30 OU or worse were examined with an autorefractor to measure spherical refractive error. Either prescription or reading glasses were then distributed to participants who had refractive errors. Epi Info, an open source program provided by the CDC, was used to analyze demographic, visual acuity and refractive error data. Results: Presenting visual acuity was evaluated in 1209 people. Of these patients, 70% had a visual acuity of 20/30 or worse. Only 23% of these patients had glasses. Among the patients who were given refractions, 13% had clinically significant myopia (−0.75 D or worse in at least one eye). In participants 20 years old and younger, only 8% had clinically significant myopia. Clinically significant hyperopia (+0.75 D or worse in at least one eye) was detected in 25% of participants. Astigmatism (−1.5 D or worse in at least one eye) was present in 18% of participants. Prescription glasses were given to 542 participants and 396 of these people received their first glasses. Reading glasses were given to 386 people. Among students only 15% presented at the clinics with glasses, while it was determined that 56% of student participants needed glasses. Conclusion: The high levels of uncorrected refractive error in this study suggest limited access to affordable eye care in neighborhoods where clinics were conducted. Prevalence of myopia among adolescents and young adults is increasing in many parts of the world. In contrast, a relatively high prevalence of hyperopia was observed in this age group in Tijuana. The data demonstrate an urgent need for eye care and correction of refractive error in the study group.

scholarly journals Application of Spectral Domain Optical Coherence Tomography to Objectively Evaluate Posterior Capsular Opacity In Vivo

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Shasha Yu ◽  
Chengzhe Lu ◽  
Xin Tang ◽  
Xiaoyong Yuan ◽  
Bo Yuan ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Objective Evaluation ◽  
Spectral Domain ◽  
Posterior Capsular Opacification ◽  
Slit Lamp ◽  
Cross Sectional ◽  
Spectral Domain Oct ◽  
Posterior Capsular Opacity ◽  
Sd Oct

Objectives. To objectively evaluate posterior capsular opacification (PCO) with RTVue-100 spectral domain-OCT and assess the agreement with the Pentacam system. Methods. Sixty-seven eyes diagnosed with PCO were included. RTVue-100 SD-OCT was used to scan the IOL outline and PCO at horizontal and vertical meridians. PCO was also imaged with a Pentacam and slit-lamp photography system. With RTVue-100 SD-OCT, the PCO area, thickness, density, and objective scores were recorded and used to evaluate the severity of PCO at 3 mm and 5 mm diameter ranges of the IOL optic region. We assessed the correlation of visual acuity, PCO characteristics, and PCO scores. PCO scores acquired from RTVue-100 SD-OCT images were also compared with those from the Pentacam. Differences between pear-type and fibrosis-type PCOs were also compared using RTVue-100 SD-OCT cross-sectional images. Results. The cross-sectional images of PCO acquired with RTVue-100 SD-OCT corresponded well to Pentacam and slit-lamp retroillumination images. IOL-posterior capsular space, area, thickness, and density of the proliferated and accumulated LECs could be clearly visualized and quantified with RTVue-100 SD-OCT. PCO scores were correlated with decreased visual acuity, which was in line with the outcomes using the Pentacam. Differences between the pear-type and fibrosis-type PCO were statistically significant; pear-type PCOs showed a wider and thicker opacification region with lower density compared with fibrosis-type PCOs. Conclusion. RTVue-100 SD-OCT could be a powerful tool in PCO objective evaluation and classification. OCT could be used to visualize the morphology and outline of PCO. Thus, it could discriminate and quantify differences between different types of PCO. PCO scores seem to be a useful factor that could reliably reflect PCO severity.

scholarly journals Thickness profiles of the corneal epithelium along the steep and flat meridians of astigmatic corneas after orthokeratology

2020 ◽  
Author(s):  
Jiaqi Zhou ◽  
Feng Xue ◽  
Xingtao Zhou ◽  
Rajeev Krishnan Naidu ◽  
Yishan Qian
Keyword(s):  
Optical Coherence Tomography ◽  
Visual Acuity ◽  
Prospective Study ◽  
Corneal Epithelium ◽  
Fourier Domain ◽  
Corneal Epithelial ◽  
Epithelial Thickness ◽  
Corneal Epithelial Thickness ◽  
A Prospective Study ◽  
Lens Wear

Abstract Background: To investigate the changes in corneal epithelial thickness along the principle meridians of astigmatic corneas after six months of overnight spherical myopic orthokeratology (OK) lens wear.Methods: A prospective study. Fifty-seven subjects with up to 1.50 diopters (D) of corneal toricity wore spherical OK lenses for 6 months. Evaluations of OK lens fit, visual acuity, refractions and corneal toricity (CT) were performed. Fourier-domain optical coherence tomography (FD-OCT) was conducted to measure the corneal epithelial thickness (ET) along the principle meridians of corneal toricity over a diameter of 6mm. The means of △ET of the same diameter at individual meridians (△ETSm and △ETFm) were calculated and compared. Results: Visual acuity and refraction improved significantly after OK lens wear. △ETFm (-4.2±3.4μm) thinned more than △ETSm (-3.4±4.0μm, P=0.027) at 1.5mm in radius. △ETSm thickened more than △ETFm at 2.5mm (△ETSm: 4.1±5.1μm, △ETFm: 2.8±4.2μm, P=0.019) and 3.0mm (△ETSm: 5.0±5.0μm, △ETFm: 3.7±4.9μm, P=0.036).∣△ETSm - △ETFm∣ were significantly correlated with the baseline central CT at 2.0mm, 2.5mm and 3.0mm (2.0mm: r=0.285, P=0.032; 2.5mm: r=0.422, P=0.001; 3.0mm: r=0.239, P=0.027). ∣△ETSm - △ETFm∣was significantly correlated with the baseline peripheral CT at 2.5mm (r=0.299, P=0.028). Conclusions: Overnight wear of spherical OK lenses resulted in differential changes in the thickness profiles of the corneal epithelium between the steep and flat meridians in eyes with corneal toricity.

Effect of the Oestrus Cycle on Coxofemoral Joint Laxity

1997 ◽  
Vol 10 (02) ◽  
pp. 69-74 ◽  
Author(s):  
G. K. Smith ◽  
M. G. Conzemius ◽  
H. M. Saunders ◽  
C. M. Hill ◽  
T. P. Gregor ◽  
...  
Keyword(s):  
Prospective Study ◽  
Hip Dysplasia ◽  
Joint Laxity ◽  
Hormone Levels ◽  
Oestrus Cycle ◽  
Clinically Significant ◽  
A Prospective Study

SummaryA few investigations in the 1960’s were performed to document the effect of exogenous oestrogens on development of hip dysplasia. These projects concluded that oestrogen administration caused a significant increase in hip dysplasia. Additionally, the Orthopaedic Foundation for Animals (OFA) has recommended that bitches should not have hip evaluation for certification during oestrus, due to the possibility of increased coxofemoral joint laxity. The purpose of this project was to determine if physiological fluctuations of oestrogen and progesterone throughout the oestrus cycle significantly affected coxofemoral joint laxity. Nine bitches were evaluated through a single oestrus cycle. Although significant fluctuations of oestrogen and progesterone occurred throughout the phases of the oestrus cycle, neither statistically nor clinically significant changes in coxofemoral joint laxity were documented.A prospective study documented the effect of fluctuations of hormone levels throughout the oestrus cycle on coxofemoral joint laxity in nine dogs. Although oestrogen and progesterone levels changed significantly throughout the oestrus cycle, neither statistically nor clinically significant changes in hip laxity were observed.

scholarly journals Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets

2020 ◽  
Vol 318 (1) ◽  
pp. G1-G9 ◽  
Author(s):  
Richard A. Jacobson ◽  
Kiedo Wienholts ◽  
Ashley J. Williamson ◽  
Sara Gaines ◽  
Sanjiv Hyoju ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Healing Process ◽  
Abdominal Sepsis ◽  
Infectious Complications ◽  
Fibrinolytic System ◽  
Clinical Safety ◽  
High Concentrations ◽  
Clinically Significant

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa-mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing. NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.

scholarly journals Epidemiological Findings of Refractive Errors and Amblyopia among the Schoolchildren in Hatta Region of the United Arab Emirates

2021 ◽  
pp. 1-7
Author(s):  
Salam Chettian Kandi ◽  
Hayat Ahmad Khan
Keyword(s):  
Visual Acuity ◽  
Visual Field ◽  
United Arab Emirates ◽  
Refractive Error ◽  
Screening Program ◽  
Low Vision ◽  
Refractive Errors ◽  
Vision Screening ◽  
Screening Programs ◽  
School Based

<b><i>Introduction:</i></b> Uncorrected refractive errors and amblyopia pose a major problem affecting schoolchildren. We had previously observed that many schoolchildren in the Hatta region presented to the ophthalmology clinic with uncorrected refractive errors and amblyopia, which led us to undertake this research. As per the WHO, the term “visual impairment” can be “low vision” or “blindness.” Based on the presenting vision, “low vision” is defined for children who have vision of &#x3c;6/18 to 3/60 or having visual field loss to &#x3c;20° in the better-seeing eye. Children defined to have “blindness” have presenting vision of &#x3c;3/60 or corresponding visual field of &#x3c;10°. <b><i>Purpose:</i></b> To estimate the magnitude of uncorrected refractive errors and amblyopia among the schoolchildren aged 6–19 years and to assess the efficacy of school-based refractive error screening programs in the Hatta region of the United Arab Emirates. <b><i>Methods:</i></b> An epidemiological, cross-sectional, descriptive study was conducted on the entire student population studying in the government schools of the region. Those who failed the Snellen visual acuity chart test and those who were wearing spectacles were evaluated comprehensively by the researcher in the Department of Ophthalmology of the Hatta Hospital. Data were entered in the Refractive Error Study in School Children (RESC) eye examination form recommended by the WHO, and were later transferred to Excel sheets and analyzed by SPSS. <b><i>Results:</i></b> 1,591 students were screened and evaluated from the end of 2016 to mid-2017. About 21.37% (<i>n</i> = 340) had impaired vision with 20.9% (<i>n</i> = 333) refractive errors, of which 58% were uncorrected. Among the refractive error group, 19% (64 subjects) had amblyopia (4% of total students). The incidence of low vision was 9.5% and blindness was 0.38%. Low vision was found to be 9.5% and blindness 0.38%, taking in to account presenting visual acuity rather than best-corrected visual acuity for defining low vision and blindness. <b><i>Conclusion:</i></b> A significant number of students were detected to have uncorrected refractive errors among the vision impaired group (59%, <i>n</i> = 197) despite a school-based vision screening program in place. Seventy-eight percent of the amblyopia cases (<i>n</i> = 50) were found to be in the 11–19 years age group. Noncompliance with optical corrections was the reason for the high number of cases. A rigorous vision screening program and refractive services, complimented with awareness among parents and teachers, are recommended.

scholarly journals Safety and efficacy of repeated crosslinking assisted by transepithelial double-cycle iontophoresis in keratoconus progression after primary corneal crosslinking

Eye ◽  
2021 ◽  
Author(s):  
Huping Wu ◽  
Lan Li ◽  
Shunrong Luo ◽  
Xie Fang ◽  
Xumin Shang ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Corneal Thickness ◽  
Good Alternative ◽  
Persistent Epithelial Defect ◽  
Safety And Efficacy ◽  
Corneal Epithelial ◽  
Epithelial Damage ◽  
Corneal Confocal Microscopy

Abstract Objectives To evaluate the safety and efficacy of repeated corneal collagen crosslinking assisted by transepithelial double-cycle iontophoresis (DI-CXL) in the management of keratoconus progression after primary CXL. Methods A retrospective analysis was conducted in the patients who underwent repeated CXL between 2016 and 2018. These patients were treated with DI-CXL if keratoconus progression was confirmed after primary CXL. Scoring of ocular pain and corneal epithelial damage, visual acuity, corneal tomography, in vivo corneal confocal microscopy (IVCM) was performed before and at 3, 6, 12, and 24 months after DI-CXL. Results Overall, 21 eyes of 12 patients (mean age 17.3 ± 1.9 years) were included in this study. Before DI-CXL, an average increase of 4.26 D in Kmax was detected in these patients with a mean follow-up interval of (23.0 ± 13.7) months. After DI-CXL, corneal epithelial damage rapidly recovered within days. Visual acuity remained unchanged with follow-up of 24 months. When compared to baseline, significant decreases were observed in Kmax (at 3 months) and K2 (at 3 and 6 months) after DI-CXL. Corneal thickness of thinnest point significantly decreased at 3 months postoperatively. When compared to baseline, no significant differences were found in any of the refractive or tomographic parameters at 12 and 24 months. IVCM revealed trabecular patterned hyperdense tissues after DI-CXL in the anterior stroma at the depth of 200 μm or more. No corneal infiltration or persistent epithelial defect was recorded after DI-CXL. Conclusion DI-CXL is safe and effective as a good alternative in stabilizing keratoconus progression after primary CXL.

scholarly journals Platelet CD36 signaling through ERK5 promotes caspase-dependent procoagulant activity and fibrin deposition in vivo

2018 ◽  
Vol 2 (21) ◽  
pp. 2848-2861 ◽  
Author(s):  
Moua Yang ◽  
Andaleb Kholmukhamedov ◽  
Marie L. Schulte ◽  
Brian C. Cooley ◽  
Na’il O. Scoggins ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Signaling Molecules ◽  
Chow Diet ◽  
Glycoprotein Vi ◽  
Platelet Signaling ◽  
Clinically Significant

Abstract Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction–induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer exposure and, subsequently, recruitment of the prothrombinase complex, resulting in the generation of fibrin from the activation of thrombin. Caspase activity was observed when platelets were stimulated with oxLDL. This was prevented by inhibiting CD36 and ERK5. Furthermore, oxLDL potentiates convulxin/glycoprotein VI–mediated fibrin formation by platelets, which was prevented when CD36, ERK5, and caspases were inhibited. Using 2 in vivo arterial thrombosis models in apoE-null hyperlipidemic mice demonstrated enhanced arterial fibrin accumulation upon vessel injury. Importantly, absence of ERK5 in platelets or mice lacking CD36 displayed decreased fibrin accumulation in high-fat diet–fed conditions comparable to that seen in chow diet–fed animals. These findings suggest that platelet signaling through CD36 and ERK5 induces a procoagulant phenotype in the hyperlipidemic environment by enhancing caspase-mediated PSer exposure.

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