Physical signs and atherosclerotic cardiovascular disease in familial hypercholesterolemia: the HELLAS-FH Registry.

AIMS: Three physical signs, namely tendon xanthomas, corneal arcus and xanthelasma, have been associated with heterozygous familial hypercholesterolemia (heFH). The prevalence and clinical significance of these signs are not well established among contemporary heFH individuals. This study explored the frequency as well as the association of these physical signs with prevalent atherosclerotic cardiovascular disease (ASCVD) in heFH individuals. METHODS: Data from the Hellenic Familial Hypercholesterolemia Registry were applied for this analysis. The diagnosis of heFH was based on the Dutch Lipid Clinic Network Score. Multivariate logistic regression analysis was conducted to examine the association of heFH-related physical signs with prevalent ASCVD. RESULTS: Adult patients ( n  = 2156, mean age 50 ±â€Š15 years, 47.7% women) were included in this analysis. Among them, 14.5% had at least one heFH-related physical sign present. The prevalence of corneal arcus before the age of 45 years was 6.6%, tendon xanthomas 5.3%, and xanthelasmas 5.8%. Among physical signs, only the presence of corneal arcus before the age of 45 years was independently associated with the presence of premature coronary artery disease (CAD). No association of any physical sign with total CAD, stroke or peripheral artery disease was found. Patients with physical signs were more likely to receive higher intensity statin therapy and dual lipid-lowering therapy, but only a minority reached optimal lipid targets. CONCLUSION: The prevalence of physical signs is relatively low in contemporary heFH patients. The presence of corneal arcus before the age of 45 years is independently associated with premature CAD.

Unilateral corneal arcus and conjunctival vessel alterations in cranial autonomic dysregulation: A case report.

BACKGROUND: Cranial autonomic dysregulation is a common symptom of patients suffering from cluster headache or migraine. The peripheral vascular dysfunction may increase the risk for ischemic or hemorrhagic strokes, myocardial infarction, retinal vasculopathy, cardiovascular mortality, and peripheral artery diseases. Furthermore, it may also manifest with ocular symptoms, e.g., increased lacrimation, conjunctival injection, and facial swelling. CASE PRESENTATION: We here report a case of a patient with migraine and ocular signs of a vascular dysregulation that have led to persisting changes of conjunctival vessels and to a corneal arcus. CONCLUSIONS: Autonomic vascular dysregulation may not only cause headaches but also persisting changes of ocular tissues, e.g., conjunctival vessel alterations and a corneal arcus.

Prevalence and associated factors of corneal arcus in the geriatric population; Tehran geriatric eye study.

PURPOSE: To determine the age and sex-standardized prevalence of corneal arcus and its associated factors in a geriatric population. METHODS: This population-based cross-sectional study was conducted in 2019 in Tehran; the capital of Iran, using a multi-stage stratified random cluster sampling method. All participants underwent a detailed interview, blood pressure measurement, laboratory blood tests, and a complete ocular examination. RESULTS: Three thousand three hundred ten of 3791 invitees participated in the study (response rate: 87.31%). The mean age of the participants was 69.35 ± 7.62 years (60-97 years) and 1912 (57.76%) were female. Overall, the age and sex-standardized prevalence (95% CI) of corneal arcus was 44.28% (41.21-47.39). Based on the multiple logistic regression, the odds of corneal arcus were higher in men than in women (OR: 1.51; 95% CI: 1.14-2.00); in the age group ≥ 80 years compared to the age group 60-64 years (OR: 2.44; 95% CI: 1.68-3.53), and in retired people compared to employed individuals (OR: 2.05; 95% CI: 1.31-3.21). CONCLUSION: The present study showed a high prevalence of corneal arcus in the geriatric population. Although various studies have reported a significant relationship between corneal arcus with blood lipid and glucose levels as well as blood pressure, these relationships were not found in the present study.

Corneal densitometry in patients with arcus senilis and its correlation with serum lipid levels.

Purpose: To evaluate corneal densitometry (CD) of patients with arcus senilis (AS) and its association with the serum lipid markers. Methods: This is a cross-sectional, case-control study. The AS diagnosis was made clinically. Forty-five eyes of 45 patients with AS and 38 eyes of 38 age-matched control subjects with no noticeable AS were enrolled in the study. All participants underwent detailed ophthalmologic examination along with corneal Scheimpflug imaging with CD measurement. The evaluated serum lipid markers of the participants included total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL). The Spearman correlation analysis was used to correlate the serum lipid values and the CD. P < 0.05 was defined as statistically significant. Results: The male to female ratio was 26/19 and 14/24 in the study and control groups, respectively (P = 0.057). The mean age was 59.56 ± 8.7 and 56.47 ± 8.6 years in the study and control groups, respectively (P = 0.117). The mean total CD values in the zones extending from 2 to 12 mm were higher in the study group than in the control group (P < 0.001). The serum HDL level was found to be significantly decreased in the study group compared to the control group (P = 0.048 and Z = -1.976). There was a significant positive correlation between the serum triglyceride level and the CD value of the outermost zone (10-12 mm) (r = 0.334 and P = 0.025). Conclusion: The CD of patients with AS was found to increase not only in the peripheral zone but also in the cornea's paracentral zone compared to the healthy controls. The serum triglyceride level should give an insight into the intensity of arcus senilis. The serum HDL levels were decreased in patients with AS.

Prevalence of corneal arcus and associated factors in a German population-Results from the Gutenberg Health Study.

PURPOSE: We aimed to determine the prevalence of corneal arcus and to identify associated factors in the general population of Germany. METHODS: The Gutenberg Health Study (GHS) is a population-based cohort study in Germany, which includes an ophthalmological assessment. Refraction, distance-corrected visual acuity, non-contact tonometry and anterior segment imaging were performed for the five-year follow-up examination. Anterior segment photographs were graded for the presence of corneal arcus. Prevalence estimates were computed, and multivariable logistic regression analysis was applied to determine associated factors for corneal arcus including sex, age, spherical equivalent, central corneal thickness, intraocular pressure (IOP), socio-economic status, smoking, BMI, systolic and diastolic arterial blood pressure, HbA1c, HDL-C, LDL-C, triglyceride, and lipid modifying agents. RESULTS: A total of 9,850 right and 9,745 left eyes of 9,858 subjects (59.2±10.8 years), 49.0% females were included in this cross-sectional analysis. 21.1% of men (95%-CI: 20.0%- 22.3%) had a corneal arcus in at least one eye, and 16.9% (95%-CI: 15.9%- 18.0%) of women. In multivariable analyses, the presence of corneal arcus was associated with male gender (OR = 0.54 for female, p<0.0001), higher age (OR = 2.54 per decade, p<0.0001), smoking (OR = 1.59, p<0.0001), hyperopia (OR = 1.05 per diopter, p<0.0001), thinner cornea (OR = 0.994 per µm, p<0.0001), higher IOP (OR = 1.02, p = 0.039), higher HDL-C-level (OR = 2.13, p<0.0001), higher LDL-C-level (OR = 1.21, p<0.0001), and intake of lipid modifying agents (OR = 1.26, p = 0.0001). Arcus was not associated with socio-economic status, BMI, arterial blood pressure, and HbA1c. CONCLUSIONS: Corneal arcus is a frequent alteration of the cornea in Germany and is associated with ocular parameters and systemic parameters of dyslipidemia.

Supravalvular Aortic Stenosis and the Risk of Premature Death Among Patients With Homozygous Familial Hypercholesterolemia.

Patients with homozygous familial hypercholesterolemia (HoFH) have a high risk for premature death. Supravalvular aortic stenosis (SVAS) is a common and the feature lesion of the aortic root in HoFH. The relation between SVAS and the risk of premature death in patients with HoFH has not been fully investigated. The present study analysis included 97 HoFH patients with mean age of 14.7 (years) from the Genetic and Imaging of Familial Hypercholesterolemia in Han Nationality Study. During the median (±SD) follow-up 4.0 (±4.0) years, 40 (41.2%) participants had SVAS and 17 (17.5%) participants experienced death. The proportion of premature death in the non-SVAS and SVAS group was 7.0% and 32.5%, respectively. Compared with the non-SVAS group, SVAS group cumulative survival was lower in the HoFH (log-rank test, p <0.001). This result was further confirmed in the multivariable Cox regression models. After adjusting for age, sex, low density lipoprotein cholesterol (LDL_C)-year-score, lipid-lowering drugs, cardiovascular disease, and carotid artery plaque, SVAS was an independent risk factor of premature death in HoFH on the multivariate analysis (hazard ratio 4.45; 95% confidence interval, 1.10 to 18.12; p = 0.037). In conclusion, a significantly increased risk of premature death was observed in HoFH patients with SVAS. Our study emphasized the importance of careful and aggressive management in these patients when appropriate.

Corneal arcus as the presenting sign of familial hypercholesterolemia in a young child.

A 2.6-year-old boy presented with prominent corneal arcus. This clinical sign is rarely seen at such a young age and led to the diagnosis of familial hypercholesterolemia (FH). Genetic analysis detected biallelic pathogenic sequence variants c.1069G>A and c.2034C>A in the LDLR gene. There is significant cardiovascular morbidity and mortality associated with FH, hence early diagnosis and treatment is imperative.

Cloudy Cornea with Arcus Juvenilis in a Case of Dense Deposit Disease.

A 25-year-old male patient presented with complaints of blurred vision in both eyes since 2 years. The patient was a known case of nephrotic syndrome with dyslipidaemia for which he was on diuretics and lipid-lowering agents for 3 years. On examination, his visual acuity was 6/9 in both eyes with cloudy cornea and arcus juvenilis. Fundus examination was within normal limits. On systemic work-up, his lipid profile was deranged with increased serum total cholesterol, very low density lipoprotein, low density lipoprotein and triglyceride. The serum high density lipoprotein was decreased. Renal function test revealed elevated serum creatinine with significant proteinuria. Renal biopsy was suggestive of dense deposit disease on immunofluorescence and transmission electron microscopy. Ocular manifestation of dense deposit disease is characterised by retinal drusen, pigmentary atrophy, choroidal neovascular membrane and atypical serous retinopathy. To the best of our knowledge, anterior segment changes in dense deposit disease has not been reported. This is the first case reporting cloudy cornea with arcus juvenilis in a case of dense deposit disease.