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.

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.

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.

Is Corneal Arcus Independently Associated With Incident Cardiovascular Disease in Asians?

PURPOSE: To examine the longitudinal relationship between baseline corneal arcus (CA) and incident cardiovascular disease (CVD) in ethnic Indian and Malay adults in Singapore. DESIGN: Population-based cohort study. METHODS: Indian and Malay adults aged 40-80 years were recruited for baseline and 6-year follow-up visits between 2004-2009 and 2010-2015, respectively (follow-up response rate 73.9%). CA was assessed by ophthalmologists using slit-lamp biomicroscopy. The main outcome was self-reported incident CVD, defined as new myocardial infarction, angina pectoris, or stroke, which developed between baseline and follow-up. Multivariable logistic regression models assessed independent associations between baseline CA and incident CVD, adjusting for traditional CVD risk factors including age, sex, serum cholesterol, hypertension, diabetes, and smoking. We further conducted sex-stratified analyses to identify possible effect modifications. RESULTS: Of the total 3637 participants (overall mean [SD] age: 56 [9] years, 46% male) with available follow-up data, without history of CVD at baseline, 208 (5.7%) incident CVD cases were reported. Participants with CA were more likely to have incident CVD (7.5%) than those without (4.9%). After controlling for traditional CVD risk factors, CA was independently associated with incident CVD (odds ratio [95% confidence interval]: 1.52 [1.07-2.16]) in adjusted models. In sex-stratified models, associations between CA and incident CVD were seen in men (1.73 [1.12-2.67]) and not in women (1.05 [0.56-1.97]). CONCLUSIONS: CA is associated with incident CVD, independent of serum lipids and traditional CVD risk factors, in ethnic Malay and Indian men. Our finding suggests that CA is an additional observable indicator of CVD in men.

Ophthalmologic Findings in H Syndrome: A Unique Diagnostic Clue.

BACKGROUND: H syndrome is an autosomal recessive histiocytosis with multisystemic involvement caused by mutations in the SLC29A3 gene. The term H syndrome was coined to denote the major clinical findings which include hyperpigmentation, hypertrichosis, hearing loss, hepatosplenomegaly, hypogonadism, hyperglycemia/diabetes mellitus and hallux valgus/flexion contractures. Almost 100 individuals affected with this disorder have been reported, however, a thorough evaluation of the ophthalmologic features of H syndrome has not yet been performed. MATERIALS AND METHODS: Ophthalmic examination of a 50-year-old male with H syndrome. Mutation analysis of SLC29A3 was also performed in this patient. RESULTS: Ophthalmic findings included; shallow orbits with exorbitism, bilateral pterygium, limbal thickening, corneal arcus and cortical cataract. We also review ophthalmologic findings in previously reported H syndrome patients. CONCLUSIONS: The presence of dilated lateral scleral vessels, corneal arcus and shallow orbits should raise the suspicion of H syndrome, especially when seen in young age.

A population-based study of corneal arcus and its risk factors in Iran.

PURPOSE: To determine the prevalence of corneal arcus, its risk factors, and its relationship to ocular and visual indices. METHODS: In this cross-sectional study, 300 clusters were randomly selected from Shahroud in the north of Iran, using multistage sampling. A total of 20 people were invited to participate from each cluster. After enrollment, all optometric, biometric and ophthalmic exams were conducted on site. RESULTS: Of 6311 people invited, 5190 (82.2%) participated in the study. The prevalence of corneal arcus was 23.3% (95% confidence interval, CI, 22.1-24.6), and 98.4% were bilateral cases. The prevalence of corneal arcus was higher in men (odds ratio, OR, 2.02, 95% CI 1.8-2.3, p < 0.001) and increased with age (OR 1.1/year, p < 0.001). In a multivariable-adjusted regression model, age (OR 1.1/year, p = 0.006), male sex (OR 1.30, p = 0.001), diabetes (OR 0.7, p < 0.001), smoking (OR 1.5, p = 0.003), outdoor activity (OR 1.4, p = 0.006), systolic blood pressure (OR 1.01, p = 0.012), and diastolic blood pressure (OR 0.99, p = 0.016) were significantly correlated with corneal arcus. Including biometric components in another model, corneal thickness (OR 0.99, p < 0.001), anterior chamber depth (OR 0.68, p < 0.001) and corneal radius of curvature (OR 1.59, p < 0.001) were significantly correlated with corneal arcus. CONCLUSION: This study adds valuable information to the epidemiology of corneal arcus in Iran and the Middle East. In people aged over 60 years, nearly 50% of the study population had corneal arcus. Older age, male sex, smoking, and systolic hypertension were risk factors for corneal arcus. Corneal arcus was also associated with thin and flat corneas and shallow anterior chamber depth.

Non-invasive measurement of transparency, arcus senilis, and scleral rim diameter of corneas during eye banking.

We developed a non-invasive device to quantify transparency (T), clear corneal diameter (CCD) excluding arcus senilis, and scleral rim diameter (SRD) of stored corneas. The T value (expressed in % on a relative scale), based on the modulation transfer function principle, referred to the ratio of local contrasts of a special LED backlit chart measured with and without cornea. CCD and SRD (in mm) were automatically calculated by morphologic operations. Firstly, we assessed measurement reproducibility. We then determined the agreement of T and CCD values with 3-level scores given independently by three experts on 179 scientific corneas. Thirdly, an eye bank was equipped with the device, and 358 consecutive organ-cultured (OC) corneas were tested for donor- and storage- related factors possibly influencing T and CCD. Reproducibility of T, CCD and SRD measurements was high, with intraclass correlation coefficients of 0.982, 0.886, and 0.999 respectively. Capacity to discriminate the three levels of transparency and arcus senilis was good, with T of 20.0 (10.0-33.6), 38.3 (24.3-75.4) and 57.9 (33.9-90.0) % respectively for T deemed poor, average, and good (P < 0.001), and CCD of 9.8 (7.3-10.6), 10.5 (8.2-11.5), and 11.1 (9.9-12.0) mm respectively for arcus senilis deemed prominent, moderate or absent (P < 0.001). T was correlated with neither donor age nor endothelial cell density nor storage time, but slightly worsened during OC for corneas assessed twice. In conclusion, the device, which can be easily integrated in the facilities of an eye bank, provides reliable objective measurement of T, CCD, and SRD. This could be a useful tool for standardizing quality assessment of stored corneas and consequently optimizing their selection for penetrating, endothelial or anterior lamellar keratoplasty.

Corneal arcus and xanthomas in homozygous familial hypercholesterolemia: first report from China.

We report the case of a 12-year-old male who developed corneal arcus and multiple skin lesions with a 10-year history of xanthomas. The lesions appeared over his fingers, hands, elbows, knees, buttocks and feet. Laboratory studies showed a total serum cholesterol level of 752.1 mg/dL; a triglyceride level of 96.6 mg/dL; a low-density lipoprotein cholesterol level of 661.3 mg/dL. Findings were consistent with homozygous familial hypercholesterolemia. To our knowledge, this is the first such case to be reported from China.

Corneal arcus is a sign of cardiovascular disease, even in low-risk persons.

PURPOSE: To examine the association of corneal arcus to cardiovascular disease (CVD) in an adult, ethnic Indian population. DESIGN: Population-based cross-sectional study. METHODS: Population-based study of ethnic South Asian Indians 40 to 80 years of age in Singapore from June 2007 through March 2009. We obtained a 75.5% response rate (3397/4497). All participants underwent standardized interview and systemic and ocular examinations, followed by nonfasting blood sampling. Corneal arcus was detected using a standardized slit-lamp examination. The main outcome measure was CVD, defined from a self-reported history of previous myocardial infarction, angina, or stroke. RESULTS: Corneal arcus, found in 1701 (50.1%) of 3397 participants, was associated with older age (odds ratio [OR], 3.07; 95% CI, 2.78 to 3.40; P < .001), male gender (OR, 2.17; 95% CI, 1.81 to 2.62; P < .001), higher levels of total cholesterol (OR, 1.14; 95% CI, 1.05 to 1.24; P = .002), hypertension (OR, 1.14; 95% CI, 1.05 to 1.24; P = .013), and cigarette smoking (OR, 1.59; 95% CI, 1.25 to 2.03; P < .001). Corneal arcus was associated with CVD (OR, 1.31; 95% CI, 1.02 to 1.7; P = .0038) independent of the above-named cardiovascular risk factors. Participants with low-risk Framingham scores were more likely to be associated with CVD if they had corneal arcus (men: OR, 2.02; 95% CI, 1.20 to 3.40; P = .008; women: OR, 2.78; 95% CI, 1.36 to 3.01; P < .001). Corneal arcus was associated with CVD independent of the Framingham score (men: Akaike information criterion, 1524.39 for Framingham Score and corneal arcus vs 1527.38 for Framingham Score alone; women: 1000.14 vs 1003.54, respectively). CONCLUSIONS: Corneal arcus is associated with CVD, independent of risk factors in ethnic Indian adults, even in those at low risk for vascular disease.

Computer-based classification of eye diseases.

Eye disorders among the elderly are a major health problem. With advancing age, the normal function of eye tissues decreases and there is an increased incidence of ocular pathology. The most common causes of age related eye disorder and visual impairment in the elderly are cataracts, iridocyclitis and corneal haze. Iridocyclitis is an inflammation of the iris (the colored part of the eye), while corneal haze is a complication of refractive surgery characterized by the cloudiness of the normally clear cornea. Computer-based intelligent system for classification of these eye diseases is very useful in diagnostics and disease management. This paper presents a comparison of three classification strategies to classify four kinds of eye data sets (three different kinds of eye diseases and a normal class). Our protocol uses three different kinds of classifiers: artificial neural network, fuzzy classifier and neuro-fuzzy classifier. Features are extracted from these raw images which are then fed to these classifiers. These classifiers are run on a database of 135 subjects using the cross-validation strategy. We demonstrate a sensitivity of more than 85% for these classifiers with the specificity of 100% and results are very promising.

[Unilateral ptosis in the background of unilateral corneal arcus lipoides -- a case report]. / Unilaterale Ptosis assoziiert mit unilateralem Arcus lipoides -- Kasuistik.

BACKGROUND: Arcus lipoides corneae is a common bilateral degenerative disorder with ageing but only rarely occurs unilaterally. Clinically visible cream-coloured ring-shaped corneal opacities are caused by excessive lipoid deposits in the corneal stroma. Our aim is to discuss theoretical aspects of the possible impact and pathomechanism of unilateral ptosis in unilateral arcus lipoides. CASE REPORT: The authors report the case of a 70-year-old female patient who was treated for chronic pancreatitis and hyperlipoproteinemia. She had congenital ptosis on the left side, and an arcus lipoides corneae in her left eye. The patient underwent extracapsular cataract extraction, and irregular high-grade astigmatism developed. An irregularity of the wound healing was apparent from the keratometric values, which decreased after removal of the corneal sutures. CONCLUSION: The known etiological factors of unilateral arcus lipoides, like contralateral stenosis of the internal carotid artery, traumatic or iatrogenic hypotony, chronic iridocyclitis of the eye were absent in our patient.

Bedside diagnosis of coronary artery disease: a systematic review.

PURPOSE: To assess the accuracy of bedside findings for diagnosing coronary artery disease and acute myocardial infarction. METHODS: A MEDLINE search was performed to retrieve articles published from January 1966 to January 2003 that were relevant to the bedside diagnosis of coronary disease in adults. RESULTS: In patients with stable, intermittent chest pain, the most useful bedside predictors for a diagnosis of coronary disease were found to be the presence of typical angina (likelihood ratio [LR]=5.8; 95% confidence interval [CI]: 4.2 to 7.8), serum cholesterol level >300 mg/dL (LR=4.0; 95% CI: 2.5 to 6.3), history of prior myocardial infarction (LR=3.8; 95% CI: 2.1 to 6.8), and age >70 years (LR=2.6; 95% CI: 1.8 to 4.0). Nonanginal chest pain (LR=0.1; 95% CI: 0.1 to 0.2), pain duration >30 minutes (LR=0.1; 95% CI: 0.0 to 0.9), and intermittent dysphagia (LR=0.2; 95% CI: 0.1 to 0.8) argued against a diagnosis of coronary disease. In patients with acute chest pain, the most important bedside predictors for a diagnosis of myocardial infarction were new ST elevation (LR=22; 95% CI: 16 to 30), new Q waves (LR=22; 95% CI: 7.6 to 62), and new ST depression (LR=4.5; 95% CI: 3.6 to 5.6). A normal electrocardiogram (LR=0.2; 95% CI: 0.1 to 0.3), chest wall tenderness (LR=0.3; 95% CI: 0.2 to 0.4), and pain that was pleuritic (LR=0.2; 95% CI: 0.2 to 0.3), sharp (LR=0.3; 95% CI: 0.2 to 0.5), or positional (LR=0.3; 95% CI: 0.2 to 0.5) argued against the diagnosis of myocardial infarction. CONCLUSION: The accuracy of bedside predictors depends on the clinical setting. In the evaluation of stable, intermittent chest pain, a patient's description of pain was found to be the most important predictor of underlying coronary disease. In the evaluation of acute chest pain, the electrocardiogram was the most useful bedside predictor for a diagnosis of myocardial infarction. Aside from the extremes in cholesterol values, the analysis of traditional risk factors changed the probability of coronary disease or myocardial infarction very little or not at all.

Pseudogerontoxon.

Pseudogerontoxon is a lesion that resembles a small segment of arcus senilis or gerontoxon and is seen in many individuals with limbal vernal or atopic keratoconjunctivitis. It is an important clinical finding because pseudogerontoxon is often times the only clinical evidence of previous allergic eye disease. To the authors' knowledge, pseudogerontoxon has only rarely been mentioned, and has never been pictured, in the peer-reviewed literature. Three examples are presented of this important clinical entity.