Corneal Arcus Research Articles

Unveiling homozygous familial hypercholesterolemia in Greece: a comprehensive analysis of baseline traits and LDL goal achievement in adults from the HELLAS-FH Registry

Abstract Background Homozygous familial hypercholesterolemia (HoFH) is a severe genetic disorder characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) levels. This study aimed to analyze demographic characteristics, lipid profile, and rate in achieving LDL-C targets in adult HoFH patients in Greece. Methods This is a cross-sectional analysis of the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Adults with genetically or clinically diagnosed HoFH were included. Median LDL-C levels were assessed during HoFH diagnosis and enrollment. Results Seventeen HoFH adults (mean age 41 years and mean age at diagnosis 31 years, men 58.8%). Genetic confirmation of HoFH was available in 10 patients, while the remaining were diagnosed based on clinical criteria. Family history of atherosclerotic cardiovascular disease was documented in 70.5% of patients. Clinical presentations varied, with 47.0% exhibiting tendon xanthomas, 17.6% xanthelasmas, 23.5% corneal arcus, and 52.9% premature coronary artery disease (CAD). Predominant treatment involved statins (88.2%), ezetimibe (58.8%),PCSK9i (23.5%), lomitapide (29.4%), while LDL apheresis was utilized in 23.5%. Median LDL-C levels were 407 mg/dL (10.53 mmol/L) at diagnosis and 226 mg/dL (5.84 mmol/L) at enrollment. None of the patients achieved the LDL-C target set by the 2019 EAS/ESC Guidelines. Conclusion The challenges of delayed diagnosis, undertreatment, and unattained LDL-C targets persist in HoFH management in Greece, emphasizing the critical need for effective lipid-lowering interventions to mitigate cardiovascular risk.

Lipoprotein(a) levels and cholesterol efflux capacity: inverse association and impact on atherosclerosis in familial hypercholesterolemia patients on lipid-lowering therapy

Abstract Backgrounds Familial hypercholesterolemia (FH) patients have higher serum lipoprotein(a) (Lp(a)) levels than non-FH patients, and high Lp(a) levels raise atherosclerotic cardiovascular disease (ASCVD) risk 1). We previously reported that decreased cholesterol efflux capacity (CEC) is a risk marker for ASCVD in patients with statin-treated FH 2). Others have reported that Lp(a) interferes with the enhancement of ABCA1-mediated cholesterol efflux by plasminogen and that ABCA1-mediated CEC is lower in patients with Lp(a) >50 mg/dL. However, the association of CEC, not necessarily ABCA1-mediated, with Lp(a) is not clear and has not been studied in patients with FH. It is also unclear whether high Lp(a) and low CEC in patients with FH are associated with the severity of atherosclerosis. Purpose We examined whether Lp(a) levels are negatively associated with ABCA1-independent CEC in patients with FH receiving lipid-lowering therapy. We also examined the impact of the combination of high Lp(a) and low CEC on the presence of corneal arcus, Achilles tendon thickness, carotid intima-media thickness (IMT), and pre-existing ASCVD. Methods This cross-sectional study included 371 patients clinically diagnosed with FH receiving lipid-lowering therapy. CEC was measured in apolipoprotein B-depleted plasma and 3H-cholesterol-labeled J774.1 cells without cAMP-stimulated ABCA1 overexpression. Lp(a) was measured by enzymatic methods (Sekisui Medical, Tokyo, Japan) using an automated analyser. Achilles tendon thickness was measured by X-ray and carotid IMT by ultrasound. Results Mean age was 55±16 years, and 191 (51%) were women. The median serum Lp(a) level was 18.7 mg/dL, higher than the previously reported median level (13 mg/dL) in a Japanese population. One hundred nineteen patients (32%) had serum Lp(a) levels of 30 mg/dL or higher, and they had significantly lower CEC (P=0.0015). This negative association persisted after adjusting for age, sex, BMI, smoking status, serum LDL-cholesterol, serum triglycerides, and eGFR in a multiple linear regression model (beta-coefficient: -0.047, 95% CI: -0.075 - -0.019, P=0.0011). In addition, patients with both Lp(a) > 30 mg/dL and CEC lower than the median had a higher percentage of corneal arcus, thicker Achilles tendons, greater carotid IMT, and a higher prevalence of pre-existing ASCVD compared to patients with either or neither. Conclusions We found an inverse relationship between Lp(a) levels and CEC in FH patients receiving lipid-lowering therapy. Our results suggest that Lp(a) may also inhibit ABCA1-independent CEC, including passive cholesterol diffusion from peripheral cells. Furthermore, the combination of high Lp(a) and low CEC may be a residual risk for patients with FH receiving lipid-lowering therapy. Future studies are needed to determine whether agents that decrease Lp(a) levels will increase CEC and thereby resolve part of the residual ASCVD risk in FH.

Cardiovascular Risk Factors Predicting Cardiovascular and Cancer Deaths in a Middle-Aged Population Followed-Up for 61 Years until Extinction.

To study the relationships of cardiovascular risk factors with cancer and cardiovascular mortality in a cohort of middle-aged men followed-up for 61 years. A rural cohort of 1611 cancer- and cardiovascular disease-free men aged 40-59 years was examined in 1960 within the Italian Section of the Seven Countries Study, and 28 risk factors measured at baseline were used to predict cancer (n = 459) and cardiovascular deaths (n = 678) that occurred during 61 years of follow-up until the extinction of the cohort with Cox proportional hazard models. A model with 28 risk factors and cancer deaths as the end-point produced eight statistically significant coefficients for age, smoking habits, mother early death, corneal arcus, xanthelasma and diabetes directly related to events, and arm circumference and healthy diet inversely related. In the corresponding models for major cardiovascular diseases and their subgroups, only the coefficients of age and smoking habits were significant among those found for cancer deaths, to which healthy diet can be added if considering coronary heart disease alone. Following a competing risks analysis by the Fine-Gray method, risk factors significantly common to both conditions were only age, smoking, and xanthelasma. A sizeable number of traditional cardiovascular risk factors were not predictors of cancer death in a middle-aged male cohort followed-up until extinction.

Presence of Corneal Arcus as a Non-invasive Method of Screening for Dyslipidemia and Its Educational Role in Lifestyle Interventions

Presence of Corneal Arcus as a Non-invasive Method of Screening for Dyslipidemia and Its Educational Role in Lifestyle Interventions

Ocular manifestations of severe familial hypercholesterolemia

BackgroundTo study ocular manifestations of patients with severe familial hypercholesterolemia (FH). MethodsIn this population-based case-control study, patients suffering from severe familial hypercholesterolemia from the Lebanese Familial Hypercholesterolemia Registry, along with age and gender-matched healthy controls were recruited. All participants underwent a comprehensive eye examination, and patients underwent fluorescein angiography as well. Logistic regression models were used to identify any association between patients with severe familial hypercholesterolemia and abnormal eye findings, while adjusting for hypertension and pack-year smoking. The main outcome measure of this study was the development of ocular vascular abnormalities. Results28 patients and 28 controls were recruited. Patients with severe familial hypercholesterolemia had significantly greater odds of developing corneal arcus and xanthelasmas than the control group (p < 0.001). Retinal vascular abnormalities (plaques) were exclusively and more significantly present in patients with familial hypercholesterolemia (18 %). Similarly, retinal arteriosclerosis was exclusively and significantly more prevalent in the familial hypercholesterolemia group (p < 0.001, adjusted odds ratio 6.8). Stratification by LDL levels and genotypes did not show any significant change in the prevalence of any ocular finding. ConclusionIn addition to the well-established increase in incidence of corneal arcus and xanthelasmas, severe familial hypercholesterolemia patients have more prevalent retinal vascular abnormalities that include vascular plaques and arteriosclerosis.

Corneal endothelial cell density and associated factors among adults at a regional referral hospital in Uganda: a cross-sectional study.

To assess the prevalence of low corneal endothelial cell density and correlates of corneal endothelial cell density among adults attending Mbarara University and Referral Hospital Eye Centre in Uganda. In this hospital-based cross-sectional study, participants 18 years and older, were enrolled. We obtained informed consent, and basic demographic data. We also conducted visual acuity, a detailed slit lamp examination, intra-ocular pressure, corneal diameter, tear-film break-up time, keratometry, A-scan, and pachymetry on all participants. A confocal microscope Heidelberg HRT3 was used to examine the central cornea and to obtain the mean cell density (cells/mm2). To calculate the proportion of low endothelial cell density, descriptive statistics were used, whereas correlates of endothelial cell density were assessed, using linear regression analyses. We evaluated a total of 798 eyes of 404 participants aged between 18 and 90 years (males = 187, females = 217). The average endothelial cell density was 2763.6 cells/mm2, and there was a decrease in endothelial cell density with increasing age, irrespective of gender. There was no significant difference in endothelial cell density between males and females. Increasing age (adjusted coefficient - 10.1, p < 0.001), history of smoking (adjusted coefficient - 439.6, p = 0.004), history of ocular surgery (adjusted coefficient - 168.0, p = 0.023), having dry eye (adjusted coefficient - 136.0, p = 0.051), and having arcus senilis (adjusted coefficient - 132.0, p = 0.08), were correlated with lower endothelial cell density. However, increasing corneal diameter (adjusted coefficient 134.0, p = 0.006), increasing central corneal thickness (adjusted coefficient 1.2, p = 0.058), and increasing axial length (adjusted coefficient 65.8, p = 0.026), were correlated with higher endothelial cell density. We found five eyes (0.63%) from different participants with a low endothelial cell density (< 1000cells/mm2). Our study established baseline normal ranges of ECD in a predominantly black African population, and found that low ECD is rare in our population. The elderly, smokers, and those with past ocular surgery are the most vulnerable. The low prevalence could be due to a lack of reference values for the black African population.

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

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. 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. Adult patients ( n = 2156, mean age 50 ± 15 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. 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.

Incidental encounter: cataract surgery reveals bilateral double arcus senilis — a rare and uncharted ocular phenomenon

Incidental encounter: cataract surgery reveals bilateral double arcus senilis — a rare and uncharted ocular phenomenon

Canonical Correlation for the Analysis of Lifestyle Behaviors versus Cardiovascular Risk Factors and the Prediction of Cardiovascular Mortality: A Population Study

Objectives: To assess the overall association of lifestyle behaviors with multiple cardiovascular risk factors and mortality. Material and Methods: In the Italian Rural Areas of the Seven Countries Study, involving 1712 middle-aged men (40–59 years) enrolled in 1960, smoking habits, physical activity, dietary habits, marital status, and socioeconomic status (SES) were studied as possible determinants of 15 measurable risk factors (body mass index, tricipital and subscapular skinfold, arm circumference, systolic and diastolic blood pressure, heart rate, double product (systolic blood pressure × heart rate), vital capacity, forced expiratory volume, serum cholesterol, urine protein, urine glucose, corneal arcus and xanthelasma) using canonical correlation (CC). Results: The first CC had a value of 0.54 (R2 0.29, p &lt; 0.0001). The role of marital status was marginal; that of a high SES was contrary to expectations. The strongest behaviors based on standardized CC coefficients were dietary habits and physical activity. The risk factors mostly associated with overall lifestyle behaviors were some anthropometric and cardiovascular measurements. The mean levels of risk factors distributed in tertile classes of the CC variate score of lifestyle behaviors were largely associated in a coherent and graded way with the expected relationship of behaviors versus risk factors. In a large series of Cox models, the CC variate scores were significantly associated with 50-year coronary heart disease (CHD) mortality and much less with stroke and other heart diseases of uncertain etiology. Conclusions: Lifestyle behaviors correlate well with cardiovascular risk factors associated with CHD mortality, and CC is a useful method of analysis to detect long-term impacting characteristics.

Double arcus cornealis: A case report

The corneal arcus is a degenerative change that involves lipid deposition and presents as a white circumferential band located in the peripheral cornea. Arcus occurs with age (arcus senilis) and is not considered pathologic; it can also be associated with hyperlipoproteinemia in younger age groups (arcus juvenilis). A single ring of arcus senilis is a universal phenomenon. Here we present a case of double arcus in a 55-year-old patient who had no history of any systemic disease. Double arcus senilis was bilateral with a circular, clear zone between the two rings as well as between the limbus and outer ring of arcus. On routine blood investigations, serum triglycerides (220.2 mg/dL) and serum very low-density lipoprotein (44.04 mg/dL) were found to be in the higher range.

Prognostic value of diagnostic criteria for familial hypercholesterolemia in men and women with dyslipidemia

Aim. To analyze the prognostic value of the Dutch Lipid Clinic Network (DLCN) and Simon Broome Register (SBR) screening criteria for familial hypercholesterolemia (FH) in men and women with dyslipidemia.Material and methods. The study included 1233 patients with dyslipidemia.Biomaterial samples from 421 patients were studied using Next Generation Sequencing (NGS) to identify FH-associated genes. Statistical analysis was carried out using the StatTech v program. 3.1.6 (OOO Stattekh, Russia).Results. The most significant factors for predicting the FH in men are the level of low-density lipoprotein cholesterol (LDL-C) (1,77 times), positive family history for coronary artery disease (CAD) (6,26 times), multivessel coronary artery disease (4,05 times); in women before menopause — LDL-C (1,77 times per 1 mmol/l) and/or family history of coronary artery disease (3,31 times), in menopausal women — total cholesterol level (1,79 times per 1 mmol/l), coronary artery disease (6,52 times) and/or family history of stroke (6,04 times), xanthomas (4,24 times). Acute myocardial infarction and/or coronary stenting, arcus senilis, extracranial artery atherosclerosis did not prove to be prognostically significant for FH diagnosis.Conclusion. Diagnostic criteria for potential FH vary among patient populations. Its diagnostic significance depends on sex, and in women, reproductive status.

Clinical characteristics of carriers of pathogenic LDLR and АРОВ mutations

Aim. To analyze the clinical characteristics of carriers of pathogenic LDLR and АРОВ mutations, as well as the prognostic value of Dutch Lipid Clinic Network Score (DLCNS) as applied to carriage of АРОВ or LDLR.Material and methods. The study included 1233 outpatient lipid clinic patients. Biomaterial samples from 421 patients with the hereditary dyslipidemia were studied using Next Generation Sequencing (NGS) to identify carriage of familial hypercholesterolemia (FH)-associated genes (LDLR, АРОВ, PCSK9, LDLRAP1), as well as polymorphism of the APOE gene. Statistical processing was performed using descriptive statistics methods.Results. According to the data obtained, the most significant predictors of pathogenic LDLR mutations are the levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), family history of coronary artery disease (CAD), and previous coronary artery bypass grafting. The level of LDL-C, family history of cerebrovascular accident or CAD, and arcus senilis were more significant for verifying the carriage of pathogenic АРОВ mutations. Using screening potential carriers of FH using the DLCN or Simon-Broome diagnostic criteria, the probability of FH may be underestimated due to the discrepancy between the scale criteria and the prognostic contribution of clinical or anamnestic data. These scales do not take into account the estrogen status of potential female carriers of FH.Conclusion. Thus, diagnostic criteria for identifying potential FH vary among different patient groups. Their diagnostic significance depends on sex, and in women, on reproductive status. Only part of DLCN and Simon-Broome criteria can be applied to assess the FH likelihood, and to a greater extent for carriage of LDLR, but not АРОВ.

Abstract 18931: A PCSK9 and APOB Double Heterozygote Presenting Phenotypically Similar to Homozygous Familial Hypercholesterolemia

Introduction: Familial hypercholesterolemia (FH) is an inherited disorder associated with mutations in APOB, PCSK9 and LDLR genes. Heterozygous FH (HeFH) generally has one gene mutation. Homozygous FH (HoFH) has two mutations in the same gene and is characterized by vastly elevated plasma LDL-C, accelerated ASCVD and resistance to standard lipid-lowering therapy. Combinations of mutations can present with a phenotype similar to HoFH. We present a double heterozygous patient with unreported mutations in PCSK9 and APOB genes, exhibiting clinical features of HoFH. Hypothesis: Patients with multiple gene mutations for FH can present clinically similar to HoFH and would benefit from novel lipid lowering therapies Methods: 73-year-old female with a history of diabetes and hyperlipidemia presented in 2018 with dyspnea on exertion. Cholesterol (TC) and triglycerides (TG) were 430 and 715 mg/dl respectively, on rosuvastatin 40 mg and omega 3 fatty acids. Physical exam showed arcus senilis. A nuclear stress test showed ST depressions in inferolateral leads but normal scintigraphy. Genetic testing revealed APOB and PCSK9 mutations. She was then treated with rosuvastatin, icosapentyl ethyl, ezetimibe and fenofibrate. TC, LDL, TG and ApoB levels were 463, 236, 747 and &gt;240 mg/dl respectively. Evolocumab was added, with reduction of TC, TG and ApoB levels to 326, 432 and 182mg/dl, despite maximal available therapy. Results: Genetic testing revealed APOB variant NP_000375.2:p.Gln3378His and PCSK9 variant NP_777596.2:pAla544Thr, which were unreported mutations with unknown clinical significance. Genetically, this patient is a double heterozygote but expresses a phenotype similar to HoFH due to a poor response to maximum therapy. Conclusions: Although usually genetically defined, the phenotype of HoFH can present with different genetic variations. Chaudhry et al established genetic diagnosis of HoFH in 0.9% of patients initially diagnosed as HeFH, of which 3 were true homozygotes and 3 were compound heterozygotes. These findings support the idea that various heterozygous combinations of mutations in the genes for LDLR, APOB and PCSK9, may present clinically similar to HoFH. Patients with these mutations could benefit from novel agents such as evinacumab.

Abstract 13180: Cardiovascular Disease and Cholesterol Lowering Therapy in Women and Men With Molecularly Proven Familial Hypercholesterolemia

Introduction: Familial Hypercholesterolemia (FH) is an autosomal dominant disease affecting women and men on the same proportion. There is scant evidence on cardiovascular disease (CVD) and therapy adequacy on contemporary FH cohorts according to sex. Goals: Evaluate whether there were differences in CVD outcomes and treatment intensity in women and men with molecularly proven FH at a specialized lipid clinic. Methods: Initially a cross-sectional analysis of 801 patients with FH enrolled between 2011 and 2022 on a genetic cascade screening program was done . All had a positive FH molecular diagnosis. Participants were then followed by a median of 5 years (0.08 to 11 years). Clinical, laboratory and, treatment parameters were compared at baseline and during follow-up according to sex. Results: The cohort consisted of 455 women (57%) and 346 men (43%), mean age 47± 15 years. At baseline there were no sex differences regarding LDL-C (196±74 mg/dL men vs 200±75 mg/dL women, p= 0.567) as well as percentage of those with LDL-C &lt; 100 mg/dL (6.8% men vs 6.1% women, p=0.712) or &lt; 70 mg/dL at baseline (0.3% men vs 0% women, p=0.238). Intensive lipid lowering treatment use was similar between men and women at baseline (75.1% vs. 74.4%; p= 0.848) and during follow-up (87.6% vs. 88.3%; p= 0.785). At baseline 23.1% of women and 38.1% of men had a previous history of CVD (p= 0.000). After follow-up, 41 women (9%) and 52 men (15%) had an incident CVD event (p=0.009). Multivariate Cox regression analysis showed that risk factors related to incident events were age (HR=1.028, 95% CI 1.005-1.052 per year, p =0.019), presence of corneal arcus (HR 1.794, 95% CI 1.096-2.937, p= 0.02), current smoking (HR 2.534, 95% CI 1.304-4.927, p=0.006) and a previous CVD event (HR= 1.793, 95%CI 1.041-3.087, p= 0.035). Conclusions: Overall FH men had a greater risk of CVD events than FH women. There was no difference in treatment intensity and CVD outcomes were associated with traditional risk factors or previous CVD.

Metabolic systems approaches update molecular insights of clinical phenotypes and cardiovascular risk in patients with homozygous familial hypercholesterolemia

BackgroundHomozygous familial hypercholesterolemia (HoFH) is an orphan metabolic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C), xanthomas, aortic stenosis, and premature atherosclerotic cardiovascular disease (ASCVD). In addition to LDL-C, studies in experimental models and small clinical populations have suggested that other types of metabolic molecules might also be risk factors responsible for cardiovascular complications in HoFH, but definitive evidence from large-scale human studies is still lacking. Herein, we aimed to comprehensively characterize the metabolic features and risk factors of human HoFH by using metabolic systems strategies.MethodsTwo independent multi-center cohorts with a total of 868 individuals were included in the cross-sectional study. First, comprehensive serum metabolome/lipidome-wide analyses were employed to identify the metabolomic patterns for differentiating HoFH patients (n = 184) from heterozygous FH (HeFH, n = 376) and non-FH (n = 100) subjects in the discovery cohort. Then, the metabolomic patterns were verified in the validation cohort with 48 HoFH patients, 110 HeFH patients, and 50 non-FH individuals. Subsequently, correlation/regression analyses were performed to investigate the associations of clinical/metabolic alterations with typical phenotypes of HoFH. In the prospective study, a total of 84 HoFH patients with available follow-up were enrolled from the discovery cohort. Targeted metabolomics, deep proteomics, and random forest approaches were performed to investigate the ASCVD-associated biomarkers in HoFH patients.ResultsBeyond LDL-C, various bioactive metabolites in multiple pathways were discovered and validated for differentiating HoFH from HoFH and non-FH. Our results demonstrated that the inflammation and oxidative stress-related metabolites in the pathways of arachidonic acid and lipoprotein(a) metabolism were independently associated with the prevalence of corneal arcus, xanthomas, and supravalvular/valvular aortic stenosis in HoFH patients. Our results also identified a small marker panel consisting of high-density lipoprotein cholesterol, lipoprotein(a), apolipoprotein A1, and eight proinflammatory and proatherogenic metabolites in the pathways of arachidonic acid, phospholipid, carnitine, and sphingolipid metabolism that exhibited significant performances on predicting first ASCVD events in HoFH patients.ConclusionsOur findings demonstrate that human HoFH is associated with a variety of metabolic abnormalities and is more complex than previously known. Furthermore, this study provides additional metabolic alterations that hold promise as residual risk factors in HoFH population.

Lipid Keratopathy: Histopathology, Major Differential Diagnoses and The Importance of Clinical Correlation.

Lipid keratopathy (LK) is a rare ophthalmological condition characterized by a progressive reduction in visual acuity caused by corneal opacification due to central lipid accumulation. LK is characterized by lipid deposits, cholesterol clefts, and neovascularization (NV) leading to disruption in corneal optical quality. LK classification includes a primary and secondary form which depend on pre-existing corneal or systemic disorders and the evidence of NV. Secondary LK is typically associated with a prior occurrence of herpetic infection, such as herpes zoster keratitis. Patients with LK usually present with progressive vision loss and dense cream-colored corneal opacification. Treatment modalities include conservative and surgical approaches focused on corneal NV elimination. When evaluating corneal lipidosis, it is crucial to consider a range of differential diagnoses, including corneal arcus, Schnyder corneal dystrophy, and other corneal deposit conditions. We report a case of a 62-year-old male with herpes zoster keratitis complicated with LK. He presented with painless progressive vision loss and corneal scarring, which raised suspicion about LK diagnosis. This paper emphasizes the importance of correlating clinical and histological findings for accurate LK diagnosis.

Lipid profile in individuals under 50 years of age with corneal arcus

Lipid profile in individuals under 50 years of age with corneal arcus

Familijarna hiperholesterolemija i kaskadni skrining za detekciju novih pacijenata

Familial Hypercholesterolemia (FH) is a metabolic disorder that is inherited in an autosomal dominant manner and is characterized by elevated cholesterol levels and the development of premature atherosclerotic cardiovascular disease (ASCVD). The prevalence of heterozygous FH is 1 in 250-500 individuals, while the prevalence of homozygous FH is 1 in a million. The molecular basis of this condition involves mutations in the genes encoding the LDL receptor (Low-Density Lipoprotein Receptor, LDLR), Apolipoprotein B (ApoB), or Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) enzyme. In patients with FH, laboratory analyses are dominated by elevated levels of low-density lipoprotein cholesterol (LDL-C) above the 95th percentile for age and gender, with most commonly normal values of high-density lipoprotein cholesterol (HDL-C) in very low-density lipoprotein cholesterol (VLDL-C), and triglycerides. The gold standard for diagnosing FH is genetic analysis and mutation detection, but it is often inaccessible due to economic reasons. Today, the diagnosis is made by applying a scoring system within well-validated questionnaires, which assess the probability of FH based on the simultaneous analysis of personal and family history, clinical findings of tendon xanthomas or corneal arcus, as well as biochemical analysis of the lipid profile. Despite clear diagnostic recommendations for FH, there is an extremely low rate of diagnosis of these patients, even in developed healthcare systems, as well as a low rate of treatment. A large number of unrecognized FH patients, along with a significantly increased risk of cardiovascular diseases in untreated young FH patients, have prompted global efforts to diagnose the disease earlier and reduce complications through appropriate treatment. Cascade screening in the detection of new patients involves analyzing the relatives, first-, second-, and third-degree, of patients with known FH (index case, proband). Upon identifying a new case, that individual becomes the new proband, and their relatives are analyzed in subsequent cascades. There are three basic models of cascade screening: clinical, genetic, and hybrid models. Currently, selective clinical cascade screening is most commonly applied. Selective cascade screening detects the disease in individuals at high risk of its manifestation. The expert consensus panel recommends a hybrid model, where genetic testing is performed in all patients with definite or probable FH, and in cascade screening, both cholesterol levels and genetic analysis are continued in their high-risk relatives. Adequate detection of FH patients and timely treatment significantly reduce their cardiovascular morbidity and mortality, justifying the implementation of cascade screening. Conducting screening through routine clinical practice does not yield satisfactory results. Therefore, it is necessary to organize a screening program at the national level, including the establishment of lipidology centers and the provision of genetic screening and genetic counseling services.

A Comparative Study of Deep Learning Parameters for Arcus Senilis Classification

Deep learning technique has recently yielded positive results that have increased productivity system for artificial intelligent task, especially the digital image processing and advance machine vision. The popularity of deep learning technique has a major impact on solving complex problems in many fields, particularly the medical science owing to its applications in medical imaging, disease diagnosis, and much more. However, successful application of deep learning depends upon the appropriate setting of the parameters to achieve better result. Therefore, this paper presents a comparative analysis of different base learning rate and batch size configurations for arcus senilis (AS) classification using deep learning techniques. In this analytical study, a dataset of 402 eye images comprising 158 normal and 244 abnormal eye images was employed. Two well-known ResNet-50, VGG-19 and pre-trained convolutional neural network (CNN) models have been trained and validated with 10-fold cross validation using the proposed dataset. Furthermore, base learning rate and batch size were adjusted accordingly to determine the optimal convergence of each model by observing the validation accuracy and error. Experimental result shows that the best combined system has achieved an overall accuracy of 99.78% with a base learning rate of 0.0001 and a batch size of 20 on CNN pre-trained model validation set. Moreover, CNN produces the best result on F1-score and standard deviation of 99.77% and 0.464 respectively. Thus, it can be concluded that CNN requires a considerably smaller number of parameters and reasonable computing time to achieve state-of-the-art performances. This study shows that CNN has the tendency to consistently improve inaccuracy with growing number of epochs, with no signs of overfitting and performance.

Lipaemia retinalis in hyperlipidemia, uncontrolled diabetes mellitus

A 52-year-old male patient presented with a chief complaint of diminution of vision over the past two months. He is a known case of type -2 diabetes mellitus for 25 years but has not been taking his medication regularly. Ocular examination revealed visual acuity of 6/18 in both the eyes, xanthelasma, arcus senilis, posterior segment examination revealed creamy white discolouration of the retinal vessels. Routine blood investigation revealed high level of triglycerides (1550 mg/dl), cholesterol (615 mg/dl), LDL-C 10 mg/dl, HDL-C (187 mg/dl), and with HBA1C of 14.4%. Hence, diagnosed this case as lipaemia retinalis. The patient was referred to a physician for treatment, and after treating with statins, lipid-lowering therapy, and blood sugar control, the patient was reviewed every month; six months later, the patient had normal retinal vessels and improved visual acuity, in addition to normal triglyceride, cholesterol, and blood glucose levels.