Lipemia Retinalis Research Articles

Beyond the retina: Lipemia retinalis as a clue to Berardinelli-Seip congenital lipodystrophy syndrome

In this rare and significant scenario, a 15-year-old female recently diagnosed with type 1 diabetes mellitus presented with moderate lipemia retinalis during routine diabetic retinopathy screening. Further investigations revealed elevated triglyceride and cholesterol levels, prompting the diagnosis of Berardinelli-Seip congenital lipodystrophy syndrome. This congenital disorder, characterized by severe insulin resistance and dyslipidemia due to near-total absence of adipose tissue, emphasizes the critical role of interdisciplinary care involving ophthalmologists, endocrinologists, and geneticists. Early recognition of ocular manifestations such as lipemia retinalis is crucial for timely diagnosis and tailored treatment strategies.

Lipemia retinalis following FLAG-Ida protocol in an 11-year-old patient with acute myeloid leukemia.

We report a case of early-onset lipemia retinalis secondary to the FLAG-Ida protocol in the treatment of acute myeloid leukemia (AML) in an 11-year-old girl. An 11-year-old patient, diagnosed with AML at four months old, experienced a relapse and was treated with the FLAG-Ida protocol (fludarabine, idarubicin, granulocyte-colony stimulating factor, and high-dose cytarabine). Prior to allogeneic stem cell transplantation, she underwent a pre-transplantation eye examination. The patient exhibited normal visual acuity in both eyes. Fundus examination revealed cream-white retinal vessels and a salmon-pink retina, indicative of grade 3 lipemia retinalis. Laboratory tests, normal before treatment initiation, showed significantly elevated serum cholesterol (727.6 mg/dL) and triglyceride (6015.6 mg/dL) levels post-treatment. After receiving fenofibrate, these levels decreased markedly, and the retinal vessels normalized on follow-up fundus examination. Lipemia retinalis, characterized by creamy-white retinal vessels resulting from hypertriglyceridemia, can develop as a secondary condition to chemotherapy. Early detection and treatment of hyperlipidemia are crucial to prevent severe ocular and systemic complications. This case highlights the importance of monitoring lipid levels and conducting thorough ophthalmologic examinations in patients undergoing chemotherapy.

Resolution of Lipemia Retinalis With Lifestyle Modification

Purpose: To describe a case of lipemia retinalis, a rare ocular manifestation of hypertriglyceridemia that is characterized by a creamy-white to salmon-colored appearance to the fundus. Methods: A 55-year-old man was referred for an evaluation for diabetic retinopathy and was subsequently found to have marked lipemia retinalis. Results: The patient’s triglyceride levels were 3141 mg/dL; therefore, treatment was initiated with high-intensity statin therapy and lifestyle modifications. At the 3-month follow-up, the patient had significantly reduced triglyceride levels (689 mg/dL) and full resolution of lipemia retinalis. Conclusions: Lipemia retinalis may be an initial finding of a severe systemic problem and a harbinger for more severe, and potentially fatal, consequences. Thus, a complete systemic assessment is warranted for any patient with signs of lipemia retinalis.

A rare case of lipemia retinalis in a 15-day-old neonate

Lipemia retinalis (LR) is characterized by creamy white discoloration of retinal vessels, a feature of chylomicronemia (triglyceride levels >1000 mg/dL). We report a case of a 15-day-old neonate admitted to the pediatric ward with complaints of breathing difficulty and respiratory distress. Ophthalmological examination revealed a whitish optic disc with diffuse tortuous creamy retinal vessels bilaterally in peripheral and posterior poles and a salmon pink retinal background. A diagnosis of grade-III LR was made. The patient was advised exclusive breastfeeding and followed up.

The scope of artificial intelligence in retinopathy of prematurity (ROP) management.

Artificial Intelligence (AI) is a revolutionary technology that has the potential to develop into a widely implemented system that could reduce the dependence on qualified professionals/experts for screening the large at-risk population, especially in the Indian scenario. Deep learning involves learning without being explicitly told what to focus on and utilizes several layers of artificial neural networks (ANNs) to create a robust algorithm that is capable of high-complexity tasks. Convolutional neural networks (CNNs) are a subset of ANNs that are particularly useful for image processing as well as cognitive tasks. Training of these algorithms involves inputting raw human-labeled data, which are then processed through the algorithm's multiple layers and allow CNN to develop their own learning of image features. AI systems must be validated using different population datasets since the performance of the AI system would vary according to the population. Indian datasets have been used in AI-based risk model that could predict whether an infant would develop treatment-requiring retinopathy of prematurity (ROP). AI also served as an epidemiological tool by objectively showing that a higher ROP severity was in Neonatal intensive care units (NICUs) that did not have the resources to monitor and titrate oxygen. There are rising concerns about the medicolegal aspect of AI implementation as well as discussion on the possibilities of catastrophic life-threatening diseases like retinoblastoma and lipemia retinalis being missed by AI. Computer-based systems have the advantage over humans in not being susceptible to biases or fatigue. This is especially relevant in a country like India with an increased rate of ROP and a preexisting strained doctor-to-preterm child ratio. Many AI algorithms can perform in a way comparable to or exceeding human experts, and this opens possibilities for future large-scale prospective studies.

Highlighting hypertriglyceridemia with a case of lipemia retinalis

Severe hypertriglyceridemia can transiently cause the appearance of a salmon-colored fundus with creamy vessels which is known as lipemia retinalis

Unusual Presentation of Lipemia Retinalis Presented with Visual Field Defect

Introduction : Lipemia retinalis is an ocular presentation that associated to hypertriglyceridemia. Most cases are usually asymptomatic, with changes detected only from fundus examination. This case report highlights a case of lipemia retinalis with decreased peripheral visual field.
 Case Illustration : Thirty four year-old female came with complaint of blurry right eye (RE) 3 months before hospital visit, especially on inferotemporal part of her right eye. She had history of diabetes mellitus and hypertriglyceridemia. Her sister also has known history of hypertriglyceridemia. Ophthalmological examination revealed 6/6 visual acuity on both eyes, with normal anterior segment of both eyes. Fundus examination showed creamy retinal vessels on both eyes. Humphrey perimetry result showed inferotemporal visual field defect of RE. At time of visit, triglyceride level was 1440 mg/dL. Patient was prescribed fenofibrate 1x300 mg daily by Endocrinology Department. After 6 months of fenofibrate therapy, serum triglyceride level was decreasing to 185 mg/dL. Ophthalmology exam revealed a significant decrease of creamy white vessel on right eye and normal vessel of left eye. Humphrey perimetry showed decreased visual field defect
 Discussion : Hypertriglyceridemia can result from familial or secondary to systemic diseases. Creamy vessel appearance in lipemia retinalis is resulted from presence of triglyceride-laden chylomicrons in the plasma. Lipemia retinalis rarely manifests with reduced peripheral vision, which is presented in this case.
 Conclusion : Lipemia retinalis is often overlooked due to its asymptomatic nature. Prompt recognition might be live saving from life-threatening condition resulting from hypertriglyceridemia. Triglyceride- lowering drug therapy is very useful in improving peripheral field defect as presented in our case report.

Pancreatitis as a Main Consequence of APOC2-Related Hypertriglyceridemia: The Role of Nonsense and Frameshift Variants.

APOC2-related hypertriglyceridemia occurs due to biallelic variants of this gene. Here, genotype-phenotype architecture of all pathogenic APOC2 variants is investigated among heterozygous and homozygous individuals. Clinical heterogeneity of various types of the variants is also described, and pancreatitis in more than half of homozygotes carrying chain-termination variants is highlighted as well. For this study, patients were selected who had a plasma triglyceride level above 250 mg/dL. The coding and intronic regions of the APOC2 gene were amplified using the Sanger sequencing to investigate the presence of variants. The genotypes, lipid profiles, and detailed clinical features were documented for all APOC2-related patients and heterozygous individuals. Pathogenicity of the variants was predicted and categorized using available bioinformatics tools such as MutationTaster and PolyPhen-2 and ACMG criteria. MetaDome and Phyre2 were applied for structural and functional in silico analyses. 40% (12 out of 30) of APOC2 variants were chain-termination (nonsense and frameshift) variants. These types of variants were determined in 60.53% of patients. 55% of these patients showed pancreatitis followed by lipemia retinalis (29%), abdominal pain (24%), hepatosplenomegaly (24%), and xanthomas (18%). The mean age of onset was about 22 years old. In at least 50% of 38 homozygous individuals, the TG level was more than 2000 mg/dL. More than 25% of heterozygous individuals showed at least one symptom. Pancreatitis and a severe form of HTG were found in 5 and 2% of heterozygous individuals, respectively. The main clinical features of APOC2-related hypertriglyceridemia include pancreatitis, lipemia retinalis, abdominal pain, hepatosplenomegaly, and xanthomas. Nonsense and frameshift homozygous variants usually lead to a severe form of hypertriglyceridemia. Pancreatitis is one of the main consequences of these types of mutations; thus, it is important to consider this point when evaluating asymptomatic individuals. Heterozygous individuals may become symptomatic due to the role of unknown modifying agent including environmental genetic factors.

Hipertrigliceridemia grave em lactente: um caso de síndrome de quilomicronemia familiar

Familial chylomicronemia syndrome (FCS) is a rare, autosomal recessive monogenic disease, affecting 1:1,000,000000. A hallmark of the disease is the severe hypertriglyceridemia caused by either lipoprotein lipase (LPL) enzyme deficiency or one of its cofactors, compromising triglycerides (TG) metabolism. The index case is a 2 months old male infant with severe hypertriglyceridemia, level at presentation was extremely high 33280 mg/dL, hepatomegaly, steatosis and lipemia retinalis. Exchange transfusion blood was performed to reduce triglycerides to acceptable levels and to minimize the potential for acute pancreatitis and clinical signs related to hypertriglyceridemia. Sequencing of the LPL gene revealed a compound heterozygous pathogenic variants. This report highlights the importance of clinical suspicion for early diagnosis of severe hypertriglyceridemia, which is needed for prompt management and prevention of severe complications and risk of death.

Severe Lipemia Retinalis in an Infant with Autosomal Recessive Lipoprotein Lipase Deficiency

Severe Lipemia Retinalis in an Infant with Autosomal Recessive Lipoprotein Lipase Deficiency

FRI105 Getting Fam-iliar With Familial Chylomicronemia Syndrome: A Case Report

Abstract Background: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive lipid disorder of chylomicron metabolism causing severe hypertriglyceridemia that affects ∼1/1,000,000 individuals. Case Presentation: A 36-year-old male with a history of severely elevated triglyceride levels, recurrent pancreatitis, and biopsy-proven focal segmental glomerulosclerosis presented with severely elevated triglycerides. His initial acute pancreatitis episode was at 30 years old and attributed to alcohol intake. Triglyceride levels were not obtained at the time. He abstained from alcohol; however, his follow up triglyceride level was elevated (5,005 mg/dL, n=35-160 mg/dL) which normalized on an insulin infusion. He started fenofibrate and fish oil. After several additional hospital admissions for either pancreatitis or asymptomatic hypertriglyceridemia with a peak triglyceride level of 14,385 mg/dL, he committed to a low fat and vegan diet. Generic fish oil was transitioned to icosapent ethyl, and he was additionally started on niacin and atorvastatin. Even after following a strict diet and medication adherence, he continued having multiple admissions for acute pancreatitis, most recently complicated by dialysis dependent acute kidney injury in the setting of necrotizing pancreatitis. He has no known history of hypertriglyceridemia in his family. Due to persistent and severe hypertriglyceridemia despite conventional treatment, we suspected an underlying genetic cause, such as FCS. FCS should be suspected in those with recurrent pancreatitis, lipemia retinalis, and/or milky colored blood specimens. Eruptive xanthomas may also be present. Our patient did not have evidence of eruptive xanthomas on physical examination, but ophthalmology evaluation did show lipemia retinalis. The most common genetic pathologic variant in FCS is in the lipoprotein lipase-1 gene (LPL) that codes for an enzyme which assists in the lipolysis of plasma triglycerides (TG) in chylomicrons. Other common genes associated with severe hypertriglyceridemia are APOC2, APOAV, LMF-1, and GPIHBP-1. The mainstay of treatment for FCS are medications to reduce triglyceride levels and a significantly low-fat diet below 25 grams daily. Medium chain triglycerides can be utilized as they do not require enzymes to break down. Otherwise, there are currently no FDA-available therapies specifically targeted for use in those with FCS. Conclusions: This case demonstrates the unfortunate outcome of familial chylomicronemia syndrome despite concerted efforts to reduce triglyceride levels and eliminate additional risk factors. Presentation: Friday, June 16, 2023

Loss-of-Function Homozygous Variant in LPL Causes Type I Hyperlipoproteinemia and Renal Lipidosis

Lipoprotein lipase (LPL) is an important enzyme in lipid metabolism, individuals with LPL gene variants could present type I hyperlipoproteinemia, lipemia retinalis, hepatosplenomegaly, and pancreatitis. To date, there are no reports of renal lipidosis induced by type I hyperlipoproteinemia due to LPL mutation. Renal biopsy was conducted to confirm the etiological factor of nephrotic syndrome in a 44-year-old Chinese man. Lipoprotein electrophoresis, apoE genotype detection, and whole-exome sequencing were performed to confirm the dyslipidemia type and genetic factor. Analysis of the 3-dimensional protein structure and invitro functional study were conducted to verify variant pathogenicity. Renal biopsy revealed numerous CD68 positive foam cells infiltrated in the glomeruli; immunoglobulin and complement staining were negative; and electron microscopy revealed numerous lipid droplets and cholesterol clefts in the cytoplasm of foam cells. Lipoprotein electrophoresis revealed that the patient fulfilled the diagnostic criteria of type I hyperlipoproteinemia. The apoE genotype of the patient was the ε3/ε3 genotype. Whole-exome sequencing revealed an LPL (c.292G > A, p.A98T) homozygous variant with α-helix instability and reduced post-heparin LPL activity but normal lipid uptake capability compared to the wild-type variant. LPL (c.292G > A, p.A98T) is a pathogenic variant that causes renal lipidosis associated with type I hyperlipoproteinemia. This study provides adequate evidence of the causal relationship between dyslipidemia and renal lesions. However, further research is needed to better understand the pathogenetic mechanism of LPL variant-related renal lesions.

LIPEMIA RETINALIS IN METABOLIC SYNDROME

A 19-year-old female with a history of pure gonadal dysgenesis and metabolic syndrome was undergoing regular diabetic eye screening. Recent clinical examination revealed bilateral creamy-white retinal vessels, in keeping with the features of lipemia retinalis (LR). Optical coherence tomography (OCT) images also show hyperreflective deposits accumulated in the dilated retinal vessels with a shadowing effect. Further investigations showed a total serum cholesterol level of 24.2 mmol/L and an unreadable triglyceride level due to a lipemic blood sample. Her medications were increased to T. atorvastatin 40 mg at night and T. ezetimibe 10 mg once daily by her physician. Unfortunately, she developed acute pancreatitis secondary to diabetic ketoacidosis with hypertriglyceridemia 3 months after the diagnosis of LR. LR is a clinical indication of a very high triglyceride level when laboratory testing is not possible. The high comorbidities associated with hypertriglyceridemia and diabetes may warrant close monitoring for cardiovascular disease and life-threatening pancreatitis.

Accelerated Progression of Diabetic Retinopathy in a Patient with Acquired Lipodystrophy Following Hematopoietic Stem Cell Transplantation.

To report a case of bilateral proliferative diabetic retinopathy and lipemia retinalis in a patient with acquired lipodystrophy. A retrospective case report. A 23-year-old woman with a diagnosis of acquired lipodystrophy was referred for ophthalmic evaluation. She had been diagnosed with acute lymphocytic leukemia at the age of 3 years and undergone hematopoietic stem cell transplantation. Best-corrected visual acuity was 20/20 in both eyes; however, funduscopy revealed bilateral diabetic retinopathy and lipemia retinalis, neither of which was apparent 2 years earlier. She had a glycated hemoglobin level of 9.6% and a triglyceride level of 7,394 mg/dL with creamy appearance of serum. Fluorescein angiography showed bilateral neovascularization. Accelerated progression of diabetic retinopathy in the present case appeared to be associated with the onset of lipemia retinalis. We encourage continued ophthalmologic monitoring of patients who underwent hematopoietic stem cell transplantation in childhood for possible accelerated course of diabetic retinopathy.

Lipaemia retinalis: A benign retinal finding associated with a medical urgency

"Lipaemia retinalis: A benign retinal finding associated with a medical urgency." Clinical and Experimental Optometry, ahead-of-print(ahead-of-print), pp. 1–2

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.

Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon.

Familial chylomicronemia syndrome is a rare autosomal recessive disorder of lipoprotein metabolism characterized by the presence of chylomicrons in fasting plasma and an important increase in plasma triglycerides (TG) levels that can exceed 22.58 mmol/l. The disease is associated with recurrent episodes of abdominal pain and pancreatitis, eruptive cutaneous xanthomatosis, lipemia retinalis, and hepatosplenomegaly. A consanguineous Syrian family who migrated to Lebanon was referred to our laboratory after perceiving familial chylomicronemia syndrome in two children. The LPL and PCSK9 genes were sequenced and plasma PCSK9 levels were measured. Sanger sequencing of the LPL gene revealed the presence of the p.(Val227Phe) pathogenic variant in exon 5 at the homozygous state in the two affected children, and at the heterozygous state in the other recruited family members. Interestingly, PCSK9 levels in homozygous carriers of the p.(Val227Phe) were ≈50% lower than those in heterozygous carriers of the variant (p-value = 0.13) and ranged between the 5th and the 7.5th percentile of PCSK9 levels in a sample of Lebanese children of approximately the same age group. Moreover, this is the first reported case of individuals carrying simultaneously an LPL pathogenic variant and PCSK9 variants, the L10 and L11 leucine insertion, which can lower and raise low-density lipoprotein cholesterol (LDL-C) levels respectively. TG levels fluctuated concomitantly between the two children, were especially high following the migration from a country to another, and were reduced under a low-fat diet. This case is crucial to raise public awareness on the risks of consanguineous marriages to decrease the emergence of inherited autosomal recessive diseases. It also highlights the importance of the early diagnosis and management of these diseases to prevent serious complications, such as recurrent pancreatitis in the case of familial hyperchylomicronemia.

A novel missense variant in CREB3L3 gene associated with severe hypertriglyceridemia

Background and Aims : Severe hypertriglyceridemia (HTG) is a rare disease consisting in increased plasma triglyceride (TG) levels (>10 mmol/L). Patients can show eruptive xanthomas, lipaemia retinalis, hepatosplenomegaly and pancreatitis. For long time five genes were considered causative of the disease with autosomal recessive inheritance: Lipoprotein lipase (LPL), Apolipoprotein A-V (APOA5), Apolipoprotein C-II (APOC2), Glycosyl-phosphatidyl-inositol-anchored HDL-binding protein (GPIHBP1) and Lipase maturation factor-1 (LMF1).

Alterations in ocular microcirculation and oxygen metabolism in patients with lipemia retinalis

PurposeThe study aims to assess the alterations in retinal oxygen saturation and retinal and choroidal blood flow in lipemia retinalis.MethodsThis was a cross-sectional study on 10 eyes (5 patients) with history of lipemia retinalis. The study comprised 10 eyes with documented history of lipemia retinalis and 10 participants as healthy controls. Patients with a confirmed history of lipemia retinalis were grouped into two cohorts based on their most recent fundus examination: untreated lipemia retinalis (abnormal fundus) and resolved lipemia retinalis (normal fundus). Both retinal arteriolar and venular oxygen saturation were measured using the non-invasive spectrophotometric retinal oximeter (Oxymap T1). The mean blur rate (MBR) of the optic nerve and choroidal blood flow were analyzed using a laser speckle flowgraph (LSFG).ResultsPatients with untreated lipemia retinalis had a significantly higher retinal arteriolar and venular oxygen saturation than that of the other two groups (p < 0.001). Moreover, patients with untreated lipemia retinalis had significantly smaller retinal arteriolar and venular diameters (p < 0.001). On LSFG, there was a significant difference in the overall MBR (p = 0.007) and vessel MBR of the optic nerve between the groups (p = 0.011). The patients with history of lipemia retinalis (untreated and resolved) exhibited a high overall MBR and vessel MBR of the optic nerve than that of the control group. There was a significant elevation of the optic nerve (p = 0.002) and choroidal blowout score (p < 0.001), while the resistivity index of the optic nerve (p = 0.001) and choroids (p = 0.002) was significantly lower in patients with resolved and untreated lipemia retinalis.ConclusionsThere was a significant alteration in retinal oximetry, in untreated lipemia retinalis, and in retinal blood flow, in both the resolved and untreated groups. The increase in retinal blood flow and oxygen saturation may elucidate the preservation of visual acuity and function despite the fundus changes observed in lipemia retinalis.

Lipaemia retinalis – A case report on a life-saving timely ocular diagnosis

No abstract available