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Abstract
A man in his 60s presented for his medical retina clinic appointment, reporting increasing shortness of breath, aches and pains, and increasing insulin requirements during a difficult early lockdown. Wide-field colour fundus imaging (Optos Optomap) and an optical coherence tomography scan (Heidelberg Spectralis) revealed whitened and enlarged hyper-reflective vessels. Retinal colour photography also confirmed a creamy white discolouration of the vessels, which prompted the team to order a lipid profile. The profile showed a raised cholesterol level of 17.5 mmol/L (normal: <4mmol/L) and a marked elevated triglyceride level of 38.41 mmol/L (normal: <1.7 mmol/L).
The clinical picture, alongside the biochemical results, suggested a diagnosis of secondary lipaemia retinalis due to poorly controlled diabetes. With aggressive treatment, the patient’s biochemistry and vessels returned to baseline.
This rare condition should be taken as an indicator of a potential underlying life-threatening medical condition and the role an ophthalmologist has in initiating potential lifesaving intervention.
- Retina
- Diabetes
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Background
Lipaemia retinalis (LR) is a retinal manifestation of severe hypertriglyceridaemia but can be a sign of poorly controlled diabetes requiring urgent intervention, as in this case. Hypertriglyceridaemia is also a risk factor for severe complications, such as coronary artery disease and acute pancreatitis.1 2 Due to the asymptomatic presentation of LR, it can easily go undiagnosed, thus missing an opportunity to rectify vascular risk factors and prevent life-threatening complications.
Although an extremely rare disease, rates of LR can be expected to increase due to rising levels of obesity, which is projected to affect 51% of the population by 2030.3 The COVID-19 pandemic has also resulted in many people with diabetes not being able to control their glucose appropriately because of reduced activity, cancelled appointments, reluctance to attend hospital appointments, and, in some cases, inability to access medication. The ophthalmologist has the opportunity to diagnose asymptomatic LR, which requires urgent investigation, treatment and medical care.
Case presentation
A man in his 60s presented to the medical retina outpatient department for his regular diabetic eye disease review. He had a medical history of type 2 diabetes mellitus, hypertension, chronic kidney disease and a coronary artery bypass graft.
With regard to his eye health, he had been previously treated for proliferative diabetic retinopathy with panretinal photocoagulation laser treatment to both eyes. He had also received treatment for diabetic macular oedema with intravitreal aflibercept injections over a period of 3 years, particularly to the left eye. His visual acuity on presentation was 6/12 in his right eye and 6/24 in his left eye.
Since his previous appointment, the patient had developed shortness of breath, aches and pains, increasing insulin requirements and fatigue, which had led to a diagnosis of anaemia. He was also not coping well with the lockdown as he was finding it difficult to exercise, and his diet had deteriorated.
He did not report any noticeable change in his vision; however, slit-lamp examination revealed diffuse creamy white discolouration of the retinal vessels in both eyes (see figure 1).
Dilated wide-field colour fundus imaging (Optos Optomap) showing creamy white discolouration of the retinal vessels surrounded by panretinal photocoagulation laser scars in both eyes.
Investigations
Wide-field colour fundus imaging (Optos Optomap) and optical coherence tomography (OCT) scans (Heidelberg Spectralis) were performed on both eyes. These revealed abnormal white vessels and enlarged hyper-reflective lumen on the B scan (Heidelberg Spectralis) as opposed to the usual hyporeflective lumen (see figures 2 and 3).
Optical coherence tomography near-infrared images (Heidelberg Spectralis) of the left (A, C and E) and right (B, D and F) eyes showing the vascular changes in their hyporeflective and hyper-reflective state during the course of the lipaemia retinalis episode before and after treatment. (A, E) and (B, F) show the darker, hyporeflective appearance of the retinal vessels 1 month before presentation and 1 month after treatment, respectively. (B and D) show the pathological, white, hyper-reflective appearance of the retinal vessels at presentation in January 2022.
(A) Arrows indicating physiological hyporeflective retinal vessels on B scan (Heidelberg Spectralis) prior to developing lipaemia retinalis (LR). (B) Arrows indicating pathological hyper-reflective retinal vessels on B scan (Heidelberg Spectralis) when presenting with LR.
In the clinic, capillary blood glucose was elevated to levels of 19.3 mmol/L (normal: <7.8 mmol/L). The patient’s last HbA1c was 10% (normal: <6%). A lipid profile was subsequently requested for the patient. The sample of blood had a turbid appearance with a layer of white lipid in the standing tube. The results revealed a cholesterol level of 17.5 mmol/L (normal: <4 mmol/L) and a markedly triglyceride level of 38.41 mmol/L (normal: <1.7 mmol/L).
Additionally, his blood samples showed a raised creatinine level of 275 µmol/L (normal: 59–104 µmol/L) due to chronic kidney disease and a reduced glomerular filtration rate of 20 mL/min/1.73 m2 (normal: >60 mL/min/1.73 m2).
Genetic diagnostic testing for familial hypercholesterolaemia was also carried out using next-generation DNA sequencing for LDLR, PCSK9, APOB, APOE and LDLRAP1, but none of these genes were detected.
Differential diagnosis
The hyper-reflective material seen on the OCT B scan (Heidelberg Spectralis) and the opaque white appearance of the sample were due to triglyceride-laden chylomicrons in the plasma. These clinical findings, along with the raised triglyceride levels on the biochemical results and creamy white discolouration of the vessels on dilated funduscopy, prompted a working diagnosis of LR.
Differential diagnoses for LR may include:
Leukaemia, which usually presents with Roth spots, intraretinal haemorrhages and cotton wool spots rather than whitening of the vessels themselves.
Advanced diabetic eye disease with sclerotic vessels, which were not present.
Retinal branch artery/vein occlusion: usually only in one quadrant and only in chronic cases.
Hypertensive retinopathy: usually associated with flame-shaped haemorrhages and increased tortuosity of vessels, which were not apparent in this case.
In LR, arteries and veins both appear as the same white colour and can only be differentiated by calibre.4
Treatment
The medical team accepted the patient and initiated aggressive treatment for LR for 7 days. The treatment plan involved strict diabetes control, which included insulin therapy and a low-fat diet. The patient’s fat intake was limited to 10% of his total calories and his diet consisted of two slices of bread per portion, baked fish, plain vegetables and skimmed milk.
Outcome and follow-up
In the succeeding months, the patient’s systemic symptoms subsided, his HbA1c decreased from 10% to 8.5%, and follow-up on imaging and scans showed his blood vessels returned to their baseline appearance (see figure 2C).
Despite successful treatment and efforts to improve the patient’s lifestyle, he died 9 months later due to his ischaemic heart disease. The ophthalmology team had last seen him 2 months previously, where his visual acuity was stable at 6/12 in his left eye and 6/36 in his right eye. He had been seen by a healthcare professional 1 month prior to his death in the diabetic clinic with a very raised blood pressure of 211/101 for which he was receiving treatment.
Discussion
Most literature published on LR is centred on familial causes of the disease. Familial causes include the presence of endogenous circulating lipoprotein lipase inhibitor, deficiency of lipoprotein lipase and a deficiency of apoprotein of lipoprotein lipase.5 A similar case was reported by Markan and Singh in 2021, in which a patient in their 40s developed familial LR due to acquired generalised dystrophy.6 Fundus examination of the patient showed a salmon-coloured fundus in addition to whitening of the retinal arteries. A salmon-coloured fundus is a sign of the most severe stage of LR, as described by Vinger and Sachs.7 Vinger and Sachs stage LR from grades I to III, with grade I representing early LR, grade II moderate LR and grade III marked LR. Our patient had creamy-coloured vessels extending towards the optic disc, which would be staged as grade III. Markan and Singh treated the patient’s hypertriglyceridaemia similarly resulting in a complete resolution of the disease.
LR can also be secondary to a host of causes including uncontrolled type 1 or type 2 diabetes mellitus, as was the cause for our patient, endocrine disorders such as metabolic syndrome, hypothyroidism and hypercortisolism, medications and pregnancy. Unlike Vinger and Sachs’ patient, our patient developed secondary LR due to his uncontrolled diabetes, as an insulin deficiency reduces the breakdown of triglycerides.
The detailed pathogenesis is described in Klaus Johansen’s clinical review of hyperlipidaemia in diabetes mellitus.8 In the normal pathway, lipoprotein lipase is responsible for converting triglycerides from the intestines into fatty acids and monoglycerides in the capillaries of the adipose tissue and skeletal muscle. These products are then transported into the fat and muscle tissue, where they are oxidised and esterified back into triglycerides for storage. The activity of the lipoprotein lipase, the enzyme responsible for the initial breakdown of the triglycerides into fatty acids and monoglycerides, is dependent on insulin levels. In a patient with diabetes with insulin deficiency, the activity of lipoprotein lipase will be decreased resulting in a reduction in the breakdown of triglycerides in the capillaries, leading to their accumulation.
Learning points
The identification of lipaemia retinalis on funduscopy serves as an indication of a potentially grave underlying medical pathology.
Lipaemia retinalis can present asymptomatically as it does not always affect visual acuity significantly.
Although rare, recognition of the association between lipaemia retinalis and diabetes can result in the ophthalmologist initiating lifesaving intervention.
Direct visualisation of the retinal vessels provides a diagnostic and monitoring indicator for not only diabetic eye disease but also hypertension, hypertriglyceridaemia and atherosclerosis.
Ethics statements
Patient consent for publication
Footnotes
Contributors The following authors were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams and algorithms, and critical revision for important intellectual content—GMM, CVS and SM. The following authors gave final approval of the manuscript—GMM, CVS and SM.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.