Ocular Manifestations of Vitamin C Deficiency
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Disease Entity
Disease
Vitamin C, or ascorbic acid, is an essential vitamin necessary for collagen production and antioxidant properties. Deficiency of vitamin C results in scurvy, which may present with bruising, poor wound healing, and swollen gums. Ocular manifestations are exceedingly rare and often accompany systemic symptoms, but may present with keratoconjunctivis sicca, keratitis, subconjunctival hemorrhages, and retinal hemorrhages.[1] Additionally, orbital hemorrhage may occur in children.[2]
Etiology
Vitamin C deficiency is most often caused by decreased nutritional intake of fruits and vegetables, which is more common in low- and middle-income countries.[3][4] Various environmental factors may impact diet. Some risk factors, such as pollution, chronic disease, and smoking are related to increased oxidative stress.[3] Foods such as oranges and other citrus fruits, tomatoes, brussels sprouts, broccoli, and strawberries contain vitamin C.
Risk Factors
- Selective diet
- Food insecurity and malnutrition
- Prevalence of vitamin deficient staple foods
- Traditional cooking practices, which may remove nutritional value
- Pollution
- Age
- Obesity
- Smoking
- Chronic disease
- Alcoholism
- Genetic differences in vitamin C transporter[3][4]
Pathophysiology
Vitamin C is implicated in the post-translational modification of collagen through the hydroxylation of proline and lysine residues, allowing for proper intracellular folding.[5] Clinical manifestations, such as perifollicular hemorrhage and gingival bleeding, are related to deficiencies of type IV collagen in blood vessel walls and skin. Vitamin C’s role in collagen basement membrane formation and blood vessels is the mechanism for hemorrhage in many organs.[5] Bleeding due to scurvy may also occur in the eye, presenting as subconjunctival hemorrhages and retinal hemorrhages.[5] Vitamin C deficiency leads to weakening of osteoid in bone, leading to subperiosteal hemorrhage as a manifestation of scurvy, more often in long bones.[5] In children, reports have demonstrated that subperiosteal hemorrhages in the orbit are possible.[6]
The cornea epithelium and lens have particularly high levels of vitamin C.[5] Scurvy may impair proper corneal wound healing, which may lead to keratitis.
Vitamin C is also an important antioxidant, and its deficiency leads to damage by reactive oxygen species (ROS). Unopposed ROS causes inflammation, damaging the tear lipid layer and causing goblet cell dysfunction. The result is a cycle of inflammation contributing to keratoconjunctivitis sicca.[7]
Diagnosis
Symptoms
Initial symptoms of vitamin C deficiency are fatigue, lethargy, and mood changes.[4] Patients may present with severe, bilateral, dry, irritated eyes that are resistant to regimens of artificial tears.[1] There are no visual defects classically associated with scurvy but deficiencies in one vitamin may also be associated with other vitamin deficiencies that can produce optic neuropathy (e.g., B12 or B9 nutritional optic neuropathy).
Clinical Signs
Ocular signs of scurvy may involve hemorrhage of the eyelids, conjunctiva, orbit, iris, and retina.[5] Subperiosteal orbital hemorrhages more common in children and are typically superior, presenting as eyelid ecchymosis and proptosis.[6] Proptosis is often described as firm, non-pulsatile, and occurring spontaneously without a history of trauma.[5] In adults, subconjunctival hemorrhage is the most common finding, although retinal hemorrhages are possible. Retinopathy of scurvy may appear similarly to diabetic retinopathy, with exudates and cotton wool spots.[8]
Work-up
Vitamin C levels may be measured from the plasma, although this reflects only the short-term intake of vitamin C. Patients are considered deficient with serum levels below 11 μmol/L, depleted between 11-28 μmol/L, and normal above 28 μmol/L.[9] Laboratory values may indicate normal prothrombin time with an increased partial thromboplastin time, as well as an increased bleeding time.
Due to the varying plasma levels of vitamin C, rapid clinical recovery after empiric vitamin C treatment may indicate deficiency. Patients who present with malnutrition should also be considered for other nutritional and vitamin deficiencies.
Management
Patients are encouraged to increase dietary sources of vitamin C. The current recommended intake is 100-200mg/day, with an increased requirement in smokers.[4] Multivitamin supplementation and smoking cessation have also been shown to increase vitamin C levels. There is no indication for large doses of vitamin C supplementation for eye health (above 2g per day) or the use of vitamin C eyedrops due to increased renal excretion.[5] In severe cases, treatment with oral vitamin C 100mg four times a day for 10 to 14 days, followed by a maintenance dose of 60mg per day until the normal recommended intake is resumed.[6] Lifestyle modifications and smoking cessation are important considerations for treatment.
Prognosis
Although symptoms vary, patients generally improve with adequate supplementation. Spontaneous bleeding may improve over days to weeks[10], and instances of pediatric orbital subperiosteal hemorrhage, retinal hemorrhage, as well as dryness have been demonstrated to resolve after repletion.[1][6][9]
Summary
In summary, Vitamin C is essential for collagen production and may rarely cause ocular symptoms in severe deficiencies. Ocular manifestations primarily include hemorrhage of the conjunctiva and retina, subperiosteal hemorrhage of the orbit in children, and severe keratoconjunctivis sicca. Management includes oral repletion and dietary changes, with good prognosis. Concomitant deficiencies in other vitamins should also be considered especially when optic neuropathy is present.
Additional Resources
References
- ↑ 1.0 1.1 1.2 Hood J, Burns CA, Hodges RE. Sjögren’s Syndrome in Scurvy. New England Journal of Medicine. 1970;282(20):1120-1124. doi:10.1056/nejm197005142822003
- ↑ Kullman, G. (2007). Nutritional deficiencies. Glaucoma Today. https://glaucomatoday.com/articles/2007-sept-oct/GT0907_06-php.
- ↑ 3.0 3.1 3.2 Carr, A. C., & Rowe, S. (2020). Factors affecting vitamin c status and prevalence of deficiency: A global health perspective. Nutrients, 12(7), 1963. https://doi.org/10.3390/nu12071963
- ↑ 4.0 4.1 4.2 4.3 Rowe, S., & Carr, A. C. (2020). Global Vitamin C Status and Prevalence of Deficiency: A Cause for Concern?. Nutrients, 12(7), 2008. https://doi.org/10.3390/nu12072008
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 Semba, R. D. (2010). Handbook of nutrition and ophthalmology. Humana.
- ↑ 6.0 6.1 6.2 6.3 S., D., Dixit, R., Khullar, T., & Rajeshwari, K. (2021). Bilateral proptosis: An unusual primary presentation of scurvy—a case report. Egyptian Journal of Radiology and Nuclear Medicine, 52(1). https://doi.org/10.1186/s43055-021-00553-7
- ↑ Seen, S., & Tong, L. (2017). Dry eye disease and oxidative stress. Acta Ophthalmologica, 96(4). https://doi.org/10.1111/aos.13526
- ↑ Bloxham CA, Clough C, Beevers DG. Retinal infarcts and haemorrhages due to scurvy. Postgrad Med J. 1990 Aug;66(778):687. doi: 10.1136/pgmj.66.778.687. PMID: 2217046; PMCID: PMC2429663.
- ↑ 9.0 9.1 Hampl, J. S., Taylor, C. A., & Johnston, C. S. (2004). Vitamin C deficiency and depletion in the United States: the Third National Health and Nutrition Examination Survey, 1988 to 1994. American journal of public health, 94(5), 870–875. https://doi.org/10.2105/ajph.94.5.870
- ↑ Maxfield L, Crane JS. Vitamin C Deficiency. [Updated 2021 Jul 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493187/
