Vitamin C (ascorbic acid) is a water-soluble vitamin essential for collagen production and antioxidant activity. Humans cannot synthesize vitamin C in the body and rely entirely on dietary intake. Severe deficiency causes scurvy, which rarely involves ocular symptoms.
Records of scurvy date back to ancient times, first described in the Ebers Papyrus of ancient Egypt (circa 1550 BC). During the Age of Exploration (15th–18th centuries), it afflicted sailors on long voyages, and in 1753, British naval surgeon James Lind discovered the therapeutic effect of citrus fruits.
Epidemiology: The estimated prevalence of vitamin C deficiency in the United States is 5.9% 1). Although rare in developed countries, it occurs sporadically in populations with poor diet or malnutrition. In recent years, reports of scurvy due to picky eating in children with developmental disorders or autism spectrum disorder have increased 2).
Overview of ocular symptoms:
Frequency: Extremely rare, and usually appears alongside systemic symptoms.
Main ocular findings: Subconjunctival hemorrhage, retinal hemorrhage, eyelid hemorrhage, orbital subperiosteal hemorrhage in children
Effects on ocular surface: Dry keratoconjunctivitis (dry eye), keratitis
Prognosis: Ocular symptoms generally improve with appropriate supplementation
Vitamin C (ascorbic acid) is involved in collagen metabolism. Deficiency leads to scurvy (bleeding tendency), and ophthalmologically, it causes bleeding in the eyelids, conjunctiva, orbit, and retina.
QAre ocular symptoms common with vitamin C deficiency?
A
Ocular symptoms are extremely rare and usually appear after systemic symptoms such as skin bleeding, gingival bleeding, and joint pain. There is no typical vision loss in scurvy, but severe deficiency can cause retinal hemorrhage, dry eye, and orbital subperiosteal hemorrhage (in children).
Early systemic symptoms often include fatigue, malaise, and mood changes.
Ocular subjective symptoms:
Dry eye symptoms: Severe bilateral irritation and dryness resistant to artificial tears
Vision loss: Scurvy itself usually does not cause vision loss. However, vitamin C deficiency may be accompanied by other vitamin deficiencies (B12, B9), which can lead to vision loss and visual field defects due to nutritional optic neuropathy
Characteristic ocular findings differ between adults and children.
Ocular Findings in Adults
Subconjunctival hemorrhage: The most common ocular finding. Presents as bright red to dark red hemorrhagic patches under the bulbar conjunctiva.
Retinal hemorrhage: May be accompanied by exudates and soft white spots (cotton-wool spots). Can resemble diabetic retinopathy in appearance.
Eyelid hemorrhage: Subcutaneous bleeding (ecchymosis) of the eyelids.
Iris hemorrhage: Occurs rarely.
Keratoconjunctivitis sicca: Caused by an inflammatory cycle due to ROS accumulation from reduced antioxidant function, damage to the tear lipid layer, and goblet cell dysfunction.
Pediatric Ocular Findings
Orbital subperiosteal hemorrhage: Usually occurs in the superior orbit. Presents as eyelid ecchymosis and proptosis.
Characteristics of proptosis: It is firm, non-pulsatile, and occurs spontaneously without a history of trauma.
Keratitis: Results from impaired corneal wound healing. The corneal epithelium and lens contain high concentrations of vitamin C, making them susceptible to deficiency.
QCan retinal hemorrhage due to scurvy be mistaken for diabetic retinopathy?
A
Scurvy retinopathy can present with exudates and cotton-wool spots, resembling diabetic retinopathy. When findings similar to diabetic retinopathy are observed in a malnourished patient, it is important to include scurvy in the differential diagnosis.
The most common cause is insufficient intake of fruits and vegetables. Foods rich in vitamin C include citrus fruits such as oranges, tomatoes, Brussels sprouts, broccoli, and strawberries.
Main risk factors:
Pick eating: especially selective eating associated with autism spectrum disorder and developmental disabilities2)
Smoking: Increases vitamin C consumption due to increased oxidative stress1)
Alcoholism: Overlap of malabsorption and inadequate intake 1)
Social isolation, institutionalization, mental illness, tooth loss: Lead to poor dietary habits 1)
Food insecurity, malnutrition: Living in low- and middle-income countries
Aging, obesity, chronic diseases: Increased demand or decreased absorption of vitamin C
Genetic differences in vitamin C transporters: A factor in individual variation
QCan vitamin C deficiency occur in a normal diet?
A
Even in developed countries, vitamin C deficiency can occur in situations such as unbalanced diet, alcoholism, social isolation, and selective eating associated with autism spectrum disorder. The estimated prevalence in the United States is 5.9%1), making it by no means a rare condition.
The criteria for plasma vitamin C concentration are shown below.
Plasma vitamin C concentration
Assessment
<11 μmol/L
Deficiency
11–28 μmol/L
Depletion
>28 μmol/L
Normal
Note: Plasma vitamin C concentration reflects only short-term intake and is highly variable. Even with normal values, tissue-level deficiency may exist.
The basic approach is to increase intake of fruits and vegetables containing vitamin C. The recommended intake is 100–200 mg per day, and smokers require a higher amount.
General administration: Vitamin C 100 mg four times daily (400 mg/day) for 10–14 days, then switch to a maintenance dose of 60 mg/day
Alternative method: 300 mg/day in divided doses for at least one month. The bioavailability of 180 mg is about 90%, but it drops below 50% for doses exceeding 1 g1)
Treatment for children2):
Oral administration of ascorbic acid 100–300 mg/day
Oral administration is sufficient even in severe cases; intravenous administration is only indicated when absorption is suspected to be impaired
When dry eye is present: Use dry eye treatment eye drops.
Management of vascular fragility: Oral carbazochrome sodium sulfonate (Adona®) is an option.
Prognosis: Symptoms generally improve with appropriate supplementation. Spontaneous bleeding improves within days to weeks, and subperiosteal orbital hemorrhage, retinal hemorrhage, and dry eye in children resolve after supplementation. In case reports, improvement in walking is often seen within a few days of starting vitamin C, with complete recovery in 1–2 months2).
QIs taking high-dose vitamin C supplements good for eye health?
A
High intake of 2 g or more per day is not recommended because renal excretion increases. Use of vitamin C eye drops is similarly not recommended. It is recommended to take an appropriate amount (100–200 mg per day) of vitamin C through diet or supplements.
Vitamin C is involved in the post-translational modification of collagen through hydroxylation of proline and lysine residues. This process enables proper intracellular folding. Deficiency leads to insufficient type IV collagen, resulting in weakened blood vessel walls.
Type IV collagen deficiency → weakened blood vessel walls → increased capillary permeability → subconjunctival hemorrhage and retinal hemorrhage. The same mechanism occurs in the skin (perifollicular hemorrhage, gingival bleeding).
Vitamin C deficiency → weakening of bone osteoid → subperiosteal hemorrhage (common in long bones). In children, it also occurs in the orbit, presenting as proptosis.
Vitamin C functions as an important antioxidant. Deficiency → accumulation of ROS (reactive oxygen species) → induction of inflammation → damage to the tear lipid layer → dysfunction of goblet cells → establishment of an inflammatory cycle → dry keratoconjunctivitis.
The corneal epithelium and lens contain particularly high concentrations of vitamin C. Vitamin C is also present in tears and contributes to antioxidant defense 3). Deficiency impairs corneal wound healing and leads to keratitis.
Vitamin C deficiency can lead to decreased endothelial NO production and HIF-1 accumulation, potentially causing pulmonary vasoconstriction and pulmonary arterial hypertension. In a systematic review by Hemilä & de Man (2024), the median mPAP in 32 cases during deficiency was 48 mmHg, which decreased to 20 mmHg after vitamin C administration4).
7. Latest Research and Future Perspectives (Research-stage Reports)
In a study of 50 diabetic patients, administration of vitamin C 1000 mg/day plus vitamin E 400 IU/day for 10 days improved tear production, stability, and goblet cell density. NO concentration in tear wash fluid significantly decreased, indicating reduced oxidative stress on the ocular surface3).
In recent years, scurvy associated with picky eating in children with developmental disorders and autism has been reported with atypical symptoms such as anemia, elevated inflammatory markers, and pulmonary hypertension, in addition to conventional musculoskeletal symptoms2). Diagnosis is often delayed in these atypical cases, requiring caution.
Pope M, Elder J. Scurvy: An elusive diagnosis. Clinical case reports. 2023;11(6):e7418. doi:10.1002/ccr3.7418. PMID:37255614; PMCID:PMC10225610.
Toscano F, Zirilli G, Foti Randazzese S, et al. Scurvy, all the faces you can see: our experience and review of the literature. Ital J Pediatr. 2025;51:159.
Markoulli M, Ahmad S, Arcot J, Arita R, Benitez-Del-Castillo J, Caffery B, et al. TFOS Lifestyle: Impact of nutrition on the ocular surface. The ocular surface. 2023;29:226-271. doi:10.1016/j.jtos.2023.04.003. PMID:37100346.
Hemilä H, de Man AME. Vitamin C deficiency can lead to pulmonary hypertension: a systematic review of case reports. BMC pulmonary medicine. 2024;24(1):140. doi:10.1186/s12890-024-02941-x. PMID:38504249; PMCID:PMC10949735.
Jones L, Craig JP, Markoulli M, Karpecki P, Akpek EK, Basu S, Bitton E, Chen W, et al. TFOS DEWS III: Management and Therapy. American journal of ophthalmology. 2025;279:289-386. doi:10.1016/j.ajo.2025.05.039. PMID:40467022.
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