A 60-year-old male presented with a past medical history of hypertension, myocardial infarction status post-coronary artery bypass graft and abdominal aortic aneurysm status post repair. He was pseudophakic in both eyes and had recurrent cystoid macular edema in the right eye.
The patient was followed by an outside ophthalmologist for 5 months due to complaints of difficulty seeing in dim conditions, especially while driving at night. His BCVA was 20/20 in both eyes, and his ocular exam was significant only for dry eyes. Visual field testing showed generalized depression in both eyes. He was referred to the neuro-ophthalmology clinic for evaluation of acquired night blindness of unclear etiology.
THE OCULAR EXAM
During his evaluation, the patient stated his vision was normal in well-lit conditions; however, he had started carrying a flashlight with him to see in dim environments. Upon further questioning, he revealed that his abdominal aortic aneurysm repair had been complicated by iatrogenic bowel injury, which necessitated removal of a significant portion of his small bowel.
The ocular exam was as follows:
- BCVA: 20/20 OD, 20/20-2 OS
- Pupils: equal, round, briskly reactive without relative afferent pupillary defect
- IOP: 15 OD, 17 OS
Slit lamp exam was significant for bilateral posterior chamber IOLs, diffuse superficial punctate keratitis and very rapid tear break-up time. The anterior chambers were deep and quiet. The posterior segment exam was normal, with sharp, pink optic nerves and no retinal changes in the macula or periphery. The physical exam was significant for significant dryness and pallor of the skin.
Given the patient’s prior bowel resection, dry skin, dry eyes and difficulty seeing in dim conditions, we were concerned vitamin deficiency secondary to an underlying malabsorption syndrome was at work. He was sent for bloodwork, specifically to measure his levels of fat-soluble vitamins (Table).
TEST | RESULT | NORMAL RANGE |
Hemoglobin | 8.4 | 14.0-18.0 g/dL |
Hematocrit | 27.5 | 42.0-52.0% |
Vitamin B12 | 403 | 239-931 pg/mL |
Folate | 12 | 3-20 ng/mL |
Vitamin A | <13 | 38-106 ug/dL |
Vitamin D | 13.8 | 30-100 ng/mL |
Vitamin E | <459 | 500-1800 ug/dL |
Vitamin K | 0.12 | 0.22-4.88 nmol/L |
Given his severe deficiencies of all fat-soluble vitamins, we diagnosed this patient with malabsorption due to his prior small bowel resection and xerophthalmia secondary to severe vitamin A deficiency (VAD). The patient was subsequently started on 200,000 units of vitamin A per day and referred to his primary care physician for further management of his vitamin deficiencies, including vitamins D, E and K.
VITAMIN A DEFICIENCY
Vitamin A is an essential, fat-soluble nutrient that humans must acquire through diet.1 The main sources of vitamin A include animal-derived products, leafy greens and yellow or orange vegetables. Once ingested, vitamin A is absorbed in the small intestine and stored mainly in the liver. VAD is most prevalent in developing countries where access to vitamin A-rich foods is limited.2 Deficiency can also result from disruption of the body’s ability to absorb, transport or store vitamin A, including gastric bypass, small bowel resection or chronic liver disease.
Vitamin A is required for normal immune function and cellular differentiation. VAD is associated with increased rates of infectious diseases, including measles and diarrheal illnesses.3 Animal studies demonstrated the importance of vitamin A in normal skin differentiation, as rats deprived of this nutrient developed keratinization of their mucus membranes.4
As it relates to our patients, vitamin A is instrumental in vision. In fact, VAD is the leading cause of preventable childhood blindness.2 Vitamin A is one of the building blocks of the light-sensitive protein rhodopsin, which is necessary for normal vision in dim-light conditions. As such, VAD is associated with nyctalopia, or the inability to see well in dark environments.5
Other ocular findings associated with VAD include corneal or conjunctival dryness or xerosis.6 Bitot spots are triangular, foamy patches of keratinized epithelial cells admixed with gas-producing Corynebacterium xerosis. Bitot spots are most often found in the temporal bulbar conjunctiva and are nearly pathognomonic for VAD. More severe corneal dryness can ultimately result in corneal ulceration and melting — a condition termed keratomalacia. Dilated examination will sometimes reveal yellow or white retinal flecks in the peripheral retina.7
WHEN VAD WALKS INTO YOUR CLINIC
Patients suspected of having VAD should undergo a complete ocular and comprehensive exam. Laboratory studies should include serum levels of vitamin A, retinol binding protein, zinc and the other fat-soluble vitamins (D, E and K). Patients presenting with symptoms of nyctalopia may undergo dark adaptometry testing or electroretinography to measure scotopic responses.
Patients diagnosed with VAD are treated with high-dose vitamin A supplementation.8 In the case of adults with ocular manifestations of VAD, 200,000 IU of vitamin A should be given immediately upon diagnosis, followed by additional doses one and 14 days later. As corneal healing will follow vitamin A supplementation by several days, patients should be started on aggressive lubrication, topical retinoid acid and monitored closely for signs of corneal decompensation or perforation.9 Patients who have undergone gastric bypass, bowel resection or who have chronic conditions leading to the malabsorption of fat-soluble vitamins should be started on daily vitamin A supplements. OM
REFERENCES
- Lee WB, Hamilton SM, Harris JP, Schwab IR. Ocular complications of hypovitaminosis a after bariatric surgery. Ophthalmology. 2005;112:1031-1034.
- World Health Organization. 2009. Global prevalence of vitamin A deficiency in populations at risk 1995-2005: WHO global database on vitamin A deficiency. World Health Organization. https://apps.who.int/iris/handle/10665/44110 . Accessed March 2, 2023.
- Imdad A, Mayo-Wilson E, Haykal MR, et al. Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age. Cochrane Database Syst Rev. 2022 Mar. 16;3:CD008524.
- Wolbach SB, Howe PR. Tissue Changes following deprivation of fat-soluble A vitamin. J Exp Med. 1925;42:753-777.
- Saari JC. Vitamin a metabolism in rod and cone visual cycles. Annu Rev Nutr. 2012;32:125-145.
- McLaren DS, Kraemer K, eds. Xerophthalmia. World Rev Nutr and Diet. 2012;103:65-75.
- Genead MA, Fishman GA, Lindeman M. Fundus white spots and acquired night blindness due to vitamin A deficiency. Doc Ophthalmol. 2009;119:229-233.
- World Health Organization, UNICEF, International Vitamin A Consultative Group Task Force, eds. Vitamin A Supplements: A Guide to Their Use in the Treatment and Prevention of Vitamin A Deficiency and Xerophthalmia. 2nd ed. World Health Organization; 1997.
- Smith J, Steinemann TL. Vitamin A deficiency and the eye: International Ophthalmology Clinics. 2000;40:83-91.