Reversible Nyctalopia and Bilateral Optic Neuropathy due to Combined Vitamin A, Zinc, and Copper Deficiency: A Case Report

Abstract

Introduction

Combined nutritional deficiency is an uncommon cause of vision loss in the USA. Notably, vitamin A deficiency can produce nyctalopia but rarely causes bilateral central vision loss. The combination of these symptoms is unusual, although likely underreported.

Case Presentation

We report an exceptionally rare case of bilateral central vision loss and nyctalopia caused by combined vitamin A, zinc, and copper deficiency, likely following bariatric surgery and alcohol use. Following mineral and vitamin supplementation, the patient’s vision improved significantly and returned to baseline within 1 month. Vision loss resulting from this specific multicombination of vitamin and mineral deficiency has never been reported previously in the English-language ophthalmic literature.

Conclusion

Given rising rates of bariatric surgery and alcohol use in the USA and abroad, clinicians should be aware that the combination of progressive nyctalopia and bilateral central vision loss may be produced by combined nutritional deficiency. Screening and supplementation of both vitamin and mineral deficiency may result in dramatic reversal of visual loss in such cases.

Introduction

Combined nutritional deficiency is an uncommon cause of vision loss in the USA. Although vitamin A deficiency can cause nyctalopia (often with initially normal visual acuity), it rarely produces bilateral central loss of acuity and visual field. The clinical combination of these symptoms is unusual and may suggest multiple coexisting causes of vision loss. We report a case of bilateral central vision loss and nyctalopia caused by combined vitamin A, zinc, and copper deficiency after bariatric surgery. Based on our review of the English language ophthalmic literature, we believe our case is novel. The CARE checklist has been completed by the authors for this case report and is attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000537830).

Case Presentation

A 32-year-old man presented with 2-month history of painless, progressive, bilateral, central vision loss worse at night (nyctalopia). Past medical history was significant for end-stage alcohol-related liver disease. The patient had gastric bypass surgery 12 years before the presentation but had poor compliance with his prescribed postoperative vitamin replacement regimen. His vitamin levels were not monitored routinely in the years preceding his presentation. He had a 10-year history of alcohol abuse (approximately eighteen drinks per day), and his alcohol intake further increased 4 years ago following his wife’s death. His diet also changed after this grief event, and he ate two meals per day with a thirty-pound weight loss in the prior year. His family and ocular histories were noncontributory. He was not taking any medications.

External examination revealed conjunctival jaundice and temporal muscle atrophy. His visual acuity was 20/70 in the right eye (OD) and 20/80 in the left eye (OS). He correctly identified only 5/14 Ishihara color plates with each eye. Automated visual field testing (Humphrey visual field [HVF] 24-2) revealed bilateral cecocentral scotomas (see Fig. 1). Slit-lamp examination revealed no abnormalities. His intraocular pressure measurements were 11 mm Hg OD and 10 mm Hg OS. Optical coherence tomography (OCT) showed thinning of the papillomacular bundle OU of the retinal nerve fiber layer (See Fig. 2). Fundoscopic examination confirmed temporal pallor of both optic discs.

Fig. 1.

HVF 24-2 over time. Patient’s HVF 24-2 at presentation showed significant cecocentral scotomas. However, after receiving nutritional supplementation, at 1-month and 4-month follow-up appointments, the patient’s repeat HVF 24-2 showed significant visual improvement and no visual field defect.

Fig. 2.

Optical coherence tomography (OCT) at presentation. The patient’s OCT upon initial presentation showed thinning of the papillomacular bundle OU of the retinal nerve fiber layer.

Laboratory testing showed low serum zinc (33 μg/dL; normal range [NR]: 60–120 μg/dL) and low serum copper (45.5 μg/dL; NR: 70–140 μg/dL). Vitamin C (8 mg/dL; NR: 23–114 mg/dL), vitamin D (11 pg/mL; NR: 18–72 pg/mL), and vitamin E (1.4 μg/mL; NR: 5.5–18 μg/mL) were also low. Serum vitamins B1, B2, B9 (folic acid), and B12 were normal. Serum vitamin A was undetectable. Liver function studies were elevated.

At follow-up exam 1 month later, after vitamin and mineral supplementation, all his vitamin and mineral levels had normalized. His visual acuity was 20/30 OD and 20/40 OS. He recognized 13/14 and 14/14 Ishihara color plates OD and OS, respectively. Repeat HVF 24-2 showed no significant residual visual defect (see Fig. 1). At 4-month follow-up, he had low zinc (42.6 μg/dL; NR: 60–120 μg/dL) and vitamin A (0.17 μg/dL; 15–60 μg/dL). However, he reported not refilling his supplements and poor compliance with the supplementation regimen. Nonetheless, he reported continued visual improvement and repeat HVF 24-2 showed no recurrent visual field defect (see Fig. 1). Written consent was obtained from the patient for publication of this case report and the accompanying image.

Discussion

Vitamin A deficiency is a well-described cause of night blindness (nyctalopia). It may also promote peripheral visual loss, although this is not always observed. The combination of nyctalopia and bilateral central visual loss is a much rarer clinical finding and could be caused by coexisting deficiency in vitamin A and various minerals. Zinc or copper deficiency are rare causes of bilateral optic neuropathy that may produce central visual loss. Clinicians should be aware of the visual manifestations of combined vitamin and mineral deficiency.

Vitamin A is a necessary fat-soluble vitamin that preserves corneal epithelium and plays a critical role in the synthesis of retinol, a necessary component of retinal rods. Vitamin A deficiency (xerophthalmia) can cause a wide range of ocular symptoms, including corneal keratinization and ulcers [1]. Often, the earliest symptom is nyctalopia or loss of night vision. Bariatric surgery may cause chronic gastrointestinal inflammation that promotes reduced vitamin A absorption, and this effect can persist for years after the initial surgery [2]. Similarly, liver disease (including alcohol-related cirrhosis) may damage hepatic stellate cells, the primary site of vitamin A storage. Chronic alcohol abuse may also negatively affect liver functioning, providing another pathway to vitamin A deficiency.

Our patient’s visual loss and nyctalopia may have been exacerbated by his coexisting zinc and copper deficiency, both of which have been very rarely associated with demyelination of the optic nerve. Consequently, deficiency of either mineral may cause bilateral central visual loss. Zinc deficiency may also produce nyctalopia by worsening vitamin A deficiency, as zinc is critical for vitamin A metabolism [3]. Deficiency of zinc, copper, and other minerals may cause vision loss in settings that also predispose patients to vitamin deficiency. Al-Hassany reported blindness caused by combined copper and vitamin A deficiency following bariatric surgery where supplementation did not reverse the patient’s symptoms [4]. Herlong et al. [5] reported 4 patients with liver disease that caused combined zinc and vitamin A deficiency and subsequent nyctalopia; most did not recover their vision loss following supplementation. The lack of visual improvement despite supplementation in these cases could be explained by a delay between patient referral and treatment. Interestingly, our patient expressed no other symptoms of copper or zinc deficiency, such as neuropathy, cognitive dysfunction, or anemia. Thus, in rare situations, central visual loss may be the presenting symptom of such mineral deficiency. Although vitamin deficiency-related visual loss is often a clinical diagnosis supported by laboratory testing and a response to supplementation therapy, electrophysiologic testing (e.g., electroretinogram or visual evoked potentials) may be helpful to support the clinical diagnosis or monitor response to therapy. Our patient’s OCT showed more subtle defects in comparison with his visual field testing, but discrepancies between the two examination methods are not uncommon and may be caused by a nonlinear temporal relationship between structure and function. It is likely that the patient’s disease was caught early and after the development of functional defects but before the manifestation of structural ones.

Clinicians should be aware that the combination of progressive nyctalopia and bilateral central vision loss may be produced by combined nutritional deficiency. Because vitamin A commonly causes nyctalopia but rarely central visual loss, clinicians should consider testing for both vitamins and minerals (zinc and copper) in high-risk individuals with these combined complaints. Supplementation may result in dramatic reversal of visual loss in such cases.

Statement of Ethics

Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Funding Sources

The authors did not receive any funding for this case report.

Conflict of Interest Statement

The authors report no conflicts of interest.

Author Contributions

Anshul Bhatnagar, Noor Laylani, Pamela Davila-Siliezar, Hilary Beaver, and Andrew G. Lee contributed to the conception and design of the manuscript, literature review, manuscript drafting and review, and provided final approval.

Funding Statement

The authors did not receive any funding for this case report.

Data Availability Statement

The data that support the findings of this study are not publicly available to maintain patient privacy and confidentiality. All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.