Combined Nutritional Keratoconjunctivitis Sicca and Optic Neuropathy due to Restrictive Dietary Multivitamin Deficiency of Vitamin C and B12 During the COVID-19 Pandemic

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Combined Nutritional Keratoconjunctivitis Sicca and Optic Neuropathy due to Restrictive Dietary Multivitamin Deficiency of Vitamin C and B12 During the COVID-19 Pandemic James Z. Fan, BA, Peter W. Mortensen, MD, Subahari Raviskanthan, MBBS, Andrew G. Lee, MD T he severe acute respiratory virus syndrome coronavirus 2 disease of 2019 (COVID-19) pandemic and subsequent shutdowns resulted in significant changes to dietary habits. Quarantined populations reported consuming fewer fresh vegetables, fruits, and legumes (1). Associated psychosocial stressors have resulted in increased alcohol consumption and smoking (1). COVID-19 lockdowns have affected the way Americans order groceries (e.g., online) and preprepared food (e.g., takeout and delivery) (2). Many have chosen grocery delivery or curbside pickup services, with unknown nutritional implications (2). Vitamin B12 is a cofactor for methionine synthase and methylmalonyl-CoA mutase that is found in animal products and is important for the myelination of neurons. B12 deficiency may produce spinal cord and optic nerve demyelination. This may present with painless, progressive, bilateral loss of visual acuity (VA), color vision, and central or cecocentral visual field loss (3). By contrast, vitamin C (ascorbic acid) is found in fruits and vegetables and has important roles in collagen production and antioxidation. Vitamin C deficiency may present with bruising and poor wound healing. Severe deficiencies of vitamin C (i.e., ocular “scurvy”) in the modern era are extremely rare, but typical findings include subconjunctival hemorrhages, keratitis, and episcleritis. McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth) (JZF), Houston, Texas; Department of Ophthalmology (PWM, SR, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; University of Texas MD Anderson Cancer Center (AGL), Houston, Texas; Texas A and M College of Medicine (AGL), UTMB and UT MD Anderson Cancer Center, Bryan, Texas; Department of Ophthalmology (AGL), Baylor College of Medicine and the Center for Space Medicine, The University of Iowa Hospitals and Clinics, Iowa City, Iowa; and University of Buffalo (AGL), Buffalo, NY. The authors report no conflicts of interest. Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology, Blanton Eye Institute Houston Methodist Hospital, 6560 Fannin Street, Suite 450, Houston, TX 77030; E-mail: aglee@ houstonmethodist.org. Fan et al: J Neuro-Ophthalmol 2023; 43: e285-e287 We present a case of severe nutritional keratoconjunctivitis sicca and optic neuropathy due to presumed combined vitamin C and vitamin B12 deficiency resulting from COVID-19–associated restriction of diet. To the best of our knowledge, this is the first such case reported in the English language ophthalmic literature. A 62-year-old woman presented with painless, progressive vision loss, severe dry eyes, and marked light sensitivity in both eyes for approximately 11 months at the height of the COVID-19 pandemic in the United States. The medical history included breast carcinoma status postresection without metastatic or recurrent disease. She reported consuming 3 standard alcoholic drinks and half a pack of cigarettes per day. The surgical history included cataract extraction in both eyes. The family history was noncontributory. Her medications only included topical artificial tears and ointments, with a history of tamoxifen for 5 years. Over the past year (2020), she reported decreased appetite and unintentional weight loss of 7 pounds. Owing to the COVID-19 shutdown, she had a significant decrease in consumption of fruits and vegetables. The patient was dissatisfied with the grocery store’s designated shoppers and their ability to select the proper produce items that she had ordered online, and so she stopped ordering. She was initially seen by 2 ophthalmologists and diagnosed with severe keratoconjunctivitis sicca, without improvement despite aggressive topical prednisone and artificial tear and ointment lubricating regimens. The patient’s symptoms worsened, and she developed loss of central vision initially attributed to severe corneal dryness. A third ophthalmologist ordered magnetic resonance imaging of the brain and orbits with and without contrast, which was normal. The patient was then referred to neuro-ophthalmology. Initial examination revealed 20/400 VA in the right eye and count fingers at 4 feet in the left eye. No relative afferent pupillary defect was noted. Intraocular pressure measurements, external examination, and motility examinations were normal in both eyes. Slitlamp examination revealed moderate conjunctival injection in both eyes, e285 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence absence of conjunctival Bitot spots, and diffuse punctate epithelial erosions of both corneas consistent with keratoconjunctivitis sicca. No tamoxifen retinopathy was seen on fundus examination. There was no optic disc edema, but the infrared photograph demonstrated nonspecific retinal pigment epithelium change and peripapillary atrophy in both eyes. Automated visual field (HVF) 24-2 showed a dense central scotoma in the left eye (Fig. 1A) with a foveal threshold of ,0 dB in both eyes. Optical coherence tomography of the optic nerve retinal nerve fiber layer demonstrated papillomacular bundle dropout corresponding to the central scotomas in both eyes (Fig. 2). Physical examination revealed no peripheral neuropathy, gingival bleeding, or nail findings. Blood work revealed that serum vitamin B12 was low at 327 pg/mL (normal .400) with elevated homocysteine levels of 18.5 mmol/L (normal ,15) and markedly low vitamin C level of ,0.1 mg/dL (normal .0.4). Methylmalonic acid, folate, and vitamin A, D, and E were within normal limits. The patient’s hemoglobin was low-normal at 12.2 g/dL with a low red blood cell count of 3.65 million/mL. The patient was advised to discontinue alcohol and tobacco use and subsequently began aggressive multivitamin supplementation. At the 2.5-month follow-up, her diet had improved, and she had markedly better vision with almost complete resolution of dry eye symptoms. VA improved to 20/200 in the OD and 20/160 in the left eye. Repeat laboratory tests demonstrated improved serum B12 of 475 pg/mL and normalized vitamin C levels of 1.7 mg/dL. Repeat HVF revealed improved central scotomas but residual left inferior nasal step (Fig. 1b) and improved foveal thresholds of 28 dB in the OD and 33 dB in the left eye. She reported an increased intake of fresh fruits, vegetables, and meat products in addition to a daily multivitamin. She reduced her alcohol consumption from 3 cocktails a day to 2–3 per week and cut her daily smoking in half. At a visit of 8 months after initial presentation, her VA had improved to 20/40 in both eyes. Nutritional optic neuropathy from inadequate dietary intake of B12 and B9 is uncommon in developed countries. Alcohol abuse, gastrointestinal surgeries, and intentionally restrictive diets can produce vitamin deficiency. Our patient’s initial presentation of severe keratoconjunctivitis sicca due to concomitant vitamin C deficiency in the setting of toxic-nutritional optic neuropathy is interesting and unique. Our patient had additional risk factors for toxic/ nutritional optic neuropathy including alcohol and tobacco use. Patients with a history of alcohol abuse may exhibit poor dietary intake, with chronic intestinal irritation and decreased liver function further reducing vitamin absorption (3). Tobacco use alone may also produce optic neuropathy because vitamin B12 is an important cofactor in the detoxification of cyanide, a known component of cigarette smoke (4). Keratoconjunctivitis sicca is a known presentation of vitamin C deficiency. In a 1970 study, 5 men were deprived of vitamin C and 3 developed dry, light sensitive eyes (5). FIG. 1. A. HVF before vitamin supplementation and lifestyle changes. B. HVF after vitamin supplementation and lifestyle changes. HVF, automated visual field. e286 Fan et al: J Neuro-Ophthalmol 2023; 43: e285-e287 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Initial optical coherence tomography. Subsequent vitamin C supplementation resolved their symptoms. Increased oxidative damage by reactive oxygen species in the inflammatory cascade is a likely contributory mechanism (6). Clinicians should be aware that indirect effects of the COVID-19 pandemic, including quarantine-related dietary restriction, may cause ocular morbidity because nutritional optic neuropathy epidemics have occurred in recent history (4). Concomitant vitamin C and vitamin B12 deficiency may present as severe keratoconjunctivitis sicca and nutritional optic neuropathy. To the best of our knowledge, this is the first such case induced by dietary restriction to be described in the English language ophthalmic literature. STATEMENT OF AUTHORSHIP Conception and design: J. Z. Fan, P.W. Mortensen, S. Raviskanthan, and A. G. Lee; Acquisition of data: J. Z. Fan, P.W. Mortensen, S. Raviskanthan, A. G. Lee; Analysis and interpretation of data: J. Z. Fan, P.W. Mortensen, S. Raviskanthan, A. G. Lee. Drafting the Fan et al: J Neuro-Ophthalmol 2023; 43: e285-e287 manuscript: J. Z. Fan, P.W. Mortensen, S. Raviskanthan, A. G. Lee; Revising it for intellectual content: J. Z. Fan, P.W. Mortensen, S. Raviskanthan, A. G. Lee. Final approval of the completed manuscript: J. Z. Fan, P.W. Mortensen, S. Raviskanthan, A. G. Lee. REFERENCES 1. Sidor A, Rzymski P. Dietary choices and habits during COVID-19 lockdown: experience from Poland. 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