Xerophthalmia due to vitamin A deficiency following Frey’s procedure for chronic calcific pancreatitis

Abstract

We report a rare presentation of xerophthalmia due to partial pancreatic exocrine insufficiency following Frey’s surgery (pancreatic resection) in a 12-year-old girl. The child had undergone this surgery for chronic calcific pancreatitis 3 years before and presented with ocular irritation and decreased vision of 3 months duration. Ocular examination showed severe conjunctival and corneal xerosis. Her serum retinol levels and 25-hydroxyvitamin D were tested and were extremely low. The condition rapidly reversed following high-dose replacement therapy with vitamin A and D. This case highlights the importance of continuous enzyme replacement therapy as well as dietary modification and nutritional supplement therapy and monitoring of ocular symptoms in post-pancreatic surgery.

Background

Xerophthalmia as a cause of preventable childhood blindness has been well reported and extensively documented.¹ While fortunately this may no longer be a leading cause of childhood blindness even in developing countries due to better institution of prevention strategies,² early recognition of this potentially reversible condition is important to avoid permanent changes. The clinical spectrum ranges from mild manifestations such as decreased vision in low illumination, night blindness and Bitot’s spots or can be of moderate severity such as conjunctival and corneal xerosis and finally can lead to corneal ulceration and melt in the severest form (keratomalacia).³ Apart from causes such as primary malnutrition, inflammatory bowel disease, chronic pancreatitis, although a rare cause, can also lead to vitamin A deficiency. To our knowledge, this is the first case report of xerophthalmia after Frey’s procedure for chronic pancreatitis, in a paediatric patient.

Case presentation

A 12-year-old girl presented with gradual onset blurring of vision and ocular irritation, photosensitivity and watering for 3 months. Systemically, she complained of loss of appetite, chronic headache and fatigue over the past 1 year. Past history was significant for undergoing Frey’s procedure for chronic idiopathic calcific pancreatitis 3 years ago, and the parents had not followed her up with her gastroenterologist for more than a year. At the time of presentation, she was not on any systemic medications or supplement therapy or dietary modification but had taken the same for about 3 months postprocedure. The parents did mention that dietary advice and supplementation were provided but they could not recall the details. The reports of the exact nature of the pancreatic enzyme replacement therapy (PERT) were not available. She did not complain of gastrointestinal symptoms of malabsorption such as abdominal cramping or bloating or chronic diarrhoea and was on a normal diet. On general examination, the child was below the third percentile for her height and weight. On ocular examination, she was extremely photophobic and unable to open her eyes comfortably. Her best-corrected visual acuity was 20/50 in the right eye and 20/40 in the left eye. Slit lamp examination showed conjunctival xerosis and a total lusterless cornea with diffuse superficial punctate keratitis (figure 1A–D). As part of the ocular surface evaluation, Schirmer’s II was performed, and value (at 5 min) were 4 mm and 8 mm in the right and left eye, respectively. The rest of the anterior and posterior segment examination was normal. A clinical diagnosis of xerophthalmia was made and the patient was advised to immediately consult her paediatric gastroenterologist for further investigations.

Figure 1.

(A–D) The right eye (A) and left eye (B) show dry ocular surface with conjunctival xerosis and a lusterless cornea. Fluorescein stain shows confluent superficial punctate keratitis in both right (C) and left (D) eye.

Investigations

The patient was advised by the treating paediatric gastroenterologist to undergo serum retinal levels, vitamin D levels and liver function tests. Her serum retinol levels were noted to be markedly reduced at 0.038 mg/dL (normal range: 0.3–0.6 mg/dL), thus confirming our clinical diagnosis of hypovitaminosis A causing xerophthalmia. Low serum levels of 25-hydroxyvitamin D, 9.8 ng/mL (normal range: 30–60 ng/mL) was an incidental finding, as our patient did not have any specific signs of vitamin D deficiency. Liver function tests revealed elevated serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvic transaminase (SGPT). Serum folate, vitamin B₁₂, parathyroid hormone, amylase, lipase, electrolytes, lipid profile and blood sugars were within the normal ranges. Ultrasound abdomen showed mild hepatomegaly with grade I fatty liver changes and normal splenoportal Doppler study.

After therapy, over the next 12 weeks, serum retinol levels improved to 0.39 ng/mL (0.3–0.6). Her SGOT and SGPT levels also reversed to normal. All the blood tests were repeated at 12 weeks and were normal.

Differential diagnosis

Since the patient had a clear history of undergoing pancreatic surgery and was not on any dietary supplementation or dietary modification at the time of presentation to us, a diagnosis of xerophthalmia secondary to vitamin A hypovitaminosis status post Frey’s procedure was made. Our patient did not have any gastrointestinal features of malabsorption. She was not following any specific diet at the time of presentation to us, and no reports suggestive of dietary modifications in the past were available. Other causes of malnutrition leading to xerophthalmia were ruled out. Other causes of dry eye such as keratoconjunctivitis sicca due to primary or secondary Sjogren’s syndrome was not considered keeping in mind the age, lack of any other systemic disease and a positive history of surgery.

Treatment

She was started on topical lubricating eye drops (polyethylene glycol 0.4 %+propylene glycol 0.3 %) 2 hourly and hydroxypropyl methylcellulose 2% eye ointment 8 hourly and referred to her paediatric gastroenterologist for a complete systemic evaluation and vitamin supplementation. After undergoing a thorough systemic evaluation and serological investigations, she received intramuscular injections of vitamin A (palmitate 100 000 IU) for 2 days followed by a third dose after 2 weeks and then daily dose of oral vitamin A (5000 IU per day) thereafter for 2 months, oral vitamin D 50 000 U once a week, Tab pancreatin 10 000 IU two times per day, oral antacids and multivitamin supplements. Additionally, a low-fat diet with small frequent meals was advised.

Outcome and follow-up

Two weeks following this therapy, there was complete recovery of her ocular condition; she was comfortable and able to tolerate light and her vision had improved to 20/20 with resolution of the xerosis (figure 2A–D). She was advised to continue dietary modification and vitamin supplementation and compliance and close monitoring of serum levels once every 3 months was emphasised.

Figure 2.

(A–D) Two weeks after vitamin A therapy: both conjunctival and corneal xerosis have reversed in the right eye (A) and left eye (B). Fluorescein stain shows decreased corneal staining in both right eye (C) and left eye (D).

Discussion

Chronic pancreatitis-associated genetic mutations, most commonly cystic fibrosis transmembrane conductor regulator mutation, followed by obstructive conditions such as pancreas divisum and gallstones are the two leading causes of chronic pancreatitis in children.³ Both these were ruled out in our case. Autoimmune and metabolic factors such as chronic smoking, and hypertriglyceridaemia are more commonly associated with chronic pancreatitis in adults.⁴ Frey’s procedure is a surgical technique used for the treatment of chronic pancreatitis, wherein the diseased portion of the pancreatic head is excised and a lateral pancreaticojejunostomy is performed.⁵

The major source of vitamin A is retinal esters in food of animal origin and provitamin A carotenoids in foods of plant origin. Intestinal absorption of retinal esters is aided by various pancreatic enzymes such as pancreatic triglyceride lipase, phospholipase B and intestinal brush border enzymes. Through an extremely complex process, these esters are incorporated into the dietary lipids like triglycerides and chylomicrons and released into the lymphatic system.⁶

Being a liposoluble vitamin, the transport is mainly dependent on dietary lipids. Patients who undergo pancreatic resection are advised dietary modifications to avoid gastrointestinal complications and also likely to suffer from severe malabsorption.⁷ This aggravates the propensity to develop vitamin A deficiency in them. Pancreatic exocrine insufficiency (PEI) is more common after Frey’s procedure compared with other pancreatic resections.^{7 8} PEI is characterised by various abdominal disturbances such as bloating, steatorrhoea, deficiency of vitamins A, D and E, elevated parathyroid hormone (secondary to vitamin D deficiency) and nutritional features like weight loss, chronic fatigue and weakness and also type 3c diabetes.^7–9

Lee et al¹⁰ reported a case of xerophthalmia with diffuse corneal scarring and nyctalopia occurring 18 months after bariatric surgery, with improvement after vitamin A therapy; however, the subepithelial scarring persisted in their case leading to mild visual loss.¹⁰ Tiang and Warne¹¹ reported a case of nyctalopia occurring 10 years after pancreaticoduodenostomy (Whipple’s procedure), which could be completely reversed with vitamin A supplementation. Donaldson and Fishler¹² reported the occurrence of severe corneal melt following post-LASIK dry eye in a 41-year-old female patient who had undergone bariatric surgery 10 years before. All three cases had a common feature of self-cessation of supplements, leading to mild to devastating ocular complications. While our patient did not complain of decreased vision in the dark, her inability to co-operate primarily from the ocular discomfort precluded an electrophysiology testing for retinal function. The xerophthalmia in our case too had developed due to cessation of supplement therapy. Other features of PEI noted in our patient also resolved within 3 months of PERT and nutritional supplements. The present case highlights the importance of routine screening for fat-soluble vitamin deficiencies and need for vitamin supplements for all patients who present to the ophthalmologist with systemic history of chronic pancreatitis.

Considering that our hospital is an exclusive eye care facility, the patient had to be referred to a paediatric gastro-endocrinologist and the importance of regular follow-up was emphasised. The patient was advised a lower fat intake, but more detailed advice on diet should ideally be provided by a dietary specialist, which was not available at the facility our patient visited. In adults, a low-fat diet is not recommended as such⁷ as patients can malabsorb carbohydrate and protein as well as fat. Rather, a ‘normal’ fat intake and adequate PERT and proton pump inhibitor therapy are recommended to ensure optimal absorption.

To conclude, detailed evaluation with pertinent history can give important clues to the ophthalmic presentation in conditions with a systemic or iatrogenic aetiology. Timely intervention with vitamin A supplementation and long-term monitoring can result in total resolution of symptoms associated with xerophthalmia, thus preventing irreversible visual loss. In a clear case of nutritional deficiency, diet-related management is paramount to prevent the occurrence of these complications as supplements alone are insufficient.

Learning points.

• Patients undergoing pancreatic resection and those with chronic pancreatic disease should be screened annually for early detection of malnutrition and diabetes.

• Pancreatic resection often results in deficiency of liposoluble vitamins, particularly vitamin A and vitamin D, which needs routine assessment of their serum levels and bone density scans.

• Conjunctival and corneal xerosis are early manifestation of vitamin A deficiency, which can be reversed by parenteral and oral supplements. Intramuscular form is more effective than oral formulations to reverse early stages of deficiency.

• Diet-related management alone with pancreatic enzyme replacement therapy and micronutrients supplements can prevent chronic long-term complications of pancreatic exocrine insufficiency following pancreatic resection.