Saudi Journal of Ophthalmology (2013) 27, 113–116

Case Report

Lacrimal glands in cystic fibrosis

Peer review under responsibilityof Saudi Ophthalmological Society,King Saud University Production and hosting by Elsevier

Access this article onlinwww.saudiophthaljournwww.sciencedirect.com

Received 17 September 2012; received in revised form 5 December 2012; accepted 1 January 2013; available online 11 January 2013.

Department of Ophthalmology, King Fahd University Hospital, Alkhober, Saudi Arabia

⇑ Corresponding author. Address: P.O. Box 40137, Alkhober, Saudi Arabia. Fax: +966 38955220.e-mail addresses: alghadyanmd@yahoo.com, alghadyanmd@gmail.com (A. Alghadyan).

Abdulrahman Alghadyan, MD ⇑; Mohana Aljindan, MD; Adra Alhumeidan, MD; Gholam Kazi, MD; Robert Mcmhon, MD

Abstract

Cystic fibrosis is a systemic disease involving defective mucus secretion in different parts of the body resulting in a wide range ofsystemic complications. We are presenting the histology of the lacrimal gland from a 25 year old male with cystic fibrosis usinglight microscopy. To the best of our knowledge this is the first report.

Keywords: Cystic fibrosis, Lacrimal gland, Tears

� 2013 Saudi Ophthalmological Society, King Saud University. All rights reserved.http://dx.doi.org/10.1016/j.sjopt.2013.01.001

Introduction

The tear film is approximately 8–9 lm thick and is com-prised of 98.2% water and 1.8% solids. The three layers thatmake up the tear film are lipid, aqueous and mucous. The (out-er) lipid layer consists of phospholipids, cholesterol and waxesters. The phospholipid end of the fatty acids interacts withthe aqueous layer while the fatty acid end interacts with otherlipids forming a layer 0.1–0.2 lm thick that mitigates evapora-tion of the tears. The lipid layer is secreted by the meibomian(tarsal) glands and the sebaceous glands of Zeis. The (middle)aqueous layer, provides nutrients to the non-vascularized ocu-lar surface tissue and is secreted by the main and the accessorylacrimal glands. The aqueous layer is 7–8 lm thick consisting ofwater, electrolytes and glycoproteins. The Na+ concentrationof tears is the same as serum, however, the concentration of K+is 5–7 times greater than that in serum. Na+, K+, and Cl� con-centration regulate the osmotic flow of fluids. The (inner) mu-cous layer is 1 lm thick and acts as a lubricating layer. Themucin layer is composed of high molecular glycoproteins, elec-trolytes, and water. It is secreted principally by the conjunctivalgoblet cells, the stratified squamous cells of the conjunctivaland corneal epithelium and minimally by the lacrimal glandsand their components.1,2

Cystic fibrosis (CF) is inherited as an autosomal trait char-acterized by defective mucus secretion in different parts ofthe body. CF is caused by a flaw, or mutation of the cystic

fibrosis transmembrane conductance regulator gene (CFTRgene) occurring at a single locus on the long arm of chromo-some 7. The damaged CFTR gene prevents function of thechloride ion channels in patients with CF resulting in exces-sive salt accumulation in the body, where some of it eventu-ally is excreted through the sweat glands. Hence, salty skin isof diagnostic value in CF. As water follows salt movement,the predicted net flux of water would be from the lumen tothe sub-mucosa and would be greater across CF epithelia.Normal water movement is required to produce thin, free-flowing mucus. The nonfunctioning chloride ion channelsresulted in less water in the lumens of the ducts resulting insticky, thick mucus that CF patients endure.3,4 Since thelacrimal glands contribute to the production of mucus wetherefore, expect some changes in the structure of the lacri-mal glands. In this report, we present the histological findingsin the lacrimal gland of a patient with CF.

Case report

The orbital contents were evaluated of the lacrimal glandsof two orbits from a 25 year old white male who died from CFrelated complications. The patient was diagnosed with CF at10 months of age by the analysis of duodenal aspirate. Thepatient’s sister was also reported to suffer from CF.The pathologist report on autopsy of the patient revealed

e:al.com

114 A. Alghadyan et al.

the multisystem involvement of CF including: (1) CF and atro-phy of the pancreas, (2) chronic obstructive bronchial dis-ease, (3) dilatation of the right ventricle, (4) passivecongestion of the liver, (5) infertility with atrophy of the testis.

The orbital contents of the lacrimal glands were obtainedimmediately after death from 9 subjects without CF with ageranging between 30 and 60 years. The glands from all sub-jects were fixed in 10% formalin for 48 h, embedded in paraf-fin wax and sectioned 6–8 lm thick with microtomes. All thesections from all subjects were stained5 with: 1. Hematoxylin–eosin (H&E), which is a popular stain in histology that stainsthe nuclei blue and the remaining tissue in different shadesof red; 2. Periodic acid Schiff stain (PAS), which is a stainingmethod used to detect polysaccharides such as glycogen,and neutral mucosubstance such as glycoproteins, glycolipidsand neutral mucins in tissues; 3. Alcian blue stain, which is acopper phthalocyanine, stains acid mucopolysaccharidesand glycosaminoglycans – the stained parts are blue to blu-ish-green. The sections were studied with light microscopy.

Results

By comparing the lacrimal gland from a subject with CF tothe glands of normal subjects we observed the following:

Figure 1. Section of the lacrimal gland stained with Periodic acid Schiff stain; Nwith cystic fibrosis (A) as compared with normal patients (B).

Figure 2. Section from lacrimal glands stained with Hematoxylin–eosin stain.compared with normal patients (B).

1. In the lacrimal gland from CF patient there were anincreased number and size of vacuoles within the aciniand outside the acini, (Fig. 1a and b).

2. There was a definite decrease in the number of the acini asshown in Fig. 2.

3. There were positive staining in both PAS and Alcian Bluestaining in both the normal lacrimal glands and the glandsfrom CF patient.

4. There was a decrease in PAS-stained material in the lacri-mal gland from the CF patient compared to the normallacrimal glands (Fig. 3a and b)

5. There was a decrease in Alcaine blue-stained material inthe lacrimal gland from the CF patient compared to nor-mal lacrimal glands (Fig. 4a and b).

Discussion

In the present case; the patient’s sister was affected withCF; which goes with the known pattern of inheritance of thedisease. In this comparison of the histopathology, of the lacri-mal gland of one CF patient to a number of normal lacrimalgland samples we found some differences. There was a de-crease in the PAS stained material as well as a decrease inthe Alcaine blue stained material compared to normal. This

ote the increase in the number and the size of the vacuoles in the patient

Note the rarefication of the acini in the patient with cystic fibrosis (A) as

Figure 3. Section from lacrimal glands stained with Periodic acid Schiff stain; note the decrease in the amount of the stained material and increase in thevacuoles (A) in patients with cystic fibrosis compared with normal patients (B).

Figure 4. Section from lacrimal gland from a patient with cystic fibrosis (A) stained with Alcian blue. Note the decrease in the stained material ascompared with the section from normal patients (B).

Lacrimal glands in cystic fibrosis 115

may indicate that glycoprotein is a part of the lacrimal secre-tion and the decrease of this material in this patient might beprimary or secondary to the complication of CF. The distur-bance in chloride channels disrupted Na+ movement and sub-sequently water movement from the duct lumen to thesubmucosa causing the mucus in the lumen to thicken, clog-ging the small ducts within the lacrimal glands resulting inthe degeneration of the acini. This is the likely explanation ofthe decrease in the acini and the presence of vacuoles notedin the present case and a previous report.6 Orzalesi6 in 1971 re-ported the presence of vacuoles and droplets which increasewith age in the orbital section of normal human lacrimal glands.The vacuoles were large and numerous in our patient despitehis young age. These vacuoles may contain fluid or fat lost dur-ing tissue processing. There was a decrease in glycoprotein(PAS and Alcaine blue positive material) which is likely second-ary to the degenerative process of the acini.7

We expect CF may affect different ocular structures8–21

based on the following observations: (1) CFTR activity wasdemonstrated in the conjunctiva8 and the epithelial cells inthe lacrimal gland ducts9; (2) In CF, conjunctival goblet cellswere reported to be normal in some studies,10 and decreased

in other studies.11 This difference may be related to the stageof the disease at the time of observation. Therefore the tearfilm is affected in CF. Patients with CF are expected to havean abnormal tear film and punctate keratitis. An abnormal tearbreakup time12 and hypo-secretion of tear fluid13 have beenpreviously reported in CF patients. It is therefore likely thatthe degenerative process (decreased acini and increased sizeand number of vacuoles) contributes to the decrease in tearsecretion. Hence the stability of the tear film will be affected.Other mechanisms to explain the punctate keratitis in CFpatients include high calcium levels which induce the precipita-tion of glycoprotein of tear as suggested for other glands.14

This decrease in water solubility of mucin causes instability ofthe tear film, which may lead to superficial punctate keratitis.Tissue culture findings suggest that metabolic error is goingon in all the cells of the body though it gives rise to clinicalmanifestation in exocrine glands.

CF is a systemic disease with abnormal NaCl movementcontributing to the production of thick, sticky mucus that clogsthe secretory channels and damages various organs. The eyemay also be affected indirectly. The thick secretion will clogthe biliary and pancreatic ducts resulting in cirrhosis and

116 A. Alghadyan et al.

impaired pancreatic function as seen in the present case. Bothliver and pancreatic complications of this disease may causerepeated gastrointestinal disturbances such as diarrhea,constipation, diabetes, mal-absorption and mal-nutrition.Mal-absorption will cause vitamin A deficiency which may re-sult in night blindness and xerophthalmia that are responsiveto vitamin A treatment.15–17 In 1998 Suttle et al.18 reportedan abnormal visual evoked potential and electroretinogramin patients with CF. Gorden et al.,19 reported the presenceof drusen involving the macula. Schupp et al20 reported thatadults with CF have dramatically low serum and macular con-centrations of carotenoids (lutein and zeaxanthin), which mayexplain the previous macular involvement.

As in the present case the bronchioles may get cloggedleading to repeated respiratory infection and chronicobstructive pulmonary disease resulting in polycythemiaand subsequent retinal vein occlusion.21 The reproductivesystem may be affected especially in males (as in the presentcase) with infertility and atrophy of the testis may be second-ary to clogging of the vas deferens. However, females withCF may become pregnant because the tubes are wider.Other CF common complications include nasal polyps of un-known etiology and sinusitis which might be due to the thickmucus.

In summary different ocular tissues may be affected by CFeither directly or indirectly. In the light of these findings thelacrimal gland is being affected by this disease which canmanifest on the ocular surface. Therefore we recommendthat patients with CF should be evaluated for tear deficiencyand tear stability.

References

1. Egeberg J, Jensen OA. The ultrastructure of the acini of the humanlacrimal glands. Acta ophthalmol 1969;47:400.

2. Basic clinical and science course in Ophthalmology. Section 2.Fundamentals and the principles of ophthalmology AmericanAcademy of, Ophthalmology 2012.

3. Thomas F Boat: cystic fibrosis; chapter 393; in Nelson Textbook ofPediatrics 17th edition (May 2003): by Richard E., Md. Behrman(Editor), Robert M., Md. Kliegman (Editor), Hal B., Md. Jenson(Editor) By W B Saunders.

4. Sharon Giddings. Genes & disease cystic fibrosis. Chelsea HousePublishers; 2009.

5. Livingston DA, Reid R, Burt AD, Harrison DJ, Fleming S, editors.Muir’s text book of pathology. 14th edition. Book Power Publisher;2008, p. 258.

6. Orzalesi N et al. The structure of human lacrimal gland. Micr Cytol1971;3:283–96.

7. Arlen R et al. The effect of parathyroid hormone on incorporation of3H-glucosamine into hyaluronic acid in bone organic culture.Endocrinology 1973;92(4):1282–5.

8. Turner HC, Bernstein A, Candia OA. Presence of CFTR in theconjunctival epithelium. Curr Eye Res 2002 Mar;24(3):182–7.

9. Lu M, Ding C. CFTR-mediated Cl-transport in the acinar and ductcells of rabbit lacrimal gland. Curr Eye Res 2012 May(11).

10. Holm K, Kessing SV. Conjunctival goblet cells in patients with cysticfibrosis. Acta Ophthalmol 1975 Mar;53(2):167–72.

11. Mrugacz M, Kasacka I, Bakunowicz-Lazarczyk A, Kaczmarski M, KulakW. Impression cytology of the conjunctival epithelial cells in patientswith cystic fibrosis. Eye (Lond) 2008 Sep;22(9):1137–40.

12. Hall DS, Goyal S. Cystic fibrosis presenting with corneal perforationand crystalline lens extrusion. J R Soc Med 2010 Jul;103(Suppl 1):S30–3.

13. Mrugacz M, Bakunowicz-łazarczyk A, Minarowska A, Zywalewska N.Evaluation of the tears secretion in young patients with cystic fibrosis.Klin Oczna 2005;107(1–3):90–2.

14. DI Saint’ Agnese PA, Grossman H, Darling RC, Denning CR. Saliva,tears and duodenal contents in cystic fibrosis of the pancreas.Pediatrics 1958 Sep;22(3):507–14.

15. Joshi D, Dhawan A, Baker AJ, Heneghan MA. An atypicalpresentation of cystic fibrosis: a case report. J Med Case Rep 2008Jun;12(2):201.

16. Lindenmuth KA, Del Monte M, Marino LR. Advanced xerophthalmiaas a presenting sign in cystic fibrosis. Ann Ophthalmol 1989May;21(5):189–91.

17. Sinha A, Jonas JB, Kurlkarni M, Nangia V. Vitamin A deficiency inschoolchildren in urban central India: The central India children eyestudy. Arch Ophthamol 2011 Aug;129(8):1093–4.

18. Suttle CM, Harding GF. The VEP and ERG in a young infant withcystic fibrosis. A case report.. Doc Ophthalmol 1998;95(1):63–71.

19. Goren JF, Shah SP, Janzen GP, Gross NE, Duker JS. Diffuse retinalpigment epithelial disease in an adult with cystic fibrosis. OphthalmicSurg Lasers Imaging 2011 Jun;9:42.

20. Schupp C, Olano-Martin E, Gerth C, Morrissey BM, Cross CE, WernerJS. Lutein, zeaxanthin, macular pigment, and visual function in adultcystic fibrosis patients. Am J Clin Nutr 2004 Jun;79(6):1045–52.

21. Bruce GM. The eye and cystic fibrosis of the pancreas: a resume.Trans Am Ophthalmol Soc 1964;62:123–39.