British Journal ofOphthalmology, 1991,75,377-380

Visual field changes following hepatictransplantation in a patient with primary biliarycirrhosis

R H B Grey

AbstractA case of severe visual field restriction com-plicating primary biliary cirrhosis is described.The clinical features demonstrated vitamin Adeficiency which did not respond to oral

supplements of vitamin A. Hepatic trans-plantation restored the visual fields to near gnormal.

Bristol Eye Hospital,Lower Maudlin Street,Bristol, Avon BS1 2LXRH B GreyCorrespondence to:Mr RH B Grey, FRCS.Accepted for publication13 November 1990

A 51-year-old woman was referred to the BristolEye Hospital by her general practitioner. Shewas known to be suffering from primary biliarycirrhosis for five years and was persistentlyjaundiced. For several months prior to herreferral she had been aware of gradual deterio-ration of vision in her left eye. She had no

relevant past ophthalmic history. She was on

treatment for biliary cirrhosis and was receivingintramuscular vitamin A, D, andK replacement.She was also taking oral loperamide, spirono-lactone, terfenadine, and cholestyramine.

Ocular examination showed her visualacuities were 6/9, N 8, in the right eye and 6/18.N 10 in the left eye. The anterior segments were

normal, but both fundi showed small discreteretinal pigment epithelial lesions extending fromthe posterior pole to the equator. Some spotswere intensely white and well demarcated,whereas others, particularly those in theperiphery, were paler with soft edges (Figs IA,B). The peripheral visual fields were markedlyconstricted to less than 100 bilaterally (Fig 2A).100-Hue testing showed error of scores of 71 inthe right eye and 237 in the left eye, with a titanaxis in each eye.

Fluorescein angiography showed slightmasking of the background choroidal fluor-escence by the pigment epithelial spots in theearly stages of the run, progressing to slight

Figure IA

Figure IB

Figure I A and B Preoperative appearance with multiplewhite punctate lesions ofvariable density throughout the fundiofboth eyes.

Table I Electrophysiological, colour vision, and serological data

SerumSerum alkaline

White light ERG Blue light ERG VEP EOG 100 Hue bilirubin phosphatase

Amplitude: RV Amplitude: RV Amplitude: RtV _ [moN IU

Photopic Scotopic 11 min DA 30minDA R L R L R L

Pretransplant(a)455 - - 11-5 8 5 235 200 71 237 346 1071(b)85 21-0 2-0 14-0Post-transplant(a)4°0 65 - - 6-0 6-0 244 250 52 151 18 105(b)85 21-0 2-0 7-0Normal values(a)5-6(SD2-1) 5-6(SD2-1) - - >3 0 > 170 -

(b) 7-6 (SD 3-1) 27-3 (SD11 1) 8-5-12-5 11-5-27-5 2-20 20-110

ERG and VEP latencies all normal. (a)= a wave. (b)=b wave. DA=dark adaptation. R= right eye. L= left eye.

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Figure 2 (a) Goldmannfields at presentation. (b) Goldmannfields after intramuscular vitamin A supplements increased. (c)Goldmann fields after transplantation.

staining of lesions from the late venous phaseonwards. A few spots showed intense staining(Figs 3A, B).

Electrophysiological studies showed delayeddark adaptation. The B wave of the electro-retinogram (ERG) to blue flashes of light was

reduced in the early stages but reached normallevels after 30 minutes. The ERG to white lightand the electro-oculogram (EOG) were normal.The methods used for electrophysiological test-ing have been described in detail.'2 The EOGwas recorded after a 10-minute period of dark

Figure 3 A andB Earlyand late stages offluoresceinangiogram showing initialmasking ofchoroidalfluorescence and subsequentstaining ofthe pigmentepithelium.

Figure 3A

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Figure 3B

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Visualfield changesfollowing hepatic transplantation in a patient with primary biliary cirrhosis

Figure 4 Postoperative fundus appearance showing partialresolution ofpunctate lesions.

adaptation followed by exposure to bright light(3000 cd/m2). The ERG was measured with skinelectrodes and stroboscopic flashes at 1-secondintervals 30 cm in front of the patient. Initiallypatients were light adapted in normal room

illumination for 15 minutes, following which thelights were extinguished. Recordings were takenimmediately and at 5 minutes for white light andat 7 and 30 minutes for blue light (stimulusreduced by 2 log units by the filter).The fundus changes were consistent with

vitamin A deficiency. Serum vitamin A was

measured and found to be 0-8 mmol/l (normal1 1 to 3 5). The vitamin A dosage was increasedfrom 300 000 units monthly to 300 000 unitsweekly and the serum vitamin A level increasedto 1 8 mmol/l. Subjectively her vision improved.Her visual acuities in February 1988 were 6/9right and left, but her visual fields remainedessentially unchanged at approximately 10° (Fig2B).The patient's general condition deteriorated,

with increased jaundice, anorexia, and weightloss, and hepatic function became grosslyabnormal (Table 1). In April 1988 she underwenthepatic transplantation, which produced rapidimprovement in her general health and resto-ration of normal hepatic function. Reassessmentof her visual function six months later showedconsiderable improvement in her visual fields(Fig 2C) and 100-hue tests, with reduction of thetitan axis. However, her fundal appearancesshowed that the white lesions had persisted butwere fainter (Fig 4). The blue flashERG remainedunchanged with delayed dark adaptation. Atfollow-up 18 months after transplantation hervisual acuities and fields remained stable.

DiscussionPrimary biliary cirrhosis is thought to be an

autoimmune disease causing destruction of thesmall intrahepatic bile ducts. There is an associ-ation with other autoimmune diseases, andfrequently a high serum IgM and circulatingimmune complexes are found. Antimito-chondrial antibodies are seen in over 90% ofcases. The patients are usually female and aged40-60 years, and the disease produces pruritus,steatorrhoea, weight loss, and hepatospleno-megaly. The development of jaundice is

considered a poor sign for survival, indicatingprogressive liver failure. Vitamin deficiencies arewell recognised, particularly of vitamins D andK, but approximately a quarter of patients havea low serum vitamin A level.3 The patient underdiscussion showed all the typical findings.

Chronic liver disease may produce sufficientvitamin A deficiency to induce ocular compli-cations: nyctalopia, peripheral visual fieldrestriction, white punctate retinal pigmentepithelial lesions, loss of dark adaptation,and reduction in the values of the EOG andscotopic ERG have been described.-"' Themechanism of these effects is presumed to bepoor absorption through the gut. Reduced bileacids in the intestinal tract impair absorption oflipids and fat soluble vitamins, including vitaminA. Chronic liver disease may also decrease theproduction of retinol binding protein and pre-albumin, which are necessary for vitamin Atransport to the retinal pigment epithelium.Plasma proteins were normal in this patient,though retinol binding protein was not measuredspecifically.

Previous reports have suggested thatintramuscular vitamin A supplements reversethe visual field and electrophysiological changes,though the fundus appearance remainsabnormal.-5 8'1 Walt et al8 recommended that inprimary biliary cirrhosis vitamin A is moreeffective by mouth than by intramuscularinjection. Parenteral administration bypasses thenormal hepatic delivery and esterification ofvitamin A following gut absorption, and it maytherefore reduce its efficacy. In the present caseinjections of vitamin A did not produce signifi-cant functional improvement in spite of severalweeks ofnormal plasma vitaminA levels, whereashepatic transplantation caused a rapid restorationof peripheral field. The outcome in this patientwould support this theory.

Functional amblyopia was considered unlikelyin view of her precise consistency on repeatedfield testing, physical changes in the pigmentepithelium, and abnormal electrophysiologicalfindings.

Colour vision abnormalities have not beendescribed before in primary biliary cirrhosis, andthough not severe in this patient there was anotable change after transplantation. This maysuggest that photopic photochemistry, likescotopic photochemistry, has some degree ofdependency on liver metabolism.ERG or EOG abnormalities have been

described as the first indication of abnormalretinal function in vitamin A deficiency, but theelectrophysiological changes in this case wereremarkably small compared with the functionalfield deficit and fundus appearances. It is alsointeresting that the mild delay in dark adaptationpersisted along with the fundus abnormalities inspite of the improvement in visual fields aftertransplantation. Prolonged hypovitaminosis hasthe capacity to induce some degree of permanentstructural and functional damage to thephotoreceptor-pigment epithelial complex, buttreatment leads to considerable improvement.

My thanks are expressed to Dr D Papakostopoulos for performingthe electrophysiological tests, Mrs Gill Bennerson for photo-graphic help, and Mrs Linda Clayton for typing the manuscript.

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1 Papakostopoulos D. Clinical electrophysiology of the humanvisual system. In: Chiarenza GA, Papakostopoulos D, eds.Clinical application of cerebral evoked potentials in paediatricmedicine. Amsterdam: Excerpta Medica, 1982: 3-40.

2 Papakostopoulos D, Dean Hart C, Cooper R, Natsikos V.Combined electrophysiological assessment of the visualsystem in central serous retinopathy. Electroencephalogr ClinNeurophysiol 1984; 59: 77-80.

3 Elta GH, Furie BC, Furie B, Jacob R, Russell RM, KaplanMM. Fat soluble vitamins in primary biliary cirrhosis.Hepatology 1982; 2: 703.

4 Bors F, Fells P. Reversal of complications of self inducedvitamin A deficiency. BrJ Ophthalmol 1971; 55: 2104.

5 Russell RM, Morrison SA, Smith FR, Oaks EV, Carney EA.Vitamin A reversal ofabnormal dark adaptation in cirrhosis.Ann Intern Med 1978; 88: 622-6.

6 Sommer A, Tjakrasudjatma S, Junaedi E, Green WR. Vitamin

A responsive panocular xerophthalmia in a healthy adult.Arch Ophthalmol 1978; 96: 16304.

7 Herlong HF, Russell-RM, Maddrey WC. Vitamin A and zinctherapy in primary biliary cirrhosis. Hepatology 1981; 1:348-51.

8 Walt RP, Kemp CM, Lyness L, Bird AC, Sherlock S. VitaminA treatment in night blindness in primary biliary cirrhosis.BrMedJ 1984 288: 1030-1.

9 Shepherd AN, Bedford GJ, Hill A, Bouchier IAD. Primarybiliary cirrhosis, dark adaptometry electro-oculography andvitamin A state. BrMedJ 1984; 284: 1484-5.

10 Kaplan MM. Primary biliary cirrhosis. N EnglJ Med 1987;316: 521-8.

11 O'Donnell M, Talbot JF. Vitamin A deficiency in treatedcystic fibrosis - a case report. BrJ Ophthalmol 1987; 71: 787-90.

FIFTY YEARS AGOMustard gas and its implicationsDEAR SIRS,-In reply to Messrs. John Eyre andFrank W Law may I state that I have seen one dropof 4 per cent solution of hyd. perchlor. in glycerineaccidentally fall on the cornea and in a few secondswhich elapsed before washing out the conjunctivalsac, severe and lengthy, but not permanent damagewas inflicted on almost the whole of the cornealepithelium. Here there was no question of absorption.I quite agree with them that in the field ofbiology thereis nothing more misleading than the argument fromanalogy, which indeed led eminent men to assume andpublish results on the assumption that because mancould accommodate the mammals could also.

But the argument from analogy hardly applies inthis instance just quoted.As regards the late effects of mustard gas on the

cornea, the few cases I have seen showed deep seatedinfiltration rather than ulceration and there was verylittle clear cornea left anywhere. So that I doubtwhether either diathermy or contact glasses would

have assisted. If such cases, which I am glad to say arerare, present themselves, the method suggested will beborne in mind. It is true that these conditions do recurwithout obvious cause. No one will be more gratefulthan myself if the writers have devised an effectivetreatment of mustard gas in the field, and will lookforward to their publication of their experimentalresults. But the practical use ofany remedy of the kindin advanced positions of any army is very difficult butnot insuperable.Some idea of the difficulty of acting efficiently in

advanced stations may be learnt from the Palestinecampaign, where towards the end men with hightemperature were given quinine at once, no matterwhat seemed to be the cause of the temperature. If themedical officers had waited until they could be surethat malaria was the cause it would at times have beentoo late. To neutralise the effects of mustard on theeyes, special instruction for the forward units will be anecessity. - Letter from James W Barrett.

BrJ Ophthalmol 1941; 25: 95.

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