Australian Journal of Oohthalmologv 1984: 12: 335-339

UNTREATED HANSEN’S DISEASE OF THE EYE: A CLINICOPATHOLOGICAL REPORT

IAN ROBERTSON, FRACO

JOHN M. WEINER, FRCPA

Ophthalmologist in Charge. Corneal Diseases Unit, The Royal Victorian €ye and Ear Hospifal

Pathologist, The C H Greer Pathology Laboratory. The Royal Mctorian Eye and Ear Hospital

ERNEST FINKELSTEIN, FRACO Senior Ophthalmologist, The Royal Victorian Eye and Ear Hospital

Abstract A Maltese immigrant presented with intermittent bilateral anterior uvertis for which no cause could be found. The inflammation did not respond to topical treatment and ultimately the left eye developed a hypopyon and was enucleated. Histological examination revealed granulomatous inflammation and large numbers of M ycobacterium leprae throughout the anterior segment. Occasional foci of inflammation containing Mycobacterium leprae were found in the vitreous extending to the retina at the posterior pole. These findings in the posterior segment have rarely been reported. Eye infection in Hansen’s disease is frequent and delays in diagnosis are common.

Key words: Untreated Hansen’s disease, Mycobacterium leprae, granulomatous uveitis.

In 1874 Hansen described the relationship between Mycobacterium leprae and leprosy. I Leprosy probably has the highest incidence of ocular involvement of any infectious disease affecting man.’ Infection of the ciliary body, iris and cornea in the human eye is common, but involvement of the choroid, retina or optic nerve is extremely rare. Many authorities consider that the occasional reports of leprosy in the posterior parts of the eye may have been due to other diseases including syphilis, tuberculosis or onchocerciasis. The apparent predilection of M. /eprae for the cooler anterior segment of the eye led to the use of the nine-banded armadillo (Dasypus novemcinctus L.) which has a low body temperature (32-35°C) and in which M. leprae can be cultured.’

CASE REPORT On 21 December 1966 a 23-year-old male, who had left Malta 1 1 years previously, attended the Casualty Department at The Royal Victorian Eye and Ear Hospital with a painful left eye. His visual acuity was right 6/18, left 6/6 and slit lamp examination showed heavy flare, cells and fine keratitic precipitates in the left anterior chamber; a faint flare and a few cells were present in the right anterior chamber. A diagnosis of bilateral iritis was made and he was treated with homatro- pine and cocaine and prednisolone drops. Two days later there was no improvement. Three months later the signs of iritis were still present. At this time, full blood examination was normal and the erythrocyte sedimentation rate was 24 mm in 1 hour. The toxoplasma antibody titre was 1 in 16. His general health was good and he

Reprint requests: Ian Robertson, 82 Collins Street, Melbourne, Victoria 3000.

UNTREATED HANSEN’S DISEASE OF THE EYE: A CLINICOPATHOLOGICAL REPORT 335

I

Figure I : White granular deposits (lepromata) on the right iris and clumped in the angle of the anterior

chamber below.

Figure 4: Histological preparation of the main segment of the right eye. The pupil and optic nerve are not present in this section. There is a granulomatous inflammatory infiltrate in the cornea and limbus (short arrow). There is a chronic granulomatous iritis. Note the clump of inflammatory cells in the vitreous overlying the retina (long arrow) (haematoxylin-eosin, original magnification x 6).

Figure 2: Discrete white opacities of varying size in the right fundus.

Figure 5: Photomicrograph of the posterior cornea and portion of the anterior chamber. Note Descemet’s membrane. There are macrophages and lymphocytes between the corneal lamellae. There is a chronic inflammatory infiltrate in the anterior chamber (haematoxylin-eosin, original magnification x 250).

Figure 3: The left eye showing opacification of the cornea with spontaneous perforation.

336 AUSTRALIAN JOURNAL OF OPHTHALMOLOGY

Figure 6: Photomicrograph of portion of the iris. There is a chronic granulomatous inflammatory infiltrate composed of large macrophages (Lepra cells) together with lymphocytes (haematoxylin-eosin,

original magnification x 250).

had no arthritis. He had been treated for gonor- rhoea five years before, but he had no urethral discharge. Wassermann and Kline tests were negative. The iritis gradually improved, but did not clear up completely, and over the next 12 months flare and cells were seen in both anterior chambers on numerous occasions. For the next I1 months he was treated successively with oral benzyl penicillin, betamethasone, demeclocy- cline, spiramycin, oxytetracycline and subconjunctival methylprednisolone. Despite this treatment the iritis persisted and became worse and posterior synechiae formed in the left eye. In August 1967 whitish granular deposits like grains of salt were seen on the right iris (Figure 1) and the left iris had a velvety appearance with loss of detail. A grey patch resembling a scar was noted in the upper outer quadrant of the left cornea. In November 1967 the iritis in the left eye became worse and a hypopyon appeared. He was admitted to hospital and. was examined by several members of the senior eye staff and various opinions were given about the cause of his iritis, ranging from sarcoid to syphilis. The Wassermann and Kline tests were positive at this stage. The intraocular pressure was raised in the left eye (right 13, left 36 mmHg). The hypopyon cleared and the iritis settled with betamethasone given orally and subconjunctivally. At this stage discrete white opacities of varying size which merged into confluent areas were seen in the right retina from 7 to 9 o'clock (Figure 2).

Figure 7: Modified Ziehl-Neelsen stain of the region shown in Figure 6. There are large numbers of acid- fast bacilli, many in clusters. The organisms (stained red) are seen both within macrophages and extra- cellularly (Fite-Faraco stain, original magnification

x400).

Figure 8: Low power view of the retina and vitreous. There is a clump of macrophages and lymphocytes in the vitreous (top of figure) with strands of chronic inflammatory cells extending from the ciliary processes to the retina (bottom of figure) (haematoxylin-eosin,

original magnification x 25).

UNTREATED HANSEN'S DISEASE OF THE EYE: A CLlNICOPATHOLOGICAL REPORT 337

Figure 9: Scanning electron photomicrograph of a thick (20 p ) paraffin section. The retina is at the bottom of the photograph (asterisk). There is a clump of inflammatory cells (long arrows) adherent to the internal limiting membrane of the retina. A line of inflammatory cells (short arrow, top of figure) stretches into

the vitreous (magnification x 120).

In December 1967 the deposits on the right iris had disappeared, but severe iritis and raised intraocular pressure persisted in the left eye. Irregular thickening of corneal nerves and decreased corneal sensation were noted. The right cornea showed non-staining interstitial keratitis superiorly.

He left hospital at the end of December and gradually the iritis in the left eye became worse and the eye became blind and painful (Figure 3). in September 1976 the left eye perforated and was enucleated.

PATHOLOGICAL FINDINGS A portion of the unfixed temporal cornea of the eye was removed. A direct smear of this tissue was positive when stained for acid-fast bacilli. Attempts at culture on Lowenstein-Jensen

Figure 10: Photomicrograph of the retina at the posterior pole. A retinal vessel is surrounded by lymphocytes and some polymorphs (perivasculitis). There is a clump of inflammatory cells adherent to the internal surface of the retina. This clump is composed of polymorphs, lymphocytes and occasional macrophages. This inflammatory focus, and those illustrated in Figures 8 and 9, correspond to the “pearls” seen clinically. Acid-fast bacilli were identified in some of these clumps (haematoxylin-

eosin, original magnification x 100).

338 AUSTRALIAN JOURNAL OF OPHTHALMOLOGY

medium for 16 weeks were unsuccessful. These findings are consistent with the organism being Mycobacterium leprae.

Histologically, there was marked chronic granulomatous infiltration in the peripheral cornea and iris (Figures 4 and 5) . This inflam- matory infiltrate was composed of large vacuolated macrophages, or “Lepra” cells, with an admixture of lymphocytes and plasma cells (Figure 6) . A modified Ziehl-Neelsen stain (the Fite-Faraco stain) revealed large numbers of acid-fast bacilli both within the Lepra cells and extracellularly (Figure 7).

There were several interesting pathological findings in the posterior segment. Strands of inflammatory cells extended from the ciliary processes through the vitreous (Figures 8 and 9). The cells in these areas were composed of lymphocytes with occasional macrophages and polymorphs. The Fite-Faraco stain revealed acid- fast bacilli in some of these clumps. Several retinal vessels had an intense perivascular infiltrate, predominantly of lymphocytes. One of these vessels had an associated inflammatory focus adherent to the internal limiting membrane near the vessel (Figure 10).

DISCUSSION This rare clinicopathological report of untreated Hansen’s disease of a human eye supports previous studies which show that the anterior segment is commonly involved in lepromatous l ep r~sy .~ This is probably due to the preference of the leprosy bacillus for cooler areas of the body. Experimentally, this natural predilection for a cooler environment is illustrated by the susceptibility of the nine-banded armadillo to leprosy infection. The body temperature of this animal ranges from 32 “C to 35 O C 5 Therefore, it is not surprising that lesions due to leprosy are not often reported in the posterior segment.

Maucione published one of the earliest descriptions of fundal involvement due to leprosy.6 This report, which appeared in the Italian literature in 1921, documented both inflammation and the presence of bacilli in the vitreous and retina in several patients with this disease.

De Barros, reporting a series of 1279 patients with leprosy, wrote that he never saw a case of

proven posterior segment involvement. * Somerset and Sen described two patients with

leprous nodules (or “pearls”) in the fundus among 224 patients with leprosy.’ Choyce has stated that these fundal lesions may originate on the pars plana of the ciliary body, and pass into the vitreous to the retina.8 Our findings support this concept, as there were strands of inflam- matory cells extending through the vitreous and ending in clumps of cells, both in the vitreous and on the retina. There was an intense perivas- culitis of the underlying retinal vessels, and the choroid itself appeared unaffected.

This case is instructive in that it highlights the delays in diagnosis which may occur in this disease. In addition, we present a clinicopatho- logical correlation of rarely reported posterior segment involvement in an untreated patient.

ACKNOWLEDGEMENTS We wish to thank Elizabeth Scanlon and Marie Hayden for technical help, Judith Quilter of the Medical Library and Glenys Grant of the Medical Illustration Department. Nanette Carroll (Melbourne University Department of Ophthalmology) performed the scanning electron microscopy. We also thank Faye Preitz for secretarial help.

Addendum: During the eight years following the diagnosis, there has been persistent uveitis and glaucoma in the remaining right eye, despite treatment including dapsone and steroids.

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Duke-Elder S. System of ophthalmology. Vol8. Diseases of the outer eye. London: Henry Kimpton, 1965: 844-852. De Barros JM. The ocular complications of leprosy. Am J Ophthalmol 1946; 29: 162-170. Hobbs HE, Harman DJ, et al. Ocular histopathology in animals experimentally infected with Mycobacteriurn leprae and M. lepraernuriurn. Br J Ophthalmol 1978; 62:

Duke-Elder S. System of ophthalmology. Vol. 9. Diseases of the weal tract. London: Henry Kimpton, 1965:

Binford CH, Meyers WM. Leprosy. In: Binford CH, Connor DH, eds. Pathology of tropical and extraordinary diseases. Washington DC: Armed Forces Institute of Pathology, 1976: 205-225. Maucione L. Contributo clinico anatomic0 e terapeutico allo studio della lepra oculare. Archivio di Ottalrnologia

Somerset EJ, Sen NR. Leprosy lesions of the fundus oculi. Br J Ophthalmol 1956; 40: 167-172. Choyce DP. Diagnosis and management of ocular leprosy. Br J Ophthalmol 1969; 53: 217-213.

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UNTREATED HANSEN’S DISEASE OF THE EYE: A CLINICOPATHOLOGICAL REPORT 339