British Journal of Ophthalmology, 1981, 65, 231-'39 Role of iris changes as a cause of blindness in lepromatous leprosy T. J. FFYTCHE From St Thomas's Hospital, Lambeth Palace Road, London SE] 7EH SUMMARY Clinical and pathological investigations in a group of 113 patients with leprosy of long duration demonstrated the importance of iris changes as a cause of blindness. In lepromatous leprosy the so called 'chronic iritis' produces iris atrophy with small nonreacting pupils which exaggerate the visual impairment created by developing lens changes and corneal opacities. The cause of this 'chronic iritis' is believed to be neuroparalytic from early involvement of the small nerves of the iris, particularly the autonomic supply. Clinical and pharmacological evidence for this theory is supported by the histological changes observed in 18 specimens of iris removed during the course of cataract surgery, with progressive atrophy of the iris preferentially affecting the dilator muscle and leading to a nonreacting miosed pupil. Further pharmacological and histo- logical studies are to be undertaken on lepromatous patients with iris involvement with a view to establishing possible methods of prevention. It has for long been realised that the main causes of blindness in leprosy lie in disease of the anterior segment and that the condition rarely affects the tissues at the posterior pole of the eye. Ocular damage in leprosy occurs in 4 ways: (1) facial and trigeminal nerve involvement; (2) hypersensitivity reactions; (3) direct bacterial invasion; (4) secon- dary infection. FACIAL AND TRIGEMINAL INVOLVEMENT Leprosy is essentially a neural disease with infection and eventual destruction of superficial nerves by Mycobacteria leprae. The anatomical position of the facial nerve, especially the zygomatic branch, and the superficial branches of the trigeminal nerve make these structures vulnerable to infection in all forms of leprosy, giving rise to abnormalities of lid position and abolition of the normal blink and corneal reflexes. A combination of these 2 nerve palsies may occur early in the course of the disease and lead to exposure keratitis, with its consequent corneal damage and opacification. The incidence of these major corneal problems is, however, less than might be expected, since preservation of the normal Bell's phenomenon prolongs the protection of the cor- nea.1 2 Even so, facial palsy has been considered to be the second commonest cause of blindness in leprosy.3 Correspondence to T. J. ffytche. HYPERSENSITIVITY REACTIONS In all forms of leprosy, but particularly when a change in polarity occurs, a hypersensitivity reaction can take place. This 'lepra' reaction usually arises when therapy is being commenced or withdrawn, but can also develop spontaneously.4-6 The reaction is generalised, with acute swelling of skin lesions, tender nerves, and at times severe fever, and these signs have given rise to the alternative name of erythema nodosa leprosum. There is often an associated acute iritis and at times a nephritis.7 The clinical manifestations are believed now to be caused by circulating immune complexes becoming deposited in the affected tissues6 8 rather than a response to bacteria, for although M. keprae have been found in the anterior chamber by paracen- tesis9-12 it is not known what role they play in the pathogenesis of the acute uveitis, and the lepra reaction can occur in the absence of organisms.8 The eye develops an acute iritis which is usually bilateral and does not differ in its clinical manifesta- tions from other forms of acute nonleprous iritis. The disease has a sudden painful onset, and, if untreated, the eye can be permanently damaged within 24-72 hours.13 Aqueous flare and cells, keratic precipitates, hypopyon, and synechiae with seclusio pupillae and secondary glaucoma can occur with secondary cataract and eventual phthisis. 231 on January 4, 2020 by guest. Protected by copyright. http://bjo.bmj.com/ Br J Ophthalmol: first published as 10.1136/bjo.65.4.231 on 1 April 1981. Downloaded from
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British Journal of Ophthalmology, 1981, 65, 231-'39
Role of iris changes as a cause of blindnessin lepromatous leprosyT. J. FFYTCHEFrom St Thomas's Hospital, Lambeth Palace Road, London SE] 7EH
SUMMARY Clinical and pathological investigations in a group of 113 patients with leprosy of longduration demonstrated the importance of iris changes as a cause of blindness. In lepromatousleprosy the so called 'chronic iritis' produces iris atrophy with small nonreacting pupils whichexaggerate the visual impairment created by developing lens changes and corneal opacities. Thecause of this 'chronic iritis' is believed to be neuroparalytic from early involvement of the smallnerves of the iris, particularly the autonomic supply. Clinical and pharmacological evidence forthis theory is supported by the histological changes observed in 18 specimens of iris removedduring the course of cataract surgery, with progressive atrophy of the iris preferentially affectingthe dilator muscle and leading to a nonreacting miosed pupil. Further pharmacological and histo-logical studies are to be undertaken on lepromatous patients with iris involvement with a view toestablishing possible methods of prevention.
It has for long been realised that the main causes ofblindness in leprosy lie in disease of the anteriorsegment and that the condition rarely affects thetissues at the posterior pole of the eye. Oculardamage in leprosy occurs in 4 ways: (1) facial andtrigeminal nerve involvement; (2) hypersensitivityreactions; (3) direct bacterial invasion; (4) secon-dary infection.
FACIAL AND TRIGEMINAL INVOLVEMENTLeprosy is essentially a neural disease with infectionand eventual destruction of superficial nerves byMycobacteria leprae. The anatomical position of thefacial nerve, especially the zygomatic branch, andthe superficial branches of the trigeminal nerve makethese structures vulnerable to infection in all formsof leprosy, giving rise to abnormalities of lid positionand abolition of the normal blink and cornealreflexes. A combination of these 2 nerve palsies mayoccur early in the course of the disease and lead toexposure keratitis, with its consequent cornealdamage and opacification. The incidence of thesemajor corneal problems is, however, less than mightbe expected, since preservation of the normal Bell'sphenomenon prolongs the protection of the cor-nea.1 2 Even so, facial palsy has been considered to bethe second commonest cause of blindness in leprosy.3Correspondence to T. J. ffytche.
HYPERSENSITIVITY REACTIONSIn all forms of leprosy, but particularly when achange in polarity occurs, a hypersensitivity reactioncan take place. This 'lepra' reaction usually ariseswhen therapy is being commenced or withdrawn,but can also develop spontaneously.4-6 The reactionis generalised, with acute swelling of skin lesions,tender nerves, and at times severe fever, and thesesigns have given rise to the alternative name oferythema nodosa leprosum. There is often anassociated acute iritis and at times a nephritis.7 Theclinical manifestations are believed now to becaused by circulating immune complexes becomingdeposited in the affected tissues6 8 rather than aresponse to bacteria, for although M. keprae havebeen found in the anterior chamber by paracen-tesis9-12 it is not known what role they play in thepathogenesis of the acute uveitis, and the leprareaction can occur in the absence of organisms.8The eye develops an acute iritis which is usually
bilateral and does not differ in its clinical manifesta-tions from other forms of acute nonleprous iritis.The disease has a sudden painful onset, and, ifuntreated, the eye can be permanently damagedwithin 24-72 hours.13 Aqueous flare and cells,keratic precipitates, hypopyon, and synechiae withseclusio pupillae and secondary glaucoma can occurwith secondary cataract and eventual phthisis.
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DIRECT BACTERIAL INVASIONDirect bacterial invasion occurs only in lepro-matous leprosy. It is now considered by mostauthors to take place as a result of a bacteraemiafollowing infection,7 812 1416 although some spreadmay occur from infected lacrimal and nasal pass-ages,6 7 17 but this method of spread may be rare.13The invasion of the cornea by leprosy bacilli
gives rise to a true leprous keratitis affecting cornealnerves and later the superficial stroma. This con-
dition of superficial stromal keratitis is regarded as
pathognomonic for lepromatous leprosy.18 It hasbeen alternatively called 'superficial avascularkeratitis',19 'avascular subepithelial punctatekeratitis',20 'diffuse punctate lepromatous keratitis',and 'diffuse superficial punctate keratitis'.4 Thecondition is, however, rarely serious for visionunless corneal deposits are substantial and is oftenasymptomatic.1921 It may progress to form a cir-cumferential pannus or an interstitial keratitiswhich does not produce the same degree of vas-
cularisation as syphilis2 19 and which rarely causessevere visual loss.22 A sclerosing form of keratitis mayfollow as a late change.13
Occasionally a leproma may occur in the centreof the cornea with substantial visual loss. This rare
lesion is known in some parts of the world asRuato's corneal leproma. It seems to be regional,occurring in South America23 and Japan,18 and itmay be provoked by local climatic conditions. Thecorneal leproma is responsible for only a very smallproportion of blindness in leprosy.
Other forms of corneal disease and opacificationoccur as a result of exposure and neuroparalytickeratopathy and include band-shaped degenerationand various chronic degenerative conditions. Directinvasion of the episclera occurs as an early event inlepromatous leprosy and gives rise to small nodulesat the limbus.4 They are often a prelude to leprouskeratitis, and occasionally they may grow across thecorneal margin as large lepromatous nodules, whichinterfere with vision.
IrisDirect bacterial invasion of the iris and ciliary bodyproduces the so-called 'chronic iritis,' which isconsidered by many to be the commonest cause ofvisual impairment in leprosy4152024-28 and termedby Weekeroon as the 'cause par excellence ofblindness.' The condition which is also known as
'insidious anterior uveitis'29 and 'chronic plasticiritis'20 30 commences quietly several years afterinfection. It is characterised by a lack of symptomsand overt signs, though slit-lamp examination may
show aqueous flare and cells with fine keraticprecipitates scattered all over the corneal endo-
thelium.31 Eventually iris atrophy develops, withloss of iris stroma and epithelium, miosis, and theformation of holes in the stroma resembling attimes the appearance in essential iris atrophy.Synechiae may be present and were originally notedby Hansen and Bull32 when they described 'iritiswithout violent symptoms with exudation aroundthe borders of the pupils and adhesions of the lensin patients who have not complained of pain orderangement of sight.' This tendency to formsynechiae is not, however, common to all caseswith chronic iritis.3334 Pupil reactions have beennoted to be sluggish and resistant to conventionalmydriatics early in the disease,24 202333 3 and apremature presbyopia, even in apparently normalpatients with lepromatous leprosy, was noted byWood.24 Equally asymptomatic is the developmentof 'iris pearls' in the early stages of the disease.These small glistening white lesions are pathogno-monic for lepromatous leprosy and have beenshown histologically to be composed of collectionsof tightly packed living and dead bacilli lyingwithin mononuclear cells (also called 'foam' or'lepra' cells), with little accompanying inflammationor foreign body reaction.33 36 Iris pearls usuallydevelop within a year or two of the commencementof the iritis and occur mainly at the pupil marginaround the collarette, described as resembling anecklace33 or the beads of a rosary.37
Pearls may develop deep in the iris stroma andoccasionally at the periphery. Their natural historyis one of slow increase in size and aggregation. Theymay become pedunculated and eventually drop offinto the anterior chamber, where they are welltolerated and produce no inflammatory reaction.They are a transient phenomenon and are rarelyresponsible for any visual impairment.
Bacterial invasion of the iris may also give rise tothe formation of a nodular leproma-sometimescalled 'voluminous leproma of the iris'.25 These arerare single polymorphic masses which may occasion-ally sufficiently disrupt the iris architecture tointerfere with vision.
LensDirect invasion of the lens by bacilli has never beendemonstrated and many authors consider that thereis no true leprosy cataract and that the lens changesare those seen in a normal aging population.4 7253839A secondary cataract may certainly develop afterthe acute iritis associated with hypersensitivity, butsome authors acknowledge a higher incidence ofsecondary cataract following chronic iritis.214 20 Apossible cause for cataract in lepromatous leprosywas suggested by Prabhakaran,40 who noted that theleprosy bacilli reacted with dopa, which is normally
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Role of iris changes as a cause of blindness in lepromatous leprosy
found in the iris and ciliary body, and that thisreaction is produced with high local concentrationsof quinones, which are known to be cataractogenic.
SECONDARY INFECTIONLoss of corneal sensitivity, poor nutritional control,and exposure and diminished tear production allcombine to make the cornea susceptible to secondarybacterial, viral, and fungal infections. The additionaldestruction of the nose and nasolacrimal passages inadvanced cases increases the local reservoir ofpathogenic organisms.The conclusions from a survey of the world
literature and from personal experience are thatchronic iritis is responsible for the major part ofblindness in lepromatous leprosy, although the roleof lens changes is still uncertain. A study of lepro-matous patients with advanced ocular diseaserequiring surgery was undertaken with a view todetermining the underlying pathogenesis of thischronic iritis in order that further preventivemeasures might be examined.
Material and methods
A total of 113 patients with advanced eye diseaserelated to leprosy were examined during 2 visits tothe Wilson Leprosy Centre and RehabilitationHospital at Yosu, South Korea, and a generalanalysis of this group of patients is presented in aseparate publication.34 110 patients had the lepro-matous form of the disease, 2 had the tuberculoidform, and 1 was classed as borderline. Slit-lampexamination was carried out in all cases, and theiris changes observed in 198 nonphthisical eyes aretabulated in Table 1.
Cataract surgery was undertaken in 88 patients,and histological and immunological examinationswere carried out in 18 specimens of iris removedby broad iridectomy. Fifteen of these patients hadlepromatous leprosy, 2 had the tuberculoid form,
and 1 was classed as borderline. In all patients theleprosy had been inactive for at least 3 years and inmost cases for 10 years or more.
Case reports
CASE 9A 60-year-old female with lepromatous leprosy for22 years. Negative for at least 12 years.
Right eye. Hand movements. Corneal scarring,posterior synechiae, cataract. Left eye. Hand move-ments. Posterior synechiae, cataract. Left intra-capsular lens extraction, postoperative visual acuity6/24.
Histology. Iris showed diffuse infiltration withplasma cells and lymphocytes with occasionalmacrophages Dilator fibres present sphincterdistorted by trauma and inflammation
CASE 16A 73-year-old female with lepromatous leprosy for25 years. Negative for at least 12 years.
Right eye. No perception of light (NPL). Extensivecorneal scarring with no view of intraocular struc-tures. Left eye. Counting fingers. Band shapedkeratopathy, iris atrophy and cataract. Rightenucleation carried out and left intracapsular lensextraction. Postoperative visual acuity 6/60.
Histology. Marked lymphocyte and plasma cellinfiltration of the perilimbal bulbar conjunctiva withsome plasmacytoid cells; Russell bodies also present.Stromal vascularisation and cellular infiltration ofthe cornea with a little superficial pannus towardsthe periphery with destruction of the underlyingBowman's layer. Scattered groups of leucocytesadherent to Descemet's membrane, and the iris andciliary body were the site of a diffuse lymphoidinfiltration with some Russell bodies present. Thesphincter pupillae was clearly recognisable but onlyan occasional dilator fibre could be identified (Fig. 1).The lens, choroid, and retina were normal. Specificstaining for leprosy bacilli was negative.
CASE 102A 77-year-old male with lepromatous leprosy for52 years. Negative for at least 15 years.
Right eye. Light perception. Corneal scarring, irisatrophy and posterior synechiae, cataract. Left eye.NPL. Phthisis. Right extracapsular lens extraction.Postoperative visual acuity 3/60.
Histology. Iris showed diffuse infiltration of thestroma with lymphocytes and plasma cells. Sphinctermuscle present but dilator fibres were equivocal.
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CASE 209A 66-year-old male with lepromatous leprosy for46 years. Negative for at least 12 years.
Right eye. Counting fingers. Iris atrophy andposterior synechiae, cataract. Left eye: NPL.Phthisis. Right intracapsular lens extraction; post-operative visual acuity 6/12.
Histology. Iris showed generalised atrophy withoutsigns of any active inflammation. Loss of dilator-muscle was noted but the state of the sphinctercould not be assessed.
Immunopathology. IgG 217 IU/ml, IgA 165 IU/ml,IgM 157 IU/ml.
CASE 261A 71-year-old male with lepromatous leprosy for63 years. Negative for at least 18 years.
Right eye. Counting fingers. Lagophthalmos, iris.atrophy, cataract. Left eye. 6/36. Iridectomy, aphakia,normal fundus. Right intracapsular lens extraction.Postoperative visual acuity 6/24.
Histology. Iris showed diffuse infiltration withmoderate numbers of lymphocytes and plasmacells. Almost complete absence of dilator musclewas noted.
Immunopathology. Aqueous showed the presenceof lgG but no IgA or IgM.
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Role of iris changes as a cause of blindness in lepromatous leprosy
CASE 377A 56-year-old male with lepromatous leprosy for25 years. Negative for at least 10 years.
Right eye. Counting fingers. Band-shaped kera-topathy, enlarged corneal nerves. Iris atrophy,cataract. Left eye. Light perception. Early bandshaped keratopathy. Iris naevus, iris atrophy,cataract. Left intracapsular lens extraction; post-operative visual acuity 6/36.
Histology. Iris showed diffuse infiltration withlymphocytes and plasma cells. There was almostcomplete absence of the dilator and sphinctermuscles. The iris naevus showed no unusual features.
CASE 384A 63-year-old male with lepromatous leprosy for42 years. Negative for at least 10 years.
Right eye. Counting fingers. Corneal opacities, irisatrophy and posterior synechiae, cataract. Left eye.3/60. Iris atrophy, cataract. Right extracapsular lensextraction. Postoperative visual acuity 6/36.
Histology. Iris showed mild degree of infiltrationwith plasma cells and lymphocytes. Dilator musclefibres present in normal amounts.
Immunopathology. IgG 202 IU/ml, IgA 183 IU/mi,IgM 302 IU/mi.
CASE 802A 56-year-old male with lepromatous leprosy for39 years. Negative for 12 years.
Right eye. Counting fingers. Lagophthalmos,corneal opacities, iris atrophy, cataract. Left eye.3/60. Lagophthalmos, band-shaped keratopathy, irisatrophy, cataract. Right intracapsular lens extraction.Postoperative visual acuity 3/60.
Histology. Iris showed some atrophy with a fewchronic inflammatory cells. Dilator fibres appearedto be normal; sphincter not available for study.
Immunopathology. IgG 189 IU/ml, IgA 158 IU/ml,IgM 118 IU/mi.
CASE 1019A 60-year-old female with borderline leprosy for37 years. Negative for 12 years.
Right eye. 3/60. Vascularised corneal scar, irisatrophy, and posterior synechiae, cataract. Left eye.NPL. Advanced vascularised corneal scarring.Right extracapsular lens extraction; postoperativevisual acuity 6/36.
Histology. Iris showed infiltration with smallnumber of plasma cells and lymphocytes, someplasmacytoid cells seen also. Dilator muscle present.
Immunopathology. Aqueous showed IgG but noIgA or IgM.
CASE 1144A 63-year-old female with lepromatous leprosy for54 years. Negative for 12 years.
Right eye. Hand movements. Iris atrophy andposterior synechiae, cataract. Left eye. Hand move-ments. Iris atrophy and posterior synechiae withdislocated lens. Right intracapsular lens extraction;postoperative visual acuity 6/24.
Histology. Iris showed mild infiltration withlymphocytes and plasma cells. The sphincterappeared to be intact but hardly any dilator fibrescould be identified.
Immunopathology. IgG 237 IU/mi, IgA 214 IU/ml,IgM 228 IU/mI. Rheumatoid factor positive to 1:10dilution, antismooth-muscle antibody titre 1:40.
CASE 141 5A 49-year-old male with tuberculoid leprosy for 31years. Negative for 12 years.
Right eye. 3/60. Posterior synechiae and cataract.Left eye. 3/60. Posterior synechiae and cataract.Right intracapsular lens extraction; postoperativevisual acuity 6/24.
Histology. Iris showed heavy but patchy infiltrationwith lymphocytes and plasma cells and some macro-phages with a distinct granulomatous arrangementin a few areas. Sphincter and dilator muscle werepresent.
Immunopathology. IgG 243 IU/mi, IgA 74 IU/ml,IgM 163 IU/ml. Rheumatiod factor positive to 1:10dilution. Aqueous showed IgG but no IgA or IgM.
CASE 2165A 75-year-old male with lepromatous leprosy for54 years. Negative for 12 years.
Right eye. Counting fingers. Lagophthalmos,trichiasis, band-shaped keratopathy, iris atrophy,cataract. Left eye. NPL. Lagophthalmos, cornealscarring, cataract, early phthisis. Right extracapsularlens extraction; postoperative visual acuity 3/60.
Histology. Iris showed no sign of active inflamma-tion. Dilator muscle was identified.
Fig. 3 Case 2294. Vascularised corneal scar withadvanced iris atrophy and nonreacting pupil. The raggedoutline of the pupil margin associated with loss of irisstroma is visible above the corneal scar. Vision,counting fingers.
cytes and plasma cells. Sphincter intact but there wasa complete absence of the dilator muscle.
CASE 2294A 62-year-old male with lepromatous leprosy for41 years. Negative for at least 5 years.
Right eye. Counting fingers. Vascularised cornealscar. Iris atrophy with posterior synechiae. (Fig. 3).Left eye. NPL. Vascularised corneal scar, cataract.Right extracapsular lens extraction; postoperativevisual acuity 3/60 with capsule remnants.
Histology. Iris showed heavy infiltration withplasma cells and lymphocytes and a few Russellbodies. No muscle tissue identified.
Immunopathology. IgG 365 IU/ml, IgA 420 IU/ml,IgM 410 IU/ml. Rheumatoid factor positive indilution of 1:10, antismooth muscle-antibody titre1:10.
CASE 2678A 70-year-old female with lepromatous leprosy for33 years. Negative for at least 11 years.
Right eye. Counting fingers. Iris atrophy andposterior synechiae, cataract. Left eye. NPL.Phthisis. Right intracapsular lens extraction; post-operative visual acuity 6/60.
Histology. Iris showed moderate infiltration withplasma cells, lymphocytes, and scanty macrophages.Sphincter muscle prominent but dilator muscleappeared to have atrophied.
CASE 3768A 70-year-old male with lepromatous leprosy for32 years. Negative for at least 3 years.
Right eye. Counting fingers. Band-shaped de-
generation, iris atrophy and posterior synechiae,cataract. Left eye. NPL. Old corneal abscess. Rightintracapsular lens extraction; postoperative visualacuity 6/60.
Histology. Iris showed a small amount of patchyleucocytic infiltration. Dilator muscle showedatrophy; sphincter not available for examination.
Immunopathology. IgG 206 IU/mI, IgA 244 IU/mI,IgM 135 IU/mi.
Results
All 18 specimens of iris showed negative immunoper-oxidase labelling for antibodies, and no acid-fastbacilli were observed with a modified Ziehl-Neelsenstain. Additional measurements of serum angio-tensin converting enzymes (SACE) were carried outin a total of 38 patients with active and inactivedisease-27 lepromatous of whom 16 had activedisease, 7 borderline of whom 4 were active, and 4tuberculoid of whom 2 were active. The serum wasanalysed at the Royal Northern Hospital and allexaminations were found to be negative.41The results of the IgG, IgA, and IgM measure-
ments and other immunological studies in the serumand aqueous were disappointing. In 4 out of 12cases the serum IgG, IgA, and IgM levels wereraised, and 1 patient had elevated antismooth-muscle antibody titres. Antigastric, antinuclear, andrheumatoid factors were all normal. Aqueousstudies in 4 cases showed IgG present in 3, but IgAand IgM absent in all specimens. The results in thissmall sample did not suggest any active granulo-matous process but reflected chronic low-gradenonspecific inflammatory changes.
Morphological examination of the iris in the 15patients with lepromatous leprosy showed that thedilator muscle was absent or grossly atrophied in 11eyes (73 %), whereas the sphincter was atrophied inonly 2 eyes. In 3 other specimens the sphincter wasnot seen, presumably because it had remainedadherent to the lens at the time of operation,indicating the presence of posterior synechiae. Boththe dilator and sphincter muscles appeared to benormal in the remaining 3 patients with tuberculoidand borderline leprosy. No relationship between theiris changes and the duration of the disease or theimmunological abnormalities could be established.
Studies on the morphology and histology of the irisnerves were not carried out but will be the subject offuture investigations.
Discussion
The clinical examinations carried out in this studyand many others emphasise the importance of iris
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Role of iris changes as a cause of blindness in lepromatous leprosy
involvement as a cause of visual impairment inlepromatous leprosy, but the underlying patho-logical processes have not yet been fully determined.The manifestations and late effects of the acuteiritis which occurs as part of the 'lepra' reaction arewell recognised and are no different from the iritisseen in other granulomatous disease. Prompt treat-ment with local mydriatics and steroids must beinstituted in order to avoid severe visual complica-tions. By contrast the so-called 'chronic iritis' thataffects such a large percentage of patients withlepromatous leprosy of long duration, especiallythose living in temperate climates, seems much moreresistant to conventional steroid and mydriatictherapy and is typically characterised by a lack ofsymptoms and overt clinical signs in the earlystages; its behaviour is unlike a chronic inflamma-tory condition.
Evidence from the literature and from personalobservations suggest that this 'chronic iritis' oflepromatous leprosy is not a true inflammation butrather a form of neuroparalytic iritis caused by earlyinvolvement of the iris nerves, particularly theautonomic fibres. The leprosy bacillus is known toattack fine nerve fibres, preferentially those lying inthe coolest parts of the body-the skin of theextremities, nose, ears, testis. Measurements oftemperature gradients in rabbits show that there is adifference of 60C between the temperature of thecorneal surface and the orbit, with a steady gradientthroughout the ocular tissues, with the iris about3-5°C below body temperature.42 The iris containssensory and autonomic nerves, the latter being small,nonmyelinated, containing Schwann cells, and, inthe case of sympathetic nerves, being intimatelyrelated to the myoepithelial cells of the dilatormuscle.43
Leprosy bacilli entering the eye as part of ageneralised bacteraemia that is known to occur inthe early stages of lepromatous leprosy are thereforelikely to lodge in the nerve fibres of the cornea, iris,and ciliary body, where the temperature is lowerthan the general body temperature, and the smallernonmyelinated autonomic nerves are more vulner-able than the larger myelinated sensory nerves.Involvement of corneal nerves is a well recognisedclinical entity, with local beading and thickeningfollowed by atrophy,17 1944-46 and pathologicalstudies confirm leprous infiltration of the cytoplasmof the Schwann cells with the development of nodulesand eventual destruction.'9 A parallel situationexists clinically in the iris with the formation of irispearls. These lesions are asymptomatic and do notappear to be associated with any marked inflamma-tory changes in the anterior chamber. They occurearly in the course of lepromatous leprosy and they
also eventually disappear, and their resemblance tocorneal beading has previously been commentedon.20 Iris pearls accumulate preferentially around thepupil margin, though they occur also in the deep irisstroma and occasionally at the periphery. Thisdistribution conforms with the major network ofiris nerves which form a plexus around the pupil.Histologically the iris pearls consist of tightlypacked bacilli within mononuclear cells with littleaccompanying foreign body reaction or inflammatorychanges-a pattern which is repeated in lepromasrelated to nerve tissue elsewhere in the body. Theevidence that iris pearls represent lepromatousinfiltration and later destruction of iris nerves isstrong but not yet conclusive. Electron microscopicstudies have shown lepra cells infiltrating the irisstroma and destroying nonmyelinated nerves,47 butthe same study revealed that many of the largernerves were unaffected, and it was therefore sug-gested that the iris involvement was primarily amyositis. Personal observation during cataractsurgery in lepromatous patients also showed that insome patients, even with advanced iris atrophy,pulling on the iris caused some discomfort, indicatingthat some sensory fibres remained intact. A possibleexplanation is that the larger sensory nerves, whichare myelinated, are more resistant to lepromatousinfiltration and damage, but obviously furtherhistological evidence for this must be sought.The suggestion that the 'chronic iritis' of lepro-
matous leprosy is in reality a neuroparalytic iritis,however, receives considerable clinical support. Theincreasingly sluggish pupils and their poor responseto mydriatics have already been commented on,together with the premature presbyopia in apparentlynormal patients. An important pharmacologicalstudy by Swift and Bauschard48 on lepromatouspatients, some of whom had no overt signs of ocularinvolvement, showed that in 11 out of 20 patientsthe pupils dilated with L-epinephrine, whereasdilatation occurred in only 1 out of 20 normalsubjects. These responses indicated an early auto-nomic denervation hypersensitivity, and the com-ment was made that the leprous iris was a primeexample of peripheral postganglionic denervation.Slem5 also considered the iritis to be neurotrophic,comparing the appearance with essential iris atrophyand recommending further studies.
These observations and the results of the presentstudy suggest early involvement of the autonomicnerves in the lepromatous iris, with their eventualdestruction, and the late effects of neuroparalysisinclude the slow atrophy of the iris muscle andassociated chronic low-grade inflammatory changes.
Histological studies presented demonstrate that in11 out of 15 cases the dilator muscle was preferenti-
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ally affected in this atrophic process. The reason forthis has not yet been established, but it may reflectthe relative size of the muscle in comparison with thesphincter pupillae, the difference in the muscle fibre,and the intimate relationship of the dilator fibreswith the terminal sympathetic nerves. This differ-ential atrophy of the iris muscles associated withautonomic denervation produced the characteristicmiosed nonreacting pupil, and this was augmentedin a number of cases (24% in this series) by posteriorsynechiae. Since dilator function is likely to beprejudiced in the early stages of the 'chronic iritis' oflepromatous leprosy, it is not surprising that theconventional anticholinergic mydriatics are ineffec-tive.
It is possible that the clinical signs of this silentiritis with faint flare, a few cells, and white eyeswithout any discomfort are the manifestations of theslow breakdown of the iris muscle following auto-nomic denervation, and the absence of widespreadinflammatory changes in many of the iris specimensexamined histologically together with lack of anyevidence of gross immunological abnormalities inthe sera and aqueous lends support to this theory.More research is required into the pharmaco-
logical responses and neuropathology of the iris inthe early stages of lepromatous leprosy, sinceidentification of autonomic involvement could leadto therapy designed to prevent dilator atrophy withits complication of persistent miosis. The clinicalstudies in lepromatous patients emphasise how oftenthe small nonreacting pupil plays a major role in thecause of the visual impairment, and prevention ofthese changes would be a positive step in combatingblindness in these already severely disabled patients.
None of this work would have been possible without the helpand support of Professor A. Garner, of the Institute ofOphthalmology, who carried out the histological studies ofthe iris specimens. I thank Dr Stanley C. Topple, Dr MiaTopple, Dr Akiko Obara, Dr Yoo Kyeung Un, and all thestaff of the Wilson Leprosy Centre and RehabilitationHospital, Yosu, South Korea for the invaluable help andhospitality.
I am indebted to LEPRA and St Thomas's Hospital forfinancial aid and to Mrs Lesley Gibbons for her secretarialassistance.
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