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Some observations on the ocular pathology of onchocerciasis
SOME O B S E R V A T I O N S O N T H E O C U L A R P A T H O L O G Y OF ONCHOCERCIASIS* Eleanor V. Paul, M.S.,t and Lorenz E. Zimmerman,.M.D.$
Abstract One blind eye was enucleated surgically from each of three African patients who had onchocerciasis. Histopathologic study revealed severe chronic sclerokeratitis and nongranulomatous uveitis with secondary glaucoma in each of these eyes. Microfilariae were readily identified in the cornea and sclera and in several other tissues of all three eyes. One eye had a focal area involving the temporal part of the macula in which all retinal layers were markedly degenerated. It is suggested that this is attributable to an earlier bout of severe choroiditis that had led to choroidal sclerosis and atrophy of the choriocapillaris.
Ocular involvement in onchocerciasis is responsible for the most significantly disabling complication of this diseaseblindness. It has been estimated that no less than halfa million Africans are blinded as a consequence of their infection by Onchocerca volwtlus~ and that in some provinces of Nigeria and the Congo 30 per cent of the entire population is blind from this cause. 2 Both in Africa and in Central America the incidence of blindness is greatest in villages 2000 to 3000 feet above sea level. In spite of the great frequency of blindness attributable to onchocerciasis, very few pathologists h~ive had an opportunity to study the ocular lesions. Rodger, however, in a comprehensive
series of papers, has provided a wealth of information on the pathology and pathogenesis of ocular onchocerciasis, based on his extensive clinical experience over a five year period in Ghana, Nigeria, and tim Cameroons, supplemented by his personal histopathologic study of 12 eyeballs and 37 pieces of tissue, as well as observations made in a series of experimental studies) The interested reader will also find an excellent summary of the literature on ocular onchocerciasis in Rodger's papers. T h e ocular lesions of onchocerciasis are the result of migration of the microfilariae into the affected tissues. The degree and extent of ocular involvement
*This work was supported ill part b)" USI'HS Trainin.g Grant EY-00032-08 from the National Eye Institute, NIH, Bethesda, Maryland. T h e opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting tile views of the Department of the Army or the Department of Defense. tltistologist, Ophthahnic Pathology Branch, Armed Forces Institute of l'athology, Washington, D.C. *Chief, Ophthalmic Pathology Branch, Armed Forces Institute of l'atholog)-. Clinical Professor of Ophthalmic Pathology, T h e George Washington University School of Medicine, Washington, D.C.
581
HUMAN PATHOLOGY--VOLUME 1, NUMBER 4 December1970 appears to depend on the density of cutaneous infestation and the proximity of the subcutaneous nodule containing adult worms.-" The living microfilariae, regardless of where they may be, seem to provoke remarkably little inflammation, but when the)' die they disintegrate rapidly, stimulating at first an intense eosinophilic response and subsequently a proliferation of mononuclear cells. Most visual disability results from the sclerosing keratitis that leads to the formation of an inflammatory pannus, but the infection may be rendered still more serious when the microfilariae invade the eye and produce iridocyclitis. This often leads to an accumulation o f exudate in the anterior chamber and the formation of anterior and posterior synechias. These complications frequently cause opacification of the lens and secondary glaucoma. Still another serious complication leading to severe visual disability is choroiditis, which may eventuate in extensive chorioretinal degeneration and scarring. In 1965, at the Sudan Interior Mission Eye Hospital in Kano, Nigeria, an eye was enucleated surgically from each of two patients who had become blind from complications of onchocerciasis. The specimens were fixed in aqueous formalin and shipped to the Armed Forces Institute of Pathology for pathologic examination. A third surgically enucleated eye was received early in 1970 from Chad, Africa. Although the Registry of Ophthahnic Pathology of the Armed Forces Institute of Pathology has on file material from nine eyes showing ocular lesions of onchocerciasis, in six of the cases we have only a few random sections. Our purpose in this paper is to describe and illustrate the most important ocular lesions observed in the three eyeballs that were received intact and that we have been able to study more thoroughly.
CASE REPORTS CASE 1 (AFIP ACCESSION NO,
1159986) Clinical History A 20 year old Nigerian man com-
582 plained of pain, photophobia, and loss of
vision bilaterally for six months. Examination revealed eccentric pupils as a result of peripheral anterior synechias, advanced inferior marginal sclerosing keratitis, secondary glaucoma, and optic atrophy bilaterally. Vision was reduced to light perception with the right eye and to counting fingers with the left. A diagnosis of onchocerciasis was made, and the right eye was enucleated. The patient had previously been given Antrypol intravenously and Hetrazan by mouth.
Macroscopic Observations The surgically enucleated right eye measured 25 by 23 by 23 mm., and a 2 ram. segment of optic nerve was attached. The cornea measured 12 by 11 ram., and the limbus was pigmented. A pigmented pannus extended throughout the inferior half of the cornea. At 2 and 10 o'clock there were small whitish opacities in the cornea near the limbus. The globe transmitted light moderately well and was opened obliquely from 10 to 4 o'clock, q~he anterior chamber was filled with a fibrinous exudate. The vitreous body was detached posteriorly, but the retina and choroid were in place. A few areas of depigmentation were noted in the choroid. The optic nerve head appeared atrophic and slightly cupped.
Microscopic Description An infiltrate of chronic inflammatory cells is present in the substantia propria of the conjunctiva, in the episcleral tissues, and in scattered foci of the sclera (Fig. 1). In many sections microfilariae are demonstrable in the cornea (Fig. 2) and sclera, especially anteriorly, but some are also found posterior to the equator (Fig. 3). The corneal epithelium is slightly irregular and in scattered areas contains a few inflammatory cells. There is edema of the basal cell layer in some areas, and subepithelial bullae are present. Melanocytic pigmentation is observed in the corneal epithelium. There is an extensive inflammatory pannus, more prominent in the periphery, and it has replaced Bowman's membrane in scattered areas. The pannus is composed of chronic inflammatory cells and fibrovascular tissue. In the moderately
(Text continued on page 587)
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Figure 1. An infil(rate ofchronic inflammatory cells is present in the subconjunctiva and episcleral tissues. Melanocytic pigmentation may be seen in the epithelium. (Hematoxylin and eosin stain. • 145, AFIP Neg. 65-2710.)
Figure 2. A, T h e r e is a bullous detachnlent of tile corneal epithelium; a microfilaria can be seen beneath the bulla (arrow). B, Higher magnification of microfilaria shown in A. (Hematoxylin and eosin stain. • and )<575. AFIP Neg. 65-2030.)
583
HUMAN PATHOLOGY--VOLUME
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Figure 3. A , Arrow indicates position of microfilaria in sclera posteriorly. B , Same microfilaria at higher magnification. (ttematoxylin and eosin stain. X50 and x440. AF1P Neg. 65-2027.)
Figure 4. Bowman's membrane is replaced b) an inflammatory pannus, and there is deep vascularization of the corneal stroma. An infiltrate of lymphocytes and plasma cells accompanies tbe blood vessels. (Hematoxylin and eosin stain. • AFIP Neg. 65-2043.)
584
THE OCULAR PATHOLOGY
O F O N C H O C E R C 1 A S I S - - P A U L , ZIMMERMAN
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Figure 5. A, Microfilaria (arrow) in corneal epithelium. (Hematoxylin and eosin stain. X485. AFIP Neg. 65-2708.) B, Microfilaria in superficial corneal stroma. (ttematoxylin and eosin stain, x305. AFIP Neg. 652023.) C, Microfilaria close to Descemet's membrane. The corneal endothelium is~degenerated, and there is proteinaceous exudate ill the anterior chamber. (ttematoxylin and eosm stain, x4,t0. AF1P Neg. 65-2028.)
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Figure 6. The shallow anterior chamber contains protei,mceous exudate. (Hematoxylin and eosin sta,n. AFIP Neg. 65-2038.)
585
HUMAN
PATHOLOGY--VOLUME
1, N U M B E R 4
December 1970
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Figure 7. Organized exudate is adherent to tile anterior surface of the iris. Two microfilariae (arrow) are present along with chronic inflatmnatory cells, pigment, and fibroblasts. (Hematoxylin and eos[n stain. • AFIP Neg. 65-2029.)
.
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Figure 8. A light infiltrate of chronic inflammatory cells, including Russell bodies, is present in the atrophic iris. (Hematoxylin and eosin stain, x305. AFIP Neg. 65-2042.)
586
T H E O C U L A R P A T H O L O G Y OF O N C H O C E R C I A S I S - P A O L , ZIMMERMAN
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Figure 9. An intact microfilaria is present in the vitreous. (Hematoxyl!n and eosin stain, x195. AFIP Neg. 66-7544.)
vascularized corneal stroma there is a 9fairly dense infiltrate of chronic inflammatory cells (Fig. 4); some neutrophils are also present. Hypertrophied corneal nerves are identified in the corneal stroma. In many of the sections studied, microfilariae are present at various levels in the cornea (Fig. 5). Some are intact, but others are fragmented or degenerated. The corneal endothelium appears to be degenerated. The anterior chamber is shallow and contains a dense proteinaceous exudate (Fig. 6), which in some areas has become organized. Some chronic inflammator) ~' ceils, pigment and pigment-laden macrophages, and, in a few sections, microfilariae may be seen in the anterior chamber (Fig. 7). T h e chamber angle is Open in some sections, but the trabecular meshwork is hyalinized. In other sections there are fine peripheral anterior synechias. The atrophic iris contains focal areas of necrosis, and its stroma is densely infiltrated with lymphocytes, plasma cells, plasmacytoid cells, and Russell bodies (Fig. 8). A similar infiltrate is also present in the ciliary body. There is moderate
atrophy of the ciliary muscles and prominent hyalinization of the ciliary processes9 There are early degenerative cbanges of the lens cortex and mild sclerosis of the nucleus. The choroid is lightly infiltrated with chronic inflammatory cells. The retinal pigment epithelium reveals focal areas of degeneration ill which the cells appear flattened and partially depigmented. Atrophy of the nerve fiber and ganglion cell layers is observed in the retina (Fig. 3). There is shallow cupping of the optic disc, and the optic nerve reveals atrophy of the nerve fibers, as well as gliosis and thickening of tile pill septa. In a few sections, intact microfilariae are present in the vitreous (Fig. 9).
Diagnoses Chronic interstitial sclerokeratitis, conjunctivitis, and nongranulomat0us uveitis resulting from onchocerciasis; secondary glaucoma with atrophy of the optic nerve and retina; secondary acquired melanosis of the cornea.
587
HUMAN I'ATHOLOGY--VOLUME 1, NUMBER 4 December1970 CASE 2 (AFIP ACCESSION NO. 1166194)
vitreotts body was very cloudy, obscuring the retina. T h e optic disc was cupped.
Clinical History A 28 year old Nigerian man gave a history of poor vision accompanied by tearing and photophobia for two )'ears. Examination revealed acute limbitis, marginal keratitis, a pigmented pannus, iritis, and secondary glaucoma bilaterally. Vision was reduced to perception of hand movements with the right eye and to 20/200 with the left. A diagnosis of"onchocereal keratitis and uveitis with secondary glaucoma" was made, and the right eye was enucleated. No medical therapy was employed prior to enucleation.
Macroscopic Observations The specimen consisted of a firm right eye measuring 28 by 25 by 25 mm. with 4 ram. of the optic nerve attached. The eye transmitted light poorly. The cornea was opaque, and there was extensive melanokeratosis (Fig. 10). The limbal conjunctiva was pigmented, and temporally it was thickened. The eye was opened in the horizontal plane. The anterior chamber was deep, and the pupil appeared round and central. Several peripheral anterior synechias were noted. The
MicroscopicDescription An inflammatory infiltrate, composed primarily of 1)'mphocytes and plasma cells with a sprinkling of eosinophils, is present in the conjunctival stroma and continues beneath the corneal epithelium as an inflammatory pannus. There is mild episcleritis, and an occasional focus of perivasculitis is observed in the sclera. In many of the serially prepared sections, fragments and whole microfilariae are present in the sclera, and some are also observed in the corneal stroma. Edema and increased pigmentation of the corneal epithelium are present, and there is a large central bulla. The substantia propria is moderately vascularized and contains a sprinkling of chronic inflammatory cells. The corneal endothelium is irregularly degenerated. Peripheral anterior synechias cover the hyalinized trabecular meshwork in many sections. Much of the dilator muscle of the iris is necrotic, and in the stroma there are numerous melanophages. A very mild chronic inflammatory infiltrate is present in tire iris and ciliary body. A marked loss
Figure 10. Main block of eye after removal of calottes. The cornea is opaque and vascularized.Tile limbal tissuesare irregularly thickenedand pigmented.(AFIP Neg. 65-2756.)
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THE OCULAR PATHOLOGY OF ONCHOCERCIASIS--PAuL, ZIMMERMAN
j Figure 11. Microfilaria on inner surface of retina. (Hematoxylin and eosin stain. • AFIP Neg. 70-2055.)
. "
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Ji o f ganglion cells and disintegration o f rods and cones, particularly anteriorly and temporally, are n o t e d in the retina. Posteriorly the retinal pigment epithelium appears flattened, m o d e r a t e l y d e g e n e r a t e d , and partially d e p i g m e n t e d . T h e r e is a d e e p glaucomatous c u p p i n g o f the optic disc, and a cross section o f the optic nerve reveals cavernous degeneration. In a few sections, microfilariae are seen in the retina, vitreous, and lamina cribrosa o f the optic nerve (Figs. 1 1 and 12).
Diagnoses Chronic interstitial sclerokeratitis and mild n o n g r a n u l o m a t o u s uveitis caused by
onchocerciasis; s e c o n d a r y glaucoma witb advanced optic atrophy; secondary acq u i r e d melanosis o f cornea.
CASE 3 (AFIP ACCESSION NO. 378722)
Clinical History A 39 year old native o f Chad, Africa, was e x a m i n e d by m e m b e r s o f a team b e a d e d by Dr. Alfred A. Buck studying onchocerciasis there. Examination revealed subcutaneous nodules on the chest wall and over the iliac crests. His right eye had no light perception. Snips o f bis right
Figure 12. Microfilaria in lamina cribrosa of optic nerve. (Hematoxylin and eosin stain. x750. AFIP Neg. 70-2054.)
589
HUMAN PATHOLOGY--VOLUME 1, NUMBER 4 December1970 flank and conjunctiva were taken, and microfilariae were found in both tissues. The blind right eye was enucleated. No information was recorded about the left eye.
Macroscopic Observations The specimen consisted of an intact right eye measuring 20 by 21 by 23 mm. with a depressed cornea measuring 10 by 10 mm. Concentric stromal opacities were present in the cornea. The limbal conjunctiva appeared hypertrophic and pigmented and had encroached on the peripheral cornea circumferentially. The corneal epithelium was disrupted. The optic nerve had been cut flush with the globe. The eye was opened in a horizontal plane, revealing a thickened cornea, a deep anterior chamber centrally, and peripheral anterior synechias. Pigment was dispersed throughout the anterior chamber. White deposits were noted on the surface of the iris. The lens appeared yellow. T h e margins of the optic nerve head were blurred and raised.
590
Microscopic Description In the conjunctival stroma there are chronic inflammatory cells, including eosinophils. This infiltrate continues into a peripheral pannus, on both sides, in which eosinophilic granules are also noted. The irregularly thinned, pigmented corneal epithelium is partially denuded. Numerous onchocercal microfilariae are present in the substantia propria of the cornea, which is moderately vascularized and exhibits a loss of keratocytes. On the posterior surface of the cornea there is an irregularly thickened, pigmented, inflammatory fibrous membrane that in some sections extends back to attach to a hyalinized fibrous pupillary membrane. In some sections a peripheral anterior synechia is present on one side, whereas in others inflammatory cells and pigmented macrophages line the trabecular meshwork. Chronic inflammatory cells and numerous pigmented clumps are seen in the iris stroma. T h e dilator muscle is largely necrotic, as is much of the pigmented epithelium. In the stroma of the iris a
Figure 13. Arrows indicate rnicrofilariaein the iris stroma. (Hematoxylinand eosin stain, x395. AFIP Neg. 70-6170.)
THE OCULAR PATHOLOGY OF ONCHOCERCIASIS--PAUL, ZI.'t,IMER3.1AN
Figure 14. .4, There is a light infiltrate of chronic inflammatory cells in the pars plicata, as well as marked hyalinization of the vascular layer. Arrow indicates two microfilariae, shown at greater magnificationin B. (,.t: Hematoxylin and eosin stain. Xl00. AFIP Neg. 70-6055. B: Hematoxylin and eosin stain. • AFIP Neg. 706054.)
n u m b e r of microfilariae are f o u n d (Fig. 13). In the r e m a i n d e r of the uveal tract there is an infiltrate of chronic inflammatory cells, sometimes accompanied by eosinophils, a n d in areas there is marked hyalinization. Well preserved microfilariae are present in the ciliary body (Fig. 14). Beginning in the temporal part of the macula, there is a discrete area of marked retinal thinning, measuring approximately 2 ram. in diameter. In this area all layers are markedly degenerated (Fig. 15). In the area of maximal damage only nuclei from the inner nuclear layer and the retinal vessels are identifiable. A n u m b e r of macrophages, heavily laden with melanin granules, are contained within this area of retinal degeneration, but similar pigment-containing macrophages are scattered along the partially degenerated layer of rods and cones. Corresponding in location to the discrete area of marked retinal thinning is a zone in which the retinal pigment epithelium appears flattened, degenerated, and partially depigmented. In this area and to a lesser
extent elsewhere the choroid reveals marked hyalinization with partial atrophy and disappearance of the choriocapillaris (Fig. 16). T h r o u g h o u t the retina there is a loss of ganglion cells. Microcystoid degeneration and loss of nuclei from the external nuclear layer are observed in the macula. In several sections of tile retina microfilariae are observed in the lumens of blood vessels in the nerve fiber layer (Fig. 17). T h e r e is gliosis in the atrophic optic nerve, and microfiIariae are f o u n d in the meningeal sheaths. Many microfilariae are located in the sclera and episcleral tissues, beside tile extraocular muscles, and near the short posterior ciliary nerves and vessels.
Diagnoses Chronic interstitial sclerokeratitis and n o n g r a n u l o m a t o u s uveitis resulting from onchocerciasis; secondary glaucoma with atrophy of tile retina and optic nerve; focal retinal degeneration; secondary acquired melanosis of the cornea.
591
HUMAN
PATHOLOGY--VOLUME
1, N U M B E R 4
December 1970
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Figure 15. There is a localized area of retinaI thinning in which all layers are markedly degenerated. The posterior surface of tile vitreous (PV) is detached from tile retina. (Hematoxylin and eosiq stain, x50. AFIP Neg. 70-6175.)
592
Figure 16. To tile left of arrow tile retinal pigment epitheliunl appears very thin and degenerated and the choriocapillaris is almost obliterated. There is diffuse hyalinization of the dmroidal stroma. (Hematoxylin and eosin stain, x260. AFIP Neg. 70-6603.)
THE
OCULAR
PATHOLOGY
OF ONCHOCERCIASIS--PAuL,
ZIMMER,MAN
Figure 17. A microfilaria is seen in tile lumen of a large blood vessel in tile nerve fiber layer of the retina. (Hematoxylin and eosin stain. • AFIP Neg. 70-6057.)
593
HUMAN PATHOLOGY--VOLUME 1, NUMBER 4 December 1970
COMMENT In these t h r e e eyes we have had an o p p o r t u n i t y to observe the m o s t typical findings o f a d v a n c e d ocular onchocerciasis. T h e patients h a d b e c o m e blind as a consequence o f the c o m b i n e d effects o f chronic sclerosing keratitis with p a n n u s f o r m a t i o n a n d chronic uveitis with s e c o n d a r y glaucoma. Microfilariae, a p p a r e n t l y viable as well as disintegrating ones, were observed in virtually all ocular tissues f r o m the c o r n e a to the optic disc, except for the lens. T h e y were readily identified in the c o r n e a a n d sclera b u t were m o r e difficult to detect in the o t h e r tissues. T h e areas o f intense choroiditis with secondar.y chorioretinal d e g e n e r a t i o n a n d scarring that have excited so m u c h interest a n d speculation t, 3 were not o b s e r v e d in the two cases f r o m Nigeria, but in the case f r o m C h a d there was a localized area o f severe retinal d e g e n e r a t i o n that m a y well have been the result o f intense choroiditis that eventually subsided with m a r k e d hyalinization o f the c h o r o i d a n d a t r o p h y o f the choriocapillaris.
pital, Kano, Nigeria, for having contributed the first two o f tile eyes on which this r e p o r t was based. T h e third eye was c o n t r i b u t e d by Drs. J a m e s P. Ganley a n d Daniel H. C o n n o r , who were m e m b e r s o f a t e a m o f physicians a n d scientists b e a d e d by Dr. A l f r e d A. Buck, G e o g r a p h i c Epid e m i o l o g y Unit, J o l m s H o p k i n s University, s t u d y i n g onchocerciasis in C h a d u n d e r the auspices o f the U.S. A r m y Medical Research a n d D e v e l o p m e n t C o m m a n d (contract n u m b e r DADA-17-70-C0028), D e p a r t m e n t o f the A r m y , Washington, D.C.
REFERENCES 1. Rodger, F. C.: Tile pathogenesis and pathology of ocular onchocerciasis. Amer. J. Ophthal., 49:104-135,327-337, and 560-594, 1960. 2. Duke-Elder, S.: Diseases of the outer eye. In DukeElder, S. (Editor): System of Ophthahnology. London, Henry Kimpton, 1965, Vol. VIII, Part I, pp. 406-414. 3. Duke-Elder, S., and Perkins, E. S.: Diseases of tile uveal tract. In Duke-Elder, S. (Editor): System of Ophthalmology. London, Henry Kimpton, 1966, Vol. IX, pp. 444-453.
ACKNOWLEDGMENTS We are grateful to Dr. Ben Kietzman o f the S u d a n I n t e r i o r Mission Eye Hos-
594
Ophthalmic l'athology Branch Armed Forces Institute of Pathology Washington, D.C. 20305 (Dr. Zimmerman)
Abstract One blind eye was enucleated surgically from each of three African patients who had onchocerciasis. Histopathologic study revealed severe chronic sclerokeratitis and nongranulomatous uveitis with secondary glaucoma in each of these eyes. Microfilariae were readily identified in the cornea and sclera and in several other tissues of all three eyes. One eye had a focal area involving the temporal part of the macula in which all retinal layers were markedly degenerated. It is suggested that this is attributable to an earlier bout of severe choroiditis that had led to choroidal sclerosis and atrophy of the choriocapillaris.
Ocular involvement in onchocerciasis is responsible for the most significantly disabling complication of this diseaseblindness. It has been estimated that no less than halfa million Africans are blinded as a consequence of their infection by Onchocerca volwtlus~ and that in some provinces of Nigeria and the Congo 30 per cent of the entire population is blind from this cause. 2 Both in Africa and in Central America the incidence of blindness is greatest in villages 2000 to 3000 feet above sea level. In spite of the great frequency of blindness attributable to onchocerciasis, very few pathologists h~ive had an opportunity to study the ocular lesions. Rodger, however, in a comprehensive
series of papers, has provided a wealth of information on the pathology and pathogenesis of ocular onchocerciasis, based on his extensive clinical experience over a five year period in Ghana, Nigeria, and tim Cameroons, supplemented by his personal histopathologic study of 12 eyeballs and 37 pieces of tissue, as well as observations made in a series of experimental studies) The interested reader will also find an excellent summary of the literature on ocular onchocerciasis in Rodger's papers. T h e ocular lesions of onchocerciasis are the result of migration of the microfilariae into the affected tissues. The degree and extent of ocular involvement
*This work was supported ill part b)" USI'HS Trainin.g Grant EY-00032-08 from the National Eye Institute, NIH, Bethesda, Maryland. T h e opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting tile views of the Department of the Army or the Department of Defense. tltistologist, Ophthahnic Pathology Branch, Armed Forces Institute of l'athology, Washington, D.C. *Chief, Ophthalmic Pathology Branch, Armed Forces Institute of l'atholog)-. Clinical Professor of Ophthalmic Pathology, T h e George Washington University School of Medicine, Washington, D.C.
581
HUMAN PATHOLOGY--VOLUME 1, NUMBER 4 December1970 appears to depend on the density of cutaneous infestation and the proximity of the subcutaneous nodule containing adult worms.-" The living microfilariae, regardless of where they may be, seem to provoke remarkably little inflammation, but when the)' die they disintegrate rapidly, stimulating at first an intense eosinophilic response and subsequently a proliferation of mononuclear cells. Most visual disability results from the sclerosing keratitis that leads to the formation of an inflammatory pannus, but the infection may be rendered still more serious when the microfilariae invade the eye and produce iridocyclitis. This often leads to an accumulation o f exudate in the anterior chamber and the formation of anterior and posterior synechias. These complications frequently cause opacification of the lens and secondary glaucoma. Still another serious complication leading to severe visual disability is choroiditis, which may eventuate in extensive chorioretinal degeneration and scarring. In 1965, at the Sudan Interior Mission Eye Hospital in Kano, Nigeria, an eye was enucleated surgically from each of two patients who had become blind from complications of onchocerciasis. The specimens were fixed in aqueous formalin and shipped to the Armed Forces Institute of Pathology for pathologic examination. A third surgically enucleated eye was received early in 1970 from Chad, Africa. Although the Registry of Ophthahnic Pathology of the Armed Forces Institute of Pathology has on file material from nine eyes showing ocular lesions of onchocerciasis, in six of the cases we have only a few random sections. Our purpose in this paper is to describe and illustrate the most important ocular lesions observed in the three eyeballs that were received intact and that we have been able to study more thoroughly.
CASE REPORTS CASE 1 (AFIP ACCESSION NO,
1159986) Clinical History A 20 year old Nigerian man com-
582 plained of pain, photophobia, and loss of
vision bilaterally for six months. Examination revealed eccentric pupils as a result of peripheral anterior synechias, advanced inferior marginal sclerosing keratitis, secondary glaucoma, and optic atrophy bilaterally. Vision was reduced to light perception with the right eye and to counting fingers with the left. A diagnosis of onchocerciasis was made, and the right eye was enucleated. The patient had previously been given Antrypol intravenously and Hetrazan by mouth.
Macroscopic Observations The surgically enucleated right eye measured 25 by 23 by 23 mm., and a 2 ram. segment of optic nerve was attached. The cornea measured 12 by 11 ram., and the limbus was pigmented. A pigmented pannus extended throughout the inferior half of the cornea. At 2 and 10 o'clock there were small whitish opacities in the cornea near the limbus. The globe transmitted light moderately well and was opened obliquely from 10 to 4 o'clock, q~he anterior chamber was filled with a fibrinous exudate. The vitreous body was detached posteriorly, but the retina and choroid were in place. A few areas of depigmentation were noted in the choroid. The optic nerve head appeared atrophic and slightly cupped.
Microscopic Description An infiltrate of chronic inflammatory cells is present in the substantia propria of the conjunctiva, in the episcleral tissues, and in scattered foci of the sclera (Fig. 1). In many sections microfilariae are demonstrable in the cornea (Fig. 2) and sclera, especially anteriorly, but some are also found posterior to the equator (Fig. 3). The corneal epithelium is slightly irregular and in scattered areas contains a few inflammatory cells. There is edema of the basal cell layer in some areas, and subepithelial bullae are present. Melanocytic pigmentation is observed in the corneal epithelium. There is an extensive inflammatory pannus, more prominent in the periphery, and it has replaced Bowman's membrane in scattered areas. The pannus is composed of chronic inflammatory cells and fibrovascular tissue. In the moderately
(Text continued on page 587)
THE
.,
,,,
OCULAR
PATHOLOGY
Z.'*-."*--'5)-~,-...'>~'~'~-,-":~
-;
2 ~
OF ONCHOCERCIASIS-PAtJe,
__5~
"...;.,2
~.'~;.-~-.~,~=r
_ ~,:-~.
ZI.MMERMAN
-',
Figure 1. An infil(rate ofchronic inflammatory cells is present in the subconjunctiva and episcleral tissues. Melanocytic pigmentation may be seen in the epithelium. (Hematoxylin and eosin stain. • 145, AFIP Neg. 65-2710.)
Figure 2. A, T h e r e is a bullous detachnlent of tile corneal epithelium; a microfilaria can be seen beneath the bulla (arrow). B, Higher magnification of microfilaria shown in A. (Hematoxylin and eosin stain. • and )<575. AFIP Neg. 65-2030.)
583
HUMAN PATHOLOGY--VOLUME
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~.
L
. ~
1, N U M B E R 4
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Figure 3. A , Arrow indicates position of microfilaria in sclera posteriorly. B , Same microfilaria at higher magnification. (ttematoxylin and eosin stain. X50 and x440. AF1P Neg. 65-2027.)
Figure 4. Bowman's membrane is replaced b) an inflammatory pannus, and there is deep vascularization of the corneal stroma. An infiltrate of lymphocytes and plasma cells accompanies tbe blood vessels. (Hematoxylin and eosin stain. • AFIP Neg. 65-2043.)
584
THE OCULAR PATHOLOGY
O F O N C H O C E R C 1 A S I S - - P A U L , ZIMMERMAN
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Figure 5. A, Microfilaria (arrow) in corneal epithelium. (Hematoxylin and eosin stain. X485. AFIP Neg. 65-2708.) B, Microfilaria in superficial corneal stroma. (ttematoxylin and eosin stain, x305. AFIP Neg. 652023.) C, Microfilaria close to Descemet's membrane. The corneal endothelium is~degenerated, and there is proteinaceous exudate ill the anterior chamber. (ttematoxylin and eosm stain, x4,t0. AF1P Neg. 65-2028.)
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Figure 6. The shallow anterior chamber contains protei,mceous exudate. (Hematoxylin and eosin sta,n. AFIP Neg. 65-2038.)
585
HUMAN
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Figure 7. Organized exudate is adherent to tile anterior surface of the iris. Two microfilariae (arrow) are present along with chronic inflatmnatory cells, pigment, and fibroblasts. (Hematoxylin and eos[n stain. • AFIP Neg. 65-2029.)
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Figure 8. A light infiltrate of chronic inflammatory cells, including Russell bodies, is present in the atrophic iris. (Hematoxylin and eosin stain, x305. AFIP Neg. 65-2042.)
586
T H E O C U L A R P A T H O L O G Y OF O N C H O C E R C I A S I S - P A O L , ZIMMERMAN
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Figure 9. An intact microfilaria is present in the vitreous. (Hematoxyl!n and eosin stain, x195. AFIP Neg. 66-7544.)
vascularized corneal stroma there is a 9fairly dense infiltrate of chronic inflammatory cells (Fig. 4); some neutrophils are also present. Hypertrophied corneal nerves are identified in the corneal stroma. In many of the sections studied, microfilariae are present at various levels in the cornea (Fig. 5). Some are intact, but others are fragmented or degenerated. The corneal endothelium appears to be degenerated. The anterior chamber is shallow and contains a dense proteinaceous exudate (Fig. 6), which in some areas has become organized. Some chronic inflammator) ~' ceils, pigment and pigment-laden macrophages, and, in a few sections, microfilariae may be seen in the anterior chamber (Fig. 7). T h e chamber angle is Open in some sections, but the trabecular meshwork is hyalinized. In other sections there are fine peripheral anterior synechias. The atrophic iris contains focal areas of necrosis, and its stroma is densely infiltrated with lymphocytes, plasma cells, plasmacytoid cells, and Russell bodies (Fig. 8). A similar infiltrate is also present in the ciliary body. There is moderate
atrophy of the ciliary muscles and prominent hyalinization of the ciliary processes9 There are early degenerative cbanges of the lens cortex and mild sclerosis of the nucleus. The choroid is lightly infiltrated with chronic inflammatory cells. The retinal pigment epithelium reveals focal areas of degeneration ill which the cells appear flattened and partially depigmented. Atrophy of the nerve fiber and ganglion cell layers is observed in the retina (Fig. 3). There is shallow cupping of the optic disc, and the optic nerve reveals atrophy of the nerve fibers, as well as gliosis and thickening of tile pill septa. In a few sections, intact microfilariae are present in the vitreous (Fig. 9).
Diagnoses Chronic interstitial sclerokeratitis, conjunctivitis, and nongranulomat0us uveitis resulting from onchocerciasis; secondary glaucoma with atrophy of the optic nerve and retina; secondary acquired melanosis of the cornea.
587
HUMAN I'ATHOLOGY--VOLUME 1, NUMBER 4 December1970 CASE 2 (AFIP ACCESSION NO. 1166194)
vitreotts body was very cloudy, obscuring the retina. T h e optic disc was cupped.
Clinical History A 28 year old Nigerian man gave a history of poor vision accompanied by tearing and photophobia for two )'ears. Examination revealed acute limbitis, marginal keratitis, a pigmented pannus, iritis, and secondary glaucoma bilaterally. Vision was reduced to perception of hand movements with the right eye and to 20/200 with the left. A diagnosis of"onchocereal keratitis and uveitis with secondary glaucoma" was made, and the right eye was enucleated. No medical therapy was employed prior to enucleation.
Macroscopic Observations The specimen consisted of a firm right eye measuring 28 by 25 by 25 mm. with 4 ram. of the optic nerve attached. The eye transmitted light poorly. The cornea was opaque, and there was extensive melanokeratosis (Fig. 10). The limbal conjunctiva was pigmented, and temporally it was thickened. The eye was opened in the horizontal plane. The anterior chamber was deep, and the pupil appeared round and central. Several peripheral anterior synechias were noted. The
MicroscopicDescription An inflammatory infiltrate, composed primarily of 1)'mphocytes and plasma cells with a sprinkling of eosinophils, is present in the conjunctival stroma and continues beneath the corneal epithelium as an inflammatory pannus. There is mild episcleritis, and an occasional focus of perivasculitis is observed in the sclera. In many of the serially prepared sections, fragments and whole microfilariae are present in the sclera, and some are also observed in the corneal stroma. Edema and increased pigmentation of the corneal epithelium are present, and there is a large central bulla. The substantia propria is moderately vascularized and contains a sprinkling of chronic inflammatory cells. The corneal endothelium is irregularly degenerated. Peripheral anterior synechias cover the hyalinized trabecular meshwork in many sections. Much of the dilator muscle of the iris is necrotic, and in the stroma there are numerous melanophages. A very mild chronic inflammatory infiltrate is present in tire iris and ciliary body. A marked loss
Figure 10. Main block of eye after removal of calottes. The cornea is opaque and vascularized.Tile limbal tissuesare irregularly thickenedand pigmented.(AFIP Neg. 65-2756.)
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THE OCULAR PATHOLOGY OF ONCHOCERCIASIS--PAuL, ZIMMERMAN
j Figure 11. Microfilaria on inner surface of retina. (Hematoxylin and eosin stain. • AFIP Neg. 70-2055.)
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Ji o f ganglion cells and disintegration o f rods and cones, particularly anteriorly and temporally, are n o t e d in the retina. Posteriorly the retinal pigment epithelium appears flattened, m o d e r a t e l y d e g e n e r a t e d , and partially d e p i g m e n t e d . T h e r e is a d e e p glaucomatous c u p p i n g o f the optic disc, and a cross section o f the optic nerve reveals cavernous degeneration. In a few sections, microfilariae are seen in the retina, vitreous, and lamina cribrosa o f the optic nerve (Figs. 1 1 and 12).
Diagnoses Chronic interstitial sclerokeratitis and mild n o n g r a n u l o m a t o u s uveitis caused by
onchocerciasis; s e c o n d a r y glaucoma witb advanced optic atrophy; secondary acq u i r e d melanosis o f cornea.
CASE 3 (AFIP ACCESSION NO. 378722)
Clinical History A 39 year old native o f Chad, Africa, was e x a m i n e d by m e m b e r s o f a team b e a d e d by Dr. Alfred A. Buck studying onchocerciasis there. Examination revealed subcutaneous nodules on the chest wall and over the iliac crests. His right eye had no light perception. Snips o f bis right
Figure 12. Microfilaria in lamina cribrosa of optic nerve. (Hematoxylin and eosin stain. x750. AFIP Neg. 70-2054.)
589
HUMAN PATHOLOGY--VOLUME 1, NUMBER 4 December1970 flank and conjunctiva were taken, and microfilariae were found in both tissues. The blind right eye was enucleated. No information was recorded about the left eye.
Macroscopic Observations The specimen consisted of an intact right eye measuring 20 by 21 by 23 mm. with a depressed cornea measuring 10 by 10 mm. Concentric stromal opacities were present in the cornea. The limbal conjunctiva appeared hypertrophic and pigmented and had encroached on the peripheral cornea circumferentially. The corneal epithelium was disrupted. The optic nerve had been cut flush with the globe. The eye was opened in a horizontal plane, revealing a thickened cornea, a deep anterior chamber centrally, and peripheral anterior synechias. Pigment was dispersed throughout the anterior chamber. White deposits were noted on the surface of the iris. The lens appeared yellow. T h e margins of the optic nerve head were blurred and raised.
590
Microscopic Description In the conjunctival stroma there are chronic inflammatory cells, including eosinophils. This infiltrate continues into a peripheral pannus, on both sides, in which eosinophilic granules are also noted. The irregularly thinned, pigmented corneal epithelium is partially denuded. Numerous onchocercal microfilariae are present in the substantia propria of the cornea, which is moderately vascularized and exhibits a loss of keratocytes. On the posterior surface of the cornea there is an irregularly thickened, pigmented, inflammatory fibrous membrane that in some sections extends back to attach to a hyalinized fibrous pupillary membrane. In some sections a peripheral anterior synechia is present on one side, whereas in others inflammatory cells and pigmented macrophages line the trabecular meshwork. Chronic inflammatory cells and numerous pigmented clumps are seen in the iris stroma. T h e dilator muscle is largely necrotic, as is much of the pigmented epithelium. In the stroma of the iris a
Figure 13. Arrows indicate rnicrofilariaein the iris stroma. (Hematoxylinand eosin stain, x395. AFIP Neg. 70-6170.)
THE OCULAR PATHOLOGY OF ONCHOCERCIASIS--PAUL, ZI.'t,IMER3.1AN
Figure 14. .4, There is a light infiltrate of chronic inflammatory cells in the pars plicata, as well as marked hyalinization of the vascular layer. Arrow indicates two microfilariae, shown at greater magnificationin B. (,.t: Hematoxylin and eosin stain. Xl00. AFIP Neg. 70-6055. B: Hematoxylin and eosin stain. • AFIP Neg. 706054.)
n u m b e r of microfilariae are f o u n d (Fig. 13). In the r e m a i n d e r of the uveal tract there is an infiltrate of chronic inflammatory cells, sometimes accompanied by eosinophils, a n d in areas there is marked hyalinization. Well preserved microfilariae are present in the ciliary body (Fig. 14). Beginning in the temporal part of the macula, there is a discrete area of marked retinal thinning, measuring approximately 2 ram. in diameter. In this area all layers are markedly degenerated (Fig. 15). In the area of maximal damage only nuclei from the inner nuclear layer and the retinal vessels are identifiable. A n u m b e r of macrophages, heavily laden with melanin granules, are contained within this area of retinal degeneration, but similar pigment-containing macrophages are scattered along the partially degenerated layer of rods and cones. Corresponding in location to the discrete area of marked retinal thinning is a zone in which the retinal pigment epithelium appears flattened, degenerated, and partially depigmented. In this area and to a lesser
extent elsewhere the choroid reveals marked hyalinization with partial atrophy and disappearance of the choriocapillaris (Fig. 16). T h r o u g h o u t the retina there is a loss of ganglion cells. Microcystoid degeneration and loss of nuclei from the external nuclear layer are observed in the macula. In several sections of tile retina microfilariae are observed in the lumens of blood vessels in the nerve fiber layer (Fig. 17). T h e r e is gliosis in the atrophic optic nerve, and microfiIariae are f o u n d in the meningeal sheaths. Many microfilariae are located in the sclera and episcleral tissues, beside tile extraocular muscles, and near the short posterior ciliary nerves and vessels.
Diagnoses Chronic interstitial sclerokeratitis and n o n g r a n u l o m a t o u s uveitis resulting from onchocerciasis; secondary glaucoma with atrophy of tile retina and optic nerve; focal retinal degeneration; secondary acquired melanosis of the cornea.
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Figure 15. There is a localized area of retinaI thinning in which all layers are markedly degenerated. The posterior surface of tile vitreous (PV) is detached from tile retina. (Hematoxylin and eosiq stain, x50. AFIP Neg. 70-6175.)
592
Figure 16. To tile left of arrow tile retinal pigment epitheliunl appears very thin and degenerated and the choriocapillaris is almost obliterated. There is diffuse hyalinization of the dmroidal stroma. (Hematoxylin and eosin stain, x260. AFIP Neg. 70-6603.)
THE
OCULAR
PATHOLOGY
OF ONCHOCERCIASIS--PAuL,
ZIMMER,MAN
Figure 17. A microfilaria is seen in tile lumen of a large blood vessel in tile nerve fiber layer of the retina. (Hematoxylin and eosin stain. • AFIP Neg. 70-6057.)
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HUMAN PATHOLOGY--VOLUME 1, NUMBER 4 December 1970
COMMENT In these t h r e e eyes we have had an o p p o r t u n i t y to observe the m o s t typical findings o f a d v a n c e d ocular onchocerciasis. T h e patients h a d b e c o m e blind as a consequence o f the c o m b i n e d effects o f chronic sclerosing keratitis with p a n n u s f o r m a t i o n a n d chronic uveitis with s e c o n d a r y glaucoma. Microfilariae, a p p a r e n t l y viable as well as disintegrating ones, were observed in virtually all ocular tissues f r o m the c o r n e a to the optic disc, except for the lens. T h e y were readily identified in the c o r n e a a n d sclera b u t were m o r e difficult to detect in the o t h e r tissues. T h e areas o f intense choroiditis with secondar.y chorioretinal d e g e n e r a t i o n a n d scarring that have excited so m u c h interest a n d speculation t, 3 were not o b s e r v e d in the two cases f r o m Nigeria, but in the case f r o m C h a d there was a localized area o f severe retinal d e g e n e r a t i o n that m a y well have been the result o f intense choroiditis that eventually subsided with m a r k e d hyalinization o f the c h o r o i d a n d a t r o p h y o f the choriocapillaris.
pital, Kano, Nigeria, for having contributed the first two o f tile eyes on which this r e p o r t was based. T h e third eye was c o n t r i b u t e d by Drs. J a m e s P. Ganley a n d Daniel H. C o n n o r , who were m e m b e r s o f a t e a m o f physicians a n d scientists b e a d e d by Dr. A l f r e d A. Buck, G e o g r a p h i c Epid e m i o l o g y Unit, J o l m s H o p k i n s University, s t u d y i n g onchocerciasis in C h a d u n d e r the auspices o f the U.S. A r m y Medical Research a n d D e v e l o p m e n t C o m m a n d (contract n u m b e r DADA-17-70-C0028), D e p a r t m e n t o f the A r m y , Washington, D.C.
REFERENCES 1. Rodger, F. C.: Tile pathogenesis and pathology of ocular onchocerciasis. Amer. J. Ophthal., 49:104-135,327-337, and 560-594, 1960. 2. Duke-Elder, S.: Diseases of the outer eye. In DukeElder, S. (Editor): System of Ophthahnology. London, Henry Kimpton, 1965, Vol. VIII, Part I, pp. 406-414. 3. Duke-Elder, S., and Perkins, E. S.: Diseases of tile uveal tract. In Duke-Elder, S. (Editor): System of Ophthalmology. London, Henry Kimpton, 1966, Vol. IX, pp. 444-453.
ACKNOWLEDGMENTS We are grateful to Dr. Ben Kietzman o f the S u d a n I n t e r i o r Mission Eye Hos-
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Ophthalmic l'athology Branch Armed Forces Institute of Pathology Washington, D.C. 20305 (Dr. Zimmerman)