Torulopsis candida (Candida famata) Endophthalmitis Simulating Propionibacterium acnes Syndrome Narsing
A. Rao,
MD; Alan V. Nerenberg, MD; David J. Forster, MD
\s=b\ Four months after undergoing extracapsular cataract extraction with implantation of a posterior chamber intraocular lens, a 74-year-old woman developed granulomatous anterior uveitis. Although she initially responded well to corticosteroid therapy, she experienced multiple
recurrences on
discontinuation of this
therapy. Slit-lamp examination showed
the ocular inflammation to be associated with white cortical material within the lens capsular sac. She underwent removal of the implant as well as the lens capsular sac. Anaerobic culture yielded no organisms, but fungus cultures yielded Torulopsis candida. Histopathologic and electron microscopic studies showed large numbers of yeast sequestered within the lens capsular sac and mild granulomatous inflammation around the sac. Torulopsis candida is occasionally isolated from specimens as a contaminant, but has not yet been shown to produce human disease. The case reported herein documents potential pathogenicity of Torulopsis candida and reveals the importance of organisms other than anaerobic bacteria in causing delayed and localized intraocular inflammation that is virtually identical to Propionibacterium acnes infection.
(Arch Ophthalmol. 1991;109:1718-1721)
Accepted for publication July 12, 1991. From the A. Ray Irvine, Jr, Eye Pathology Laboratory, Doheny Eye Institute, and the Departments of Ophthalmology (Drs Rao, Nerenberg, and Forster) and Pathology (Dr Rao), University of Southern California School of Medicine, Los Angeles. Reprint requests to the Doheny Eye Institute, 1355 San Pablo St, Los Angeles, CA 90033 (Dr Rao).
Tt is now widely recognized that anaerobic bacteria can cause an indo¬
endophthalmitis after ex¬ tracapsular cataract extraction with posterior chamber intraocular lens im¬
lent form of
plantation.1"7 Clinical features of the intraocular inflammation induced by Propionibacterium
acnes
are
unique
among these anaerobic infections. Re¬
cently, however,
it has been
pointed
out that clinical features similar to acnes endophthalmitis can those of be produced by another related organ¬
ism,8,9 Propionibacterium granulosum, and other unrelated organisms, such as Staphylococcus epidermidis. Common to these organisms has been
their low virulence and their tendency to cause infection in association with various prosthetic devices, including indwelling intravenous catheters. To our knowledge, Toruiopsis candida in¬ fection in humans has not been re¬ ported.10 In the case reported herein, of indolent endophthalmitis due to candida, we noted clinical features that were virtually identical to those reported in association with acnes
endophthalmitis.
REPORT OF A CASE A 74-year-old woman underwent extra¬ capsular cataract extraction in the left eye with implantation of a posterior chamber intraocular lens (model UVN 304-07, IOPTEX Ine, Azusa, Calif) in March 1987. Preoperative visual acuity was 20/50; 3 months after surgery, corrected visual acuity was 20/40 and there was some opaci¬ fication of the posterior capsule. According¬
ly, posterior capsulotomy was performed with the neodymium (Nd)-YAG laser in July 1987. She had recurrent anterior uve¬ itis, characterized by trace to 1 + flare and
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/21/2015
cells in the anterior chamber and vitreous cavity, with visual acuity ranging between 20/70 and 20/30. There were increasing numbers of keratic precipitates that, initial¬ ly, were small, but on subsequent examina¬ tions had become larger. Fluorescein angi¬ ography revealed cystoid macular edema. She was treated with corticosteroid drops and subtenon corticosteroid injections, with some improvement initially; however, sub¬ sequently, there was no improvement in the ocular inflammation. Her medical and family history were not significant for any systemic disease related to uveitis, except for mild osteoarthritis. Her visual acuity in January 1989 was 20/30 OD and 20/40-1 OS. Her pupils were unequal, with the right pupil being 7 mm and the left pupil 5 mm, but both showed good reaction to light and there was no afferent pupillary defect. Extraocular movements were full and orthophoric. Ex¬ ternal examination results were normal bi¬ laterally. Results of slit-lamp and funduscopic examinations of the right eye were within normal limits, with the exception of mild arcus senilis and moderate nuclear sclerosis. Examination of the left eye showed normal conjunctiva. The cornea showed mild arcus senilis as well as mutton fat and smaller keratic precipitates in the inferior half. There were 1 + to 2 + large cells and 1 + flare in the anterior chamber. The implant was in good position. There was a posterior capsular discission, but within the capsular sac, there was fluffy cortical material that was somewhat refractile (Fig 1). The vitreous showed 2+ cells and some debris. Funduscopic examination revealed mild thickening of the parafoveal area and a few hard exudates in the fovea; there were no frank cystoid spaces in the macula. The disk and peripheral retina were normal. The clinical impression was that of a chronic low-grade granulomatous anterior uveitis in the left eye, that had its onset following Nd-YAG laser capsulotomy short-
Fig 1 .—Deposits of white cortical material seen within the lens capsu¬ lar sac.
Fig 2.—Organisms sequestered
in the lens
acid-Schiff; original magnification: left,
Fig
capsular
3.—Oval
or
(periodic 400).
sac
100, and right,
round
organisms noted 400).
stain, original magnification
ly
after cataract extraction and intraocular lens implantation. The most likely diagnosis was acnes endophthalmitis. A trial of oral penicillin V potassium was administered at a dose of 500 mg four times daily for 3 weeks, but there was no response to this therapy. The patient subsequently under¬ went removal of the implant as well as removal of the remnants of lens capsule, which contained white, crystalline material. At the conclusion of surgery she was given an intravitreal injection of 1 mg of vanco¬ mycin hydrochloride in a volume of 0.1 mL, and a subconjunctival injection of 25 mg of vancomycin in a volume of 0.25 mL. Tobra-
mycin sulfate was instilled topically. A por¬ tion of the lens capsule was submitted for aerobic and for anaerobic cultures, and the remainder of the material underwent light and electron microscopic examination. Gram's staining performed at the time of surgery revealed no organisms. On the first postoperative day, yeast was reported to be growing in one of the cultures. The patient was taken back to the operating room where 0.1 mL of aqueous was aspirated from the anterior chamber, and an intra¬ vitreal injection of 0.05 mg of miconazole nitrate was given in a volume of 0.1 mL. A subconjunctival injection of 7.5 mg of mi-
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/21/2015
in the
capsular
sac
(Gram's
conazole nitrate in a volume of 0.75 mL was also given. A topical solution of 0.8% micon¬ azole was prescribed to be used four times daily. The anaerobic culture yielded no or¬ ganisms after 10 days. The fungus culture was identified as candida, and it was found to be susceptible to ketoconazole,
miconazole, flucytosine (5-fluorocytosine antifungal), and amphotericin B, with inter¬ mediate susceptibility to fluconazole.
Pathologic Findings The specimen consisted of a white, wellformed, scalloped mass measuring 9x3.6
Fig 4.—Viable and necrotic organisms noted within the sac of the lens capsule. The viable organism shows a distinct large nucleus and a multilayered cell wall (original magnification 15 750).
The specimen was bisected; one half submitted for routine histopathologic study and the other half was submitted for electron microscopic study. Histologie examination of the specimen showed anterior as well as posterior lens capsule and cortical material, with disrup¬ tion in the anterior and posterior capsule. Histiocytes, epithelioid cells, and giant cells containing melanin pigment were seen on the external surface of the lens capsule; a few lymphocytes were present on the poste¬ rior surface of the posterior lens capsule. The capsular sac contained remnants of cortical material, and within the cortical remnants there were multiple periodic mm.
was
acid-Schiff-positive organisms exhibiting the morphologic features of yeast (Fig 2). These organisms were present predomi¬ nantly along the anterior surface of the posterior capsule, along the posterior sur¬ face of the anterior lens capsule, and within the cortical remnants. The organisms also stained positive with Gomori methenamine silver technique and Gram's stain (Fig 3). There were no budding yeast forms. Electron microscopic study of tissue pro¬ cessed according to a previously described method11 revealed
multiple
oval
or
round
organisms in various stages of degeneration (Fig 4). There were also several organisms that appeared to be viable. These organ¬ isms showed markedly thickened walls and contained a large nucleus and a prominent nucleolus. The degenerating organisms re¬ vealed loss of nuclear material and folded, crescent-shaped walls. The pathologic diag¬
nosis was remnants of lens material contain¬ ing Candida species and granulomatous in¬ traocular inflammation.
Postoperative Course Because of its good intraocular penetra¬ tion and because it can be taken orally, flucytosine was prescribed to be taken at a dosage of 2.0 g orally four times daily for 6 weeks. Liver and bone marrow function were monitored. The patient experienced nausea, palpitations, nervousness, and de¬ pression; after peak and trough blood levels were obtained, the dose was reduced to 4.0 g/d. Anterior chamber reaction gradual¬ ly subsided, and vitreous debris gradually cleared. Three months after surgery, cor¬ rected visual acuity was 20/50.
COMMENT
Toruiopsis
is
a
medically important
yeast and it is considered synonymous
with Candida. Most Toruiopsis infec¬ tions are caused by Toruiopsis (Candi¬ da.) glabrata, and occur in immunocom¬ promised individuals. As it is a symbiont with humans, and is a com¬ mon isolate from urine and other speci¬ mens, pathogenicity from this organ¬ ism is considered only when the inflamed tissue shows invasion by these organisms. In contrast to gla¬ brata, other yeasts belonging to the candida genus Toruiopsis, such as
(Candida famata),
isolated from
are
occasionally
contami¬ candida has not yet been shown to produce human dis¬ ease.1" However, the present case shows the potential of candida to nant.
specimens
as a
Toruiopsis
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/21/2015
induce low-grade, chronic, intraocular inflammation. Demonstration of yeast in the tissue and growth of this organ¬ ism from the infected tissue establish¬ candida in es the pathogenicity of human eyes. The clinical and laborato¬ ry findings of this case emphasize the importance of histopathologic examina¬ tion in conjunction with bactériologie isolation of organisms that may be considered laboratory contaminants. Delayed onset of intraocular inflam¬ mation or endophthalmitis is a wellrecognized complication of extracapsu¬ lar cataract extraction with posterior chamber intraocular lens implantation, and has been shown to be caused by various organisms, including S epider¬ midis, Candida parapsilosis, acnes, and others.1"9,12 Among these infectious causes of endophthalmitis, the intra¬ ocular inflammation produced by ac¬ nes is perhaps the most common clini¬ cal entity. Several investigators have emphasized the unusual and unique clinical features of acwes-induced intraocular inflammation.1"9 These clini¬ cal features include onset of inflamma¬ tion 2 to 6 months after the surgical procedure; limited positive response to corticosteroids in the form of transient reduction in the inflammation; devel¬ opment of hypopyon during the course of the disease; and development and continued growth of a white plaque on the residual lens capsule.1"3 The present case of intraocular in¬ flammation induced by candida ex¬ hibited several clinical features de¬ scribed in association with acnes intraocular infection. Similar to ac¬ nes infection, the present case showed delayed onset of intraocular inflamma¬ tion, first noted following Nd-YAG la¬ ser capsulotomy performed approxi¬ mately 4 months after cataract extraction with posterior chamber lens implantation; limited positive response to topical corticosteroid therapy, with
fluctuation of vision between 20730 and 20/70 during the treatment period; and an enlarging white plaque within the lens capsular sac. Our patient also showed large keratic precipitates and association of retained lens cortex with the infectious agent. The present case thus showed clinical features virtually identical to those observed in patients with intraocular inflammation due to acnes.
The present
case
and
some
of the
previously reported cases of delayedonset endophthalmitis after intraocular lens implant surgery indicate that many different organisms can induce
clinical features similar to those ob¬ served in acnes infection. The basis for such delayed onset of inflammation
appears to be sequestration of the or¬ ganism within the capsular bag and the low virulence of the organisms, both of which are apparent in the present case. Our, patient did not develop signs of intraocular inflammation until she underwent Nd-YAG capsulotomy. This suggests that sequestered from nutrients for their growth, the organ¬ isms had been slowly dividing within the capsular bag, and that when the posterior capsule was opened, the or¬ ganisms gained access to the vitreous cavity, which led to the overt intraocu¬ lar inflammation. It appears that or¬ ganisms can remain within the capsu¬ lar bag without inciting intraocular
inflammation until they are exposed directly to ocular cavities such as the vitreous or anterior chamber. The second factor that may play a role in the delayed onset of inflamma¬ tion is the virulence of the organisms. The organisms isolated in cases of de¬ layed onset of intraocular inflammation have generally been considered to be of low virulence or nonpathogenic.3
These organisms include S epidermi¬ dis, C parapsilosis, diphtheroids, granulosum, acnes, and others.1'9 Similar to these organisms, candida is considered to be nonpathogenic.10 However, the present case and cases reported by others indicate that the organisms considered to be of low viru¬ lence or nonpathogenic in extraocular or other systemic tissues can induce low-grade intraocular inflammation, particularly after an intraocular surgi¬ cal procedure. A characteristic feature of acnes intraocular inflammation is the associa¬ tion of the organisms with retained lens cortex.4 Histopathologic examina¬ tions have shown such gram-positive bacteria at the site of the degenerating lens cortex. Such proximity of bacteria to the lens cortex, and the known immunostimulatory property of ac¬ nes, has led to the belief that autoimmunity to lens cortex may play a role in the induction or perpetuation of these intraocular inflammations and in the development of phacoanaphy-
Iaxis.113 However, pathologie studies of
lens cortex removed from acnes-infected patients showed no evidence of a zonal type of granulomatous inflam¬ mation centered around the cortex.3,4,14 Moreover, the lens cortex is not in¬ volved in the inflammatory process, and the granulomatous inflammation in these infections is seen around the lens capsule, away from the cortex. These morphologic features, and the demon¬ stration of other infectious agents in a similar location causing similar clinical features, suggest that the intraocular inflammation noted with acnes could be a toxic reaction to the organisms, and it is unlikely that acnes, either alone or in conjunction with lens cor¬ tex, induces phacoanaphylaxis. This study was supported in part by a core grant for vision research Y 03040 from the National Eye Institute, National Institutes of Health, Bethesda, Md, and by an unrestricted grant from Research to Prevent Blindness Ine, New York, NY. Dr Rao is a recipient of the Dolly
Green Award from Research to Prevent Blind¬ ness Inc.
References 1. Meisler DM, Palestine AG, Vastine DW, et al. Chronic Propionibacterium endophthalmitis after extracapsular cataract extraction and intraocular lens implantation. Am J Ophthalmol. 1986;102:733\x=req-\ 739. 2. Meisler DM, Zakov ZN, Bruner WE, et al. Endophthalmitis associated with sequestered intraocular Propionibacterium acnes. Am J Ophthalmol. 1987;104:428-429. 3. Roussel TJ, Culbertson WW, Jaffe NS. Chronic postoperative endophthalmitis associated with Propionibacterium acnes. Arch Ophthalmol.
1987;105:1199-1201. 4. Piest KL, Apple DJ, Kincaid MC, Roberts WH, Tetz MR, Price FW Jr. Localized endophthal-
mitis: a newly described cause of the so-called toxic lens syndrome. J Cataract Refract Surg. 1987; 13:498-510. 5. Meisler DM, Mandelbaum S. Propionibacterium-associated endophthalmitis after extracapsular cataract extraction: review of reported cases.
Ophthalmology. 1989;96:54-61. 6. Beatty RF, Robin JB, Trousdale MD, Smith RE. Anaerobic endophthalmitis caused by Propionibacterium acnes. Am J Ophthalmol. 1986;101:114-116. 7. Jaffe GJ, Whitcher JP, Biswell R, Irvine AR.
Propionibacterium acnes endophthalmitis seven months after extracapsular cataract extraction and intraocular lens implantation. Ophthalmic Surg.
1986;17:791-793. McManaway JW III, Weinberg RS, Coudron
8. PE.
Coryneform endophthalmitis: two case reports. Arch Ophthalmol. 1990;108:942-944. 9. Walker J, Dangel ME, Makley TA, Opremcak EM. Postoperative Propionibacterium granulosum endophthalmitis. Arch Ophthalmol. 1990; 108:1073-1074. 10. Silva-Hunter M, Cooper BH. Yeasts of medical importance. In: Lenete EH, Ballows A, Hausler WJ Jr, Traunt JP, eds. Manual of Clinical Microbiology. Washington, DC: American Society for
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/21/2015
Microbiology; 1980:562-575. 11. Rao NA, Font RL. Toxoplasmic retinochoroiditis: electron-microscopic and immunofluorescence studies of formalin-fixed tissue. Arch Ophthalmol. 1977;95:273-277. 12. Bialasiewicz AA, Koniszewski G, Naumann GOH. Pseudo-'Toxic lens'-Syndrom \l=u"\bervier jahre durch Staphylokokkus epidermidis Endophthalmitis. Klin Monatsbl Augenheilkd. 1988;193:142-145. 13. Apple DJ, Mamalis N, Steinmetz RL, Loftfield K, Crandall AS, Olson RJ. Phacoanaphylactic endophthalmitis associated with extracapsular cataract extraction and posterior chamber intraocular lens. Arch Ophthalmol. 1984;102:1528-1532. 14. Sawusch MR, Michaels RG, Stark WJ, Bruner WE, Annable WL, Green WR. Endophthalmitis due to Propionibacterium acnes sequestered between IOL optic and posterior capsule. Ophthalmic Surg. 1989;20:90-92.
A. Rao,
MD; Alan V. Nerenberg, MD; David J. Forster, MD
\s=b\ Four months after undergoing extracapsular cataract extraction with implantation of a posterior chamber intraocular lens, a 74-year-old woman developed granulomatous anterior uveitis. Although she initially responded well to corticosteroid therapy, she experienced multiple
recurrences on
discontinuation of this
therapy. Slit-lamp examination showed
the ocular inflammation to be associated with white cortical material within the lens capsular sac. She underwent removal of the implant as well as the lens capsular sac. Anaerobic culture yielded no organisms, but fungus cultures yielded Torulopsis candida. Histopathologic and electron microscopic studies showed large numbers of yeast sequestered within the lens capsular sac and mild granulomatous inflammation around the sac. Torulopsis candida is occasionally isolated from specimens as a contaminant, but has not yet been shown to produce human disease. The case reported herein documents potential pathogenicity of Torulopsis candida and reveals the importance of organisms other than anaerobic bacteria in causing delayed and localized intraocular inflammation that is virtually identical to Propionibacterium acnes infection.
(Arch Ophthalmol. 1991;109:1718-1721)
Accepted for publication July 12, 1991. From the A. Ray Irvine, Jr, Eye Pathology Laboratory, Doheny Eye Institute, and the Departments of Ophthalmology (Drs Rao, Nerenberg, and Forster) and Pathology (Dr Rao), University of Southern California School of Medicine, Los Angeles. Reprint requests to the Doheny Eye Institute, 1355 San Pablo St, Los Angeles, CA 90033 (Dr Rao).
Tt is now widely recognized that anaerobic bacteria can cause an indo¬
endophthalmitis after ex¬ tracapsular cataract extraction with posterior chamber intraocular lens im¬
lent form of
plantation.1"7 Clinical features of the intraocular inflammation induced by Propionibacterium
acnes
are
unique
among these anaerobic infections. Re¬
cently, however,
it has been
pointed
out that clinical features similar to acnes endophthalmitis can those of be produced by another related organ¬
ism,8,9 Propionibacterium granulosum, and other unrelated organisms, such as Staphylococcus epidermidis. Common to these organisms has been
their low virulence and their tendency to cause infection in association with various prosthetic devices, including indwelling intravenous catheters. To our knowledge, Toruiopsis candida in¬ fection in humans has not been re¬ ported.10 In the case reported herein, of indolent endophthalmitis due to candida, we noted clinical features that were virtually identical to those reported in association with acnes
endophthalmitis.
REPORT OF A CASE A 74-year-old woman underwent extra¬ capsular cataract extraction in the left eye with implantation of a posterior chamber intraocular lens (model UVN 304-07, IOPTEX Ine, Azusa, Calif) in March 1987. Preoperative visual acuity was 20/50; 3 months after surgery, corrected visual acuity was 20/40 and there was some opaci¬ fication of the posterior capsule. According¬
ly, posterior capsulotomy was performed with the neodymium (Nd)-YAG laser in July 1987. She had recurrent anterior uve¬ itis, characterized by trace to 1 + flare and
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/21/2015
cells in the anterior chamber and vitreous cavity, with visual acuity ranging between 20/70 and 20/30. There were increasing numbers of keratic precipitates that, initial¬ ly, were small, but on subsequent examina¬ tions had become larger. Fluorescein angi¬ ography revealed cystoid macular edema. She was treated with corticosteroid drops and subtenon corticosteroid injections, with some improvement initially; however, sub¬ sequently, there was no improvement in the ocular inflammation. Her medical and family history were not significant for any systemic disease related to uveitis, except for mild osteoarthritis. Her visual acuity in January 1989 was 20/30 OD and 20/40-1 OS. Her pupils were unequal, with the right pupil being 7 mm and the left pupil 5 mm, but both showed good reaction to light and there was no afferent pupillary defect. Extraocular movements were full and orthophoric. Ex¬ ternal examination results were normal bi¬ laterally. Results of slit-lamp and funduscopic examinations of the right eye were within normal limits, with the exception of mild arcus senilis and moderate nuclear sclerosis. Examination of the left eye showed normal conjunctiva. The cornea showed mild arcus senilis as well as mutton fat and smaller keratic precipitates in the inferior half. There were 1 + to 2 + large cells and 1 + flare in the anterior chamber. The implant was in good position. There was a posterior capsular discission, but within the capsular sac, there was fluffy cortical material that was somewhat refractile (Fig 1). The vitreous showed 2+ cells and some debris. Funduscopic examination revealed mild thickening of the parafoveal area and a few hard exudates in the fovea; there were no frank cystoid spaces in the macula. The disk and peripheral retina were normal. The clinical impression was that of a chronic low-grade granulomatous anterior uveitis in the left eye, that had its onset following Nd-YAG laser capsulotomy short-
Fig 1 .—Deposits of white cortical material seen within the lens capsu¬ lar sac.
Fig 2.—Organisms sequestered
in the lens
acid-Schiff; original magnification: left,
Fig
capsular
3.—Oval
or
(periodic 400).
sac
100, and right,
round
organisms noted 400).
stain, original magnification
ly
after cataract extraction and intraocular lens implantation. The most likely diagnosis was acnes endophthalmitis. A trial of oral penicillin V potassium was administered at a dose of 500 mg four times daily for 3 weeks, but there was no response to this therapy. The patient subsequently under¬ went removal of the implant as well as removal of the remnants of lens capsule, which contained white, crystalline material. At the conclusion of surgery she was given an intravitreal injection of 1 mg of vanco¬ mycin hydrochloride in a volume of 0.1 mL, and a subconjunctival injection of 25 mg of vancomycin in a volume of 0.25 mL. Tobra-
mycin sulfate was instilled topically. A por¬ tion of the lens capsule was submitted for aerobic and for anaerobic cultures, and the remainder of the material underwent light and electron microscopic examination. Gram's staining performed at the time of surgery revealed no organisms. On the first postoperative day, yeast was reported to be growing in one of the cultures. The patient was taken back to the operating room where 0.1 mL of aqueous was aspirated from the anterior chamber, and an intra¬ vitreal injection of 0.05 mg of miconazole nitrate was given in a volume of 0.1 mL. A subconjunctival injection of 7.5 mg of mi-
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/21/2015
in the
capsular
sac
(Gram's
conazole nitrate in a volume of 0.75 mL was also given. A topical solution of 0.8% micon¬ azole was prescribed to be used four times daily. The anaerobic culture yielded no or¬ ganisms after 10 days. The fungus culture was identified as candida, and it was found to be susceptible to ketoconazole,
miconazole, flucytosine (5-fluorocytosine antifungal), and amphotericin B, with inter¬ mediate susceptibility to fluconazole.
Pathologic Findings The specimen consisted of a white, wellformed, scalloped mass measuring 9x3.6
Fig 4.—Viable and necrotic organisms noted within the sac of the lens capsule. The viable organism shows a distinct large nucleus and a multilayered cell wall (original magnification 15 750).
The specimen was bisected; one half submitted for routine histopathologic study and the other half was submitted for electron microscopic study. Histologie examination of the specimen showed anterior as well as posterior lens capsule and cortical material, with disrup¬ tion in the anterior and posterior capsule. Histiocytes, epithelioid cells, and giant cells containing melanin pigment were seen on the external surface of the lens capsule; a few lymphocytes were present on the poste¬ rior surface of the posterior lens capsule. The capsular sac contained remnants of cortical material, and within the cortical remnants there were multiple periodic mm.
was
acid-Schiff-positive organisms exhibiting the morphologic features of yeast (Fig 2). These organisms were present predomi¬ nantly along the anterior surface of the posterior capsule, along the posterior sur¬ face of the anterior lens capsule, and within the cortical remnants. The organisms also stained positive with Gomori methenamine silver technique and Gram's stain (Fig 3). There were no budding yeast forms. Electron microscopic study of tissue pro¬ cessed according to a previously described method11 revealed
multiple
oval
or
round
organisms in various stages of degeneration (Fig 4). There were also several organisms that appeared to be viable. These organ¬ isms showed markedly thickened walls and contained a large nucleus and a prominent nucleolus. The degenerating organisms re¬ vealed loss of nuclear material and folded, crescent-shaped walls. The pathologic diag¬
nosis was remnants of lens material contain¬ ing Candida species and granulomatous in¬ traocular inflammation.
Postoperative Course Because of its good intraocular penetra¬ tion and because it can be taken orally, flucytosine was prescribed to be taken at a dosage of 2.0 g orally four times daily for 6 weeks. Liver and bone marrow function were monitored. The patient experienced nausea, palpitations, nervousness, and de¬ pression; after peak and trough blood levels were obtained, the dose was reduced to 4.0 g/d. Anterior chamber reaction gradual¬ ly subsided, and vitreous debris gradually cleared. Three months after surgery, cor¬ rected visual acuity was 20/50.
COMMENT
Toruiopsis
is
a
medically important
yeast and it is considered synonymous
with Candida. Most Toruiopsis infec¬ tions are caused by Toruiopsis (Candi¬ da.) glabrata, and occur in immunocom¬ promised individuals. As it is a symbiont with humans, and is a com¬ mon isolate from urine and other speci¬ mens, pathogenicity from this organ¬ ism is considered only when the inflamed tissue shows invasion by these organisms. In contrast to gla¬ brata, other yeasts belonging to the candida genus Toruiopsis, such as
(Candida famata),
isolated from
are
occasionally
contami¬ candida has not yet been shown to produce human dis¬ ease.1" However, the present case shows the potential of candida to nant.
specimens
as a
Toruiopsis
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 06/21/2015
induce low-grade, chronic, intraocular inflammation. Demonstration of yeast in the tissue and growth of this organ¬ ism from the infected tissue establish¬ candida in es the pathogenicity of human eyes. The clinical and laborato¬ ry findings of this case emphasize the importance of histopathologic examina¬ tion in conjunction with bactériologie isolation of organisms that may be considered laboratory contaminants. Delayed onset of intraocular inflam¬ mation or endophthalmitis is a wellrecognized complication of extracapsu¬ lar cataract extraction with posterior chamber intraocular lens implantation, and has been shown to be caused by various organisms, including S epider¬ midis, Candida parapsilosis, acnes, and others.1"9,12 Among these infectious causes of endophthalmitis, the intra¬ ocular inflammation produced by ac¬ nes is perhaps the most common clini¬ cal entity. Several investigators have emphasized the unusual and unique clinical features of acwes-induced intraocular inflammation.1"9 These clini¬ cal features include onset of inflamma¬ tion 2 to 6 months after the surgical procedure; limited positive response to corticosteroids in the form of transient reduction in the inflammation; devel¬ opment of hypopyon during the course of the disease; and development and continued growth of a white plaque on the residual lens capsule.1"3 The present case of intraocular in¬ flammation induced by candida ex¬ hibited several clinical features de¬ scribed in association with acnes intraocular infection. Similar to ac¬ nes infection, the present case showed delayed onset of intraocular inflamma¬ tion, first noted following Nd-YAG la¬ ser capsulotomy performed approxi¬ mately 4 months after cataract extraction with posterior chamber lens implantation; limited positive response to topical corticosteroid therapy, with
fluctuation of vision between 20730 and 20/70 during the treatment period; and an enlarging white plaque within the lens capsular sac. Our patient also showed large keratic precipitates and association of retained lens cortex with the infectious agent. The present case thus showed clinical features virtually identical to those observed in patients with intraocular inflammation due to acnes.
The present
case
and
some
of the
previously reported cases of delayedonset endophthalmitis after intraocular lens implant surgery indicate that many different organisms can induce
clinical features similar to those ob¬ served in acnes infection. The basis for such delayed onset of inflammation
appears to be sequestration of the or¬ ganism within the capsular bag and the low virulence of the organisms, both of which are apparent in the present case. Our, patient did not develop signs of intraocular inflammation until she underwent Nd-YAG capsulotomy. This suggests that sequestered from nutrients for their growth, the organ¬ isms had been slowly dividing within the capsular bag, and that when the posterior capsule was opened, the or¬ ganisms gained access to the vitreous cavity, which led to the overt intraocu¬ lar inflammation. It appears that or¬ ganisms can remain within the capsu¬ lar bag without inciting intraocular
inflammation until they are exposed directly to ocular cavities such as the vitreous or anterior chamber. The second factor that may play a role in the delayed onset of inflamma¬ tion is the virulence of the organisms. The organisms isolated in cases of de¬ layed onset of intraocular inflammation have generally been considered to be of low virulence or nonpathogenic.3
These organisms include S epidermi¬ dis, C parapsilosis, diphtheroids, granulosum, acnes, and others.1'9 Similar to these organisms, candida is considered to be nonpathogenic.10 However, the present case and cases reported by others indicate that the organisms considered to be of low viru¬ lence or nonpathogenic in extraocular or other systemic tissues can induce low-grade intraocular inflammation, particularly after an intraocular surgi¬ cal procedure. A characteristic feature of acnes intraocular inflammation is the associa¬ tion of the organisms with retained lens cortex.4 Histopathologic examina¬ tions have shown such gram-positive bacteria at the site of the degenerating lens cortex. Such proximity of bacteria to the lens cortex, and the known immunostimulatory property of ac¬ nes, has led to the belief that autoimmunity to lens cortex may play a role in the induction or perpetuation of these intraocular inflammations and in the development of phacoanaphy-
Iaxis.113 However, pathologie studies of
lens cortex removed from acnes-infected patients showed no evidence of a zonal type of granulomatous inflam¬ mation centered around the cortex.3,4,14 Moreover, the lens cortex is not in¬ volved in the inflammatory process, and the granulomatous inflammation in these infections is seen around the lens capsule, away from the cortex. These morphologic features, and the demon¬ stration of other infectious agents in a similar location causing similar clinical features, suggest that the intraocular inflammation noted with acnes could be a toxic reaction to the organisms, and it is unlikely that acnes, either alone or in conjunction with lens cor¬ tex, induces phacoanaphylaxis. This study was supported in part by a core grant for vision research Y 03040 from the National Eye Institute, National Institutes of Health, Bethesda, Md, and by an unrestricted grant from Research to Prevent Blindness Ine, New York, NY. Dr Rao is a recipient of the Dolly
Green Award from Research to Prevent Blind¬ ness Inc.
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