- Email: [email protected]
Conjunctival Granulomas Caused by Synthetic Fibers: Report of Two Cases and Review of Literature
Conjunctival Granulomas Caused by Synthetic Fibers: Report of Two Cases and Review of Literature Ingo Schmack, MD,a,b Shin J. Kang, MD, PhD,a Hans E. Grossniklaus, MD,a and Scott R. Lambert, MDa Purpose: We sought to demonstrate the histopathologic and ultrastructural features of conjunctival foreign body granulomas because of synthetic fibers and to compare them to other cases published in the literature. Methods: A 2- and a 7-year-old girl were referred for the surgical removal of slow-growing unilateral inferior conjunctival masses with a lack of primary trauma or surgery. In this report, we describe the light and electron microscopic findings of the 2 cases and review the literature of similar cases using the Medline database. Results: Histopathologic and ultrastructural examination of both specimens revealed a granulomatous inflammatory cell response, including histiocytes and multinucleated foreign body giant cells around acellular, uniform sized, oval to round birefringent fibers with manufacturing artifacts. Thirteen other patients with conjunctival synthetic fiber granulomas were identified from the literature. Conclusions: On the basis of the findings in our cases and the review of literature, it appears that conjunctival synthetic fiber granulomas are not a rare entity but are not recognized frequently by ophthalmologists. The most reliable clinical sign to suggest this diagnosis is the presence of a unilateral inferior conjunctival mass in a child or adolescent. Histopathologic and ultrastructural evaluation appears to be the only way to specifically diagnose this condition with certainty. (J AAPOS 2005;9:567-571) oreign body granuloma of the conjunctiva can be induced by the inoculation of a large variety of nonsynthetic and synthetic exogenous materials commonly found throughout nature.1-4 Recently, a few case reports have demonstrated synthetic fibers as a possible source for a granulomatous foreign body reaction of the conjunctiva in children.4-6 They have sometimes been called “teddy bear” granulomas because some cases were caused by materials of stuffed toy animals. These lesions usually are unilateral and located in the inferior fornix of the lower lid. We report 2 additional cases of unilateral conjunctival synthetic fiber granulomas in the inferior fornix. The lesions were both completely excised surgically and evaluated by light and electron microscopy. Histopathologic and ultrastructural examination revealed a granulomatous inflammation composed of acute and chronic inflammatory cells surrounding numerous uniform, birefringent foreign bodies. The findings in both patients were consistent with a synthetic fiber granuloma.
F
a
From the Emory Eye Center Emory University School of Medicine, Atlanta Georgia b Department of Ophthalmology Ruprecht-Karls-University, Heidelberg, Germany Submitted February 23, 2005. Revision accepted July 19, 2005. Reprint requests: Scott R. Lambert, MD, Emory Eye Center, 1365-B Clifton Road, N.E., Atlanta, GA 30322 (e-mail: [email protected]). Copyright © 2005 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2005/$35.00 ⫹ 0 doi:10.1016/j.jaapos.2005.07.006
Journal of AAPOS
METHODS AND MATERIALS Gross Examination The two excised specimens were examined grossly before being trisected and processed for light and electron microscopy. Histology and Immunohistochemistry One third of each specimen was fixed in formalin, dehydrated in a graded series of alcohol solutions, cleared with xylene solution, infiltrated, and embedded in paraffin for sectioning. Five-micron thick sections were cut and stained with hematoxylin and eosin (H&E), periodic acid Schiff (PAS), and with antibodies against immunoglobulin G (IgG), CD68, and S-100 protein according to routine procedures. The slides of each specimen were evaluated by light microscopy (Olympus BH-2 microscope Tokyo Japan) and the histopathologic findings were recorded. Transmission Electron Microscopy (TEM) Glutaraldehyde-fixed portions of the specimens were rinsed in 0.1 mol/L cacodylate buffer and postfixed in 1% osmium tetroxide. After dehydration, the samples were embedded in LX 112 epoxy resin according to standard techniques. Thick sections (1.5 m) were then stained with toluidine blue and evaluated by light microscopy to detect the areas of pathology. The blocks were trimmed around these areas, and thin sections (70 – 80 nm) were cut, placed in a copper grid, double-stained with uranyl acetate December 2005
567
Journal of AAPOS Volume 9 Number 6 December 2005
568 Schmack et al and lead citrate, and examined with a JEM-100 CXII transmission electron microscope (JEOL Ltd., Tokyo Japan) at magnifications ranging from 1400x to 4800x. Scanning Electron Microscopy (SEM) Glutaraldehyde-fixed portions of the specimens were rinsed in 0.1 mol/L cacodylate buffer and postfixed in 1% osmium tetroxide. After dehydration, the samples were mounted, sputter coated with gold-pallidium and observed with JEOL 35 CF (JEOL Ltd., Tokyo Japan) scanning electron microscope at magnifications ranging from 100x to 1000x. Images were taken from the cross-sectioned surface.
CASE REPORTS Case 1 A 2-year-old girl was referred with a white conjunctival mass in the inferior fornix of her right eye. The patient’s mother reported that her daughter’s right eye has been puffy, crusty and tearing for the last five months. Simultaneously, she also noted that a mass had been gradually growing in the inferior fornix of the right eye. The child was otherwise healthy and had no history of ocular trauma or surgery. Topical antibiotics (polymyxin B sulfate, 3x daily) had been administrated to her right eye for several weeks. The ocular examination was normal aside from a mass in the right inferior fornix. It was white in color and there appeared to be eyelashes embedded in it. The mass was not adherent to the conjunctiva and was completely excised surgically using topical anesthesia. Case 2 A 7-year-old girl was referred for the biopsy of a conjunctival mass in the inferior fornix of her right eye, which was noticed 4 weeks earlier. Her past ocular history was unremarkable. She was asymptomatic without a history of trauma or placement of a foreign body in the eye. Complete surgical excision was performed with topical anesthesia.
RESULTS Case 1 Gross examination revealed a translucent brown mass with a nodular configuration (Fig. 1, bottom). A few eyelashes were protruding from one side of the tissue. The entire specimen measured 5 ⫻ 4 ⫻ 2 mm. Microscopic evaluation showed a nonkeratinized stratified squamous epithelium with goblet cells and numerous cross-sections of round to oval shaped, markedly polarizable fibers in the underlying substantia propria (Fig. 2A and 2B). A focus of acute and chronic inflammatory cells composed of lymphocytes, plasma cells, epithelioid macrophages, and polymorphonuclear leukocytes were present around the fibers (Fig. 2A, inset bottom right). Occasional
FIG 1. Excised specimens from case 1 (left, bottom) and case 2 (right, inset). Eyelashes (dark brown) and filamentous fibers (white) are seen in the biopsy of patient 2 (inset).
foreign body giant cells were directly adjacent to the fibers (Fig. 2A, inset top right). The fibers did not react to PAS staining, and many of them contained tiny scattered, dark granules. The vast majority of the fibers were surrounded by cuffs of homogenous eosinophilic material, which markedly stained positive for IgG. Immunohistochemistry disclosed also IgG in plasma cells and showed a strong reactivity for CD68 in epithelioid macrophages and multinucleated foreign body giant cells. No reactivity was found with S-100 protein. Electron microscopic examination (TEM and SEM) showed that the fibers were acellular in origin with a lack of a central core and smooth external surfaces (Fig. 3A and 3B). The fibers were fairly uniform in size, measuring between 17 to 29 microns in diameter. Some of them presented prominent longitudinal grooves in various degrees on their external surfaces (Fig. 3B, inset). Additionally, diagonal, parallel scratches were commonly seen on cross sections of the fibers. Many of the fibers were encapsulated by a thin layer of mononuclear inflammatory cells and showed a rim of amorphous material along the external surfaces (Fig. 3A). Case 2 The specimen was white-yellow in color and measured grossly 10 ⫻ 4 ⫻ 3 mm (Fig. 1, inset). Light- and electronmicroscopic evaluation showed similar findings as the first case with the notable exception being that numerous embedded fibers also eroded through the conjunctival epithelial surface.
DISCUSSION Common causes for conjunctival granulomas are foreign bodies composed of nonsynthetic and synthetic exogenous
Journal of AAPOS Volume 9 Number 6 December 2005
FIG 2. Case 1. A, The lesion contains an acute and chronic inflammatory cell infiltrate surrounding numerous synthetic fibers in the substantia propria of the conjunctiva (PAS, 25x, insets 100x [bottom] and 250x [top]). Occasional foreign body giant cells are seen close to the fibers (arrow) (inset, top). Many fibers demonstrate scattered black granules on the surface (asterisks). (B) Polarization shows numerous birefringent foreign synthetic fibers (H&E, 100x).
material.1-4 Whereas in the past nonsynthetic particles such as caterpillar hairs have been the predominant cause, these lesions are now more commonly caused by commercial manufactured synthetic and nonsynthetic fibers.3-5,7 Objects known to contain synthetic fibers are quite numerous and common, including materials such as beddings, toys, and pullover sweaters. Saer and coworkers8 reported in a randomly performed postmortem histopathologic study of adults that the prevalence of conjunctival foreign body granulomas is 10.3%. The prevalence in children has never been calculated, but might be even higher than adults. Additionally, these cases may be overlooked or unrecognized by the parents because children commonly have more tolerance to ocular irritation by foreign bodies.4 Usually, foreign body material is removed from the ocular surface by blinking and tearing, but occasionally it may be retained on the ocular surface. This retaining
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FIG 3. Case 1. Photomicrographs demonstrate cross-sections of synthetic fibers. A, Many synthetic fibers are embedded in a thin layer of mononuclear inflammatory cells (arrowheads) and demonstrate focal areas of amorphous homogenous material (asterisks). The cut surfaces of the synthetic fibers contain dark granules (arrows, black) and diagonal scratches (arrows, white) caused by sectioning (TEM, 1900x). B, Additionally, longitudinal extrusion marks (arrows, black) are present along the lateral surface of the synthetic fibers (SEM, 200x).
usually occurs because the material becomes encapsulated by mucous, embeds in the underlying stroma, and may induce a local inflammatory response. The acute inflammatory reaction typically is characterized by the exudation of plasma and fibrin and infiltration of polymorphonuclear leukocytes and macrophages. During later stages, a chronic nongranulomatous or granulomatous inflammatory cell reaction usually occurs with lymphocytes, plasma cells, epithelioid macrophages, and multinucleated giant cells in the latter case. The degree and duration of the inflammatory response depend upon a number of factors, including the type of foreign material deposited in the conjunctiva and whether it eventually gets digested or extruded from the body. In 1984, Weinberg and associates4 first reported 5 patients with foreign body granulomas caused by synthetic
Journal of AAPOS Volume 9 Number 6 December 2005
570 Schmack et al TABLE 1 Demographics and macroscopic findings in patients with synthetic fiber granulomas Author Weinberg JC et al4
Shields et al5 Arocker-Mettinger et al9 Resnick et al10* Offret et al11 Ferry et al8 Lueder et al12 Yang et al13 Enzenauer et al6 Schmack et al, this article
Case
Age (years)
Gender
Duration
Location (conjunctival)
Size (mm)
Color
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
6 8 16 4 17 2.2 2.6 5 5 6 4 13 4.5 2 7
Male Female Female Male Female Female Male Female Female Female Female Female Female Female Female
2 months 6 months 6 weeks 2 months several months 3 months several weeks 2 weeks N/D N/D 1 month N/D 10 months 5 months 4 weeks
Inferior fornix, OS Inferior fornix, OS Superior fornix, OD Inferior fornix, OD Inferior fornix, OD Inferior fornix, OD Inferior fornix, OS Inferior fornix, OD Inferior fornix, OD Inferior fornix, OD Inferior fornix, OS Inferior fornix, OS Inferior fornix, OS Inferior fornix, OD Inferior fornix, OD
10⫻4⫻2 7⫻2.5 7⫻5⫻3 N/D 4⫻4 7⫻7⫻5 N/D 4⫻3 N/D 10⫻10 2⫻1 4⫻3 15⫻10 5⫻4⫻2 10⫻4⫻3
Pink Green White, blue-black N/D N/D Red-yellow Yellow–green Yellow–green N/D Yellow–white White Blue White White–yellow Brown
N/D, no data available. *Granulomas composed of synthetic and nonsynthetic fibers.
fibers. Subsequently, 8 other case reports in which synthetic fibers contributed to conjunctival granuloma formation have been published (Medline database research; Table 1).5,6,7-13 Although usually found in young children, synthetic fiber granuloma also may occur in adolescents.4,13 The ages of the reported patients ranged from 26 months to 17 years old.4,5 The granulomas were usually unilateral and predominantly were found in the inferior fornix (Table 1). Symptoms typically became present from a few weeks up to several months after exposure.6,10 On the basis of all the published cases, including ours, the clinical appearance of synthetic fiber granulomas is rather nonspecific. The color may vary from white–yellow to blue-black, to green or even pink, depending on the color of the manufactured synthetic fibers. Slit-lamp examination commonly shows a nonspecific conjunctival mass with follicular conjunctivitis, papillary conjunctivitis or chemosis of the conjunctiva. The differential diagnosis of a conjunctival fiber granuloma also should include ophthalmia nodosa (insect and plant hairs), chalazion, pyogenic granuloma, ligneous conjunctivitis, papillary hyperplasia related to vernal conjunctivitis, sarcoidosis, atypical dermoid or dermolipoma, and neoplasms, such as vascular tumors and rhabdomyosarcoma.1,5,12 In contrast to the clinical signs, the histologic and especially the ultrastructural features of synthetic fiber granulomas are very characteristic and usually diagnostic, even if the source of the fibers is not known like in both of our cases. Microscopic evaluation shows numerous acellular synthetic fibers that are fairly uniform in diameter and generally round to oval in configuration (Fig. 2A). The size of the fibers in our cases ranged from 17 to 29 m in diameter, which is similar those published by Weinberg and associates (21 to 27 m).4 Synthetic fibers also are characterized by a lack of a central hollow core as well as a negative reactivity to PAS staining in comparison to
various natural, nonsynthetic filamentous structures including eyelashes, caterpillar hairs, or cotton fibers.1,4-6,11 In contrast to nonsynthetic materials, synthetic fibers typically exhibit a more markedly pronounced birefringence with polarized light due to their highly organized chemical composition (Fig. 2B).2,5,7 The filamentous foreign bodies commonly are surrounded by a mixture of acute and chronic inflammatory cells and occasionally may have a centrally located rim of a homogeneous eosinophilic material, which includes aggregates of antigen-IgG-antibody complexes (Fig. 2A).4,5 This latter immune response is termed the Splendore-Hoeppli phenomenon.4,14 On the basis of the properties of synthetic fibers, several specific fabrication and processing artifacts commonly can be observed on the fibers.4,5,7,10 They include numerous small, irregular-shaped black granular particles scattered on the transverse surface of the fibers as demonstrated in our patients (Figs. 2A and 3A). These granules represent remnants of de-lustering agents (eg, titanium, barium or zinc) used to diminish the plastic characteristics of the final fabric fibers.4,7 Parallel scratches on the cut ends of fibers as well as variable longitudinal grooves on the axis of many fibers may also be detected by electron microscopy (Fig. 3B). The thin diagonal scratches are artifacts caused by a steel blade during sectioning of the fibers, whereas the grooves represent extrusion marks related to the fabrication process rather than degeneration artifacts.4 The variety in the degree as well as the lack of grooves on the external surface of the synthetic fibers can be explained by fluctuations during fabrication and processing of various kinds of synthetic fibers in stuffed toy animals. In addition to identifying and removing the potential primary source of synthetic fibers, the treatment generally involves the removal of the foreign material and associated inflammatory reaction (eg, excision and débridment). As demonstrated in our cases, this procedure is very simple to
Journal of AAPOS Volume 9 Number 6 December 2005
perform at a slit-lamp with local or topical anesthesia.10 Nevertheless, in very young, anxious, or noncompliant patients, general anesthesia may be needed.6,12 The authors wish to thank Nancy L’Hernault for the electron microscopic studies. References 1. Gundersen T, Heath P, Garron LK. Ophthalmia nodosa. Am J Ophthalmol 1952;35:555-6. 2. Ainbinder DJ, O’Neill KP, Yagci A, Karcioglu ZA. Conjunctival mass formation with unexpected foreign body. J Pediatr Ophthalmol Strabmismus 1991;28:176-7. 3. Venkatesh P, Lakshmaiah NC, Chawla R. Insect wing conjunctival granuloma. Cornea 2003;22:489-90. 4. Weinberg JC, Eagle RC, Font RL, et al. Conjunctival synthetic fiber granuloma: a lesion that resembles conjunctivitis nodosa. Ophthalmology 1984;91:867-72. 5. Shields JA, Augsburger JJ, Stechschulte J, Repka M. Synthetic fiber granuloma of the conjunctiva. Am J Ophthalmol. 1985;99:598-600.
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6. Enzenauer RW, Speers WC. Teddy bear granuloma of the conjunctiva. J Pediatr Ophthalmol Strabismus 2002;39:46-8. 7. Ferry AP. Synthetic fiber granuloma. ‘Teddy Bear’ granuloma of the conjunctiva. Arch Ophthalmol 1994;112:1339-41. 8. Saer JB, Karcioglu GL, Karcioglu ZA. Incidence of granulomatous lesions in post-mortem conjunctival biopsy specimens. Am J Ophthalmol 1987;104:605-6. 9. Arocker-Mettinger E, Haddad R, Grabner G. Bindehautgranulom durch synthetische Fasern. Klin Monatsbl Augenheilkd 1986;189: 479-81. 10. Resnick SC, Schainker BA, Ortiz JM. Conjunctival synthetic and nonsynthetic fiber granulomas. Cornea 1991;10:59-62. 11. Offret H, Quillard J. Granulome á fibres synthetiques de la conjonctive. J Fr Ophtalmol 1992;15:308-10. 12. Lueder GT, Matsumoto B. Synthetic fiber granuloma. Arch Ophthalmol. 1995;113:848-9. 13. Yang YF, James CRH. A conjunctival synthetic fibre granuloma in a child. Eye 1996;10:143-5. 14. Rodig SJ, Dorfman DM. Splendore-Hoeppli phenomenon. Arch Pathol Lab Med 2001;1515-6.
An Eye on the Arts – The Arts on the Eye
When she realized that Amaranta was dressing the saints in the bedroom she pretended to show the boy the differences in the colors. “Let’s see,” she would tell him. “Tell me what color the Archangel Raphael is wearing.” In that way the child gave her the information that was denied her by her eyes, and long before he went away to the seminary Ursula could already distinguish the different colors of the saints’ clothing by the texture. Sometimes unforeseen accidents would happen. One afternoon when Amaranta was embroidering on the porch with the begonias Ursula bumped into her. “For heaven’s sake,” Amaranta protested, “watch where you’re going.” “It’s your fault,” Ursula said. “You’re not sitting where you’re supposed to.” She was sure of it. But that day she began to realize something that no one had noticed and it was that with the passage of the year the sun imperceptibly changed position and those who sat on the porch had to change their position little by little without being aware of it. From then on Ursula had only to remember the date in order to know exactly where Amaranta was sitting. —Gabriel García Márquez (from One Hundred Years of Solitude, HarperCollins)
F
a
From the Emory Eye Center Emory University School of Medicine, Atlanta Georgia b Department of Ophthalmology Ruprecht-Karls-University, Heidelberg, Germany Submitted February 23, 2005. Revision accepted July 19, 2005. Reprint requests: Scott R. Lambert, MD, Emory Eye Center, 1365-B Clifton Road, N.E., Atlanta, GA 30322 (e-mail: [email protected]). Copyright © 2005 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2005/$35.00 ⫹ 0 doi:10.1016/j.jaapos.2005.07.006
Journal of AAPOS
METHODS AND MATERIALS Gross Examination The two excised specimens were examined grossly before being trisected and processed for light and electron microscopy. Histology and Immunohistochemistry One third of each specimen was fixed in formalin, dehydrated in a graded series of alcohol solutions, cleared with xylene solution, infiltrated, and embedded in paraffin for sectioning. Five-micron thick sections were cut and stained with hematoxylin and eosin (H&E), periodic acid Schiff (PAS), and with antibodies against immunoglobulin G (IgG), CD68, and S-100 protein according to routine procedures. The slides of each specimen were evaluated by light microscopy (Olympus BH-2 microscope Tokyo Japan) and the histopathologic findings were recorded. Transmission Electron Microscopy (TEM) Glutaraldehyde-fixed portions of the specimens were rinsed in 0.1 mol/L cacodylate buffer and postfixed in 1% osmium tetroxide. After dehydration, the samples were embedded in LX 112 epoxy resin according to standard techniques. Thick sections (1.5 m) were then stained with toluidine blue and evaluated by light microscopy to detect the areas of pathology. The blocks were trimmed around these areas, and thin sections (70 – 80 nm) were cut, placed in a copper grid, double-stained with uranyl acetate December 2005
567
Journal of AAPOS Volume 9 Number 6 December 2005
568 Schmack et al and lead citrate, and examined with a JEM-100 CXII transmission electron microscope (JEOL Ltd., Tokyo Japan) at magnifications ranging from 1400x to 4800x. Scanning Electron Microscopy (SEM) Glutaraldehyde-fixed portions of the specimens were rinsed in 0.1 mol/L cacodylate buffer and postfixed in 1% osmium tetroxide. After dehydration, the samples were mounted, sputter coated with gold-pallidium and observed with JEOL 35 CF (JEOL Ltd., Tokyo Japan) scanning electron microscope at magnifications ranging from 100x to 1000x. Images were taken from the cross-sectioned surface.
CASE REPORTS Case 1 A 2-year-old girl was referred with a white conjunctival mass in the inferior fornix of her right eye. The patient’s mother reported that her daughter’s right eye has been puffy, crusty and tearing for the last five months. Simultaneously, she also noted that a mass had been gradually growing in the inferior fornix of the right eye. The child was otherwise healthy and had no history of ocular trauma or surgery. Topical antibiotics (polymyxin B sulfate, 3x daily) had been administrated to her right eye for several weeks. The ocular examination was normal aside from a mass in the right inferior fornix. It was white in color and there appeared to be eyelashes embedded in it. The mass was not adherent to the conjunctiva and was completely excised surgically using topical anesthesia. Case 2 A 7-year-old girl was referred for the biopsy of a conjunctival mass in the inferior fornix of her right eye, which was noticed 4 weeks earlier. Her past ocular history was unremarkable. She was asymptomatic without a history of trauma or placement of a foreign body in the eye. Complete surgical excision was performed with topical anesthesia.
RESULTS Case 1 Gross examination revealed a translucent brown mass with a nodular configuration (Fig. 1, bottom). A few eyelashes were protruding from one side of the tissue. The entire specimen measured 5 ⫻ 4 ⫻ 2 mm. Microscopic evaluation showed a nonkeratinized stratified squamous epithelium with goblet cells and numerous cross-sections of round to oval shaped, markedly polarizable fibers in the underlying substantia propria (Fig. 2A and 2B). A focus of acute and chronic inflammatory cells composed of lymphocytes, plasma cells, epithelioid macrophages, and polymorphonuclear leukocytes were present around the fibers (Fig. 2A, inset bottom right). Occasional
FIG 1. Excised specimens from case 1 (left, bottom) and case 2 (right, inset). Eyelashes (dark brown) and filamentous fibers (white) are seen in the biopsy of patient 2 (inset).
foreign body giant cells were directly adjacent to the fibers (Fig. 2A, inset top right). The fibers did not react to PAS staining, and many of them contained tiny scattered, dark granules. The vast majority of the fibers were surrounded by cuffs of homogenous eosinophilic material, which markedly stained positive for IgG. Immunohistochemistry disclosed also IgG in plasma cells and showed a strong reactivity for CD68 in epithelioid macrophages and multinucleated foreign body giant cells. No reactivity was found with S-100 protein. Electron microscopic examination (TEM and SEM) showed that the fibers were acellular in origin with a lack of a central core and smooth external surfaces (Fig. 3A and 3B). The fibers were fairly uniform in size, measuring between 17 to 29 microns in diameter. Some of them presented prominent longitudinal grooves in various degrees on their external surfaces (Fig. 3B, inset). Additionally, diagonal, parallel scratches were commonly seen on cross sections of the fibers. Many of the fibers were encapsulated by a thin layer of mononuclear inflammatory cells and showed a rim of amorphous material along the external surfaces (Fig. 3A). Case 2 The specimen was white-yellow in color and measured grossly 10 ⫻ 4 ⫻ 3 mm (Fig. 1, inset). Light- and electronmicroscopic evaluation showed similar findings as the first case with the notable exception being that numerous embedded fibers also eroded through the conjunctival epithelial surface.
DISCUSSION Common causes for conjunctival granulomas are foreign bodies composed of nonsynthetic and synthetic exogenous
Journal of AAPOS Volume 9 Number 6 December 2005
FIG 2. Case 1. A, The lesion contains an acute and chronic inflammatory cell infiltrate surrounding numerous synthetic fibers in the substantia propria of the conjunctiva (PAS, 25x, insets 100x [bottom] and 250x [top]). Occasional foreign body giant cells are seen close to the fibers (arrow) (inset, top). Many fibers demonstrate scattered black granules on the surface (asterisks). (B) Polarization shows numerous birefringent foreign synthetic fibers (H&E, 100x).
material.1-4 Whereas in the past nonsynthetic particles such as caterpillar hairs have been the predominant cause, these lesions are now more commonly caused by commercial manufactured synthetic and nonsynthetic fibers.3-5,7 Objects known to contain synthetic fibers are quite numerous and common, including materials such as beddings, toys, and pullover sweaters. Saer and coworkers8 reported in a randomly performed postmortem histopathologic study of adults that the prevalence of conjunctival foreign body granulomas is 10.3%. The prevalence in children has never been calculated, but might be even higher than adults. Additionally, these cases may be overlooked or unrecognized by the parents because children commonly have more tolerance to ocular irritation by foreign bodies.4 Usually, foreign body material is removed from the ocular surface by blinking and tearing, but occasionally it may be retained on the ocular surface. This retaining
Schmack et al
569
FIG 3. Case 1. Photomicrographs demonstrate cross-sections of synthetic fibers. A, Many synthetic fibers are embedded in a thin layer of mononuclear inflammatory cells (arrowheads) and demonstrate focal areas of amorphous homogenous material (asterisks). The cut surfaces of the synthetic fibers contain dark granules (arrows, black) and diagonal scratches (arrows, white) caused by sectioning (TEM, 1900x). B, Additionally, longitudinal extrusion marks (arrows, black) are present along the lateral surface of the synthetic fibers (SEM, 200x).
usually occurs because the material becomes encapsulated by mucous, embeds in the underlying stroma, and may induce a local inflammatory response. The acute inflammatory reaction typically is characterized by the exudation of plasma and fibrin and infiltration of polymorphonuclear leukocytes and macrophages. During later stages, a chronic nongranulomatous or granulomatous inflammatory cell reaction usually occurs with lymphocytes, plasma cells, epithelioid macrophages, and multinucleated giant cells in the latter case. The degree and duration of the inflammatory response depend upon a number of factors, including the type of foreign material deposited in the conjunctiva and whether it eventually gets digested or extruded from the body. In 1984, Weinberg and associates4 first reported 5 patients with foreign body granulomas caused by synthetic
Journal of AAPOS Volume 9 Number 6 December 2005
570 Schmack et al TABLE 1 Demographics and macroscopic findings in patients with synthetic fiber granulomas Author Weinberg JC et al4
Shields et al5 Arocker-Mettinger et al9 Resnick et al10* Offret et al11 Ferry et al8 Lueder et al12 Yang et al13 Enzenauer et al6 Schmack et al, this article
Case
Age (years)
Gender
Duration
Location (conjunctival)
Size (mm)
Color
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
6 8 16 4 17 2.2 2.6 5 5 6 4 13 4.5 2 7
Male Female Female Male Female Female Male Female Female Female Female Female Female Female Female
2 months 6 months 6 weeks 2 months several months 3 months several weeks 2 weeks N/D N/D 1 month N/D 10 months 5 months 4 weeks
Inferior fornix, OS Inferior fornix, OS Superior fornix, OD Inferior fornix, OD Inferior fornix, OD Inferior fornix, OD Inferior fornix, OS Inferior fornix, OD Inferior fornix, OD Inferior fornix, OD Inferior fornix, OS Inferior fornix, OS Inferior fornix, OS Inferior fornix, OD Inferior fornix, OD
10⫻4⫻2 7⫻2.5 7⫻5⫻3 N/D 4⫻4 7⫻7⫻5 N/D 4⫻3 N/D 10⫻10 2⫻1 4⫻3 15⫻10 5⫻4⫻2 10⫻4⫻3
Pink Green White, blue-black N/D N/D Red-yellow Yellow–green Yellow–green N/D Yellow–white White Blue White White–yellow Brown
N/D, no data available. *Granulomas composed of synthetic and nonsynthetic fibers.
fibers. Subsequently, 8 other case reports in which synthetic fibers contributed to conjunctival granuloma formation have been published (Medline database research; Table 1).5,6,7-13 Although usually found in young children, synthetic fiber granuloma also may occur in adolescents.4,13 The ages of the reported patients ranged from 26 months to 17 years old.4,5 The granulomas were usually unilateral and predominantly were found in the inferior fornix (Table 1). Symptoms typically became present from a few weeks up to several months after exposure.6,10 On the basis of all the published cases, including ours, the clinical appearance of synthetic fiber granulomas is rather nonspecific. The color may vary from white–yellow to blue-black, to green or even pink, depending on the color of the manufactured synthetic fibers. Slit-lamp examination commonly shows a nonspecific conjunctival mass with follicular conjunctivitis, papillary conjunctivitis or chemosis of the conjunctiva. The differential diagnosis of a conjunctival fiber granuloma also should include ophthalmia nodosa (insect and plant hairs), chalazion, pyogenic granuloma, ligneous conjunctivitis, papillary hyperplasia related to vernal conjunctivitis, sarcoidosis, atypical dermoid or dermolipoma, and neoplasms, such as vascular tumors and rhabdomyosarcoma.1,5,12 In contrast to the clinical signs, the histologic and especially the ultrastructural features of synthetic fiber granulomas are very characteristic and usually diagnostic, even if the source of the fibers is not known like in both of our cases. Microscopic evaluation shows numerous acellular synthetic fibers that are fairly uniform in diameter and generally round to oval in configuration (Fig. 2A). The size of the fibers in our cases ranged from 17 to 29 m in diameter, which is similar those published by Weinberg and associates (21 to 27 m).4 Synthetic fibers also are characterized by a lack of a central hollow core as well as a negative reactivity to PAS staining in comparison to
various natural, nonsynthetic filamentous structures including eyelashes, caterpillar hairs, or cotton fibers.1,4-6,11 In contrast to nonsynthetic materials, synthetic fibers typically exhibit a more markedly pronounced birefringence with polarized light due to their highly organized chemical composition (Fig. 2B).2,5,7 The filamentous foreign bodies commonly are surrounded by a mixture of acute and chronic inflammatory cells and occasionally may have a centrally located rim of a homogeneous eosinophilic material, which includes aggregates of antigen-IgG-antibody complexes (Fig. 2A).4,5 This latter immune response is termed the Splendore-Hoeppli phenomenon.4,14 On the basis of the properties of synthetic fibers, several specific fabrication and processing artifacts commonly can be observed on the fibers.4,5,7,10 They include numerous small, irregular-shaped black granular particles scattered on the transverse surface of the fibers as demonstrated in our patients (Figs. 2A and 3A). These granules represent remnants of de-lustering agents (eg, titanium, barium or zinc) used to diminish the plastic characteristics of the final fabric fibers.4,7 Parallel scratches on the cut ends of fibers as well as variable longitudinal grooves on the axis of many fibers may also be detected by electron microscopy (Fig. 3B). The thin diagonal scratches are artifacts caused by a steel blade during sectioning of the fibers, whereas the grooves represent extrusion marks related to the fabrication process rather than degeneration artifacts.4 The variety in the degree as well as the lack of grooves on the external surface of the synthetic fibers can be explained by fluctuations during fabrication and processing of various kinds of synthetic fibers in stuffed toy animals. In addition to identifying and removing the potential primary source of synthetic fibers, the treatment generally involves the removal of the foreign material and associated inflammatory reaction (eg, excision and débridment). As demonstrated in our cases, this procedure is very simple to
Journal of AAPOS Volume 9 Number 6 December 2005
perform at a slit-lamp with local or topical anesthesia.10 Nevertheless, in very young, anxious, or noncompliant patients, general anesthesia may be needed.6,12 The authors wish to thank Nancy L’Hernault for the electron microscopic studies. References 1. Gundersen T, Heath P, Garron LK. Ophthalmia nodosa. Am J Ophthalmol 1952;35:555-6. 2. Ainbinder DJ, O’Neill KP, Yagci A, Karcioglu ZA. Conjunctival mass formation with unexpected foreign body. J Pediatr Ophthalmol Strabmismus 1991;28:176-7. 3. Venkatesh P, Lakshmaiah NC, Chawla R. Insect wing conjunctival granuloma. Cornea 2003;22:489-90. 4. Weinberg JC, Eagle RC, Font RL, et al. Conjunctival synthetic fiber granuloma: a lesion that resembles conjunctivitis nodosa. Ophthalmology 1984;91:867-72. 5. Shields JA, Augsburger JJ, Stechschulte J, Repka M. Synthetic fiber granuloma of the conjunctiva. Am J Ophthalmol. 1985;99:598-600.
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6. Enzenauer RW, Speers WC. Teddy bear granuloma of the conjunctiva. J Pediatr Ophthalmol Strabismus 2002;39:46-8. 7. Ferry AP. Synthetic fiber granuloma. ‘Teddy Bear’ granuloma of the conjunctiva. Arch Ophthalmol 1994;112:1339-41. 8. Saer JB, Karcioglu GL, Karcioglu ZA. Incidence of granulomatous lesions in post-mortem conjunctival biopsy specimens. Am J Ophthalmol 1987;104:605-6. 9. Arocker-Mettinger E, Haddad R, Grabner G. Bindehautgranulom durch synthetische Fasern. Klin Monatsbl Augenheilkd 1986;189: 479-81. 10. Resnick SC, Schainker BA, Ortiz JM. Conjunctival synthetic and nonsynthetic fiber granulomas. Cornea 1991;10:59-62. 11. Offret H, Quillard J. Granulome á fibres synthetiques de la conjonctive. J Fr Ophtalmol 1992;15:308-10. 12. Lueder GT, Matsumoto B. Synthetic fiber granuloma. Arch Ophthalmol. 1995;113:848-9. 13. Yang YF, James CRH. A conjunctival synthetic fibre granuloma in a child. Eye 1996;10:143-5. 14. Rodig SJ, Dorfman DM. Splendore-Hoeppli phenomenon. Arch Pathol Lab Med 2001;1515-6.
An Eye on the Arts – The Arts on the Eye
When she realized that Amaranta was dressing the saints in the bedroom she pretended to show the boy the differences in the colors. “Let’s see,” she would tell him. “Tell me what color the Archangel Raphael is wearing.” In that way the child gave her the information that was denied her by her eyes, and long before he went away to the seminary Ursula could already distinguish the different colors of the saints’ clothing by the texture. Sometimes unforeseen accidents would happen. One afternoon when Amaranta was embroidering on the porch with the begonias Ursula bumped into her. “For heaven’s sake,” Amaranta protested, “watch where you’re going.” “It’s your fault,” Ursula said. “You’re not sitting where you’re supposed to.” She was sure of it. But that day she began to realize something that no one had noticed and it was that with the passage of the year the sun imperceptibly changed position and those who sat on the porch had to change their position little by little without being aware of it. From then on Ursula had only to remember the date in order to know exactly where Amaranta was sitting. —Gabriel García Márquez (from One Hundred Years of Solitude, HarperCollins)