DIFFUSE UNILATERAL SUBACUTE NEURORETINITIS: A CASE OF MISTAKEN IDENTITY Kelly D. Schweitzer, MD,* Karen L. McClean, MD,† Kevin R. Kazacos, DVM, PHD,‡ Rau´l Garcı´a, MD§
Background: The report details a case of diffuse unilateral subacute neuroretinitis (DUSN) wherein a subretinal parasite was visualized and subsequently destroyed with laser photocoagulation. Methods: Full historical and serologic investigations were carried out. A literature search to determine all possible causes of DUSN was also completed. Results: Serologic results supported Baylisascaris procyonis as the cause of infection, but imaging of the worm before destruction did not support this organism as the etiologic agent. On the basis of morphologic evaluation of still imaging and videoimaging, patient exposure information, and known causes of DUSN, the infection was likely due to Alaria species, providing further evidence of a trematode cause. Conclusions: The report adds to the literature that trematodes should be recognized as a possible cause of ocular larva migrans. Although laser therapy is appropriate and effective for both nematode and trematode infections of the eye, in the case of adjunctive medical therapy, identification of the parasite group is essential. RETINAL CASES & BRIEF REPORTS 2:344 –346, 2008
direct laser photocoagulation to prevent further migration and progressive vision loss.2
From *University of Saskatchewan, Regina, Saskatchewan, Canada; †University of Saskatchewan, Saskatoon, Saskatchewan, Canada; ‡Purdue University, Department of Veterinary Pathobiology, West Lafayette, Indiana, USA; and §Pasqua Hospital Eye Centre, Regina, Saskatchewan, Canada.
Case Report A healthy 50-year-old aboriginal man was found to have an extrafoveal white lesion in the left eye during routine optometric examination. Corrected vision was 20/20 with no associated ocular or systemic complaints. Two months later, vision had deteriorated to 2/200 in the left eye. Anterior segment examination demonstrated a trace of flare, the vitreous contained 2⫹ cells, and the intraocular pressure was normal. A tracklike lesion extended from the inferotemporal peripheral retina from just behind the ora serrata into the macular area (Fig. 1). Extensive subretinal white lesions were observed. Fluorescein angiography demonstrated blockage of choroidal fluorescence that corresponded to the subretinal lesions with late staining, findings suggestive of retinitis. Results of examination of the right eye were normal. A parasite was visualized inferotemporally to the center of the fovea. The worm could be seen extending, contracting, and moving away from the light of the slit lamp (see video; Fig. 2). The worm had refringent areas corresponding to an oral sucker and penetration glands/ventral sucker (Fig. 2). The parasite was destroyed with laser. The yellow argon laser photocoagulator was chosen to minimize absorption by retinal tissue and thus limit subsequent damage. Immediately after laser treatment, 4 mg of triamcinolone acetonide was injected intravitreally to help prevent an inflammatory
T
he initial stage of diffuse unilateral subacute neuroretinitis (DUSN) includes unilateral visual loss, vitritis, papillitis, and recurrent gray white retinal lesions. Progressive loss of vision with optic atrophy, narrowing of major retinal vessels, and atrophic pigment epithelial changes ensues.1 Parasite migration in the subretinal space is considered the primary cause of this syndrome.1,2 Suggested treatment of DUSN is
Presented as a poster at the Canadian Ophthalmology Society General Meeting; Edmonton, Alberta, Canada; June 23–25, 2005. The authors have no proprietary interest in any portion of this article. See web site for a video accompanying this article. Reprint requests: Rau´l Garcı´a, Pasqua Hospital, 1 4101 Dewdney Avenue, Regina, Saskatchewan, Canada, S4T 1A5; e-mail: [email protected]
344
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DIFFUSE UNILATERAL SUBACUTE NEURORETINITIS
Fig. 1. A tracklike lesion coming from the inferotemporal peripheral retina beginning just behind the ora serrata and extending into the macular area can be seen.
Fig. 3. An image 6 months after treatment showing no ocular inflammation, attenuation of the retinal vasculature, or optic nerve atrophy. Twelve months after treatment, vision in the affected eye was 20/300.
reaction to worm antigens within the eye. There was no significant inflammation or associated complications related to treatment of the worm infection by laser. Morphometric analysis of fundus photographs estimated the parasite’s length to vary from 450 m (contracted) to 625 m (extended) with a width of ⬇200 m. Investigations revealed mild eosinophilia (eosinophil count, 0.9 ⫻ 109/L) and a serum IgE level of 1,416 kU/L (normal range, 0 –230 kU/L). Results of serologic testing for IgM and IgG antibodies to Toxoplasma and antibodies to Toxocara were negative. Enzyme-linked immunosorbent assay revealed moderately elevated levels of Baylisascaris procyonis with an absorbance of 0.603 (absorbance of ⬎0.250 considered positive; Department of Veterinary Pathobiology, West Lafayette, IN). On the basis of serologic findings and history of exposure to raccoon feces, a
diagnosis of baylisascariasis was considered; however, review of the retinal images by a veterinary parasitologist indicated that the worm was incompatible with a nematode but consistent with a trematode (fluke). Size, shape, and movement were most consistent with a mesocercaria larva of Alaria species. One year after treatment, visual acuity was 20/300. There was no ocular inflammation, attenuation of the retinal vasculature, or optic nerve atrophy (Fig. 3). There was no history of travel outside Canada or direct contact with wild animals, but the patient had recently visited an area where there was extensive raccoon activity and may have handled firewood contaminated by raccoon feces. He had an adult cat that was allowed to forage outdoors. He was an avid ice fisher, eating walleye and perch, but had not done so for 5 years or 6 years before his problem. He did not hunt or eat wild game or much meat at home other than hamburger. He denied eating frog’s legs, other lower vertebrates, or wild birds. He did eat regularly at Chinese restaurants both locally and while on the road for business, including one or two lower-quality establishments for which overall cleanliness, food preparation practices, and possible inclusion of unknown/unstated ingredients were suspect. He often ate from the buffet that included pork, chicken, shrimp, and vegetables but occasionally ate combination dishes, wonton soup, pork meatballs, and steamed Chinese sausage for which all ingredients were not known. The possibility existed of inclusion of unknown meat products or cross-contamination. Two restaurants (one of lower quality) were contacted and denied serving frog’s legs, turtle, or other lower vertebrates or exotic meats.
Discussion
Fig. 2. A parasite ⬇200 ⫻ 500 m in size can be seen inferotemporal to the center of the fovea. It is expanding its anterior region as it prepares to extend forward. The extensive retinal damage and reaction caused by the organism also can be seen.
Many different helminths have been implicated in ocular larva migrans (OLM). In North America, the dog (Toxocara canis) and cat (Toxocara cati) roundworms are most commonly reported and are particularly important in children with geophagia. B. procyonis, the raccoon roundworm, is also well recognized as a cause of DUSN. Animals infected with Toxocara or Baylisascaris shed large numbers of eggs in their feces,
346
RETINAL CASES & BRIEF REPORTSℜ
extensively contaminating their environment. Gnathostoma species and Angiostrongylus cantonensis may also cause DUSN. Both primarily infect travelers, and these infections are acquired through consumption of various lower vertebrates and invertebrates. There are few trematodes known to cause OLM. Of these, Alaria is noteworthy in having a highly migratory larva known to invade the tissues of various paratenic hosts, including humans. The mesocercarial stage of Alaria is the only trematode reported to cause OLM and DUSN, most likely acquired through consumption or handling of frog’s legs,2,3 although snakes, birds, rodents, and various other mammals could also be a source. Although most case reports ascribe infection to ingestion of the parasite, there is case and experimental evidence that Alaria is also able to penetrate the mammalian eye after external contamination (via food preparation, etc).3,4 In our case, a subretinal parasite was visualized. Historical and serologic data suggested a possible etiology of B. procyonis; however, parasite morphology was indicative of a trematode, and positive serologic results were ascribed to covert infection due to Baylisascaris. The lack of travel history limits consideration to trematodes endemic in Canada, including Alaria (which occurs in various wild and domestic carnivores such as raccoons, skunks, coyotes, dogs, etc). Alaria is the only reported trematode etiology of OLM and DUSN and was likely the cause of our patient’s infection based on morphologic features of the larva, which matched those seen in previous cases.2,3 Although a specific association could not be made, ingestion or handling the tissues of various mammals and birds could have resulted in infection. The patient’s food habits suggested infection from a Chinese restaurant where he unwittingly ingested meat or cross-contaminated food containing mesocercariae. In two other cases of OLM/DUSN due to Alaria that occurred in northern California, a direct association was made to ingestion of frog’s legs or cross-contaminated food items in Chinese restaurants. Although infection due to Alaria is most likely involved in this case, the worm was not removed and identified; therefore, we cannot rule out the possible involvement of another trematode as yet unidentified in OLM and DUSN. For example, another trematode common to Canada, the Canadian liver fluke (Metorchis conjunctus), causes infection in a wide range of fish-eating carnivores, including bears and sled dogs, which are the definitive hosts.5 Second intermediate hosts include several fish species, most frequently the white sucker (Catostomus commersoni). As an avid ice fisher with extensive fish handling and consumption, our patient was thought to be at risk of
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infection through ingestion or possible hand-to-conjunctiva contact. However, this is not a fluke that normally undergoes somatic migration or uses paratenic hosts, and it has a well encapsulated metacercarial stage. In addition, the time involved since fishing also excluded this from consideration in our case. Infection due to Metorchis would typically have resulted in acute abdominal symptoms and abnormal liver enzyme levels, as reported by MacLean et al,5 not in systemic migration or ocular involvement. This case has several instructive features. It points out the fallibility of serologic diagnosis of parasitic infections and that serologic test results must be considered in light of morphologic features of the parasite seen. Background seropositivity is always possible, as are cross-reactions between parasites, both within and across groups. Furthermore, although photocoagulation is the treatment of choice for DUSN, should antihelmintic therapy be considered because of systemic disease or subfoveal location of the parasite, determination of the parasite group is critical to selection of the appropriate chemotherapeutic agent. When a motile parasite is observed, DUSN has usually been ascribed to nematodes. Alternatively, our case provides further evidence that trematodes may also cause DUSN and highlights the value of accurate parasite identification in providing medical treatment. Thiabendazole, albendazole, and ivermectin have been used as treatment in cases of DUSN, and treatment failures with these agents have been reported. None of these agents are effective in the treatment of trematode infections, for which praziquantel would be indicated. Finally, our case indicates that a thorough history is of critical importance, because particular food habits and associations of the patient are necessary in helping to establish the likely parasite involved. Key words: Alaria, diffuse unilateral subacute neuroretinitis, ocular larva migrans, trematodes. References 1.
Gass JD, Braunstein RA. Further observations concerning the diffuse unilateral subacute neuroretinitis syndrome. Arch Ophthalmol 1983;101:1689–1697. 2. McDonald HR, Kazacos KR, Schatz H, Johnson RN. Two cases of intraocular infection with Alaria mesocercaria . Am J Ophthalmol 1994;117:447–455. 3. Shea M, Maberley AL, Walters J, et al. Intraretinal larval trematode. Trans Am Acad Ophthalmol Otolaryngol 1973;77: OP784–OP791. 4. Walters JC, Freeman BS, Shea M, Fallis AM. Penetration and survival of mesocercariae (Alaria spp.) in the mammalian eye. Can J Ophthalmol 1975;10:101–106. 5. MacLean JD, Arthur JR, Ward BJ, et al. Common-source outbreak of acute infection due to the North American liver fluke Metorchis conjunctus. Lancet 1996;347:154–158.
Background: The report details a case of diffuse unilateral subacute neuroretinitis (DUSN) wherein a subretinal parasite was visualized and subsequently destroyed with laser photocoagulation. Methods: Full historical and serologic investigations were carried out. A literature search to determine all possible causes of DUSN was also completed. Results: Serologic results supported Baylisascaris procyonis as the cause of infection, but imaging of the worm before destruction did not support this organism as the etiologic agent. On the basis of morphologic evaluation of still imaging and videoimaging, patient exposure information, and known causes of DUSN, the infection was likely due to Alaria species, providing further evidence of a trematode cause. Conclusions: The report adds to the literature that trematodes should be recognized as a possible cause of ocular larva migrans. Although laser therapy is appropriate and effective for both nematode and trematode infections of the eye, in the case of adjunctive medical therapy, identification of the parasite group is essential. RETINAL CASES & BRIEF REPORTS 2:344 –346, 2008
direct laser photocoagulation to prevent further migration and progressive vision loss.2
From *University of Saskatchewan, Regina, Saskatchewan, Canada; †University of Saskatchewan, Saskatoon, Saskatchewan, Canada; ‡Purdue University, Department of Veterinary Pathobiology, West Lafayette, Indiana, USA; and §Pasqua Hospital Eye Centre, Regina, Saskatchewan, Canada.
Case Report A healthy 50-year-old aboriginal man was found to have an extrafoveal white lesion in the left eye during routine optometric examination. Corrected vision was 20/20 with no associated ocular or systemic complaints. Two months later, vision had deteriorated to 2/200 in the left eye. Anterior segment examination demonstrated a trace of flare, the vitreous contained 2⫹ cells, and the intraocular pressure was normal. A tracklike lesion extended from the inferotemporal peripheral retina from just behind the ora serrata into the macular area (Fig. 1). Extensive subretinal white lesions were observed. Fluorescein angiography demonstrated blockage of choroidal fluorescence that corresponded to the subretinal lesions with late staining, findings suggestive of retinitis. Results of examination of the right eye were normal. A parasite was visualized inferotemporally to the center of the fovea. The worm could be seen extending, contracting, and moving away from the light of the slit lamp (see video; Fig. 2). The worm had refringent areas corresponding to an oral sucker and penetration glands/ventral sucker (Fig. 2). The parasite was destroyed with laser. The yellow argon laser photocoagulator was chosen to minimize absorption by retinal tissue and thus limit subsequent damage. Immediately after laser treatment, 4 mg of triamcinolone acetonide was injected intravitreally to help prevent an inflammatory
T
he initial stage of diffuse unilateral subacute neuroretinitis (DUSN) includes unilateral visual loss, vitritis, papillitis, and recurrent gray white retinal lesions. Progressive loss of vision with optic atrophy, narrowing of major retinal vessels, and atrophic pigment epithelial changes ensues.1 Parasite migration in the subretinal space is considered the primary cause of this syndrome.1,2 Suggested treatment of DUSN is
Presented as a poster at the Canadian Ophthalmology Society General Meeting; Edmonton, Alberta, Canada; June 23–25, 2005. The authors have no proprietary interest in any portion of this article. See web site for a video accompanying this article. Reprint requests: Rau´l Garcı´a, Pasqua Hospital, 1 4101 Dewdney Avenue, Regina, Saskatchewan, Canada, S4T 1A5; e-mail: [email protected]
344
345
DIFFUSE UNILATERAL SUBACUTE NEURORETINITIS
Fig. 1. A tracklike lesion coming from the inferotemporal peripheral retina beginning just behind the ora serrata and extending into the macular area can be seen.
Fig. 3. An image 6 months after treatment showing no ocular inflammation, attenuation of the retinal vasculature, or optic nerve atrophy. Twelve months after treatment, vision in the affected eye was 20/300.
reaction to worm antigens within the eye. There was no significant inflammation or associated complications related to treatment of the worm infection by laser. Morphometric analysis of fundus photographs estimated the parasite’s length to vary from 450 m (contracted) to 625 m (extended) with a width of ⬇200 m. Investigations revealed mild eosinophilia (eosinophil count, 0.9 ⫻ 109/L) and a serum IgE level of 1,416 kU/L (normal range, 0 –230 kU/L). Results of serologic testing for IgM and IgG antibodies to Toxoplasma and antibodies to Toxocara were negative. Enzyme-linked immunosorbent assay revealed moderately elevated levels of Baylisascaris procyonis with an absorbance of 0.603 (absorbance of ⬎0.250 considered positive; Department of Veterinary Pathobiology, West Lafayette, IN). On the basis of serologic findings and history of exposure to raccoon feces, a
diagnosis of baylisascariasis was considered; however, review of the retinal images by a veterinary parasitologist indicated that the worm was incompatible with a nematode but consistent with a trematode (fluke). Size, shape, and movement were most consistent with a mesocercaria larva of Alaria species. One year after treatment, visual acuity was 20/300. There was no ocular inflammation, attenuation of the retinal vasculature, or optic nerve atrophy (Fig. 3). There was no history of travel outside Canada or direct contact with wild animals, but the patient had recently visited an area where there was extensive raccoon activity and may have handled firewood contaminated by raccoon feces. He had an adult cat that was allowed to forage outdoors. He was an avid ice fisher, eating walleye and perch, but had not done so for 5 years or 6 years before his problem. He did not hunt or eat wild game or much meat at home other than hamburger. He denied eating frog’s legs, other lower vertebrates, or wild birds. He did eat regularly at Chinese restaurants both locally and while on the road for business, including one or two lower-quality establishments for which overall cleanliness, food preparation practices, and possible inclusion of unknown/unstated ingredients were suspect. He often ate from the buffet that included pork, chicken, shrimp, and vegetables but occasionally ate combination dishes, wonton soup, pork meatballs, and steamed Chinese sausage for which all ingredients were not known. The possibility existed of inclusion of unknown meat products or cross-contamination. Two restaurants (one of lower quality) were contacted and denied serving frog’s legs, turtle, or other lower vertebrates or exotic meats.
Discussion
Fig. 2. A parasite ⬇200 ⫻ 500 m in size can be seen inferotemporal to the center of the fovea. It is expanding its anterior region as it prepares to extend forward. The extensive retinal damage and reaction caused by the organism also can be seen.
Many different helminths have been implicated in ocular larva migrans (OLM). In North America, the dog (Toxocara canis) and cat (Toxocara cati) roundworms are most commonly reported and are particularly important in children with geophagia. B. procyonis, the raccoon roundworm, is also well recognized as a cause of DUSN. Animals infected with Toxocara or Baylisascaris shed large numbers of eggs in their feces,
346
RETINAL CASES & BRIEF REPORTSℜ
extensively contaminating their environment. Gnathostoma species and Angiostrongylus cantonensis may also cause DUSN. Both primarily infect travelers, and these infections are acquired through consumption of various lower vertebrates and invertebrates. There are few trematodes known to cause OLM. Of these, Alaria is noteworthy in having a highly migratory larva known to invade the tissues of various paratenic hosts, including humans. The mesocercarial stage of Alaria is the only trematode reported to cause OLM and DUSN, most likely acquired through consumption or handling of frog’s legs,2,3 although snakes, birds, rodents, and various other mammals could also be a source. Although most case reports ascribe infection to ingestion of the parasite, there is case and experimental evidence that Alaria is also able to penetrate the mammalian eye after external contamination (via food preparation, etc).3,4 In our case, a subretinal parasite was visualized. Historical and serologic data suggested a possible etiology of B. procyonis; however, parasite morphology was indicative of a trematode, and positive serologic results were ascribed to covert infection due to Baylisascaris. The lack of travel history limits consideration to trematodes endemic in Canada, including Alaria (which occurs in various wild and domestic carnivores such as raccoons, skunks, coyotes, dogs, etc). Alaria is the only reported trematode etiology of OLM and DUSN and was likely the cause of our patient’s infection based on morphologic features of the larva, which matched those seen in previous cases.2,3 Although a specific association could not be made, ingestion or handling the tissues of various mammals and birds could have resulted in infection. The patient’s food habits suggested infection from a Chinese restaurant where he unwittingly ingested meat or cross-contaminated food containing mesocercariae. In two other cases of OLM/DUSN due to Alaria that occurred in northern California, a direct association was made to ingestion of frog’s legs or cross-contaminated food items in Chinese restaurants. Although infection due to Alaria is most likely involved in this case, the worm was not removed and identified; therefore, we cannot rule out the possible involvement of another trematode as yet unidentified in OLM and DUSN. For example, another trematode common to Canada, the Canadian liver fluke (Metorchis conjunctus), causes infection in a wide range of fish-eating carnivores, including bears and sled dogs, which are the definitive hosts.5 Second intermediate hosts include several fish species, most frequently the white sucker (Catostomus commersoni). As an avid ice fisher with extensive fish handling and consumption, our patient was thought to be at risk of
●
2008
●
VOLUME 2
●
NUMBER 4
infection through ingestion or possible hand-to-conjunctiva contact. However, this is not a fluke that normally undergoes somatic migration or uses paratenic hosts, and it has a well encapsulated metacercarial stage. In addition, the time involved since fishing also excluded this from consideration in our case. Infection due to Metorchis would typically have resulted in acute abdominal symptoms and abnormal liver enzyme levels, as reported by MacLean et al,5 not in systemic migration or ocular involvement. This case has several instructive features. It points out the fallibility of serologic diagnosis of parasitic infections and that serologic test results must be considered in light of morphologic features of the parasite seen. Background seropositivity is always possible, as are cross-reactions between parasites, both within and across groups. Furthermore, although photocoagulation is the treatment of choice for DUSN, should antihelmintic therapy be considered because of systemic disease or subfoveal location of the parasite, determination of the parasite group is critical to selection of the appropriate chemotherapeutic agent. When a motile parasite is observed, DUSN has usually been ascribed to nematodes. Alternatively, our case provides further evidence that trematodes may also cause DUSN and highlights the value of accurate parasite identification in providing medical treatment. Thiabendazole, albendazole, and ivermectin have been used as treatment in cases of DUSN, and treatment failures with these agents have been reported. None of these agents are effective in the treatment of trematode infections, for which praziquantel would be indicated. Finally, our case indicates that a thorough history is of critical importance, because particular food habits and associations of the patient are necessary in helping to establish the likely parasite involved. Key words: Alaria, diffuse unilateral subacute neuroretinitis, ocular larva migrans, trematodes. References 1.
Gass JD, Braunstein RA. Further observations concerning the diffuse unilateral subacute neuroretinitis syndrome. Arch Ophthalmol 1983;101:1689–1697. 2. McDonald HR, Kazacos KR, Schatz H, Johnson RN. Two cases of intraocular infection with Alaria mesocercaria . Am J Ophthalmol 1994;117:447–455. 3. Shea M, Maberley AL, Walters J, et al. Intraretinal larval trematode. Trans Am Acad Ophthalmol Otolaryngol 1973;77: OP784–OP791. 4. Walters JC, Freeman BS, Shea M, Fallis AM. Penetration and survival of mesocercariae (Alaria spp.) in the mammalian eye. Can J Ophthalmol 1975;10:101–106. 5. MacLean JD, Arthur JR, Ward BJ, et al. Common-source outbreak of acute infection due to the North American liver fluke Metorchis conjunctus. Lancet 1996;347:154–158.
