Onchocerciasis or river blindness is a disease that affects 17.7 million people worldwide, with some 123 million people living in its endemic regions; ivermectin is usually the drug of choice, but has not eradicated the disease.
Worms of two sizes have been described in eyes with DUSN.
The number of parasitic disorders affecting the eye is very large.
Onchocerciasis or river blindness is a disease that affects 17.7 million people worldwide, with some 123 million people living in its endemic regions. It is estimated that some 270 000 are blind and a half million are severely visually handicapped because of this disease. In developing countries, blindness occurs at 10 times the rate reported in the industrialized world. , Ocular onchocerciasis has been declared by the World Health Organization to be one of the five major preventable causes of blindness (the others include cataract, trachoma, glaucoma, and xerophthalmia). The disease is caused by a tissue-dwelling parasite, the nematode Onchocerca volvulus . It is spread by the blackflies of the Simulium species and is found in a broad belt across western and central Africa, as well as in Central America with small pockets in northern South America and the Arabian peninsula. Zoonotic infections have been reported in many countries, including Hungary. The blackfly needs rapid running water to propagate, and therefore the endemic areas are usually the most fertile, which makes this disease of extraordinary importance for the Third World countries affected.
The infected blackfly bites humans, thereby introducing the infection. Polymerase chain reaction-mediated amplification methods and immunoblotting of the silk proteins permit the identification of sibling species of biting adult females. Adult worms will ultimately develop and form into nodules found throughout the body, often subcutaneously. These adults will produce microfilariae that are released in extraordinary numbers. The diagnosis of the disease and the determination of the infestation rate is made by skin snips and by counting the number of microfilariae found ( Fig. 17-1 ) The microfilariae are the major cause of most of the ocular disease. Table 17-1 describes other ocular manifestations involved in parasitic infections of the eye.
|Hyphema||Loiasis (Central and West Africa), gnathostomiasis (Asia)|
|Hypopyon||Amebiasis (worldwide), cysticercosis (Latin America, India), gnathostomiasis, onchocerciasis (Africa, Latin America), toxocariasis|
|Anterior uveitis||Amebiasis, angiostrongyliasis (Pacific), hookworm, ascariasis, schistosomiasis (tropics), caterpillar hairs, cestodes (sparganosis), cysticercosis, giardiasis, gnathostomiasis, leishmania (Asia, Latin America), loiasis, myiasis, onchocerciasis, tapeworm trichinosis, toxocariasis, trypanosomiasis (Africa, Latin America), Kala-Azar (with HIV+) Bancroft’s filariasis (tropics)|
|Hemorrhage||Ascariasis, schistosomiasis, loiasis, trichinosis|
|Vitreitis||Schistosomiasis, caterpillar hairs, cysticercus, gnathostomiasis, onchocerciasis, toxocariasis, trichinosis|
|Degeneration, exudates, nodules, detachment||Angiostrongyliasis, amebiasis, babesiosis, caterpillar hairs, cysticercus, echinococcus (hydatid cyst), leishmania, loiasis, myiasis, onchocerciasis, trichinosis, toxocariasis|
|Hemorrhage||Amebiasis, hookworm, ascariasis, schistosomiasis, cysticercus, giardiasis, gnathostomiasis, leishmania, linguatulosis, loiasis, myiasis, malaria, toxocariasis, trichinosis, trypanosomiasis|
|Arteriolar and venule occlusion||Toxocariasis, schistosomiasis, loiasis|
|Inflammation of retinal pigment epithelium and retinal vasculitis||Filariasis ( Wuchereria bancrofti ), onchocerciasis, kala-azar (with HIV+)|
A major complication of Onchocerca infestation is corneal disease. Microfilarial infestation in the cornea is related to visual loss over time, and the presence of a large number of microfilariae in the anterior segment is related to irreversible visual loss. In the cornea there is a punctate keratitis; the presence of ‘snowflake’ opacities in the cornea is associated with a fairly mild infestation. With more intense infestation and over time, a sclerosing keratitis and loss of vision are seen ( Figs 17-2 and 17-3 ).
An iridocyclitis can be seen in conjunction with other aspects of the disease, although the intensity of the reaction can vary considerably. In addition to atrophy of the iris, more serious complications such as glaucoma and cataract can occur. Glaucoma has been recognized as a possibly important cause of irreversible visual loss in these patients. In addition, even without the presence of the inflammatory response, microfilariae can be seen in the anterior chamber. However, the patient needs to be placed in a darkened room with his/her head down between the knees for a few minutes. With the use of a slit lamp the observer will note the presence of the swirling microfilariae in the anterior chamber.
Alterations of the posterior pole have been seen as well, and the degree of visual impairment caused by these changes has probably been underestimated in the past. Large areas of chorioretinitis as well as optic nerve disease leading to atrophy can be seen ( Fig. 17-4 ). Newland and colleagues examined 800 persons in a hyperendemic region of the rainforest in Liberia, West Africa. They found chorioretinal changes in 75% of those examined, which strongly suggests that the visual impairment in this region was due largely to chorioretinal disease and not to anterior segment changes. In a report describing recent Ethiopian immigrants to Israel, Enk et al examined 1200 patients and found that 83 had cutaneous signs of onchocerciasis, with 48% having positive skin snips for microfilaria. Of the 65 patients who had an ocular examination, four eyes had evidence of active anterior segment inflammation and 11 had retinal or choroidal changes.
Relatively few eyes with this condition have been studied histologically. It is thought that the microfilariae may enter through the ciliary vessels, both the short and the long. , Another possibility is the passage of microfilariae through the cerebrospinal fluid into the optic nerve sheath or direct invasion through the sclera by the parasite’s release of digestive enzymes.
It should be noted that the ocular disease in most patients is thought to be a result of slow, chronic, and relatively insidious changes. However, acute episodes of glaucoma, uveitis, and optic nerve disease may be an important component to some patients’ disease. Egbert and co-workers examined patients in Ghana and found that 10.6% of those with glaucoma had concomitant onchocerchiasis, compared to 2.6% of those needing cataract extraction.
Laboratory studies have been attempted to better deduce the mechanism of systemic infestation, and to a lesser degree work has concentrated on ocular disease. The only known natural animal host besides the human is the gorilla, although the disease has been induced in the chimpanzee and the cynomolgus monkey, in which Onchocerca lienalis was used. Using a rabbit model, Duke and Garner placed O. volvulus into the vitreous or subretinally and observed chorioretinal alterations. The injection of O. lienalis subconjunctivally in guinea pigs produced a lesion resembling that seen in human onchocercal punctate keratitis. A monkey model for this disease that was induced with the injection of 10 000 live O. volvulus microfilariae into the vitreous of monkeys has produced posterior segment lesions similar to those seen in the human disease.
Laboratory studies suggest that the parasite induces a complex immune response, perhaps partly autoimmune. Immunoglobulin (Ig) E production is a prominent feature of Onchocerca infestation, and circulating immune complexes that presumably contain parasite antigen can be detected. Cell-mediated responsivity is reduced, a phenomenon also noted in other helminth infections. Indeed, it appears that in addition to a predominantly B-cell (i.e., antibody) response, the immune system tries to minimize the bystander tissue damage after death of the microfilariae by producing blocking antibodies and downregulating cytokines. Chan and colleagues examined the ocular fluids and sera from patients with onchocerciasis for the presence of antiretinal autoantibodies, and found that these patients had antibodies directed toward the inner retina (nerve fiber, ganglion cell, and Müller cell) that could not be absorbed with the use of either S-antigen or the interphotoreceptor binding protein. These observations suggested that autoimmune mechanisms may play a role in the retinal degeneration and optic nerve disease seen so frequently in these patients. Van der Lelij and colleagues, in finding high titers of anti- Onchocerca antibodies in the aqueous of patients with onchocerciasis and ocular disease, believed that retinal autoimmunity was an improbable factor in the pathogenesis of onchocercal chorioretinopathy.
However, an immunologic cross-reactivity between an antigen of O. volvulus and that found in the retinal pigment epithelium was identified. Antisera from patients with onchocerciasis identified a 22 kDa antigen from Onchocerca , whereas a 44 kDa antigen from cultured human retinal pigment epithelium immunoprecipitated with the same antiserum. Klager and colleagues used Western blots and showed that antibody reactions to this antigen were seen in all patients tested with onchocerciasis and posterior pole disease, but were not seen in controls. These provocative results suggest that molecular mimicry plays a role in the development of at least certain aspects of the ocular complications noted in this disorder. It further strengthens the notion that as with ocular toxoplasmosis our notions of inflammatory systems can no longer be restricted to only one mechanism but rather to many, and in some ways intellectually contradictory routes may have been stimulated. Autoantibody responses are not restricted to the eye. Such cross-reactivity has been reported against five major autoantigens, anticalreticulin activity, and the 65-kDa arthritis-associated mycobacterial heat shock protein.
The corneal lesions of onchocerciasis have been studied using animal models. There is an infiltration of granulocytes and eosinophils into the clear structures. Kaifi and co-workers found that vascular adhesion molecules are important in this process. They demonstrated a regulatory role for platelet endothelial cell adhesion molecule 1 and intercell adhesion molecule in their recruiting neutrophils and eosinophils to the cornea as does P-selectin. Because antibodies exist that are directed against these molecules, it raises the possibility of their use in immune therapy to the cornea. Work by the same group , demonstrated the importance of CD4+ T cells in the development of corneal opacification but not in the early stages of the disease. Saint Andre and colleagues proposed that the predominant inflammatory response seen in the cornea of Onchocerca -infected animals is really directed against the endosymbiont of Onchocerca , Wolbachia . Indeed, it may be the essential player in the pathogenesis of river blindness. This endosymbiont is so essential to the nematode that embryogenesis of the Onchocerca is completely dependent on the presence of Wolbachia . The O.volvulus/Wolbachia combination initiates activation of many immune indicators ( Table 17-2 ). Indeed this may open a new avenue for therapy (see below).
|Response||Mechanisms Operative in Immunopathogenesis of Onchocerciasis|
|Regulatory cells||Th2, Th1 a||Th3|
|Macrophage||Alternatively activated macrophage|
|Regulatory molecules||IL-5, IL-4, IL-13 b||IL-10, TGF-β c|
|TNF-α e , IL-8, IL-12|
|Effector cells||B cell||B cell|
|Eosinophil, neutrophil||Alternatively activated macrophage|
|Macrophage, mast cell|
|Effector molecules||IgG1, IgG3, IgE f||IgG4, polyclonal IgE|
|MBP, EDN, ECP|
|Peroxidases (EPO, MPO)|
|Oxygen, nitrogen radicals|
With the study of the specialized mechanisms of the parasite, a provocative concept has recently emerged. Lipid-binding proteins in the nematode, with no known counterpart in mammalian systems, exist. One of these, Ov-FAR-1, has a high affinity for retinal and fatty acids and is present in all life stages of the parasite. Retinol is believed to be important for the growth and differentiation as well as for the embryogenesis and glycoprotein synthesis of the organism. The concentration of retinol is eight times higher in the Onchocerca nodule than in the surrounding tissue. It is possible that Ov-FAR-1 causes a relative local or systemic depletion of vitamin A in patients with onchocerciasis and may also be a trigger for the production of collagen, which is found in large quantity in Onchocerca nodules. These could explain why ivermectin therapy may not be effective for retinal disease in this disorder, because microfilaria already in the retina would continue to produce this lipid-binding protein (see later discussion on ivermectin).
The regulation of interleukin (IL)-5 production in onchocerciasis has been evaluated. It has been suggested that in some helminthic infections the production of IL-5 may be associated with an immune or resistant state. It appears that in patients who are ‘immune’ to the effects of Onchocerca , both IL-2 and IL-5 are produced in significantly higher levels than in those with acute infection. IL-2 production is required to induce IL-5. Toll-like receptor 2 (TLR2) appears to regulate chemokine production and neutrophil recruitment to the cornea in experimentally induced Onchocerca/Wolbachia keratitis. Interferon (IFN)-γ responses from TLR2 knockout mice are also deficient.
Therapeutic strategies have been varied. A long-term approach has been to attempt to rid the endemic regions of the vector, the blackfly. This approach has been moderately successful in a large area of West Africa, but it has been expensive, needs constant monitoring to prevent encroachment of blackflies from non-insecticide-treated regions, and is officially coming to an end. Three modalities were traditionally available to treat the patient. The first was nodulectomy, i.e., removing the adult worms that produce the microfilariae. Nodulectomy was reported by Rodolfo Robles in Central America in 1915 to improve the ophthalmic disease, and this approach has been practiced in Guatemala since 1935. Indeed, although hard evidence concerning its effectiveness is lacking, the rate of blindness in the endemic regions has decreased from 1935 to 1979, during which time 1.5 million people have been examined and 257 883 nodules excised. Nodulectomy has not significantly altered the number of microfilariae in skin snips from patients in West Africa.
Other modalities available are specific therapies against the Onchocerca organism. For many years these were limited to diethylcarbamazine citrate (DEC-C) and suramin. DEC-C is microfilaricidal, and with the massive killing of these organisms a severe systemic reaction occurs (Mazzotti reaction). An aggravation of the ocular condition, with limbitis, an increase in corneal opacities, and advancement of sclerosing keratitis, can also occur. Further, Bird and colleagues observed that DEC-C administration induced transient pigment epithelial lesions, optic disc leakage, and visual field loss. Its administration sometimes necessitates corticosteroid treatment. Although suramin is more toxic to adult worms than to microfilariae, killing of the microfilariae still leads to secondary reactions. Further, this drug has an intrinsic toxicity that may be fatal. For these reasons, suramin is best given in progressive doses over 6–8 weeks until a total dosage of 60–67 mg/kg is reached. Both of these drugs were used with great care, and patients needed to be followed up closely by physicians with experience in their use. They are not used much today.
Other drugs that have been evaluated include the benzimidazoles, and a quantification of ocular reactions as a result of the therapy has been published. These compounds have an effect on the embryogenesis of various Onchocerca species, thereby sterilizing the adult worms. Testing of these compounds suggested that embryogenesis was interrupted in adult worms in the nodules of patients with onchocerciasis 2 months after therapy. However, these drugs are poorly absorbed orally, and standard dosages may not be particularly effective.
The agent ivermectin was shown to be successful for treatment of onchocerciasis in 1982. Given as a single oral dose of 150 µg/kg, the belief was that it would control or curtail the disease if given on a wide scale in endemic areas. , Ivermectin is not thought to kill adult worms, nor does it effect embryogenesis or spermatogenesis, but rather it prevents the release of the microfilariae from the adult female worm, resulting in their in utero degeneration. Ivermectin was compared to DEC-C in a randomized, double-masked study in the treatment of the ocular changes caused by onchocerciasis. It was found that although DEC-C caused a marked increase in both living and dead microfilariae in the cornea, inducing a limbitis and punctate keratitis, ivermectin did not. Further, ivermectin resulted in a long-term reduction in intraocular microfilariae when given in a single oral dose of 200 µg/kg. Other studies have demonstrated similar results. , Diallo and colleagues noted that microfilarial densities reached 4% of pretherapy levels 1 year after a single 12-mg dose of ivermectin, but one of 10 ivermectin-treated patients needed systemic steroid therapy to deal with adverse systemic reactions. In this study, adult worms taken from patients treated with ivermectin were examined; they contained deformed and degenerated intrauterine forms of the microfilariae. In one report outlining preliminary findings for the distribution of ivermectin to 118 925 persons in Nigeria, Ogunba and Gemade found that the drug was extremely well tolerated: only 0.7% of recipients reported adverse reactions within 3 days of treatment. Whitworth and colleagues reported the results of a randomized, double-masked study in Sierra Leone that compared the effects of ivermectin with those of placebo on ocular disease. They found that the 296 persons who received ivermectin had less anterior segment disease, a lower prevalence of microfilariae in the anterior chamber and cornea, and less punctate keratitis and iritis than that seen in the 272 patients who received placebo. No difference was found between the two groups for optic atrophy or chorioretinitis, and the visual acuities in the two groups were not statistically significantly different, although the results for the ivermectin group were more favorable. Dadzie and colleagues found very low ocular microfilariae loads in 334 patients in Ghana who were treated twice with the medication. Blindness did occur in three patients in the ivermectin group; these patients were thought to have advanced disease. Because of these and other reports, between March 1992 and February 1993 an estimated 1.5 million people were treated in the Onchocerciasis Control Programme (OCP) area. The OCP has covered 11 countries in West Africa, and by 2002 10 million people had received ivermectin; by 2006 nongovernmental development organizations had helped to treat 62 million people ( Fig. 17-5 ). Will this therapeutic program eradicate this disease? In some smaller endemic regions, such as Ecuador, it has the potential to do so. However, in the vast area of West Africa the challenge is enormous. Because of the characteristics of ivermentin, it has been estimated that 90 million at-risk individuals would need to be treated for 25 years, a daunting task. Reports such as those by Semba and co-workers and Njoo and colleagues are not heartening. In the study reported by Njoo and colleagues of a fairly small number of patients with onchocerciasis from an hyperendemic area with no vector control, 44% of 25 patients who received three doses of ivermectin still had positive results for skin snips, but the number of adverse reactions did decrease with repeated administration. In one long-term follow-up study performed in Sierra Leone and reported by Mabey and colleagues, ivermectin-treated patients had full ocular examinations in 1989 and again in 1994. These authors concluded that annual treatment with ivermectin controlled all aspects of ocular disease except chorioretinal lesions. Changing the dosing interval to every 6 months did not seem to help either. Chippaux and colleagues found that repeated ivermectin doses failed to prevent the appearance of initial retinal lesions or the worsening of preexisting ones. Awadzi and coinvestigators treated patients with doses of ivermectin varying from 150 µg/kg to 1600 µg/kg of body weight. Their findings suggested that administration of larger doses of the medication was probably no better than giving repeated lower doses. It appears that ivermectin therapy needs to be given regularly to produce any long-term benefit. A controlled study using ivermectin every 3 months showed that this regimen greatly reduced the number of female worms as well as acute itching and skin lesions. Studies in the past with at least a 1-year follow-up did not show a statistically significant better visual outcome between ivermectin and placebo. Awadzi et al. reported that over a 30-month period they were able to confirm the existence of a population of female O. volvulus that respond poorly to ivermectin. A randomized study giving patients high doses (800 µg/kg) annually, or the normal dose at 3-month intervals, did show a greater effect than the standard dose (150 µg/kg) annually. However, in this particular study transitory ocular complaints were noted, suggesting that the higher-dose approach should be considered only with caution. Studies suggest that therapy alone without vector control may not control disease in endemic areas, and models , suggest that therapy alone (without vector control) will not control disease in the next quarter-century. These projections once again point to the need to find new drugs to treat this disorder. There have been recent new therapeutic considerations. As mentioned earlier, Wolbachia appears to be one of the major sources of antigenic stimulation for the corneal disease, and in its symbiotic relationship with Onchocerca appears to be essential for the fertility of O. volvulus . Treatment with doxycycline, 100mg/day for 6 weeks, will deplete Wolbachia in the Onchocerca after several months and inhibit embryogenesis. Further, even if a medication that safely kills adults appears, there is an interest in other medications such as moxidectin. This inhibits embryogenesis and may last longer than ivermectin.
Giardia lamblia is a flagellated binucleate protozoan about 12–14 µm in length. It can be in a motile form (trophozoite) or in a cystic state. The organism was first seen microscopically by van Leeuwenhoeck in 1681. Ingestion of contaminated food or drinking water is the usual mode of spread. Giardia has a propensity to inhabit the jejunum of humans, where it will multiply and cause swelling of the microvilli of the intestinal epithelial cells. Gastrointestinal symptoms include epigastric burning, cramps, diarrhea, constipation, and weight loss. Although extraintestinal spread of the organism has not been documented to date, there have been reports of patients with extraintestinal manifestations attributed to Giardia . , These include nervousness, headache, and emotional instability. To our knowledge, Barraquer was the first to make the association between giardiasis and ocular inflammatory disease, noting choroiditis, hemorrhagic retinopathy, and iridocyclitis. Knox and King reported finding Giardia in the stools of three patients with retinal arteritis, which was associated with an iridocyclitis in two of them. It was felt that antiparasitic therapy improved their ocular state. Pettoello Mantovani and colleagues examined 90 children with intestinal Giardia for ocular disease. They noted that eight of them (9%) had ‘salt and pepper’ alterations at the level of the retinal pigmented epithelium in all quadrants of the midperiphery. Some of these patients also had atrophic regions and hard exudates associated with the lesions. In addition, one other patient was noted to have temporal ‘discoloration’ of the optic disk, and another had a chorioretinitis that resolved with steroid therapy. These patients were treated, and after 1 year of follow-up no alteration in the salt and pepper changes were noted. In two control groups, one of 200 children with gastrointestinal symptoms not due to Giardia and 200 healthy children did not have salt and pepper changes. In a similar study reported by Corsi and colleagues, 141 children with Giardia were examined and 28 (19.9%) were noted to have salt and pepper changes in their fundus.
The underlying cause of the ocular inflammatory disease is unknown, although the most plausible explanation at this point is that the inflammation results from a hypersensitivity reaction. The organism has never been isolated from lesions (besides the gut) associated with the parasite (such as urticarial lesions). Immune complexes have been reported in patients with Giardia , and it has been suggested that the ocular lesions are a hypersensitivity reaction. HLA studies have been performed, with a higher expected frequency seen for HLA-A1 (46.7% vs 32%) and HLA-B12 (47.8% vs 25.3%).
The diagnosis is based on finding the organism in the stool, which is not always easy to do. Multiple examinations or even biopsy of jejunal tissue are needed. In the past the disease was treated with quinacrine hydrochloride (Atabrine) (100 mg) given three times a day for 10 days, but a single dose of tinidazole (50 mg/kg) has been used more recently. In one report, oral corticosteroids and metronidazole (250 mg tid) were used.
The term ophthalmomyiasis refers to the infestation of the eye by the larval forms of flies (maggots) of the order Diptera. Ophthalmomyiasis externa indicates infestation of the conjunctiva, whereas ophthalmomyiasis interna (posterior or anterior) means infestation inside the globe. Usually, these larval forms are obligate tissue parasites that require the host’s tissue to complete their developmental cycle. In addition to humans, the usual hosts for these larvae include cattle, deer, sheep, horses, and reindeer. The larvae may get to the eye via a vector such as an adult fly that carries the larvae or eggs to the region, or by touching of the ocular region with hands contaminated with the larvae. Most patients do not give a history of being ‘bitten.’ The larva is thought to bore through the coats of the eye until they come to rest within. However, an early report by DeBoe described the emergence of the larva from the optic nerve head into the vitreous. A handful of cases have been described in the literature.
Seventeen patients with ophthalmomyiasis externa were seen by Amr and colleagues in northern Jordan. These occurrences were due to the sheep nasal botfly, Oestrus ovis ; the symptoms were mild to severe conjunctivitis, cellulitis, and lacrimation. Four cases due to O. ovis in Kuwait both before and after Operations Desert Shield and Desert Storm were reported. Another species involved is Cochliomyia hominivorax , whose larvae can lie over the conjunctiva and can be removed with a cotton swab ( Fig. 17-6 ).
With ophthalmomyiasis interna the invading larva may initially cause little or no pain, but discomfort and an intraocular inflammatory reaction can certainly occur, particularly after its death. The characteristic features of ophthalmomyiasis interna include the presence of subretinal tracks , along with the finding of an encysted larva either subretinally or even free floating in the vitreous. Without finding the maggot in the eye, a definitive diagnosis cannot be made; the maggot is white or semitranslucent, segmented, and tapered at both ends. Vision may be lost because of macular hemorrhage, optic nerve invasion by the maggot, or retinal detachment. Jakobs and colleagues reported a patient with a larva that appeared to enter the eye via the optic nerve, migrated subretinally yielding tracts, and then apparently entered the optic nerve again. Billi and co-workers reported such a case after cataract extraction, conjecturing that the site of entry into the eye was the surgical wound. The organism was removed from the eye by vitrectomy and thought to be of the Sarcophagidae family of flies. Interestingly, no retinal pigment epithelium tracking was noted. Campbell and colleagues reported that an interesting retinopathy that resembled ophthalmomyiasis interna was seen in 10% of a sample Chamorro population examined on the island of Guam. In addition, this retinopathy was found in 50% of a population with amyotrophic lateral sclerosis–parkinsonism–dementia complex. Although the retinopathy appears to be similar to the changes seen with parasitic infestation, they were not able to establish a definitive diagnosis despite obtaining eyes for histologic study.
The treatment of ophthalmomyiasis must be tailored to the ocular findings. If the worm is situated in the anterior chamber it should be removed as quickly as possible, as it may migrate elswehere in the eye. A Fuchs’ heterochromic iridocyclitis has been been described after a case of ophthalmomyiasis interna posterior. Saraiva and colleagues reported a case of the removal of a worm from the anterior segment, and histology showed the larva to be covered with macrophages and foreign body giant cells ( Fig. 17-7 ). The granulomatous reaction cleared with removal of the worm. In the case of an immobile subretinal worm, with no inflammatory disease and good vision, the ophthalmologist may elect to follow the patient. However, if there is a severe inflammatory reaction, antiinflammatory therapy should be instituted. Hemorrhage may require a vitrectomy because it may indicate that the larva is alive and migrating. If the larva can be visualized in the subretinal space, and if the decision is made to treat it, Gass and Lewis have recommended the use of photocoagulation over removal of the organism by sclerotomy. Others have suggested either laser or vitrectomy. Forman and colleagues described a case of a 16-year-old patient with a subretinal fly larva in which the larva was killed with argon laser therapy. The patient’s visual acuity improved from 20/200 to 20/20. Syrdalen and colleagues reported that removal of a reindeer warble fly larva through a pars plana opening after vitrectomy freed the surrounding vitreous attachments. Others have reported a caribou botfly infecting an eye. The patient retained good vision. However, the visual result varies, depending on whether the macula and the optic nerve were involved in the process.