**9. Endogenous helminthic endophthalmitis**

Helminths at either the larval or adult stage can lead to the infection of ocular tissues through adjacent structures or may have a predilection for ocular tissue as they migrate through the vascular system [267]. Helminths generally only have a unilateral eye presentation, but there is no observed difference in eye predominance [192]. Although infrequent, helminth infections are more common in areas of consumption of contaminated water, raw meat, and freshwater fish [268, 269], so travel history to endemic areas is essential to ascertain the source of the infection. However, due to movement via rapid transport, such history might not be present [267]. Helminth endogenous endophthalmitis is much less frequent compared to bacterial, viral, and fungal causes. Pediatric populations are more likely to have zoonotic infections, such as *Toxocara canis*, due to ingestion of eggs or larvae in the feces of infected animals [270]. As such, rates for infections from parasitic sources are higher than the adult population [192] and more likely to be from less virulent organisms [192]. A common misdiagnosis in pediatric patients with an ocular helminth infection is retinoblastoma, requiring enucleation of the eye [192].

Due to the nature of these parasites, pathological lesions show a wider variety of clinical presentations compared to other causes of EE. Perhaps the most common cause of helminth infection is *Toxocara*, a notable cause of unilateral visual loss. Autopsy of affected individuals has shown infection of the brain, eye, lungs, and liver [268–270]. Human infection is noted in populations with a high prevalence of the consumption of freshwater raw fish [271]. Diagnosis of ocular toxocariasis is mainly a clinical one as the definitive diagnosis of histologic demonstration of larva is unfeasible and rarely done. Ophthalmic presentation of ocular toxocariasis include granuloma located in the posterior pole (25%) or the periphery with associated fibrous bands extending posteriorly (50%) [272]. Chronic endophthalmitis is also a common presentation (25%) [272]. Serum ELISA antibody test is commonly used to detect exposure to toxocariasis; however, intraocular fluid (aqueous humor and vitreous) ELISA antibody testing can be positive despite negative serum [270, 272]. Systemic or topical corticosteroid is commonly used to control the acute inflammatory reaction [270]. Albendazole is the current antihelminth drug of choice; however, it has yet to be proven that antihelminth drugs can kill intraocular larva [273, 274]. Pars plana vitrectomy or laser photocoagulation to remove the causal agent is also recommended in some patients [268, 270].

Two helminths with ocular manifestations are *Onchocerca volvulus* and *Loa loa*. Humans with an *Onchocerca volvulus* infection generally have an adult worm that produces microfilariae over a bony prominence. The microfilariae migrate throughout the connective tissue, skin, and ocular structures. Predominant ocular findings include punctate keratitis, iridocyclitis, chorioretinitis, and optic atrophy [268]. Diagnosis is accomplished via slit-lamp examination of microfilariae, with the aid of a punch biopsy [268, 275]. Treatment includes removal of the adult worm and administration of ivermectin. *Loa loa* is also diagnosed via circulating microfilariae; however, the adult worm is more commonly found in the conjunctiva [268]. Treatment of *Loa loa* includes removal of the worm and use of diethylcarbamazine [268]. Another helminth involved in EE is *Angiostrongylus cantonesis*. Patients generally present with blurred vision and poor visual acuity, and ocular symptoms generally occur two weeks to two months after ingestion of the *Pila* snail [268]. Patients are diagnosed via indirect ophthalmoscopy. Patients generally do not have favorable outcomes with an ocular infection of the nematode *Angiostrongylus*. Surgery, laser, and corticosteroid interventions do not improve visual acuity, as alteration of the RPE and retina are caused by the parasite directly. There is no specific therapy for *Angiostrongylus* EE [268]. Many other helminth infections have been implicated in endogenous helminth endophthalmitis, including dirofilarisis, taenia solium, fascioliasis, and schistosomiasis [268, 276, 277].

One helminth unique to the pediatric population is *Baylisascariasis procyonis*, a raccoon roundworm originating in North America. Seven cases document children with a history of pica and raccoon exposure who developed unilateral subacute neuroretinitis [278]. The worm can be identified via immunofluorescence assay of the serum or CSF, but the definitive diagnosis is visualization of the offending organism in the eye. Treatment options include albendazole and corticosteroids, but patients have a poor prognosis [279].

The most common helminths in the pediatric population are *Toxocara* and *Cysticercus*. Pediatric infections generally have fewer systemic symptoms, causing a delayed diagnosis of endogenous endophthalmitis [192]. Results in pediatric populations are not as favorable as in adult populations due to the delay in diagnosis and diffuse infection of the eye. Advantages of an early vitrectomy in pediatric populations include improved outcomes in patients, though visual rehabilitation is still a challenge for this population [192].

Helminths have also shown surprising manifestations in immunocompromised hosts. One patient with a history of systemic lupus erythematosus (SLE) presented with decreased bilateral vision in both eyes. Fundoscopy showed granulomas in the posterior poles bilaterally, with new granulomas developing in subsequent exams. Serology was positive for *Toxocara*. The patient was initially treated with intravitreal amphotericin B, vancomycin, and ceftazidime. After a full course of antibiotics and with albendazole, the patient had improved visual acuity of both eyes [280].

Another subset of immunocompromised patients who are at risk for helminthinduced endogenous endophthalmitis is the IVDU population. One patient with a history of IVDU reported two weeks of worsening right eye pain with decreased visual acuity. Endophthalmitis was suspected and a vitreous tap was performed. Gram stain showed no organisms, but rare white blood cells were present. Initial labs, bacterial and fungal cultures were negative. The patient was admitted for the endogenous spread of infection and placed on IV antibiotics. The patient's repeat serology was found to be positive for *Toxocara* titers [269].

Diagnosis of *Toxocara* or other helminths can be difficult in immunocompromised patients. Presentations can vary from granuloma formation to chronic retinal manifestations [269, 280]. Additionally, the parasitic load may not be high enough to give a positive serology result [269]. Serial optical coherence tomography (OCT) to observe for larval movement might aid diagnosis.

Immunocompromised patients with significant animal contact who present with suspicion of endogenous endophthalmitis should be considered for a helminth cause [4, 9]. Treatment of ocular toxocariasis should be tailored to the clinical presentation of the host, and patients with inflammation should be placed on steroids to reduce the risk of retinal detachment. Anti-helminthic agents and IV antibiotics have been successful, but surgical intervention may be necessary if complications occur [280].
