Animal model of human disease with optic neuritis: neuropapillitis in a rat model infected with Angiostrongylus cantonensis.

Human Angiostrongylus cantonensis (A. cantonensis) is a food-borne parasitic disease and can cause optic neuritis. Increasing clinical angiostrongyliasis cases with optic neuritis have been reported, but the pathogenesis has not been fully understood until now. Here, we applied rats with A. cantonensis infection as an animal model to study the pathogenesis of optic neuritis caused by the infection. We observed that the optic disk of experimental rats appeared hyperemic, the retina vein became thick, and the visual evoked potential (VEP) latency was prolonged. There were obvious inflammatory cell infiltration in the retina and optic nerve adventitia followed with obvious optic nerve fiber demyelination and retina ganglion swelling. We also evaluated the effect of dexamethasone combined with albendazole on optic neuritis of rats infected with A. cantonensis. The results showed it had no obvious effect to prevent progressive visual deterioration for optic neuritis caused by A. cantonensis. The studies provided evidence that the pathogenesis of optic neuritis in infected rats was correlated to optic nerve demyelination and ganglion cell damage caused by optic nerve inflammation, and the common therapy to this disease was not so effective. Based on the above results, it may be necessary to combine neuroprotective agents with common therapy to treat and protect optic nerve and ganglion cells from their secondary injury.

Comprehensive review of ocular angiostrongyliasis with special reference to optic neuritis.

Angiostrongyliasis, caused by Angiostrongylus cantonensis infection, is a food-borne parasitic disease. Its larvae evoke eosinophilic inflammation in the central nervous system, but can also cause pathological changes in the eyes. Among ocular angiostrongyliasis cases, the incidence of optic neuritis is low and only few sporadic reports exist. Some patients with optic neuritis developed obvious hypopsia or even vision loss, which would seriously influence the quality of life of patients. Prompt treatment of optic neuritis caused by A. cantonensis is the key factor for minimizing the incidence of serious complications of this disease. In this review, we first provide a comprehensive overview of ocular angiostrongyliasis, and then focus on the clinical features of optic neuritis caused by A. cantonensis.

Clinical Features of Toxocara-Seropositive Optic Neuritis in Korea.

Purpose: This study was undertaken to analyze the characteristics of optic neuritis in Korean patients seropositive for Toxocara. Methods: We retrospectively reviewed data from patients diagnosed with optic neuritis and followed up for at least one month between 2012 and 2016. Patients were grouped according to Toxocara serological testing outcomes (positive or negative) and clinical characteristics were compared. Results: The seropositive and seronegative groups comprised 13 and 12 patients, respectively. The seropositive patients were older (56.8 years versus 34.5 years), reported ocular pain less frequently (30.8% versus 91.7%), and showed more frequent asymmetric optic disc swelling (72.7% versus 22.2%). During follow-up, visual acuity of all seronegative patients improved to 20/40 or better, compared with 38.5% of the seropositive group. Conclusion: Atypical features such as painless, older age, or asymmetric disc swelling in optic neuritis may be related to seropositivity for Toxocara, suggesting the possibility of undiagnosed Toxocara optic neuropathy.

Optic neuritis caused by intraocular angiostrongyliasis.

A 21-year-old Thai man first presented with eosinophilic meningitis. One week later he developed visual impairment of the left eye with a visual acuity of 20/600. He had a Marcus Gunn pupil, constricted visual field, prolongation of visual evoked potential and the presence of inflammatory cells in the vitreous cavity of the affected eye. On funduscopic examination there was disc swelling with hyperemia of the left eye. These ocular findings are compatible with optic neuritis. The causative agent, Angiostrongylus cantonensis, was identified in the vitreous cavity. To our knowledge this is the first case of optic neuritis caused by intraocular angiostrongyliasis. Ten days after administration of corticosteroid his severe headache was resolved, and by 4 weeks the disk swelling of the left eye subsided. Eight months after treatment the visual acuity of the left eye had not improved due to permanent damage to the retinal pigment epithelium caused by the intraocular parasite.

Isolated optic neuritis from an identified Gnathostoma spinigerum.

PURPOSE: To describe a patient with isolated monocular optic neuritis caused by an identified Gnathostoma spinigerum infestation. CASE REPORT: A 21-year-old man developed a swollen eyelid and painful monocular visual loss of his left eye which did not improve after treatment by intravenous steroid and albendazole. A remarkable eosinophilia in his peripheral blood count was demonstrated. The patient subsequently found a live parasite emerged from his lower eyelid and it was successfully removed by himself. Gross and histopathology examinations of the obtained parasite was undertaken. The parasite was identified as Gnathostoma spinigerum. His blood test for Gnathostoma antibody was positive. DISCUSSION: The etiology of isolated optic neuritis in this patient was Gnathostoma spinigerum which was confirmed by the histopathology of the obtained parasite and the positive serologic test. CONCLUSIONS: We could identify the exact parasite that was proven to cause an isolated optic neuritis. The immediate removal of a causative parasite maynot result in an improvement of the injured tissue but is beneficial in preventing further destruction as well as future complications.

Optic neuritis secondary to Angiostrongylus cantonensis infection.

PURPOSE: To describe a case of optic neuritis secondary to Angiostrongylus cantonensis infection. METHOD: Case report of a patient with eosinophilic meningitis secondary to A. cantonensis infection. The patient developed a sudden decrease in visual acuity with a visual field defect and color vision loss in his left eye. Both visual evoked potential and clinical manifestations suggested the diagnosis of optic neuritis (os). RESULT: After two weeks of larvicidal drugs and steroid treatment, the patient's visual acuity and color vision had dramatically improved. CONCLUSION: Optic neuritis may occur in patients with A. cantonensis meningitis. Treatment with a combination of steroid and larvicidal agents may be beneficial to these patients.

Optic nerve cysticercosis.

Optic nerve cysticercosis is rare but causes significant visual morbidity. A high index of suspicion is warranted for patients in endemic areas who present with sudden vision loss. Visual morbidity can be prevented by early imaging studies and therapeutic interventions.

Effects of albendazole combined with TSII-A (a Chinese herb compound) on optic neuritis caused by Angiostrongylus cantonensis in BALB/c mice.

BACKGROUND: Angiostrongylus cantonensis (A. cantonensis) infection can lead to optic neuritis, retinal inflammation, damage to ganglion cells, demyelination of optic nerve and visual impairment. Combined therapy of albendazole and dexamethasone is a common treatment for the disease in the clinic, but it plays no role in vision recovery. Therefore, it has been necessary to explore alternative therapies to treat this disease. Previous studies reported the neuro-productive effects of two constituents of Danshen (a Chinese herb)-tanshinone II-A (TSII-A) and cryptotanshinone (CPT), and this study aims to evaluate the impacts of TSII-A or CPT combined with albendazole on optic neuritis caused by A. cantonensis infection in a murine model. METHODS: To assess the effects of TSII-A or CPT combined with albendazole on optic neuritis due to the infection, mice were divided into six groups, including the normal control group, infection group and four treatment groups (albendazole group, albendazole combined with dexamethasone group, albendazole combined with CPT group and albendazole combined with TSII-A group). The infection group and treatment groups were infected with A. cantonensis and the treatment groups received interventions from 14 dpi (days post infection), respectively. At 21 dpi, the visual acuity of mice in each group was examined by visual evoked potential (VEP). The pathologic alteration of the retina and optic nerve were observed by hematoxylin and eosin (H&E) staining and transmission electronic microscopy (TEM). RESULTS: Infection of A. cantonensis caused prolonged VEP latency, obvious inflammatory cell infiltration in the retina, damaged retinal ganglions and retinal swelling, followed by optic nerve fibre demyelination and a decreasing number of axons at 21 dpi. In treatment groups, albendazole could not alleviate the above symptoms; albendazole combined with dexamethasone lessened the inflammation of the retina, but was futile for the other changes; however, albendazole combined with CPT and albendazole combined with TSII-A showed obvious effects on the recovery of prolonged VEP latency, destruction and reduction of ganglion cells, optic nerve demyelination and axon loss. Compared with albendazole-CPT compound, albendazole combined with TSII-A was more effective. CONCLUSIONS: The current study demonstrates that albendazole combined with TSII-A plays a more effective role in treating optic neuritis caused by A. cantonensis in mice than with dexamethasone, as applied in conventional treatment, indicating that albendazole combined with TSII-A might be an alternate therapy for this parasitic disease in the clinic.

Diffuse bilateral subacute neuroretinitis: first patient with documented nematodes in both eyes.

OBJECTIVE: To describe the first patient with documented evidence of diffuse unilateral subacute neuroretinitis (DUSN) in both eyes. METHODS: A 10-year-old healthy Brazilian girl was first seen with signs of late-stage DUSN in both eyes. A careful search for a nematode was performed in each eye. RESULTS: A motile 550- to 660-microm nematode was found in the inferotemporal retina of the left eye. A similar-sized motile nematode was found in the superotemporal retina of the right eye. Both nematodes were treated with argon green laser applications with bilateral improvement of visual function. CONCLUSION: Although most patients with DUSN do not develop the disease in the fellow eye, this case demonstrates that DUSN can occasionally affect both eyes.

Histopathological features of ocular toxoplasmosis in the fetus and infant.

BACKGROUND: Ocular disease is a frequent manifestation of congenital Toxoplasma gondii infection. There are only limited data available in the literature concerning early stages of this disease in fetuses and infants. The purpose of our study was to characterize histopathological features in the eyes of 10 fetuses and 2 infants with congenital toxoplasmosis. METHODS: Fifteen eyes from 10 fetuses, 3 eyes from 2 premature infants, and both eyes from a 2-year-old child with congenital toxoplasmosis were examined by light microscopy. Immunohistochemical analysis to identify inflammatory cells and T gondii antigens was performed. The findings in infected eyes were compared with those of age-matched control eyes. RESULTS: Retinitis (10/18 eyes), retinal necrosis (4/18 eyes), disruption of the retinal pigment epithelium (12/18 eyes), and choroidal inflammation and congestion (15/18 eyes) were characteristic findings. Optic neuritis was present in 5 of 8 fetal eyes with associated optic nerve available for evaluation. An eye obtained from a 32-week-old fetus showed retinal rosettes at the edge of a scar. T cells predominated in retinal lesions and choroid. Parasites were identified by immunohistochemical analysis in 10 of 18 eyes. CONCLUSIONS: Ocular toxoplasmosis causes irreversible damage to the retina in utero. The fetus and infant mount inflammatory responses that may contribute to ocular damage. These findings have important implications for serological screening programs and in utero therapy.

Antihelminthic drugs in diffuse unilateral subacute neuroretinitis.

PURPOSE: To evaluate the efficacy of ivermectin and thiabendazole in confirmed cases of diffuse unilateral subacute neuroretinitis. METHODS: Two patients with diffuse unilateral subacute neuroretinitis were treated with anthelminthic drugs. The first patient was treated with ivermectin and the second, with thiabendazole. RESULTS: The worms were still mobile after treatment with ivermectin or thiabendazole. With the application of photocoagulation, the organisms were destroyed, and the patients' vision improved. CONCLUSION: In these two patients, ivermectin and thiabendazole were not effective in treating confirmed diffuse unilateral subacute neuroretinitis.

Diffuse unilateral subacute neuroretinitis.

The clinical syndrome of diffuse unilateral subacute neuroretinopathy (DUSN) has been characterised in its early and late stages. Different types of migrating worms in the subretinal and intraretinal space have been described as the cause of the clinical syndrome. We observed a patient with a long history of visual loss, vitritis, and a fundus of abnormal appearance where the worm was noted to migrate to different areas over the course of hours.

Cutaneous larva migrans, sacroileitis, and optic neuritis caused by an unidentified organism acquired in Thailand.

We report the case of a 32-year-old pregnant woman with an unidentified intraocular parasite. The parasite, which had been acquired in Thailand, caused cutaneous larva migrans, sacroileitis, and 2 years later optic neuritis and panuveitis. The patient was successfully treated with ivermectin and albendazole. The diagnostic possibilities of this peculiar presentation are discussed. Parasitic infections are a leading cause of medical problems in travelers to tropical countries.1 While most parasites cause gastrointestinal problems, some may migrate throughout the body and lodge in critical organs. Ocular parasitic infections may occur by direct inoculation onto the eye,2 or incidentally during systemic migration. Subconjunctival parasites are easily diagnosed by removal and careful microscopic examination.3 Parasites, which lodge within the eye, are more difficult to diagnose, especially if not removed. In this report we describe a patient who presented with an intraocular parasite causing optic neuritis and panuveitis, 2 years after travel to Thailand.

Ocular toxoplasmosis presenting as neuroretinitis: report of two cases.

BACKGROUND: Neuroretinitis is a clinical entity usually seen in young healthy adults, that is characterized by rapid profound unilateral loss of vision and includes optic nerve head edema, splinter hemorrhages, macular exudate in a stellate pattern, and variable vitreous inflammation. There are numerous entities that can cause a picture of neuroretinitis ranging from vascular to infectious to autoimmune. PATIENT AND METHODS: We report two patients with neuroretinitis, who presented with unilateral blurred vision and had serologic evidence of Toxoplasma gondii infection. RESULTS: Both patients responded well to treatment with systemic antibiotics and corticosteroids. Visual acuity returned to 20/60 in one patient and 20/20 in the other. CONCLUSION: Although the etiology is usually idiopathic, infectious causes of neuroretinitis, including toxoplasmosis, should be kept in mind in order to maintain visual acuity by early diagnosis and appropriate therapy.

Diffuse unilateral subacute neuroretinitis in Europe.

BACKGROUND: Diffuse unilateral subacute neuroretinitis is thought to be caused by a solitary helminth migrating within the subretinal space. Laser photocoagulation of the located worm is the preferred mode of therapy. METHODS: We describe the clinical and electrophysiological features of a case of a 15-year-old Caucasian male with a longstanding diffuse unilateral subacute neuroretinitis (DUSN), in whom two worms were seen in the fundus examination. Focal photocoagulation of the worms was applied as treatment. RESULTS: No signs of inflammation could be seen after treatment. Three months later, the patient was doing well. Follow-up examination 4 years later revealed an unchanged fundus appearance in the affected eye, with no evidence of progression of the syndrome. CONCLUSIONS: If a worm is identified in DUSN, focal laser treatment of the located area is the treatment of choice, regardless of whether fundus changes suggest late stages of the disease. However, the eye of the patient should be thoroughly examined to rule out the presence of more than one worm that might cause the failure of therapy.

The pathogenesis of optic neuritis caused by Angiostrongylus cantonensis in BALB/c mice.

BACKGROUND: One of the most common causes of meningitis in South East Asia is angiostrongyliasis or infection by the parasitic nematode Angiostrongyliasis cantonensis. Although this nematode usually resides in the pulmonary arteries of rats, its incidental occurence in other hosts such as humans can cause optic neuritis and lead to serious vision sequelae. Nevertheless, there are currently no systematic studies conducted in this area. METHODS: In order to study the pathogenesis of optic neuritis, mice were tried as a new animal model to study and challenge with A. cantonensis on 7d, 14d and 21d, respectively. Electroretinogram (ERG), visual evoked potential (VEP), ophthalmoscopy and histology were examined on day 7d, 14d and 21d and tribendimidine (TBD) was later used to treat optic neuritis on day 14d for a week to evaluate its therapeutic effects. RESULTS: Infection of A. cantonensis caused obvious inflammatory cell infiltration in the retina and optic nerve adventitia in day 14d and 21d followed by optic nerve fiber demyelination and retinal ganglion swelling at day 21d in the challenged mice. Prolonged VEP latency and decreased ERG amplitude were also observed on day 21. After treatment of TBD in the infected mice, retinal and optic nerve inflammation were alleviated, but VEP latency and ERG amplitude did not improve on day 21d and 28d. CONCLUSIONS: The current study provides evidence that A. cantonensis can cause optic neuritis along with optic nerve demyelination and retinal ganglion cell damage in a mouse model. TBD alone treatment can improve the symptoms of optic neuritis, but does not aid in vision recovery, suggesting that both neuroprotective agents and Dexamethasone should be administered, along with treatment for the infection, to protect the optic nerve and ganglion cells. Furthermore, as the symptoms of optic neuritis caused by A. cantonensis in mice are similar to the optic neuritis in multiple sclerosis (MS) human patients, we suggest that the BALB/c mouse model provided in this study may be useful to explore therapies of optic neuritis in MS patients.