angiostrongyliasis caused by infection with angiostrongylus cantonensis is primarily characterized by eosinophilic meningitis , meningoencephalitis , or myelitis . ingestion of raw or half - cooked apple snails containing third stage larvae ( l3 ) of a. cantonensis is the commonest route of infection . after ingestion by humans , the l3 migrate to the central nervous system ( cns ) via blood stream and cause eosinophilic meningitis , often associated with encephalitis and myelitis ( meningo - encephalo - myelitis ) . at the same time , the larvae also can invade the eyes and cause various ocular symptoms including optic neuritis . recently diao et al .   summarized a total of 35 cases of ocular angiostrongyliasis . we also made an extensive literature survey on ocular angiostrongyliasis and found 42 cases including the cases reviewed by diao et al . . of these , nearly a half ( 19 cases ) were from thailand [ 4 - 13 ] , including the first case report from that country in 1962   and the most recent case reported in 2013 . there are a few sporadic reports of ocular angiostrongyliasis from other countries , mostly from asia . we have found 5 cases from sri lanka [ 14 - 18 ] , 2   of which were cited by diao et al . . although diao et al .   noted 3 cases from india , they mistakenly included 1 case from taiwan ( their reference # 17 , in our reference # 25 ) as an indian case . four cases have been reported from mainland china [ 21 - 24 ] and 2 cases from taiwan . among them , 1 case from taiwan   was not cited in the review of diao et al . . one case from vietnam   was not included in the list of diao 's cases . one case each was reported from indonesia , papua new guinea , malaysia , south africa , nepal , and jamaica , in the order of the reported year . the cases from malaysia and jamaica were not mentioned in the review of diao et al . . however , the picture provided in the publication   shows that the worm is definitely not a gnathostoma larva : the body is filariform without an apparent head bulb , indicating that this worm is highly likely to be the larva of a. cantonensis . the oldest records were reported by joseph   and nicholls   in sri lanka in 1925 ( redescribed by dissanike and cross in 2004 ) . the most recent one was the optic neuritis case reported from khon kaen , thailand , by sinawat et al .   in 2013 . except for the case from jamaica , 41 out of 42 were recorded in asia , corresponding to the geographical distribution of this parasite . among 42 ocular angiostrongyliasis cases , 19 were from thailand , 5 from sri lanka and only 1 or 2 cases from other countries . since 47% of all angiostrongyliasis cases in general are from thailand and 27% from china , a high prevalence of ocular cases in thailand is to be expected . however , the low number of ocular cases reported from other countries in the region is unexpected . given the low frequency of the condition even in thailand , cases elsewhere might not be diagnosed correctly . alternatively , there might be an intra - species variation in the pathogenicity and behavior of the l3 in the host . related to this , genetic variation in relation to the geographic location of a. cantonensis has been reported . in addition to the sporadic cases listed in table 1 , punyagupta et al .   analyzed clinical features of 484 cases of typical eosinophilic meningitis and found that 16% of patients had visual impairment , while 12% had an optic disc abnormality such as papilledema or atrophy . in china , clinical features of angiostrongyliasis cases of an outbreak in wenzhou were analyzed   and the ocular manifestation was listed as one of the major features . lv et al .   reported 2 ocular cases among 33 angiostrongyliasis cases in an outbreak in dali . reported 16 cases of visual disorders with different degrees of severity , such as photophobia , blurred vision , diplopia , defect in the field vision and eye floaters out of 81 cases in an outbreak of angiostrongyliasis in beijing . in this outbreak , 25 patients showed severe symptoms and all ocular cases were found in this group . these reports indicate that the actual incidence of ocular angiostrongyliasis is likely much higher than commonly appreciated . the average age of the patients in 39 cases was 34 years ( 3 - 72 years ) , and unknown in the remaining 3 cases . there was an obvious sex difference ( 28 males , 12 females , and 2 unknown ) . except for 1 case from taiwan , all patients were affected only in 1 eye with no significant difference for the frequency of the affected sides ( 22 left and 19 right , including a case of bilateral necrotizing retinitis , data not available for 2 cases ) . in most instances , worms were found and surgically removed from the anterior chamber ( 14 cases ) or from vitreous fluid ( 15 cases ) . in 10 cases , worms were found either on the retina or sub - retina . even in such retinal involvement cases , worms were successfully removed surgically . in 4 retinal involvement cases in thailand , laser ablation with or without oral steroids was successfully performed . among 30 cases of successful surgical removal , only 1 recorded the presence of 2 worms . in all other cases , ocular lesions seemed to be caused by a single worm . these ranged in length from 5 to 28 mm , but the majority was juveniles ( young adults ) around 10 mm long . the majority of ocular cases was not associated with cns symptoms . among the 42 ocular cases peripheral blood eosinophilia was noted in 11 cases and 6 of them were among the cases with cns symptoms . the very first report of optic neuritis due to a. cantonensis infection described a case from china . subsequently , 4 cases have been reported from thailand   and 1 case from taiwan . the diagnosis of optic neuritis can be made clinically by visual symptoms , positive rapid relative afferent pupillary defect ( rapd ) , and prolongation of visual evoked potentials ( vep ) . in the first a. cantonensis infection - associated optic neuritis case from china , the patient complained of mild headache , a low - grade fever , and slight ataxia . at the beginning , this patient was treated as a case of influenza because of non - specific symptoms , but a. cantonensis infection was suspected after the sudden onset of retinal detachment . the first angiostrongyliasis - associated optic neuritis case in thailand   was a 21-year - old man suffering from progressive headache for 2 weeks . repeated lumbar puncture could not relieve his headache and a week later he developed blurred vision in his left eye . the rapd of his left eye was positive and vep showed prolonged latency for this eye . angiostrongylus worm was found in the vitreous space and treated with the argon laser . in 2008 , sinawat et al .   studied 3 cases of optic neuritis caused by a. cantonensis . in all 3 cases , the fundus examination revealed generalized retinal pigment epithelial alteration , subretinal tracks , retinal edema , macular edema . and a pale disc , suggesting optic neuritis . in the first case , the patient , a 47-year - old man , complained of blurred vision in the left eye but denied headache . an immature male worm in the anterior chamber was aspirated by simcoe cannula after laser photocoagulation . the second case was a 27-year - old man presented with progressive visual loss in the left eye for 3 weeks . he presented with a 2-month history of eosinophilic meningitis before the onset of blurred vision . diode laser was directly applied to the parasite and the dead worm was surgically removed . the third case was a 36-year - old man who developed visual loss in his right eye for 1 week without any history of headache . in this case , the intraocular inflammation was not detected and the rapd was negative . the patient was a 27-year - old thai male presenting with progressive visual loss and a membrane - like floater in the right eye that had persisted for 1 month . the parasite found in the subretinal space was treated with a diode laser and surgically removed . a case of optic neuritis reported from taiwan was a 38-year - old man who suffered from headache and neck stiffness with blurred vision and color blindness in the left eye associated with binocular horizontal diplopia . the optic neuritis was confirmed by having a positive rapd and delayed vep in his left eye . the patient received larvicidal drugs and steroid treatment for 2 weeks , and his visual accuracy and color sense in the left eye were improved . as an overview ( table 2 ) , all optic neuritis patients were males . two cases in thailand were affected in the right eye and the other 4 in the left eye . unlike other infectious causes of optic neuritis , optic neuritis associated with ocular angiostrongyliasis is almost always unilateral . if both conditions coexist , eosinophilic meningitis will occur prior to optic neuritis or ocular involvement based on its life cycle . the postulated mechanism for optic neuritis is an increased intracranial pressure   or direct invasion . in 2008 , jin et al . performed mri examinations for 74 angiostrongyliasis patients and found 33 with abnormal mri including 1 optic neuritis case . in this optic neuritis case , related to this , optic nerve compression due to a. cantonensis was also reported from china . ocular involvement other than optic neuritis in angiostrongyliasis included blepharospasm , uveitis , macular edema , retinal edema , necrotic retinitis , panophthalmitis , papilledema , and optic nerve compression . in the case of necrotic retinitis reported from taiwan , the patient had sudden loss of vision in both eyes and yellow transudate of retina accompanied by bulla formed by bilateral retinal detachment . both serum and cerebrospinal fluid were antibody - positive against a. cantonensis by elisa , and serum and subretinal fluid were positive for a. cantonensis by western blotting . the most common diagnostic method for optic neuritis caused by a. cantonensis infection is ophthalmological examination ( ophthalmoscope , erg , and vep ) . furthermore , inquiry of history of eating intermediate hosts of a. cantonensis is also a key for diagnosis . immunodiagnosis , including elisa , western blotting , and use of specific monoclonal antibodies , provide strong supportive evidence . the most reliable diagnostic method so far is to find put larvae or juveniles of a. cantonensis by ophthalmoscopy . the usual method of treatment of optic neuritis caused by a. cantonensis is surgical removal of the parasites . if the parasites have not yet caused tissues damage , laser - mediated killing of living worms is a recommended therapeutic measure , which is better than surgical removal . in addition , oral administration of steroids may improve visual acuity by reducing intraocular inflammation . anthelmintics , such as albendazole , are not recommended because dead parasites may cause serious intraocular inflammation . in spite of these therapeutic measures , as shown in table 2 , only slight improvement of visual acuity occurred after treatment in most cases . for both optic and general ocular angiostrongyliasis , the outcome of therapy depends on the duration of infection and the initial visual acuity at the first visit of patients to doctors . although the incidence of optic neuritis in a. cantonensis infection is far lower than that of eosinophilic meningitis , its poor prognosis in terms of vision loss seriously affects the quality of the life of patients . at present , we do not fully know the answers to the following questions : 
 how do larvae migrate into the eyes ? via blood flow or by other routes?what is the relationship between optic neuritis and eosinophilic meningitis?what is the relationship among clinical symptoms , pathological changes , and the prognosis ? what causes those pathological changes?how can we treat cases of optic neuritis due to a. cantonensis infection ? how do larvae migrate into the eyes ? via blood flow or by other routes ? what is the relationship among clinical symptoms , pathological changes , and the prognosis ? what causes those pathological changes ? how can we treat cases of optic neuritis due to a. cantonensis infection ? because only a limited number of optic neuritis cases have been reported , development of an animal model for a. cantonensis - associated optic neuritis is necessary . in the past 20 years , many animal experiments have been carried out using rodent models of a. cantonensis infection . among them , mice have been studied most extensively because of their susceptibility to the parasite . until now , however , there are no animal models for optic neuritis caused by a. cantonensis . rats and mice have provided research models for optic neuritis caused by other conditions , such as multiple sclerosis . in these models , histopathological changes of the retina and optic nerve were observed by h - e staining , and demyelination of the optic nerve was observed by electron microscopy . similarly , fundoscopy has been used to observe the damage to the optic papilla and erg / vep used to examine changes in vision and visual acuity . ganglion cells of the retina were also the focal point of the study of optic neuritis . similar methodology should be adopted for the study of optic neuritis caused by a. cantonensis . in our preliminary animal study using mice infected with a. cantonensis , we found the infected animals manifested obvious inflammatory infiltration in the retina and optic nerve , and demyelination was found in the optic nerve . meanwhile , vep and erg were very different compared with normal control animals ( unpublished results ) . these results indicate a. cantonensis can cause pathological and clinical changes of eyes in experimental animals . in conclusion , ocular angiostrongyliasis was comprehensively reviewed with special focus on optic neuritis caused by a. cantonensis , and we put forward questions about the urgent problems which need to be solved . this study provides a baseline for future research on optic neuritis caused by a. cantonensis .