Ocular dirofilariasis: a case series of 8 patients.

PURPOSE: Dirofilaria repens is an endemic parasite in Mediterranean countries that mostly affects animals. Rarely, however, it can infect humans. This case series presents patients with ocular infections due to D. repens.
MATERIALS AND METHODS: A chart review was performed of patients with ocular dirofilariasis after the year 2000, treated at a tertiary referral centre in Greece. Data were collected on the ocular, microbiological, or/and histopathological aspects and treatment.
RESULTS: Eight cases of unilateral ocular dirofilariasis were identified, of which 5 were subconjunctival (1 masquerading as nodular scleritis) and were removed through a conjunctival incision, 2 cases were intravitreal and were removed with vitrectomy, and 1 was intraorbital (adjacent to the roof of the orbit). The latter appeared as an encapsulated mass and subsequent histological examination revealed the presence of the parasite. Of the 8 cases recorded after the year 2000, 7 appeared within the last 6 years (4 cases within the last 3 years). The majority of cases involved residents of the Ionian Islands (7 of 8 cases).
CONCLUSIONS: D. repens can affect various ocular and periocular tissues. A progressive increase in the incidence of dirofilariasis was observed, which is potentially associated with climate changes in warm and moist areas where this parasite is endemic.

INTRODUCTION

Dirofilariasis is a helminthic infection caused by parasites of the Dirofilaria genus (genus Dirofilaria, family Onchocercidae, which is included in the class of Nematodes).1

It is a common zoonotic disease affecting mostly dogs (lord hosts), other canines (wolves, coyotes), foxes, and cats. It is transmitted to humans through arthropods; mosquitoes are the vector for dirofilaria. Humans are the final host of this parasite.2

We present cases with ocular dirofilariasis with regard to the localization of the parasite in ocular and orbital tissues, management, and identification of the dirofilaria species and discuss the increased incidence in Northwest Greece.

MATERIAL AND METHODS

This retrospective, descriptive case-study was carried out in a tertiary referral center. The study adhered to the principles of the Declaration of Helsinki. A chart review was performed of cases with ocular dirofilariasis treated during the last 12 years (2000-2012) at a tertiary eye care referral center in Greece. A total of 8 patients (8 eyes) diagnosed with ocular dirofilariasis were included in this study. All cases were clinically examined (including slit-lamp and fundus examination) by a uveitis expert. All cases were positively identified via microbiological and/or histopathological studies of the parasite, by both a veterinarian and a pathologist. Laboratory diagnosis was based on macroscopic and microscopic characteristics of the nematode. The details and characteristics of each case were compiled by reviewing the patient files (demographic features such as age, sex, residence, and presenting symptoms and signs). Visual acuity (using Snellen's optotypes) and clinical examination findings were recorded at presentation and during follow up. The cases were followed up at the Ocular Inflammation Unit until 2012.

RESULTS

The mean age of patients was 49.5 years (range, 32-65 years). There were 4 males and 4 females all with unilateral infection (8 eyes).

There were 5 (62.5%) cases of subconjunctival infection, 2 (25%) intravitreal cases, and 1 (12.5%) intraorbital case [Figure 1]. In all cases, the parasite was isolated and identified as Dirofilaria repens.

Figure 1

The location of ocular dirofilariasis in a case series of 8 patients in Northwest Greece

Macroscopically, the isolated helminths were thin and cylindrical, whitish in color [Figure 2a], measuring 10-12 cm in length and 0.3-0.4 mm in width, and appeared to be structureless nematodes. Microscopically, the anterior rounded end of the helminths was observed to be slightly wider than the posterior end. Furthermore, the cuticle of the helminthic worm had longitudinal ridges. Morphologically, the helminths in our case series resembled the genus Dirofilaria and the size, typical location in the majority of our cases (subconjunctival), and ridges on the cuticle supported the diagnosis of D. repens.

Figure 2

Subconjunctival dirofilariasis: (a) The helminth after removal. Note the macroscopic characteristics of Dirofilaria, (b) A typical subconjunctival coil-like configuration of Dirofilaria, (c) Removal of a Dirofilaria through a conjunctival incision

In 4 out of 5 cases, the parasite appeared as a whitish vermiform mass under the conjunctiva at slit-lamp examination [Figure 2b]. In one case of a 50-year-old female presenting with ocular redness and disturbing pain at nighttime, subtenon dirofilariasis was initially misdiagnosed as nodular scleritis [Figure 3a]. This patient presented to the emergency department late at night and a nodular mass was recognized under the conjunctiva. The next day, in daylight, in order to carry out a differential diagnosis between scleritis or episcleritis, pressure was applied on the nodule and surprisingly, the shape changed as the parasite unfolded [Figures 3b and c]. In 5 patients, the entire parasite was removed while alive through an incision in the conjunctiva [Figure 2c].

Figure 3

A subconjunctival mass mimicking nodular scleritis (a), which is unfolded (b and c) moving (arrows) after pressure; a case of live Dirofilaria

Two cases of intravitreal dirofilariasis were also noted. Both patients had good visual acuity but complained of floaters (described as “shadows”), redness, and ocular discomfort. Best-corrected visual acuity (BCVA) was 20/20 but with difficulty due to the floaters. On fundus examination, the parasite was recognized in the vitreous behind the lens [Figure 4a]. Both eyes underwent vitrectomy in order to remove and identify Dirofilaria [Figure 4b]. The parasites were found dead with intense adhesion to the surrounding vitreous. During vitrectomy, lesions on the retina were not observed.

Figure 4

(a) Intravitreal Dirofilaria, (b) Pars plana vitrectomy was performed for the removal of the dead parasite; around the helminth there is a dense inflammatory reaction of the surrounding vitreous with strong adherence

A 52-year-old female patient presented with a palpable mass below the roof of the left orbit located temporally, proximal to the superior orbital rim (adjacent to the lacrimal gland). Blood analysis indicated an increase in eosinophils (9%). Subsequently, the mass was removed through a transpalpebral approach [Figure 5a and b] and sent for histological examination. Pathologic studies indicated a circumscribed encapsulated mass 1 × 0.7 × 0.7 cm in dimension. On dissection, the lesion was filled with serous fluid. Microscopic histopathological examination reported sections of a nematode helminth in the cystic lesion. The cystic wall was infiltrated by an abundant number of eosinophils along with the presence of granulomatous inflammatory tissue; neutrophils were also recognized in the fluid [Figures 5c and d]. The nematode had the characteristic features of D. repens, as already described in the results. One month after the surgical excision of the parasite, peripheral blood eosinophils returned to normal levels (3%).

Figure 5

Transpalpebral removal of an orbital cystic lesion (a and b). Histopathology revealed cellular infiltration of the cystic wall and fluid with sections of encapsulated Dirofilaria (PAS stain, ×100) (c); the parasite in a cross section (hematoxylin-eosin stain, ×40) (d)

Since the year 2000, we experienced a continuous increase of ocular dirofilariasis cases characterized by a sudden increase of incidence within the last 6 years [Figure 6].

Figure 6

Increased incidence of Dirofilaria cases referred to our Department of Ophthalmology

All patients were residents of Northwest Greece; the majority of cases (7 of 8, 87.5%) involved residents of the Ionian Islands Corfu and Lefkas. Only 1 patient originated from the mainland (Epirus, Greece).

During follow up (for at least 1 year), neither inflammatory signs nor visual impairment were noted in all treated patients.

DISCUSSION

Dirofilaria is a parasite that can be detected in various ocular and periocular tissues. Once it enters the blood circulation of the lord host, the adult female helminths produce microfilariae that typically are found in peripheral blood. A mosquito takes a blood meal of the infected host and ingests microfilariae. Once in the vector's midgut, the microfilariae reach the infectious stage in about 2 weeks, based on the environmental conditions.3 The larvae are injected into human tissues via the mosquito proboscis and usually, they do not survive crossing the tissues. The larvae that manage to survive evolve into adult helminths, which are reproductively inactive and cannot produce microfilariae. This infection is not contagious in humans.

In the eye, Dirofilaria can be found subconjunctivally or in Tenon's layer45, periorbital tissues (lids, orbit),6 and intraocularly (anterior chamber7, vitreous8). The parasite migrates as microfilaria into the vitreous and anterior chamber via the blood stream of the eye and into the lids and orbit through the subconjunctival and subcutaneous tissues and develops into an adult helminth.

It is a common zoonosis that rarely infects humans and is considered endemic to Mediterranean countries (Italy, France9, Greece, and Croatia10). Of the reported cases of human dirofilariasis in Europe, Italy has the highest burden (66% of cases), followed by France (22%), Greece (8%), and Spain (4%). Although dirofilariasis is considered endemic in these countries, reports have been published from many parts of the world including Africa, Australia, America, Europe, and Asia.6 The clinical forms of dirofilariasis in humans are pulmonary, subcutaneous, ocular, and rarely, infection of the cerebrum, testicles, and female breast, invariably leading to an incorrect diagnosis of malignant tumor.11 Six out of 40 species of Dirofilaria are known to cause diseases in human: D. immitis, D. repens, D. striata, D. tenuis, D. ursi, and D. spectans2. D. immitis is responsible for pulmonary dirofilariasis, whereas D. repens is responsible for subcutaneous and ocular dirofilariasis. During the last decade, ocular dirofilariasis has increasingly been reported from countries previously considered non-endemic, such as in parts of South Asia.12

Additionally, there have been reports of ocular dirofilariasis in Serbia13, Denmark4, Russia,14 and Tunisia.15 Within the last 6 years, cases of ocular dirofilariasis were described in India, which is considered a non-endemic country.7 Our review of the literature, indicated that the majority of articles were case reports of up to 3 patients, with the exception of Dzamic et al.13 who presented 19 cases of human dirofilariasis in Serbia, both ocular and subcutaneous. Our case series includes 8 patients, one of the highest numbers of patients with ocular dirofilariasis to be reported.

In published reports of ocular dirofilariasis, most of the cases were located under the conjunctiva (>60% of all cases) followed by orbital/eyelid dirofilariasis (approximately 25%). One case of dirofilariasis of the anterior chamber was reported by Chopra et al.7 in India. In our series, most patients presented with subconjunctival dirofilariasis (62.5%), but there were also two cases of intravitreal dirofilariasis (25%) and one case of orbital dirofilariasis (12.5%). Due to the easy access of vectors to conjunctiva, it is the most common ocular tissue for Dirofilaria infection. All patients complained mostly of discomfort, ocular pain, and redness. In some reports, conjunctival dirofilariasis has been misdiagnosed as allergic conjunctivitis. Orbital or eyelid dirofilariasis is less frequent, and patients usually present with a palpable mass having well-demarcated boundaries. The diagnosis of dirofilariasis is made following histopathological examination of the surgically excised mass. Most patients with orbital or eyelid dirofilariasis experienced multiple mosquito bites on the head or periorbital skin. A review of the literature indicates that human ocular dirofilariasis usually affects middle-aged patients with a slight male preponderance.

Intravitreal dirofilariasis should be distinguished from diffuse unilateral subacute neuroretinitis (DUSN). DUSN is a potentially blinding form of uveitis caused by ocular nematode infestation infiltrating the subretinal space. Several nematodes have been proposed as the etiologic agent of DUSN (Toxocarra canis, Ancylostoma caninum, Baylisascaris prayonis) but no conclusive evidence has been provided for a specific nematode. To date, D. repens has not been implicated as a cause of DUSN. In our case series, D. repens was strongly attached to the surrounding vitreous and there was mild vitritis without retinal involvement. However, DUSN is characterized by the presence of gray-white lesions in the deep retina, optic disc edema and vitreous inflammation. Late features of DUSN include narrowing of the retinal optic vessels, optic nerve atrophy, and development of focal, linear crisscrossing or diffuse atrophic changes in the retinal pigment epithelium. Usually, patients with DUSN have a poor visual outcome unlike patients with intravitreal dirofilariasis. The treatment of choice for DUSN consists of laser photocoagulation of the visible intraretinal worm. If laser photocoagulation cannot be performed, high dose albendazole has been suggested.16

Removal of the parasite is the only treatment for ocular dirofilariasis. Subconjunctival Dirofilaria is removed through an incision in the conjunctiva. The entire parasite must be removed in order to avoid an allergic reaction due to parasite remnants. In our series, intraorbital Dirofilaria was excised en block into a cystic mass lesion whereas intravitreal Dirofilaria was removed with vitrectomy. No additional treatment was required in any of our cases. Anti-helminthic drugs are not indicated since Dirofilaria is reproductively inactive and has a single location. If Dirofilaria is suspected, blood analysis should show an increase in the number of eosinophils. After removal of the parasite, the number of eosinophils returns to normal levels. Peripheral blood eosinophilia and/or presence of eosinophils in affected tissues suggest an allergic reaction caused by the inflammatory response induced by the nematode. The histological findings from our case series are in keeping with this pathogenesis.

To the best of our knowledge, most reports of ocular dirofilariasis originate from Europe (Italy, France, Greece, Croatia, Serbia, Denmark, and Russia), 1 case from Africa (Tunisia), and 6 cases from South Asia (India). It should be noted that there has been an increase in the incidence in countries that were considered non-endemic, such as India.

Approximately 70% of all reports with human ocular dirofilariasis were documented within the last 6 years (2006-2012). Only 30% of cases were documented earlier than year 2000. These reports concur with our case series where a progressive increase in the incidence of dirofilariasis was noted within the last 6 years. Additionally, the majority of patients originated from the Ionian Islands (87.5%) where the climate is warmer and moister. However, Chopra et al. noted that the increased incidence of dirofilariasis may be due to the increased awareness regarding Dirofilaria infection or traveling to endemic areas.12 Simon et al. suggested that because dirofilariasis is vector-borne disease, the distribution and infection rates may have undergone significant modifications due to global climate change.3 Mosquitoes proliferate in warm and moist areas and they become more infectious. Climate change favors the increase of mosquitoes in number and infectiousness, making the transmission of Dirofilaria easier.

In conclusion, ocular dirofilariasis is observed mainly in warm and moist areas, and its incidence in those areas has increased in recent years (as with our cases in Greece) probably due to climatic changes. D. repens is responsible for ocular dirofilariasis and removal of the entire parasite is the only appropriate management.