Systemic Envenomation via Ocular Route from a Neurotoxic Snake Venom Ophthalmia––A Case Report

Abstract

Snake envenomation is a neglected tropical disease with two million snake bites reported each year (WHO). Much less common is snake venom ophthalmia secondary to eye exposure from spitting snakes. This paper reports an unusual case of systemic envenomation via the ocular route of a 14-year old male from the Philippines. A mixture of snake blood and venom came in contact with the patient’s left eye causing severe pain and blurring of vision, shortly followed by generalized body weakness and ptosis. Copious irrigation with normal saline was done at the emergency room, and Purified Cobra Antivenin (PCAV) was administered. Symptoms of systemic envenomation abated following PCAV administration. Ofloxacin ophthalmic drops and eye lubrication were prescribed for seven days to minimize complications, and the patient was discharged well after three days of hospitalization. Although difficult to ascertain, signs and symptoms pointed to systemic envenomation, and this could be the first case of an unconventional venom route to date. This paper opens possibilities and serves as precedent for future research - ocular envenomation, snake venom, and blood components, and symptomatic management.

Introduction

Snake envenomation is a neglected tropical disease with two million snake bites reported each year (WHO). 1 Only a few cases of venom ophthalmia appear in literature. Most of these cases originate in rural Africa from various species of the genus Naja . In Taiwan, 39 cases were reported from 1990 to 2016, and all were from cobra spit of Naja atra . 2 In Singapore from 2007 to 2012, only three cases were recorded, all of Naja sumatrana . 3 In the Philippines, only one case of snake venom ophthalmia by Naja samarensis was reported. 4 This paper presents a case of snake venom ophthalmia sustained by a 14-year old patient in the Philippines following contact with a presumed mixture of snake blood and venom after hitting the snake’s head multiple times.

The most common sequelae of snake venom eye contact include conjunctivitis, photophobia, hyperemia, and uveitis. Various compounds have been identified to cause eye complaints that include nuerotoxins, cytotoxins, enzymes, and other proteins. 5 In spitting cobras of the family Elapidae , venom is stored in the Duvernoy’s gland, a modified salivary gland, and is secreted through the fangs when the snake is threatened. 6 Without proper identification of snake species from an expert, demographics and symptomatology are equally important in ascertaining which species most likely caused the insult.

Case Presentation

A 14-year old Filipino complaining of left eye pain was transferred to our institution in December 2023 from a rural health center in the south of the Philippines. The patient was walking outside in the dark, when he suddenly noticed a snake described to be about three feet in length, brownish-gray in color alternating with yellow stripes. Out of fear, he took a katana from their house, went back outside and finding the snake still in the same spot, hit its head multiple times until blood splattered onto his left eye, causing pain which prompted consult at a nearby health center.

Upon receiving at our institution, irrigation with normal saline was done, and referrals to ophthalmology and toxicology services were facilitated. On eye examination, ptosis was apparent (see Fig. 1 ). Visual acuity was 20/20 for both eyes; pupils were equally brisk and reactive to light; full extraocular movements; and tonometry of both eyes revealed normal intraocular pressure at 12 mmHg each. There was minimal ciliary injection of the left eye; however, fundoscopy was unremarkable.

Fig. 1 . Minimal ciliary injection of left eye and bilateral partial ptosis.

Past medical and surgical histories are unremarkable. Vaccinations are up to date, including tetanus toxoid. Baseline laboratory values of hepatic and renal functions were obtained indicating within reference range (see Appendix Tables for values).

There were no bulbar symptoms such as dysphonia and dysphagia, however there was noted difficulty of breathing within one hour of stay at the emergency department. The patient was given Purified Cobra Antivenin (PCAV) 800 MU/vial 1 vial in 20 mL D5W intravenously slow push. Ofloxacin 0.3% and sodium hyaluronate ophthalmic drops were also started, both given one drop on the affected eye every six hours. There was resolution of ptosis one hour post-PCAV administration (see Fig. 2 ), and the patient was subsequently transferred to the pediatrics ward for observation and admission. He was discharged after three days and was prescribed with amoxicillin/clavulanic acid 500 mg/125 mg tablet twice a day for seven days. The course in the wards was unremarkable. Fig. 3 shows the timeline from ocular contact to hospital discharge.

Fig. 2 . Resolution of ophthalmic symptoms after one hour of administering Purified Cobra Antivenin (PCAV).

Fig. 3 . Symptoms and corresponding interventions following neurotoxic snake venom ophthalmia.

PCAV: Purified Cobra Antivenin.

Discussion

Eye complications from snake venom usually are from direct injection via bite, or in rare cases through direct eye contact by spitting elapids when threatened. Systemic symptoms are more notable in snake bites, and to our knowledge there has been no reported case of systemic cobra envenomation through ocular contact. 7 There is a lone report however of systemic envenomation through a possible ocular route from coral snake Micrurus tener . 8

Anectodal sources of snake encounters are best evaluated if the snake species is properly identified by an expert such as a herpetologist. For obscure cases without proper species identification, one can only suppose based on history, species demographics, and symptomatology. This report presumes a neurotoxic snake envenomation primarily with the history and species distribution attributing to a possible Naja spp . and the physical finding of ptosis.

The mechanism of ophthalmic envenomation for this patient is unclear, but these could be attributed to the major components of the venom found in neurotoxic snake species: 3-FTX (three-finger toxin), PLA2 (phospholipase A2), and SVMP (snake venom metalloproteinase). Within the 3-FTX family, CTX-1 (cardiotoxin) is responsible for producing eye pain by activating sensory neurons in the eye. Types B and C muscarinic toxins, also of the 3-FTX family are thought to cause ptosis. 9

The venom of genus Naja (“true cobra”) is produced in the post-orbital glands and are subsequently stored Duvernoy’s gland ( Fig. 4 ). Once threatened, these snakes can spit onto the prey’s eye up to 10 ft in distance with accuracy. 10 , 11 Our patient is a singular case because it was more likely a mixture of venom and blood that came in contact with the eye after hitting the snake’s head multiple times, and not just venom sprayed from a threatened snake.

Fig. 4 . Duvernoy’s venom gland.

Compared to the case series by Paghubasan et al., 4 which presented the only recorded case of venom ophthalmia in the Philippines, the subject sustained ophthalmic symptoms after N . samarensis spat onto its left eye. The species was identified, and symptoms were eye pain and redness; no systemic manifestations were observed. The patient was discharged on the same day, with no complications over the two-year follow-up.

It is difficult to ascertain if there was indeed a systemic envenomation through the ocular route. Eye examination showed no violation of the sclera, and even so, the stromal layer is avascular and collagen-rich, which effectively hinders systemic absorption of the venom. 12 A limitation however in this study was to perform Seidel Test being the gold standard in determining corneal or scleral perforation. 13 A more plausible explanation for the systemic envenomation is the absorption of venom into the lymphatic-rich conjunctiva, while the cornea and the retina being devoid of them. 14 Similar to venom injection via snake bite, venom is absorbed via the lymphatic system eventually causing systemic manifestations. This is contrary to the belief that venom travels along the bloodstream to cause systemic toxicity.

The only sign that gave way in considering the diagnosis is bilateral ptosis, knowing from history that only the left eye was in direct contact with the venom. Complications of snake venom ophthalmia is often localized, with eye pain as the primary complaint followed by swelling, redness, chemosis, and blindness through corneal keratinization. 15 Nonetheless, an aggressive approach was followed by treating the case as systemic envenomation primarily with the presentation of ptosis.

Although not internationally validated, we re-introduce the term “toxungen,” originally used by Nelsen, et. al. 16 to describe toxic biological secretions delivered onto a body surface area without inflicting any wound. Following this definition, our patient suffered the symptoms with a toxungen, and not a toxin nor a venom. Using the term “toxungen” may lessen confusion in future reports.

In conclusion, venom ophthalmia is uncommon especially in urban areas, and there is only one possible case of systemic envenomation through the ocular route in academic journals to date. Ophthalmic injuries range from mild erythema to blindness, and treatment should be justified according to clinician’s judgment. This paper reported a probable case of a systemic neurotoxic snake envenomation following entry into the patient’s eye. Due to lack of compelling references and previously cited similar events, contentions and opportunities for research arise as to ascertain if envenomation was localized vs. systemic, and to which components of the toxungen correspond to the clinical presentation.

Appendix Tables. Laboratory Values .