Case Report: Snake Venom Ophthalmia Caused by Cobra Exposure: A Report of 26 Cases

ABSTRACT.

We report 26 cases of eye injuries resulting from cobra venom sprayed by Naja atra. This accounts for 14.5% of patients (26/173) treated for cobra injuries who presented to the emergency department of a snakebite treatment center in Guangzhou, South China. Pain, blurred vision, lacrimation, photophobia, and foreign body sensation were the most common symptoms, found in 24 patients. Ophthalmic examination revealed eyelid swelling and conjunctival congestion. Eye slit lamp examination showed obvious punctate corneal epithelial defects in four patients. Five patients received an intravenous infusion of antivenom. All patients’ eyes were rinsed completely with normal saline after their arrival at the hospital. Prophylactic topical antibiotics were given to all patients. All eyes were cured without long-term sequelae.

INTRODUCTION

Cobra venom is harmless when sprayed on intact skin, but in cases of snake venom ophthalmia, it can cause symptoms such as pain, blepharospasm, conjunctivitis, edema, erosion in the conjunctiva and cornea, and even blindness in severe cases.^1,2 Naja atra, one of the three primary cobra subspecies in China (the others are Naja kaouthia and the recently described Naja fuxi), has been found to have the ability to spit venom.^3–7 Sporadic cases of cobra venom sprayed into the eyes have been reported, but the exact incidence of snake venom ophthalmia in mainland China remains unknown. A survey found that only 1% of patients (3/303) with cobra venom exposure were identified as having snake venom ophthalmia in Guangxi Province, China.⁸ It is unclear whether the effects of N. atra venom sprayed into the eyes are as severe as cases involving African species. In a recent study, the highest mortality in chicken embryos was observed after administration of venom from Naja nigricollis.⁹ However, we cannot draw any definite conclusions that the effects of venom from African species sprayed into the eyes are more serious than those caused by Asian species. Although the incidence of venomous ophthalmia is low, it is relatively common in areas with a high incidence of cobra bites, and this particular type of snake envenoming has not received much attention.¹⁰ Physicians without professional training may prescribe antivenom intravenously or topically in the treatment of snake venom ophthalmia, referring to the procedure for venomous snakebites.^5,11 However, no evidence has been found in animal studies or clinical cases that venom sprayed into the eyes can enter the blood circulation and cause systemic toxic symptoms, which makes the administration of antivenom unnecessary.^10,12–14 According to the current guidelines for the management of snakebites,^15,16 the administration of antivenom is not recommended in the treatment of snake venom ophthalmia; instead, sufficient immediate irrigation is the key to removing venom from the eyes.¹⁵

Among the three cobra species in China, only N. atra is widely distributed in the Guangzhou area,^6,7,17 and the clinical features and emergency management of snake venom ophthalmia caused by N. atra need to be reaffirmed. Thus, we report on cases of patients with N. atra venom ophthalmia enrolled at our center in Guangzhou.

CASE REPORTS

According to medical records from January 2013 to August 2022, 173 patients with cobra injuries were admitted to the emergency department of the First Affiliated Hospital of Guangzhou Medical University. Twenty-six patients with snake venom ophthalmia caused by N. atra accounted for 14.5% of these patients (26/173). The involvement of N. atra was confirmed by dead or live snakes or on-site photographs brought to the hospital. Patients who only witnessed the snake were asked to identify the species from color pictures and specimens. Most of the victims were men. The average age of all patients was 48.5 (interquartile range 30.5–55.5) years. Cases occurred in all months except March and November, with a total of five cases in July. The time from injury to arrival at the hospital ranged from 2 hours to 4 days. The reported causes of the injuries were catching snakes, working outdoors, watching snakes, teasing snakes, and killing snakes (Table 1). Most of the patients were sprayed with venom directly into the eyes. However, one patient was sprayed on the orbit, and another patient was sprayed on the skin around the eyes under the protection of framed glasses. These two patients had no ocular symptoms. Pain, blurred vision, lacrimation, blepharospasm, photophobia, and foreign body sensation were common symptoms found in the remaining 24 patients. A total of 16 patients washed their eyes with water on-site immediately after injury. Ophthalmic examination revealed eyelid swelling and conjunctival congestion. Eye slit lamp examination showed obvious punctate corneal epithelial defects in four patients. Five patients received an intravenous infusion of antivenom, including Agkistrodon halys antivenom and N. atra antivenom. All antivenoms were produced by Shanghai Institute of Biological Products (Shanghai, China). However, these patients had no symptoms of systemic envenoming. All 24 symptomatic patients underwent irrigation with normal saline and received antibiotic eye drops/ointment. None of the patients had vision problems, and they all recovered fully within 1 week. Two typical cases of ocular exposure to N. atra venom are described below.

Table 1.

Characteristics of 26 patients with snake venom ophthalmia

Characteristics	Number	Percentage
Age, years, median (IQR)	48.5 (30.5–55.5)	–
Sex
Male	24	92.3
Time of occurrence
Daytime	18	69.2
Cause of injury
Catching snakes	6	23.1
Working outdoors	5	19.2
Watching snake	4	15.4
Teasing snakes	2	7.7
Slaughtering snakes	2	7.7
Undocumented	7	26.9
Injured eye
Left	10	38.4
Right	6	23.1
Both	6	23.1
Undocumented	4	15.4
Symptom
Pain	14	53.8
Blurred vision	10	38.4
Lacrimation	13	50
Photophobia	9	34.6
Foreign body sensation	7	26.9
Conjunctival congestion	14	53.8
Blepharospasm	14	53.8
First aid
Wash eyes with water	16	61.5
Treatment
Normal saline irrigation	24	65.4
Antibiotic eye drops	24	69.2
Administration of antivenom	5	19.2

IQR = interquartile range.

Case 1.

A 67-year-old female farmer without a medical history was picking beans in front of her home. Suddenly, the venom of a nearby N. atra was sprayed into her left eye. The patient was sent to our hospital after 4 hours. She exhibited obvious symptoms, including eye pain, blurred vision, tearing, photophobia, foreign body sensation, and conjunctival congestion.

Her visual acuity was 20/33 optical density. Fluorescence staining showed scattered punctate defects in the corneal epithelium (Figure 1). Copious irrigation with normal saline combined with levofloxacin eye drops was administered to the injured left eye. Follow-up by phone 1 week later confirmed her full recovery.

Figure 1.

Images of an elderly female patient’s left eye. (A) Photo of the left eye showing eye redness, edema, tears, and conjunctivitis. (B) Eye with fluorescein staining showing corneal erosion.

Case 2.

A 21-year-old male worker was sprayed with venom in his left eye at night while watching an N. atra caught by his colleagues. An eye flush was performed at the scene. He was transferred to our hospital 4 hours later. Symptoms of his injured eye included pain, blurred vision, and lacrimation. Conjunctival hyperemia was observed during the examination, which showed positive fluorescence staining (Figure 2). Normal saline irrigation and levofloxacin hydrochloride eye gel were administered. At follow-up, he reported that the symptoms had improved daily and had fully resolved after 9 days.

Figure 2.

Left eye image of a young male patient. (A) Eye pain, blurred vision, redness, and lacrimation. (B) Corneal defect found by slit lamp examination in the left eye. (C) Corneal fluorescein sodium staining showing scattered punctate defects in the cornea.

DISCUSSION

In our study, the main symptoms were pain, blurred vision, tearing, and sensitivity to light. Therefore, a more detailed eye examination was also necessary. Corneal epithelial defects or erosions may occur depending on the extent of venom damage, and corneal abrasions must be ruled out by fluorescein staining and/or slit lamp examination. Our data showed that eye injury induced by N. atra was mild, and only four patients had corneal damage detected by fluorescent staining, which was similar to other reports of spitting cobra injuries in the previous literature.^{3,5,10,12–14}

According to a previous study, N. atra shows a higher concentration-dependent cytotoxicity than two other Asian spitting cobras, Naja sumatrana and N. kaouthia.^12,18,19 However, several reports showed that N. nigricollis, a type of African spitting cobra, can cause severe clinical outcomes such as corneal ulcer, anterior uveitis, and even blindness.^1,2,8 It seems that N. nigricollis can cause more serious symptoms and prognosis than N. atra. Although the highest embryonic mortality rate in an animal study was observed after administration of venom from N. nigricollis, horizontal toxicology in Asian and African cobras, such as the abundance of phospholipase A2, three-finger toxins, and other cytotoxins, and the physical properties of venom need to be compared.⁸

Our study showed that the majority of patients can flush their eyes with water at the scene after being sprayed with venom, which is a simple and effective way to mitigate the damage by reducing eye exposure to venom. In a prior study, rabbit corneas were exposed to snake venom and then immediately rinsed with water. However, damage and edema were still observed, which indicates that water irrigation cannot reverse damage to the cornea but does slow the process.²⁰ A previous study showed that careful eye rinsing can reduce or even eliminate eye complications within days of first aid in 77% of cases.⁵ The WHO guidelines emphasize that the main first aid method for venom spitting is to use water or other liquids for heavy lavage.¹⁵ After venom spraying in the eyes, turning the head to the affected side can prevent polluted water and diluted venom from flowing into the normal eye and causing a secondary injury. The patient can be seated or lying down with the head slightly turned to the affected side while the liquid is poured. The irrigating fluid can be copious amounts of tap water, saline, or any other bland liquid available, including milk or even urine.¹⁶

Other than irrigation, topical drugs are needed to control inflammation, minimize ulceration, and prevent infection. Local allergic reactions may occur after snake venom enters the eye because it is a heterogeneous protein. Topical vasoconstrictors with weak mydriatic effects, such as 0.5% epinephrine drops, can be used to relieve pain and inflammation.¹⁰ Local anesthetics are also effective but should only be used temporarily and once the patient is in the acute phase, considering the potential damage to the insensate cornea.¹⁰ Prophylactic topical antibiotics were used in our patients. Existing eye lesions, such as corneal ulcers and bulbar conjunctiva, may allow a variety of pathogens to invade the eyes. The oral flora of snakes is composed of a variety of aerobic and anaerobic microorganisms, especially fecal gram-negative bacilli.²¹ Therefore, antibiotics are necessary to prevent possible endophthalmitis, blinding corneal opacities, and other secondary infections. Tetracyclines, chloromycin, and ciprofloxacin ointment are suitable.¹⁰

In our study, five patients were injected with antivenom, although none of them showed features of systemic envenomation. Snake venom ophthalmia has not been reported to lead to systemic envenomation effects, such as hemostatic abnormalities, external ophthalmoplegia, cardiac arrhythmia, and acute kidney injury, which result in mismatched indications for the use of antivenom.^15,22 An animal study showed that topical heparin and antivenom significantly improved ocular complications caused by venom exposure.^4,23 Only a few cases mentioned the effectiveness of local use of antivenom in the treatment of venom ophthalmitis. However, guidelines discourage topical treatment with diluted antivenom because it may cause local irritation.¹¹ In addition, the use of antivenom may lead to fatal reactions, such as allergic reactions. The worldwide incidence of adverse reactions after antivenom injection is approximately 10%. Therefore, neither injection nor topical application of antivenom is recommended. Our research shows that almost 20% of patients are treated with antivenom. This indicates that some emergency physicians are not familiar with the procedure for dealing with snake venom ophthalmia and administer the same treatment method that is used for cobra bites. It is thus necessary to supplement the training of emergency physicians in areas with a high incidence of eye injuries from venomous snake spray.

Limitations.

The main limitation of this study is that it was a single-center retrospective study, so selection bias was inevitable.

CONCLUSION

Timely irrigation and topical antibiotic administration can result in a good prognosis in cases of venom ophthalmia caused by N. atra. Antivenom is not recommended for the treatment of snake venom ophthalmia.