Palytoxin Keratitis (Coral Keratitis)

Key Points at a Glance

Highlights of This Disease

• Palytoxin (PTX) is a potent marine toxin found in soft corals such as zoanthids.
• It occurs when the eye is exposed to PTX while handling corals in home aquariums.
• Characteristic slit-lamp findings include ring-shaped infiltration, Descemet’s membrane folds, and corneal epithelial defects.
• Systemic symptoms (dyspnea, metallic taste, nausea) may be present.
• First-line treatment is irrigation to remove the toxin, with topical steroids as the main pharmacotherapy.
• Severe cases may lead to corneal perforation, requiring emergency corneal transplantation.

1. What is Palytoxin Keratitis (Coral Keratitis)?

Palytoxin keratitis is an inflammation of the cornea or conjunctiva caused by local ocular exposure to palytoxin (PTX). It is also called coral keratitis.

PTX is a non-protein polyether toxin with a molecular weight of 2,680 kDa, first isolated in Hawaii in 1971. It is found in soft corals, primarily zoanthids, but has also been detected in sea anemones, dinoflagellates, algae, polychaetes, crabs, and fish ²⁾.

This disease is extremely rare, but the number of reports has been increasing with the popularity of home aquariums ^2,3). In 2017, Farooq et al. reported a multicenter retrospective case series of 7 cases of corneal toxicity, showing a wide range of findings from mild punctate epithelial keratopathy to bilateral corneal melting and perforation ¹⁾.

Systemic exposure to PTX can be fatal. It begins with a bitter/metallic taste, malaise, and dyspnea, and in severe cases can lead to respiratory or cardiac failure and death ^2,3).

Q Are corals in home aquariums dangerous?

A

Not all corals of the genus Zoanthus contain PTX, but it is impossible to distinguish by appearance, so all should be handled as if they are toxic. Awareness of the dangers of PTX is limited even among aquarium enthusiasts.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

Acute symptoms appear immediately after exposure.

• Burning pain: The first symptom that occurs immediately after the toxin contacts the eye
• Decreased vision: Occurs with corneal edema and epithelial defects
• Photophobia: Becomes prominent when accompanied by anterior chamber inflammation
• Foreign body sensation: Due to corneal epithelial damage

In addition to ocular symptoms, systemic symptoms (dyspnea, chest pain, cough, tachycardia, nausea/vomiting, headache, fever, myalgia, metallic taste) may appear.

Clinical Findings

Slit-lamp microscopy findings are diverse, but representative findings are shown below^1,2).

Finding	Frequency	Characteristics
Conjunctival injection	High frequency	Appears immediately after exposure
Limbal infiltration	High frequency	Characteristic finding of PTX keratitis
Descemet’s membrane folds	High frequency	Associated with corneal edema

• Diffuse epithelial defect: extensive loss of corneal epithelium
• Anterior chamber reaction: may be accompanied by iritis
• Eyelid swelling: edema around the exposed area
• Limbal white plaque / limbal stem cell deficiency: occurs in severe cases. Suggests damage to corneal epithelial stem cells¹⁾
• Conjunctival avascularization: partial ischemic changes
• Corneal perforation: complication of the most severe cases. Requires emergency surgery^1,3)

High-resolution evaluation with anterior segment optical coherence tomography (AS-OCT) reveals hyperreflective findings in the corneal stroma and Descemet’s membrane folds, and some cases without corneal thinning have been reported⁶⁾.

3. Causes and Risk Factors

Exposure routes

PTX exposure to the eye occurs through the following routes^2,3).

• Direct spray: The coral ejects venom in response to external stimuli, reaching the eye directly.
• Splashing of aquarium water or seawater: Contaminated water splashes during tank cleaning or coral handling.
• Contact with contaminated hands: Rubbing the eyes with hands that have touched coral without protective gloves⁶⁾.
• Inhalation of aerosol: Inhaling PTX-containing steam generated when hot water is poured over coral for removal. Inhalation is the most common exposure route, but eye exposure is the rarest³⁾.

Risk Factors

• Aquarium hobbyists: The highest risk group. Exposure occurs during the care, cleaning, and removal of soft corals.
• Scuba divers: Contact with coral underwater.
• Fishermen: Exposure to PTX from coral attached to catches.

Prevention and Daily Care

Always wear protective goggles, masks, and gloves when handling coral. Avoid pouring hot water over tank rocks, as this can aerosolize PTX. Never rub your eyes with hands that have touched coral. If exposure is suspected, immediately rinse the eyes with plenty of water and seek emergency care.

Q How can I handle coral safely?

A

The basics include wearing protective goggles, waterproof gloves, and a mask. Using hot water to remove coral should be avoided as it can aerosolize PTX. Work in a well-ventilated area and always wash your hands after handling.

4. Diagnosis and Testing Methods

Clinical Diagnosis

There is no definitive test to detect PTX exposure. Diagnosis is made clinically, and the following two points are essential.

• A clear history of exposure to PTX
• A clear temporal relationship between exposure and symptom onset

Laboratory Findings

• Ocular pH measurement: Usually normal, but may be elevated in the early stages
• Microbial culture: Usually negative. However, a positive culture should not rule out PTX, and the possibility of secondary infection should be considered.

Differential Diagnosis

Because it presents with nonspecific clinical features, the differential diagnosis is broad.

• Infectious keratoconjunctivitis: Bacterial, fungal, or viral keratitis. Differentiate by culture.
• Acanthamoeba keratitis: Ring-shaped infiltration is similar, but contact lens use history is a clue.
• Ophthalmia nodosa: Ocular inflammation caused by mechanical irritants. Differentiate by exposure history.
• Drug-induced corneal melting: Toxic corneal melting due to NSAIDs, etc.
• Other chemical injuries: Acid or alkali injuries.

5. Standard Treatment

There is no established treatment protocol. Management is based on empirical findings from published case reports.

First Aid

The first step in treatment is removal of the toxin by irrigation. Perform copious irrigation promptly with saline or artificial tears ^2,5). If contact lenses are worn, remove them immediately, as lenses can increase toxin concentration and exposure time ²⁾.

Treatment by Severity

Mild

Topical steroids: Prednisolone acetate 1% eye drops six or more times daily ^2,5).

Prophylactic antibiotics: Use topical antibiotics to prevent secondary infection ⁵⁾.

Moderate

Intensified topical steroids: Prednisolone acetate 1% eye drops every hour ²⁾.

Ascorbic acid: To prevent corneal stromal melting.

Oral doxycycline: Suppresses collagenase activity and prevents corneal melting.

Oral steroids: Added in cases of severe inflammation.

Severe

Amniotic membrane transplantation: Performed for persistent epithelial defects ⁴⁾.

Tarsorrhaphy: To promote epithelial healing.

Corneal transplantation: Emergency penetrating keratoplasty is required for ulceration or perforation ^1,3).

For mild cases, it has been reported that complete healing can be achieved with about two weeks of conservative treatment using topical steroids and antibiotics ⁵⁾. On the other hand, in the cases reported by Ruiz et al., severe courses requiring amniotic membrane transplantation occurred, and some cases required systemic management in the intensive care unit ^3,4).

Precautions in treatment

PTX keratitis may be accompanied not only by ocular symptoms but also by systemic symptoms (metallic taste, nausea/vomiting, dyspnea). Even with ocular exposure, consider systemic toxicity and provide systemic management as needed. Since the time until the start of steroid treatment greatly affects the prognosis, promptly initiate treatment if exposure history is suspected.

Q What should be done as first aid if a toxin enters the eye?

A

Immediately irrigate the eye with plenty of water or saline. If wearing contact lenses, remove them promptly. Avoid rubbing the eye and seek emergency ophthalmological care as soon as possible.

6. Pathophysiology and detailed mechanisms

The effects of PTX on corneal cells are not fully understood, but several mechanisms have been proposed.

Na+/K+ ATPase inhibition

The primary cytotoxic mechanism of PTX is inhibition of Na+/K+ ATPase (sodium-potassium pump) ²⁾. This pump normally functions as an active ion transporter, but binding of PTX converts it into a non-selective ion channel, leading to uncontrolled influx of cations across the cell membrane. Accumulation of intracellular Ca²⁺ and disruption of the intracellular ionic environment trigger cell death ²⁾.

Disruption of the actin cytoskeleton

PTX disrupts actin microfilaments. This reduces the migratory ability of corneal epithelial cells and delays the wound healing process.

Vasoconstriction and inflammation

PTX has a vasoconstrictive effect and can cause partial avascularization of the conjunctiva. In addition, it induces inflammatory responses.

Progression of corneal damage

These mechanisms act in combination, leading to the progressive development of the following pathological conditions.

• Death of corneal epithelial cells → diffuse epithelial defect
• Destruction of stromal cytoskeleton → corneal melting (keratolysis)
• Ulcer formation → perforation

Histopathological examination of corneal transplant specimens shows severe corneal melting, acute and chronic keratitis (with relatively few inflammatory cells), and stromal scarring ¹⁾.

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8. References

1. Farooq AV, Gibbons AG, Council MD, Harocopos GJ, Holland S, Judelson J, et al. Corneal Toxicity Associated With Aquarium Coral Palytoxin. Am J Ophthalmol. 2017;174:119-125. (PMID: 27793603)

2. Moshirfar M, Hastings J, Ronquillo Y, Patel BC. Palytoxin Keratitis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. (PMID: 31985993, Bookshelf ID: NBK553212)

3. Barrett RT, Hastings JP, Ronquillo YC, Hoopes PC, Moshirfar M. Coral Keratitis: Case Report and Review of Mechanisms of Action, Clinical Management and Prognosis of Ocular Exposure to Palytoxin. Clin Ophthalmol. 2021;15:141-156. (PMID: 33469260, PMC: PMC7811479)

4. Ruiz Y, Fuchs J, Beuschel R, Tschopp M, Goldblum D. Dangerous reef aquaristics: Palytoxin of a brown encrusting anemone causes toxic corneal reactions. Toxicon. 2015;106:42-45. (PMID: 26365918)

5. Begaj T, Ong Tone S, Ciolino JB. Toxic Keratoconjunctivitis from Coral Reef. Case Rep Ophthalmol. 2021;12(2):694-698. (PMID: 34594206)

6. Berges Marti M, Aragon-Roca D, Trejo-Velasco F, Garrido-Marin M, Oliveres J, Martin Nalda S. Palytoxin-Related Keratoconjunctivitis Assessed by High-Resolution Anterior Segment Optical Coherence Tomography. Turk J Ophthalmol. 2021;51(6):393-397. (PMID: 34963267, PMC: PMC8715661)