Conjunctival Lymphangiectasia

Key Points at a Glance

Conjunctival lymphangiectasia is a rare disease in which lymphatic vessels within the conjunctiva become focally dilated, presenting as edematous elevations on the conjunctiva. The prevalence in the general population is approximately 1%. There are two forms: diffuse type (conjunctival edema) and localized type (“string of pearls” appearance). When communication with blood vessels occurs, it is called hemorrhagic conjunctival lymphangiectasia. Most cases resolve spontaneously, but if symptoms persist, treatment options include surgical excision, cryocoagulation, anti-VEGF injection, and high-frequency electrocautery.

1. What is Conjunctival Lymphangiectasia?

Conjunctival lymphangiectasia (CL) is a disease in which the lymphatic vessels of the conjunctiva become focally and abnormally dilated, presenting as localized edematous elevations on the conjunctiva. The conjunctival lymphatics are responsible for draining excess fluid and waste from the ocular surface, and their dilation can cause hyperemia, swelling, irritation, and epiphora.

Classification

Type	Features
Diffuse type	Widespread conjunctival edema
Localized type	String of pearls appearance
Hemorrhagic	Blood filling within lymphatic vessels

In the localized type, small translucent bumps arranged in a beaded pattern are characteristic, described as a “string of pearls.” Hemorrhagic conjunctival lymphangiectasia is a condition in which communications form between dilated lymphatic vessels and blood vessels, leading to intermittent blood filling within the lymphatic vessels.

Epidemiology

The prevalence in the general population is approximately 1%. It is significantly higher in patients with hereditary transthyretin amyloidosis, and it has been suggested that it may serve as a biomarker for severe systemic disease.

Q What is the difference between conjunctival lymphangiectasia and lymphangiocyst?

A

Conjunctival lymphangiectasia is a localized dilation of lymphatic vessels, while lymphangiocyst is a cystic form of dilated lymphatic vessels. Pathologically, they lie on the same spectrum, and it may be difficult to distinguish between them. If there is a beaded appearance or repeated episodes of bleeding and resolution, lymphangiectasia is more likely.

2. Main Symptoms and Clinical Findings

Transparent tortuous lymphatic vessels of conjunctival lymphangiectasia

Cristea AP, Bălănescu I, Voinea LM. Conjunctival Lymphangiectasia - case report. Rom J Ophthalmol. 2022 Oct-Dec;66(4):365-368. Figure 1. PMCID: PMC9773120. License: CC BY.

Beaded, translucent dilated vessels tortuously running on the bulbar conjunctiva, showing sausage-shaped clear channels typical of conjunctival lymphangiectasia. This clinical photograph clearly links the disease name and findings.

Subjective Symptoms

Often asymptomatic. When symptoms are present, patients complain of foreign body sensation, hyperemia, and tearing. In the hemorrhagic type, bloody discharge may be observed. Some patients visit due to cosmetic concerns.

Clinical Findings

Slit-lamp examination reveals translucent to yellowish edematous elevations on the bulbar conjunctiva. In the localized type, small beaded elevations (string of pearls appearance) are characteristic. The diffuse type presents with extensive conjunctival edema (chemosis).

In the hemorrhagic type, blood fills the dilated lymphatic vessels, and a pseudohypopyon-like horizontal level may form within the cyst. Communication with veins becomes apparent after trauma or inflammation.

3. Causes and Risk Factors

Acquired (Secondary)

Chronic inflammation, scarring after eye surgery or trauma, and impaired lymphatic circulation are suspected causes. It may also occur idiopathically, and the mechanism of onset is not fully understood.

Congenital (Primary)

Lymphangiectasia in infancy results from underdevelopment of the lymphatic system and is often associated with the following systemic diseases.

Associated Systemic Diseases

Turner syndrome: accompanied by lymphedema

Klippel-Trénaunay-Weber syndrome: vascular malformation

Nonne-Milroy-Meige disease: hereditary lymphedema

Lymphedema with distichiasis: conjunctival and peripheral lymphedema

Associated Metabolic Diseases

Fabry disease: In classic Fabry disease, the prevalence of CL is high (approximately 80–85%) even under enzyme replacement therapy, and it has been reported that it may serve as a biomarker for undiagnosed cases ¹⁾

Hereditary transthyretin amyloidosis: prevalence is significantly higher than in the general population ¹⁾

If conjunctival lymphangiectasia is found in an infant, a thorough systemic examination is necessary to rule out systemic disease.

Possibility of Systemic Disease

Bilateral conjunctival lymphangiectasia is more commonly associated with systemic diseases. When diagnosed in infants or young patients, evaluation for systemic diseases such as Turner syndrome and Fabry disease is recommended.

4. Diagnosis and Examination Methods

Slit-Lamp Microscopy

Evaluate the morphology, distribution, and color of edematous elevations on the conjunctiva. Findings such as bead-like chains or repeated resolution and recurrence of hemorrhage suggest this disease.

Anterior Segment OCT (ASOCT)

Low-reflectance cystic lesions of various sizes are observed. It can noninvasively assess the extent and degree of lymphatic dilation and is useful for confirming the diagnosis as “fluid-filled dilated lymphatic vessels” without the need for biopsy ²⁾.

Histopathological Examination

Definitive diagnosis is based on pathological findings. Dilated lymphatic vessels are lined by a single layer of endothelial cells, with lymph fluid accumulation in the lumen.

Differential Diagnosis

Differential Disease	Key Differentiating Points
Conjunctival Inclusion Cyst	Solitary, spherical, mobile
Lymphangioma	Multilocular, deep infiltration
Allergic conjunctivitis	Redness, itching, papillae

Differential diagnoses include conjunctivochalasis, pinguecula, conjunctival intraepithelial neoplasia, and conjunctival nevus cyst. A bead-like appearance with recurrent bleeding and resolution is highly suggestive of this condition.

Q The conjunctiva is swollen like a blister. What could it be?

A

Blister-like swelling of the conjunctiva can be caused by various conditions including conjunctival lymphangiectasia, conjunctival inclusion cyst, chemosis, and allergic conjunctivitis. It may resolve spontaneously, but if it persists or is accompanied by bleeding, an ophthalmologic examination is recommended.

5. Standard Treatment

Observation

Many cases of conjunctival lymphangiectasia resolve spontaneously without intervention. If asymptomatic, observation is sufficient.

Medication

If the patient complains of a foreign body sensation or experiences recurrent bleeding, eye drops are used. A combination of artificial tears (e.g., Soft Santear 6 times daily) and low-potency steroid eye drops (e.g., Flumetholon 0.1% twice daily, tapered as improvement occurs) is a typical prescription. Antihistamine eye drops may also be used.

Surgical Treatment

Surgery is indicated when eye drops are insufficient or for cosmetic concerns.

Surgical Excision

Procedure: Lesion excision followed by conjunctival autograft or amniotic membrane transplantation

Features: Lowest recurrence rate

Indications: Cases resistant to drug therapy

Cryotherapy

Method: Freezing with liquid nitrogen

Features: Effective as an alternative to surgical excision

Note: Multiple sessions may be required for optimal results

Other Treatments

A single subconjunctival injection of anti-VEGF agent (bevacizumab) targets VEGF involved in lymphangiogenesis, and its efficacy has been reported³⁾. In a case report by Tan et al. (2016), conjunctival edema improved 5 days after injection, and symptoms completely resolved at 1 month³⁾. High-frequency electrocautery preserves more conjunctival tissue than surgical excision and is gaining attention as a first-line treatment option⁴⁾.

Recurrence and Follow-up

Conjunctival lymphangiectasia generally does not recur after complete excision. However, incomplete excision may lead to recurrence, so regular postoperative follow-up is important.

Q Does conjunctival lymphangiectasia resolve on its own?

A

Many cases of conjunctival lymphangiectasia resolve spontaneously. If asymptomatic, observation alone is sufficient. However, if symptoms persist or bleeding recurs, eye drops or surgery may be necessary. Recurrence is usually not seen after complete excision.

6. Pathophysiology and Detailed Mechanism

Structural Abnormalities of Lymphatic Vessels

The conjunctival lymphatic vessels are more developed than in other ocular tissues, and the lamina propria of the bulbar conjunctiva consists of loose connective tissue, making it highly mobile. In lymphangiectasia, the wall structure of the lymphatic vessels becomes fragile due to some cause, and the lumen dilates due to increased internal pressure or impaired drainage of lymph fluid.

Hemorrhagic Conditions

When a communication forms between dilated lymphatic vessels and veins at the site of vascular malformation, blood flows into the lymphatic vessels. Trauma or inflammation often triggers the manifestation of this communication. The blood accumulated in the lymphatic vessels settles due to gravity, forming a horizontal level resembling pseudohypopyon.

Congenital Pathogenesis

Congenital conjunctival lymphangiectasia results from lymphatic system hypoplasia. In Turner syndrome and Klippel-Trenaunay-Weber syndrome, conjunctival lesions appear as part of systemic lymphatic malformations.

Disclaimer

This article is for educational purposes targeting healthcare professionals and medical students, and does not serve as a guide for diagnosis or treatment of individual patients. In actual clinical practice, please follow the latest guidelines and the judgment of specialists.

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7. References

1. Sivley MD, Wallace EL, Warnock DG, Benjamin WJ. Conjunctival lymphangiectasia associated with classic Fabry disease. Br J Ophthalmol. 2018;102(1):54-58.
2. Cristea AP, Petrescu LT, Stan C. Conjunctival lymphangiectasia - case report. Rom J Ophthalmol. 2022;66(4):365-368.
3. Tan JCK, Mann S, Coroneo MT. Successful treatment of conjunctival lymphangiectasia with subconjunctival injection of bevacizumab. Cornea. 2016;35(10):1375-1377.
4. Song J, Yu JF, Du GP, Huang YF. New surgical therapy for conjunctival lymphangiectasia. Int J Ophthalmol. 2010;3(4):365-367.