Noninfectious conjunctival conditions

The conjunctiva are highly vascularized mucous membranes that line the inside of the eyelids and sclera. They are susceptible to a wide range of conditions, of which only degenerative, traumatic, and neoplastic ones are treated here (see “Eye and orbit” for more information on the anatomy of the eye and “Conjunctivitis” for inflammatory conditions). Pinguecula is a small, yellowish, raised plaque on the conjunctiva composed of protein, fat, or calcium. Pterygium is a benign, triangular, fibrovascular wedge of conjunctival tissue, which typically grows laterally starting from the nasal conjunctiva. Subconjunctival hemorrhage is a collection of blood between the conjunctiva and the sclera that is most commonly caused by trauma. Foreign bodies are a common source of ocular trauma, e.g., dust and debris that is propelled into the eye during activities such as grinding, drilling, sawing, or welding. Pigmented lesions include ocular melanosis, a benign, unilateral, congenital pigmentation of the episclera, and primary acquired melanosis, a benign, congenital pigmentation of the conjunctiva. Benign tumors of the conjunctiva include limbal dermoid, a congenital tumor in the region of the corneal limbus, and conjunctival nevus, a pigmented tumor of the conjunctiva. Malignant tumors include squamous cell carcinoma, a mainly keratinizing squamous cell carcinoma of the conjunctiva, conjunctival melanoma, a rare malignant tumor of the conjunctiva with a high rate of recurrence and metastasis, and conjunctival lymphoma, a salmon-pink colored, malignant tumor of the conjunctiva.

• Definition: a small, yellowish, raised plaque on the conjunctiva composed of protein, fat, or calcium
• Epidemiology: most commonly occurs in adults > 40 years
• Etiology: chronic irradiation with UV light
• Clinical features
  • Yellowish raised plaque
    • Most commonly located on the medial conjunctiva but can also develop on the lateral conjunctiva
    • Does not develop on the cornea
  • Symptoms of local irritation: redness, lacrimation, foreign body sensation
• Differential diagnosis
  • Pterygium
  • Dry eye syndrome
• Management
  • Not required
  • Surgical excision may be necessary in severe inflammation or for cosmetic reasons.
• Prognosis: good (usually only causes cosmetic problems)

References:^[1]

• Definition: a benign, triangular, fibrovascular wedge of conjunctival tissue, which typically grows laterally starting from the nasal conjunctiva
• Epidemiology: more commonly occurs in areas with high UV radiation
• Etiology
  • Chronic irradiation with UV light
  • Environmental irritation (e.g., hot, dry weather)
  • Genetic predisposition
• Clinical features
  • Triangular, fibrovascular wedge of conjunctival tissue
    • Typically grows laterally starting from the nasal conjunctiva
    • Can extend to the cornea, leading to visual impairment
  • Symptoms of local irritation: scleral/corneal redness, lacrimation, foreign body sensation
  • Mild visual impairment
• Differential diagnosis
  • Pinguecula
  • Dry eye syndrome
  • Ocular surface squamous neoplasia (OSSN)
• Management ^[2][3]
  • Conservative management: for symptomatic relief in patients with small lesions and no visual impairment
    • UV protection (e.g., sunglasses, hats)
    • Topical lubricants (e.g., artificial tears)
    • Topical NSAIDS or steroids should be considered in inflamed pterygium.
  • Surgery
    • Indications
      • Visual impairment (e.g., due to irregular astigmatism or visual axis involvement)
      • Restrictive ocular motility
      • Disease progression
      • Chronic inflammation
    • Procedure: excision with conjunctival autograft has a lower risk of recurrence than other techniques (e.g., bare sclera excision). ^[4]
• Complications
  • Recurrence after surgical removal
  • Visual impairment
  • Reduced ocular motility
• Prognosis
  • Good
  • Recurrence after surgical removal indicates a high risk of recurrence after subsequent procedures. ^[4]

• Definition: a collection of blood between the conjunctiva and the sclera
• Etiology
  • Transiently increased venous pressure (the most common cause of spontaneous SCH) due to, e.g., Valsalva maneuver, coughing, vomiting
  • Traumatic eye injury: blunt ocular trauma, contact lens use (more common in adults < 40 years)
  • Hypertension (most common cause in elderly individuals)
  • Diabetes mellitus
  • Coagulopathy
  • Fat embolism (e.g., in the context of long-bone fractures)
  • Antiplatelet and anticoagulation therapy
  • Vaginal delivery is a common cause of SCH in neonates
  • Ocular surgery
  • Tumors of the conjunctiva (e.g., cavernous hemangioma, lymphangioma)
• Clinical features
  • Painless red focal lesion visible against the sclera
  • Signs and symptoms of traumatic eye injury
    • Changes in visual acuity, photophobia, eye pain, foreign body sensation
    • Bullous SCH: elevated hemorrhage indicates underlying severe intraocular injury (e.g., scleral laceration)
• Diagnostics
  • In patients with a history of blunt trauma
    • Slit lamp examination to rule out conjunctival lacerations, abrasions, and foreign bodies
    • CT to rule out intraocular or intraorbital injury
      • Eye globe rupture (open globe injury, closed globe injury)
      • Orbital fractures
      • Retrobulbar hemorrhage
  • Recurrent SCH: rule out underlying conditions (e.g., bleeding disorder, severe hypertension)
    • Blood pressure measurement
    • Coagulation studies to rule out bleeding diathesis or overmedication with anticoagulants
  • A suspicious or unlikely history of trauma in infants aged 1–12 months with SCH should raise concern for child abuse.
• Management
  • Spontaneous SCH: reassurance (usually resolves spontaneously)
  • Traumatic SCH with conjunctival injury
    • Antibiotic ointment (e.g., erythromycin)
    • Removal of superficial foreign bodies (via slit lamp or saline irrigation)
    • Emergency ophthalmologic consultation
    • See “Traumatic eye injuries” for more details.
• Prognosis: good (usually resolves spontaneously within 2–3 weeks)

References:^[5][6]

Ocular melanosis (conjunctival melanosis) ^[7]

• Definition: a benign, unilateral, congenital pigmentation (blue nevus) of the episclera
• Epidemiology: more common in dark-skinned individuals
• Etiology: accumulation of melanocytes in the eye
• Clinical features
  • Iris heterochromia
  • Patchy slate-gray or bluish discoloration of the sclera
    • Usually unilateral
    • Subepithelial location without involvement of the conjunctiva (lesion is not displaceable with motion of the conjunctiva )
  • Increased pigmentation of the ipsilateral fundus
• Management
  • Reassurance
  • Regular ophthalmic examination to monitor progression
• Complications: increased risk of glaucoma and melanoma in the affected eye
• Prognosis: The risk of progression to malignancy is ∼ 8%. ^[8]

Primary acquired melanosis (PAM)

• Definition: a benign, congenital pigmentation of the conjunctiva
• Epidemiology
  • Usually affects light-skinned individuals
  • Peak incidence at 50–60 years of age ^[9]
• Clinical features
  • Flat, brown, irregularly arranged pigmentation
    • Displaceable with motion of the conjunctiva
    • Usually unilateral
    • Without cyst formation
• Management
  • Small lesions: reassurance and regular ophthalmic examination to monitor progression
  • Mid-sized to large lesions: surgical excision and histopathologic examination
• Complications: PAM with atypia may develop into conjunctival melanoma
• Prognosis: increased risk of malignancy in PAM with atypia (up to 21%) ^[10]

Benign tumors of the conjunctiva

Limbal dermoid (epibulbar dermoid) ^[11]

• Definition
  • A congenital, benign tumor in the region of the corneal limbus
  • Contain choristomatous tissue (e.g., epidermal, connective, endocrine, muscle, dental, and nervous tissue)
• Clinical features
  • Round, bulging (dome-shaped) tumor,
    • Located over the cornea and sclera
    • Hair follicles and cilia may be visible.
  • May cause visual abnormalities: astigmatism, encroachment onto the visual axis, infiltration of fat into the cornea
  • Possibly symptoms of local irritation: scleral/corneal redness, lacrimation, foreign body sensation
  • Associated with other ocular abnormalities, e.g., colobomata, staphyloma, anomalies of the lacrimal glands
• Management
  • In mild cases: reassurance and regular ophthalmic examination to monitor progression
  • In severe cases: surgical excision

Conjunctival nevus

• Definition: a benign tumor of the conjunctiva that can vary in color from clear to dark brown depending on degree of pigmentation and often contains clear cysts
• Epidemiology: most common benign tumor of the conjunctiva
• Clinical features
  • Well-defined macula with small, clear inclusion cysts
    • Usually unilateral and most commonly in the lateral eyelid region
    • Pigmentation can be partial or complete
    • Pigmentation may increase or decrease with hormonal changes (e.g., pregnancy). ^[12]
• Management
  • Reassurance
  • Regular ophthalmic examination to monitor progression
  • Surgical excision if the nevus is suspicious for malignancy or for cosmetic reasons
• Prognosis: risk of malignancy is low (< 0.01%) ^[13]

Malignant tumors of the conjunctiva

Conjunctival squamous carcinoma ^[14]

• Definition: a malignant, mainly keratinizing squamous cell carcinoma of the conjunctiva
• Epidemiology
  • Most common ocular tumor
  • Higher rates in equatorial Africa
• Etiology
  • Risk factors include:
    • Increased exposure to UV radiation
    • Infection: HIV, HPV
    • Allergic conjunctivitis
• Clinical features
  • A white, bulging, painless mass with an irregular surface
    • Lesion can be pigmented, especially in equatorial populations
    • Feeder vessel is often present
    • Mostly located in the (nasal) interpalpebral fissure
    • Typically unilateral
  • Signs of ocular inflammation: redness, tearing, blurry vision, photophobia, foreign body sensation
• Diagnostics
  • Clinical examination
  • Biopsy and histopathology
• Management: surgical excision with subsequent radiation
  • Surgical excision (larger lesions might require exenteration)
  • Adjuvant therapies include: cryotherapy, topical cytotoxic drugs (e.g., 5-fluorouracil, mitomycin C), interferon-alpha 2b, radiotherapy
  • Regular follow-ups in case of tumor recurrence ^[14]
  • HIV testing and treatment
• Prognosis: The risk of recurrence after primary excision is high. ^[15]

Conjunctival melanoma ^[16]

• Definition: a rare malignant tumor of the conjunctiva with a high rate of recurrence and metastasis
• Epidemiology
  • Conjunctival melanoma is the second most common type of melanoma (after cutaneous melanoma) and the second most common conjunctival malignancy (after conjunctival squamous cell carcinoma). ^[9]
  • Median age of onset: 60 years ^[9]
• Etiology: can arise from primary acquired melanosis (PAM), conjunctival nevi, or de novo
• Risk factors
  • Light skin/eye color, atypical nevi
  • Occupational sun exposure, tanning
• Clinical features
  • Poorly defined, painless brown or pink lesion on the conjunctiva
  • Surrounding nodules and feeder vessels are often present
  • Can cause blurry vision, visual field defects, flashing lights, redness, irritation, and sensation of pressure
  • Most common sites of metastases are ipsilateral preauricular/submandibular lymph nodes, the brain, lung, and liver.
• Diagnostics: clinical examination
  • Occasionally ultrasound is necessary to exclude intraocular invasion.
  • MRI can be useful in cases of suspected orbital extension and/or brain metastasis.
  • Whole body PET scan in cases of suspected metastasis
• Differential diagnosis
  • Conjunctival nevus
  • Primary acquired melanosis
  • Squamous cell carcinoma
  • Staphyloma
• Management
  • Local excision, possibly with adjuvant chemotherapy (mitomycin C)
  • In the case of inoperability or residues postsurgery: radiotherapy and/or chemotherapy
  • Recurrent PAM after excision should be treated with excision, cryotherapy, or topical mitomycin C OR interferon-alpha.
  • Patients with conjunctival melanoma should be monitored 2–3 times a year for metastatic disease (also after tumor excision).
• Prognosis: The risk of local recurrence of conjunctival melanoma and metastatic disease is high. ^[9]
  • Local tumor recurrence is reported to occur in approx. 50%.
  • Metastatic disease develops in 20–30% of affected individuals.

Conjunctival lymphoma

• Definition: a salmon-pink colored, malignant tumor of the conjunctiva
• Epidemiology
  • Approx. 15% of all lymphomas are ocular lymphomas; of these ∼ 25% involve the conjunctiva. ^[17]
  • 98% of conjunctival lymphomas are B-cell lymphomas ^[17]
• Etiology
  • Potentially caused by a chronic infection or inflammation → chronic proliferation of lymphoid cells → genetic mutations → monoclonal B cell or T cell proliferation
  • Risk factors ^[17]
    • Immunodeficiency
    • Autoimmune conditions (e.g., Sjögren syndrome, autoimmune thyroid disease, SLE, rheumatoid arthritis)
    • Infectious agents (e.g., Chlamydia psittaci, Chlamydia pneumoniae, Helicobacter pylori, hepatitis C virus)
    • Prior radiation exposure
• Clinical features
  • Salmon-pink color (referred to as “salmon patch”)
    • Slightly raised mass
    • Usually located in the inferior conjunctival fornix
  • Patients might present with chronic follicular conjunctivitis
  • Signs of ocular inflammation: redness, tearing, blurry vision
  • In the case of significant orbital involvement: ptosis or exophthalmos
  • Most conjunctival lymphomas manifest as isolated conditions (up to 90% of cases), concurrent systemic dissemination is rare. ^[17]
• Diagnostics
  • Optical coherence tomography: hyporeflexive, homogeneous subepithelial mass
  • Surgical biopsy and histopathological examination
• Differential diagnosis
  • Benign lymphoid hyperplasia
  • Chronic conjunctivitis, episcleritis
  • Pterygium
  • Nonpigmented melanoma, squamous cell carcinoma
  • Pyogenic granuloma
• Management
  • External beam radiation therapy (EBRT) is the gold standard.
  • Other options include immunotherapy (e.g., interferon-alpha, rituximab), antibiotic therapy (e.g., doxycycline), or radiotherapy.
  • In cases of systemic involvement or aggressive bilateral disease: chemotherapy (e.g., chlorambucil, bendamustine), often in combination with immunotherapy
  • Long-term follow-ups are required for every type of lymphoma.
• Prognosis: 5-year survival rate ranges between 50–94%. ^[17]