Corneal Edema

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Article initiated by:

Marianna Kavalaraki MD, Msc

All contributors:

Vatinee Y. Bunya, MD, MSCE, Colleen Halfpenny, M.D., Marianna Kavalaraki MD, Msc, Neha Shaik, MD, Megan Kasetty, MD

Assigned editor:

Megan Kasetty, MD

Review:

Assigned status Update Pending

 by Megan Kasetty, MD on August 1, 2025.

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Disease Entity

Disease

Corneal edema is defined as the increase in corneal thickness due to the accumulation of extracellular fluid in the epithelium and stroma resulting in loss of corneal transparency.

Etiology

Conditions that cause corneal edema can be categorized according to etiology:

Corneal Dystrophies

• Fuchs endothelial corneal dystrophy (FECD)
• Posterior polymorphous corneal dystrophy (PPCD)
• Congenital hereditary endothelial dystrophy (CHED)
• X-linked endothelial corneal dystrophy (XECD)

Inflammatory / Infectious

• Viral endotheliitis
• Keratitis (e.g. microbial, sterile persistent epithelial defect)

Trauma

• Surgery (e.g. pseudophakic bullous keratopathy)
• Direct injury (e.g. blunt trauma, foreign body)

Toxic

• Chemical exposure (e.g. alkali or acid burns, benzalkonium chloride,)
• Drug-induced (e.g. amantadine, ketamine, levetiracetam)
• Organic matter (e.g. Calotropis procera, Asclepias fruticosa)

Elevated Intraocular Pressure

• e.g. acute angle closure, neovascular glaucoma, post-operative IOP spikes

Pathophysiology

The cornea remains in a relatively dehydrated state by maintaining a 78% hydration level. Corneal hydration is influenced by 5 factors:

1. Stromal swelling pressure (SP)

• The stroma has a tendency to swell due to the anionic repulsion of stromal glycosaminoglycans, which expand the tissue, allowing fluid to seep into the stroma.
• Imbibition pressure (IP) is a negative pressure drawing fluid into the stroma.
• IP = IOP – SP

2. Barrier function

• The zonula occludens tight junctions of the epithelium offer twice the resistance to water flow compared to the semipermeable endothelium, and the electrolyte resistance is 200 times higher in the epithelium than the endothelium.

3. Endothelial pump

• The endothelium pump function ensures, through active transport, the passage of fluid out of the corneal stroma into the aqueous humor.
• Corneal endothelial permeability gradually increases as central endothelial cell density decreases below 2000 cells/mm².
• Compensatory metabolic pump mechanisms maintain the dehydrated state until a central endothelial density of 500 cells/mm² is reached.

4. Tear evaporation

• Normal tear evaporation (rate 2.5ml/cm²/hour ) renders the tear hypertonic resulting in osmotic extraction, thus thinning the cornea. But this loss is readily replaced by aqueous.
• Evaporation can be a factor in maintaining epithelial dehydration, as is observed in the diurnal variations of visual acuity in patients with the early stage Fuchs endothelial dystrophy.

5. Intraocular Pressure

• When the IOP (> 50-60 mmHg) exceeds the stromal pressure, forward flow of fluid into the epithelium occurs, resulting in epithelial microcystic edema.

Diagnosis

Clinical Diagnosis

Clinical evaluation with a careful slit lamp examination is of utmost importance to ascertain the cause of edema.

Assess IOP

Evaluate the extent of edema

• Localized edema – Descemet membrane detachment, instrument or tube shunt touch, vitreous wick

• Disciform - Herpetic
• Limbus to limbus edema – Toxic anterior segment syndrome (TASS), drug-induced, toxic exposure

Shape of pupil

• Peaked Pupil – look carefully for the presence of vitreous
• Dilated pupil – TASS – iris sphincter muscle damage
• Patchy atrophy of iris – Herpetic

Anterior Chamber

• Reaction / Hypopyon
• Keratic precipitates
• Vitreous strands
• Hyphema
• Retained lens material

Diagnostic Investigations

Pachymetry

• Many devices can be used to estimate corneal thickness; however, presence of corneal edema poses challenges to obtaining accurate, reproducible measurements. Wongchaisuwat et al. published a comparison of central corneal thickness measurements in corneal edema using ultrasound pachymetry, Visante AS-OCT, Cirrus OCT and Pentacam tomography, concluding that “all devices reliably measured the CCT < 650 μm. In eyes with edema exceeding 650 μm, CCT measurements from the Visante OCT, Cirrus OCT, and ultrasound pachymetry devices showed good reproducibility and were well correlated, while the Pentacam overestimated the values compared to the other devices. Pentacam and ultrasound pachymetry should not be used in eyes with extreme corneal edema and opacity.”

Specular Microscopy

• Significant corneal edema can hinder the ability to obtain an accurate endothelial cell count using specular microscopy. Nevertheless, it remains a valuable tool for preoperative assessment and can reveal inter-eye differences in endothelial health.

Anterior Segment OCT (AS-OCT)

• AS-OCT can be a useful adjunct in the evaluation of corneal edema, particularly when clinical examination is limited. It may reveal underlying pathology such as Descemet membrane detachment or other structural abnormalities not readily apparent on slit-lamp exam.

Management

General treatment

Treatment approaches to managing corneal edema generally involve eliminating the underlying causative factors, such as inflammation, infection, elevated IOP, or Descemet membrane detachment, by administering topical medical therapy and/or surgical interventions if indicated for irreversible endothelial cell loss.

Medical therapy

Medical treatment options aim to minimize corneal edema and provide relief of the associated symptoms of discomfort and poor vision.

• Hypertonic solutions, typically 5% sodium chloride ophthalmic preparation or 5% ointment, can improve mild corneal edema by enhancing surface dehydration, as these agents act by creating a hypertonic tear film, thereby drawing water out of the cornea. Considering that evaporation from the tear film is minimal at night with the eyes closed, corneal edema tends to worsen in the morning. Use of hypertonic sodium chloride 5% ointment at night applied to the conjunctival cul-de-sac can limit this build-up of edema. Use of hypertonic solutions in the morning can also help to minimize edema accumulation. Some clinicians may recommend a gentle hair dryer to the cornea in the morning to accelerate corneal deturgescence and therefore improved vision. Hypertonic agents seem to be more beneficial in cases where the swelling is mostly confined to the corneal epithelium. Stromal edema does not respond as well to hypertonic solutions and can be more difficult to treat medically. Another hyperosmotic agent, polyoxyethylene, may be used to reduce corneal swelling. Anhydrous glycerin is a highly concentrated solution that can rapidly dehydrate the cornea but often causes significant burning and photophobia, making it unsuitable for routine therapeutic use.

• Bandaged contact lenses (BCL), especially extended-wear hydrophilic contact lenses, may be useful as an adjunct to medical treatment for the temporary relief of corneal pain and discomfort associated with epithelial bullae. These lenses act as a pre-corneal protective layer that shields the swollen epithelium from the lid movement and prevents the rupture of bullae. Although constant contact lens usage can cause mild corneal edema, extended-wear bandage contact lenses are well tolerated in appropriate patients as a temporary solution. These patients should be monitored for infectious keratitis and are often prescribed a prophylactic broad-spectrum topical antibiotic while wearing a BCL.

• Topical anti-hypertensive medications are used to reduce elevated IOP.
• Topical steroids are used primarily in uveitis cases. Some studies have shown that dexamethasone can increase the endothelium Na+/K+-ATPase pump activity and function.

Surgery

Patients who have poor visual potential and severe pain from epithelial bullae may benefit from anterior stromal puncture. A 25-gauge needle is used to place multiple small superficial punctures in the affected area of the cornea. The depth of the puncture site is just at or below the Bowman layer. The epithelium subsequently scars firmly over the treated area. This often results in resolution of bullae and pain relief. Excimer laser phototherapeutic keratectomy, epithelial debridement following by placement of amniotic membrane and conjunctival flaps have also been used to achieve this effect.