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Disease Entity

Disease

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

Etiology

Conditions that cause corneal edema can be categorized into 5 groups, according to etiological factors:

Corneal Dystrophies

Fuch’s Endothelial Dystrophy (FED)
Posterior Polymorphous Corneal Dystrophy (PPCD)
Congenital Hereditary Endothelial Dystrophy (CHED)

Inflammatory

Primary endothelitis
Stromal Viral Keratitis

Toxic

Chemicals like Lime, acid etc.
Drug-induced (ammiodarone, cefaclor)
Vegetable matter like Akanda Gum

Pathophysiology

The cornea remains in a relatively dehydrated state by maintaining a 78% hydration level. Corneal hydration depends on 5 factors.

1. Stromal swelling pressure (SP)

This is the tendency of the stroma to swell due to the presence of interfibrillary proteoglycans and other proteins within in.
Normal stromal pressure is 55mmHg.
Imbibition pressure (IP) is a negative pressure exerted by glycosaminoglycans by which fluid is drawn into the cornea.
Intraocular pressure (IOP) = SP + IP

2. Barrier function

The epithelium (Zonula occludens tight junction) offers twice the resistance to water flow compared to the endothelium (macula occludens tight junction) and the electrolyte resistance is 200 times higher in the epithelium than 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/mm^2.
Compensatory metabolic pump mechanisms maintain the dehydrated state until a central endothelial density of 500cells/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 by 5%. 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 mm Hg) exceeds the stromal pressure epithelial edema occurs. e.g. High IOP and normal SP – Acute glaucoma, normal IOP and low SP – endothelial dystrophy

Diagnosis

Clinical diagnosis

Clinical evaluation with

A careful Slit Lamp examination is of utmost importance to ascertain the cause of edema.

Extent of edema

Localized edema – Descemet Membrane Detachment, Instrument touch, Vitreous wick, Herpetic keratitis
Predominantly stromal edema – Check IOP
Limbus to limbus edema – TASS

Shape of pupil

Peaked Pupil – look carefully for the presence of vitreous

Dilated pupil – TASS – iris sphincter muscle damage

Patchy atrophy of iris – Herpetic etiology

Anterior Chamber

Reaction / Hypopyon – Endophthalmitis, TASS
Vitreous strands
Hyphema
Retained lens material
Keratic Precipitates

Diagnostic Investigations

Pachymetry

There are many devices that can be used to estimate corneal thickness. But corneal edema offers some significant challenges for the machines to record corneal thickness accurately. Nida et al19 published the Comparison of central corneal thickness measurements in corneal edema using ultrasound pachymetry, Visante anterior-segment optical coherence tomography, Cirrus optical coherence tomography, and Pentacam Scheimpflug camera tomography in 2018 in which the conclusion was 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

In corneas with significant corneal edema often the specular microscopy fails to give any reading. In such cases, the other eye can be checked for the following factors. It is a very useful tool for preoperative screening in suspected corneas.

ASOCT

This is the single most important investigation to find the clue for the diagnosis of corneal edema like descemet membrane detachment if not seen clinically. This is a reliable method to ascertain the corneal thickness in huge corneal edema.

Management

General treatment

Treatment approaches to managing corneal edema generally involve eliminating the underlying causative factors , such as inflammation, infection, elevated IOP, or Descemet’s membrane detachment, by administering topical medical therapy or/and various surgical interventions in more severe cases.

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 (therefore, the tears are less hypertonic), corneal edema tends to be worse in the morning. Use of hypertonic sodium chloride 5% ointment at night applied to the conjunctival cul-de-sac limits this build-up of edema. Use of hypertonic solutions in the morning also helps eliminate some of this nightly fluid accumulation. Some clinicians even 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 usually respond to hypertonic solutions and can be more difficult to treat. Another hyperosmotic agent is polyoxyethylene, also leads to reducing of corneal swelling. The most intensive, hydrophobic solution is anhydrous glycerine, which can cause a burning sensation and lead to photophobia, or sensitivity to light, as a long-term side effect.

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. Their mechanism of action involves creating an effective precorneal 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, bandage contact lenses are best tolerated, as they allow greater oxygen transmissibility. However, prolonged use of BCL is discouraged due to the potential risk of infection and patients for whom a bandage lens is prescribed should be treated with a broad-spectrum antibiotic (eg, Polytrim, Azasite) or an aminoglycoside 2-4 times a day.. They are used as a temporary solution, while waiting for further medical treatment for the underlying cause, and require close follow-up care

Topical anti-glaucoma medications are used to reduce elevated IOP . Carbonic anhydrase inhibitors and Prostaglandin analogues (PGA) are both contraindicated, considering Inhibition of corneal endothelial carbonic anhydrase pumps can lead to decreased fluid flow from stroma to aqueous, resulting in precipitation of corneal edema. PGA, theoretically, have the potential to induce flare up of the intraocular inflammation.
Topical steroids should be administered in causes of associated intraocular inflammation (uveitis). Some studies have shown that dexamethasone can increase the endothelium Na+/K+-ATPase pump activity and function in corneal.

Surgery

Patients who have poor visual potential and severe pain sometimes can benefit from anterior stromal puncture. [37] 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. A bandage lens should be placed over the cornea for 1-2 weeks to allow the epithelium to adhere to the underlying cornea. Excimer laser phototherapeutic keratectomy has also been used to achieve this effect, as has epithelial debridement or lamellar keratectomy.

Finally, amniotic membrane in the form of a free graft protected by a bandage CTL or a ring-mounted contact lens (ProKera, BioTissue) can provide adjunctive benefits through intrinsic wound healing and growth factors, as well as anticollagenolytic and antimicrobial properties.

Corneal Edema

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