Corneal Edema – Feline

Synonyms:
Bullous keratopathy
Corneal stromal edema
Corneal hydrops

Disease Description:
Definition

Corneal edema refers to abnormal fluid accumulation in the corneal stroma. Stroma is the middle layer of the cornea. It comprises ~90% of corneal thickness, and is composed of primarily collagen fibers. Corneal stroma is normally in a dehydrated state (detergescence) to allow for transmittance of visible light, and blockage of nonvisible light in the ultraviolet and infrared spectra in order to protect intraocular structures.¹

Etiology and Pathophysiology

Corneal edema may result from disruption of both endothelium (i.e. deepest layer of the cornea adjacent to aqueous humor) and epithelium (i.e. most superficial layer adjacent to precorneal tear film). Disruption of epithelium causes a 200% increase in corneal thickness from edema.¹ Disruption of endothelium causes a 500% increase in corneal thickness from edema, making endothelium more important in maintaining  detergescence.¹

Corneal endothelium is a single cell layer that rests on Descemet’s membrane posterior to corneal stroma. It is composed of hexagonal cells that have almost no reproductive capacity.¹ Endothelial cells have an active pumping mechanism for moving water out of the cornea into the anterior chamber, and they provide a passive fluid barrier between aqueous humor and corneal stroma.¹

Unlike dogs, inherited or primary corneal endothelial disease has not been described in the cat. Cats have been used historically as an animal model for human endothelial transplantation;^2,3 however, this is because cat corneas have similar healing patterns to human corneas after transplantation, not because cats have endothelial decompensation as a naturally-occurring disease. Endothelial disease may result in the cat from anterior uveitis, anterior lens luxation or glaucoma. These disease states can variably alter the endothelium, thereby altering the endothelial cells’ ability to maintain the stroma in a state of detergescence. Typically, these disease states cause variable degrees of corneal edema, but do not result in severe stromal decompensation.

A different disease process called bullous keratopathy or acute corneal hydrops has been reported in the cat. While dogs can also develop bullous keratopathy, the clinical appearance and underlying pathology are different in these species. Cats can develop a severe, typically acute form of corneal edema resulting in severe keratoconus (anterior bowing of the cornea due to accumulation of fluid and disruption of the collagen fibers). This has been linked to various systemic diseases, a history of various corneal diseases and oral administration of cyclosporine. Many cases occur for reasons that have not been identified. This syndrome is associated with severe disruption of the corneal stroma without endothelial disease. In addition, spontaneously or with treatment, bullous keratopathy often resolves in cats. A case report describes possible Descemet’s membrane detachment as a cause of corneal hydrops in a young cat, although this is not a typical feature of bullous keratopathy in cats.⁴

Diagnosis

Physical Examination Findings/History: Corneal edema is characterized by a bluish-white discoloration of the cornea that may appear to have a reticulated or cobble-stone pattern. Corneal edema in the cat has a more uniformly blue to white color while corneal edema in the dog has a more “cobble-stone” appearance. Edema is best visualized with magnification and slit lamp biomicroscopy. Typically in the cat, onset of corneal edema caused by bullous keratopathy is sudden, even though the underlying cause may be chronic (e.g. chronic oral prednisolone or cyclosporine administration). Other causes of corneal edema in the cat (e.g. acute glaucoma, uveitis, anterior lens luxation) may cause a sudden or gradual progression of corneal edema. Age of onset and clinical progression also vary based on the underlying cause.

Ocular Examination Findings: Unlike in dogs, endothelial disruption such as with anterior lens luxation and anterior uveitis does not typically cause significant corneal edema in cats. It is rare that a cat would have edema significant enough to cause keratoconus (outward bowing of the cornea) caused by endothelial damage. In the case of anterior lens luxation, this is likely in part because cats have a deep anterior chamber and the lens does not contact the cornea extensively. Anterior uveitis and glaucoma in cats are also causes of edema, but tend to be insidious and slowly progressive diseases that do not cause significant edema. Unlike in dogs, cats may have more severe corneal edema with superficial corneal diseases such as ulcers than with endothelial trauma or damage.

In the case of bullous keratopathy in the cat, the cornea is usually severely thickened and keratoconus is dramatic. Thickening of the stroma can be appreciated by transillumination with a focal light source; transillumination using the slit beam on a direct ophthalmoscope; and with slit lamp biomicroscopy. In most cases of bullous keratopathy in cat, outward bowing of the corneal curvature (i.e. keratoconus) is severe.

Progressive or advanced stromal corneal edema can lead to overhydration of corneal epithelium and secondary epithelial erosion or ulceration. Other secondary abnormalities may include corneal vascularization with reduced vision or formation of corneal bullae. Cats may develop significant corneal vascularization and hyperemia in the case of corneal edema caused by ulceration. In most cases of corneal edema caused by intraocular disease or in the case of bullous keratopathy, hyperemia is often not present. Corneal edema is not inherently painful; however, underlying causes (e.g. glaucoma, uveitis) and associated changes (e.g. corneal ulceration) may cause pain. 

Ultrasonography: Ocular ultrasonography may be considered when intraocular structures cannot be visualized. In most cases in cats, the underlying cause of edema is typically apparent on a full ophthalmic examination. Referral may be indicated to an ophthalmologist prior to imaging or for imaging since most causes of corneal edema in cats can be diagnosed based on examination with an ophthalmologist.

Advanced imaging: Other than using the cat for experimental models, confocal microscopy, optical coherence tomography, pachymetry, and high-resolution ultrasound biomicroscopy has not been utilized to date for diagnostic information in the cat. This is likely because the cause of edema is usually apparent in the cat with a full slit lamp biomicroscopic and indirect ophthalmoscopic examination.

Other Tests: Other testing depends on suspected underlying causes for the corneal edema.

Etiology and Clinical Signs

Intraocular disease: In cats, corneal edema may be due to intraocular disease like glaucoma, anterior lens luxation and uveitis. Unlike the dog, intraocular disease does not typically cause severe corneal edema or endothelial decompensation. Primary, inherited endothelial decompensation has not been reported in the cat.

Bullous Keratopathy: This syndrome is typically an acute, rapidly progressive decompensation of the corneal stroma in cats without endothelial disease. This syndrome is unique to cats although the same term is used in dogs when severe edema with or without ulceration causes keratoconus (anterior bowing of the cornea). Bullous keratopathy in cats may occur as a result of immune-suppressive systemic medications like prednisolone or cyclosporine. This may also spontaneously occur for reasons that are not completely clear.

Corneal ulceration and infection: (Assume covered elsewhere to link). Corneal ulceration and infection may cause severe corneal edema in cats. This type of edema is typically more severe than edema caused by intraocular disease in cats. This is in direct contrast to the dog, which typically develops more severe corneal edema from endothelial decompensation. 

Developmental Malformations: Focal corneal edema is sometimes associated with corneal fibrosis that occurs with iris-to-cornea persistent pupillary membranes. Anterior segment dysgenesis and more severe abnormalities may also cause diffuse corneal edema. In cats, symblepharon (conjunctival adhesions to the cornea) may also cause corneal edema, fibrosis and pigmentation.

Breed/Sex/Age: None reported in the literature to be overrepresented

Clinical findings:     

• Conjunctival hyperemia/scleral injection
• Blue-white discoloration to cornea, sometimes with a “cobblestone appearance”
• Corneal vascularization or infiltrate
• Corneal edema
• Glaucoma    
• Lens luxation or subluxation
• Anterior uveitis
• Keratic precipitates

Diagnostic Procedures/Results:

Ocular examination:          

• Anterior chamber shallow or absent (lens endothelial touch)
• Aqueous flare
• Corneal penetration
• Elevated intraocular pressure
• Anterior uveitis
• Anterior segment dysgenesis
• Persistent pupillary membranes to cornea
• Keratic precipitates
• Corneal ulceration or infiltrate

Treatment/Management:

Specific Therapy

In cats, the underlying cause of edema should be identified and treated. Some intraocular causes of corneal edema are painful in cats and patient comfort should be a priority when treating intraocular disease. Because conditions such as anterior lens luxation and glaucoma are typically secondary to chronic uveitis in cats, referral should be considered for a full ophthalmic examination as well as treatment options and risk assessment to the contralateral eye if only one eye is affected.

Medical therapy

Topical therapy in cats can be difficult. If corneal ulceration and/or infection is present, topical therapy may be necessary for control of the surface disease. Topical therapy may also be beneficial in cases of glaucoma (see glaucoma chapter in cats). Either systemic or topical medical therapy may be utilized for intraocular disease causing corneal edema, depending on the severity and underlying pathology. Referral for ongoing medical therapy should be considered in cats since many of these conditions require ongoing management.

Topical sodium chloride may be considered for feline bullous keratopathy, especially if the disease is relative mild. In cases of moderate to severe feline bullous keratopathy, surgery should be considered since topical hyperosmotic treatment is not effective and typically not well-tolerated by patients.

Underlying medication that may predispose the patient to bullous keratopathy (e.g. cyclosporine, prednisone) should be weaned to the lowest effective dose.

Corneal collagen cross linking has been used in cats for infected ulcers and keratomalacia,^5,6 but this has not been utilized for bullous keratopathy or other causes of corneal edema in cats to date.

Surgical therapy

In cases of acute feline bullous keratopathy, treatments to tamponade the fluid have a high success rate. Options for this include temporary tarsorrhaphies or third eyelid flaps. Third eyelid flaps render the patient temporarily blind in the treated eye and this is important for client education and if the patient is visually impaired in the contralateral eye or does not have a contralateral eye. When performing temporary tarsorrhaphies or third eyelid flaps, it is important to avoid suture irritation to the cornea since this will worsen corneal disease.

In some cases of feline bullous keratopathy unresponsive to surgical tamponade therapy or medical therapy, conjunctival grafting with or without corneal transplantation is warranted. This surgery has a high success rate, but visual outcome can be impacted by the amount of corneal affected and grafted.

Enucleation may be considered for cats that have chronic, unresponsive intraocular disease and are blind. Glaucoma, especially, is a painful disease and enucleation is the best option for advanced glaucoma in cats. In addition, ocular histopathology should be pursued if enucleation is performed in these cases to identify underlying conditions that may impact the contralateral eye. In addition, referral should be considered for evaluation of the contralateral eye if a globe is removed for painful intraocular disease in cats since many intraocular diseases in cats are insidious and difficult to detect in the mild or early stages without slit lamp biomicroscopy.

Monitoring

Frequency of monitoring depends on the underlying cause of corneal edema. If intraocular disease is present (e.g. anterior lens luxation, uveitis), evaluation every 3-4mo may be indicated to assess for glaucoma or other conditions that are painful or uncomfortable. Identifying the underlying disease is important in these situations. Patients with glaucoma should be evaluated in 7-10d after instituting medical therapy, then every 2-3mo after that since glaucoma is a painful disease.

In cases of feline bullous keratopathy, after tamponade treatment, re-evaluation is warranted in 10-14d. After the tarsorrhaphy or third eyelid flap is removed, evaluation in 3-4w is recommended. With resolution, evaluation may be performed q4-6mo.

Prognosis

The prognosis for feline bullous keratopathy is guarded to good. This may recur; however, if there is an underlying cause of the keratopathy (e.g. immunosuppressive oral medication). Prognosis after corneal surgery, if indicated, to treat feline bullous keratopathy is good to excellent.

The prognosis for corneal edema due to intraocular disease is poor to guarded. This is because the edema often is present after a lengthy period of disease and/or the disease is end-stage in the cat. Edema may resolve if the underlying cause is treated.

The prognosis for corneal edema due to corneal ulceration in the cat is guarded to excellent depending on many factors (covered in corneal ulcer chapter in cats).

References:

1. Fan, T, et al. Transplantation of tissue-engineered human corneal endothelium in cat models. Mol Vis. 2013;19:400-7.
2. Bahn, CF, et al. Penetrating keratoplasty in the cat. A clinically applicable model. Ophthalmology. 1982 Jun;89(6):687-99.
3. Schlesener, B, et al. An unusual case of feline acute corneal hydrops: atypical disease presentation and possible in vivo detection of Descemet’s membrane detachment in the cat’s unaffected eye. Vet Ophthalmol. 2018 Jul;21(4):426-31.
4. Spiess, B. Corneal collagen cross-linking (CXL) for the treatment of melting keratitis in cats and dogs: a pilot study. Vet Ophthalmol. 2014 Jan;17(1):1-11.
5. Pot, S, et al. Corneal collagen cross-linking as treatment for infectious and noninfectious corneal melting in cats and dogs: results of a prospective, nonrandomized, controlled trial. Vet Ophthalmol. 2014 Jul;17(4):250-60.