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A Review of Corneal Edema in the Ocular Hypertensive Patient

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The cornea is an avascular tissue, which relies on the atmosphere for the majority of its oxygen requirements and the aqueous humor for most of its other nutritional needs.  The dehydrated state of the cornea is what allows for corneal transparency. When this dehydrated state is compromised, the result is corneal edema.  The main factors involved in control of corneal hydration are the barrier function of corneal epithelium and the endothelium, stromal swelling pressure (SP), endothelial pumps, and intraocular pressure.  

Corneal edema occurs when there is an imbalance of hydration in the cornea.  

  • Factors that draw water into cornea–> swelling pressure of stromal matrix and intraocular pressure
  • Factors which prevent flow of water into the cornea–>mechanical barriers, Na/K active pump of the endothelium
Example of patient with microcystic (epithelial) edema
Contact Lens Spectrum, Volume: 33, Issue: November 2018, page(s): 34-41

 

 

 

 

 

 

 

 

 

Example of patient with stromal edema with descemet membrane folds
Welder J, Kardon RH, Cohen A, Wagoner MD, Bilateral Corneal Edema Associated with Amantadine Use. Eyerounds.org. September 27, 2010; Available from: http://www.EyeRounds.org/cases/123-amantadine-corneal-edema.htm.

 

 

 

 

 

 

 

Corneal endothelium is the most influential layer of the cornea in the mediation of corneal hydration.  This is due the presence of active metabolic ATPase pumps.  These pumps secrete solutes into the aqueous humor and create an osmotic gradient, drawing fluid out of the stroma to balance its swelling tendency.  The density of endothelial cells in this important layer naturally decrease as we age and do not have the ability to regenerate. However, corneal endothelial cells have a remarkable ability to enlarge and maintain normal function in the face of cellular inadequacies or deficiencies. 

Corneal stroma is the largest layer of the cornea. It is composed of collagen fibers approximately 22 to 32 microns in diameter, which run uninterrupted from limbus to limbus in a fairly uniform diameter.  The small diameter and uniform spacing of these collagen fibers allows for minimal scattering of light, thus a transparent structure.  The extracellular matrix surrounding these collagen fibers contain a high content of hydrophilic glycosaminoglycans (GAGs).  With increasing stromal hydration, the spacing between these collagen fibers increases, due to the GAGs capacity to imbibe fluid. This process leads to increased light scattering and what we clinically know as stromal edema. When stromal edema occurs, the stroma will only swell posteriorly, due to an uneven distribution of proteoglycans throughout the stroma.  Dermatan sulfate is found mainly in the anterior portion of the stroma and has a greater ability to retain water,  but low capacity to absorb it. Keratan sulfate is found mainly in the posterior portion of the stroma and has a greater capacity to absorb water, but a lower ability to retain it. Thus, water absorption in this posterior portion resolves quickly when the endothelial pump function restarts after transient damage. 

Corneal epithelium offers twice the resistance to water flow compared to the endothelium. This anterior portion of the cornea is composed of 4-6 layers of cells.  The layers are composed of squamous, basal, and wing cells.  Swelling seen in the epithelium is predominantly extracellular, with fluid beginning to accumulate in the space between the basal epithelial cells and the bridging desmosomes.  The anteriormost wing cells are usually not affected, as there is resistance to this anterior fluid movement situated in this layer. Epithelial edema can range in clinical presentation from microcystic edema to large bullae, characteristic of bullous keratophy.  In addition, epithelial edema is the most common form of edema found in patients with acute ocular hypertension.

How can high IOP cause corneal edema?

Intraocular pressure generates a forward movement of stromal fluid and aqueous on the cornea. This pressure normally commutes through the stroma and is dissipated by stress on the anterior stromal lamellae.  This intraocular pressure (IOP) can be combined with the stromal swelling pressure (SP)  to determine the stromal imbibition pressure (IP), an important trifecta for discussing the nature of epithelial edema.

IP=IOP-SP

Swelling pressure (SP)= force necessary to prevent stromal swelling at various hydrations

  • Normally ~55mmHg
  • Drops off exponentially with stromal edema (ex: when endothelial dystrophy present)

Stromal imbibition pressure (IP)= a negative pressure that draws fluid into the cornea (**dependent on intact endothelial barrier)

  • When (+) corneal edema occurs
  • When (-) no corneal edema occurs

When the IOP exceeds the SP, IP is positive, resulting in epithelial edema.

  • Acute angle closure or high IOP, when IOP is greater than ~55mHg.
  • Normal IOP and low SP, when endothelial dystrophy is present
    • Stromal edema can follow microcystic epithelial changes
https://www.researchgate.net/figure/Schematic-representation-of-IOP-dependent-corneal-swelling-which-was-used-in-the_fig3_264433094

 

 

 

 

 

 

Resources:

“Corneal oedema and its medical treatment.” Clinical and Experimental Optometry. 96.6,Nov 2013: 529-535.

Morris, Daniel S. Somner, JE. Scott, KM. “Corneal Thickness at High Altitude.” Cornea. April 207; 26(3):308-311.

Vanmeter, Woodford. Lee,BL. Katz,DG. “Corneal Edema.” http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v4/v4c016a.html.

https://www.researchgate.net/figure/Schematic-representation-of-IOP-dependent-corneal-swelling-which-was-used-in-the_fig3_264433094

Welder J, Kardon RH, Cohen A, Wagoner MD, Bilateral Corneal Edema Associated with Amantadine Use. Eyerounds.org. September 27, 2010; Available from: http://www.EyeRounds.org/cases/123-amantadine-corneal-edema.htm.

Contact Lens Spectrum, Volume: 33, Issue: November 2018, page(s): 34-41

Dohlman, C.. “The function of the corneal epithelium in health and disease. The Jonas S. Friedenwald Memorial Lecture.” Investigative ophthalmology 10 6 (1971): 383-407.


Author: Emily A. Bucher, OD, FAAO

Specialties: Medical Eye Care

Seattle

Working in the glaucoma clinic alongside Dr. Cameron, we often see patients presenting with ocular hypertension and epithelial edema.  It is important to realize the difference in types of corneal edema in order to help differentiate between possible diagnoses and guide to proper treatment.

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