Living Library

Corneal Neovascularization

CLINICAL DESCRIPTION:
Corneal neovascularization is the in-growth of blood vessels into the avascular corneal tissue secondary to chronic hypoxia, chronic inflammatory disease, trauma or anterior segment pathology including interstitial keratitis, Mooren’s ulcer formation and Terrien’s marginal degeneration. (1,2) It can further be divided into superficial and deep, where superficial is more common with contact lens wear and deep is a result of a chronic inflammatory condition or anterior segment pathology. (3)
Due to the various possible causes of corneal neovascularization, it is important to rule out conditions not related to contact lens wear before making a definitive diagnosis.
SYMPTOMS:
Patients may present with no symptoms or they may notice limbal hyperemia. Upon slit lamp examination, vessels can be seen proliferating anterior to the limbus into the corneal tissue.
Additional symptoms may include eye pain, tearing and photophobia, injection, contact lens intolerance after only a few hours of wear and decreased vision – these symptoms are seen more in extended wear contact lens patients and will be discussed further below.
INCIDENCE: 
Corneal neovascularization and other signs of corneal hypoxia are mainly seen in soft lens extended wear patients, especially those fit in low Dk/t hydrogel soft lens materials given that other possible causes previously mentioned have been ruled out. (4) In addition to this, corneal neovascularization has been found to occur in patients wearing polymethyl methacrylate (PMMA) or low Dk/t rigid gas permeable materials although this is rare due to the cornea not being completely covered by a gas permeable lens. (3) Vascularization can also occur in patients wearing tight fitting soft hydrogel lenses due to the impingement and compression on the limbal conjunctiva and associated vessels. (5)
There appears to be a higher incidence of corneal neovascularization in soft lens extended wear patients as opposed to gas permeable wearers. Fonn et. al conducted a study involving a soft hydrogel lens material and concluded that at least 65% of the subjects showed signs of corneal neovascularization to a certain extent at the conclusion of the study. (6) In gas permeable wearers, localized neovascularization can be seen if there is a poor lens fit causing 3 and 9 o’clock staining. Over time, this situation may lead to corneal defects and desiccation that can result in limbal vessel engorgement and epithelial disruption. This is called vascularized limbal keratitis (VLK). (7)
ETIOLOGY:
The general opinion is that several factors play a role in the development of neovascularization with hypoxia being a front-runner. The different degrees of neovascularization has been neatly summarized by Liesegang (8)
  1. Limbal hyperemia: engorgement of existing limbal capillaries and common in soft hydrogel wearing patients.
  2. Superficial neovascularization: progression of limbal hyperemia and in-growth of vessels up to 4mm into the cornea.
  3. Deep stromal neovascularization: secondary to chronic hypoxia and can lead to the development of an active inflammatory or fibrovascular response with vessels extending past 4mm into the cornea.
  4. Intracorneal hemorrhage in severe cases
The Role of Oxygen
Dk/t measures the oxygen transmissibility of a lens and is a factor of the lens’ oxygen permeability (Dk) and thickness (t) and is measured by the simple formula Dk/t. Oxygen permeability is further related to the water content of the lens as atmospheric oxygen first dissolves in the tears, moving into the water part of the lens and finally to the cornea. A minimum Dk/t of 25 has been recommended for daily wear lenses and 87 for extended or overnight wear in order to prevent more than 4% corneal swelling which is the amount that occurs in the normal closed eye environment. (9) Other investigators have countered that 3.2% corneal swelling occurs overnight, and using this have concluded that a Dk/t of at least 125 is required to avoid the corneal change. (10)
The cornea is avascular and therefore acquires oxygen from the atmosphere. When the cornea is devoid of oxygen, it will under go an 8% increase in corneal thickness over a three hour period (4). When there is no or low amounts of oxygen available for the proper functioning of corneal tissue, the normal aerobic reactions switch over to an anaerobic mechanism producing lactate which accumulates within the tissues along with carbon dioxide. This accumulation produces an acidic pH, thereby causing the influx of water via osmosis subsequently leading to corneal edema and an increase in corneal thickness. (4, 3, 8)
Increasing acidosis affects the corneal epithelium and stroma but with negligible effects on the endothelium until the glycogen and adenosine triphosphate energy stores are depleted. This results in the slower functioning of sodium and potassium pumps in the endothelium that normally regulates the amount of water in the cornea thereby causing additional water to be retained within corneal tissues. (8) These reactions set off a chain which can lead to various clinical findings. A closed eye environment or a contact lens can mimic such an environment and can result in the following sequelae: striae, corneal vascularization, microcysts, refractive error change, endothelial changes, decreased corneal sensitivity, depressed metabolic rate, compromised epithelial junction integrity, stromal thinning and increased microbial adherence (8).
Figure 1(1) Figure 2(2)
Figure 1 and 2. Previous soft hydrogel multifocal lens wearing patient exhibiting a localized area of neovascularization. This patient was subsequently refit into into a silicone hydrogel material.
Figure 3
Figure 3. Soft hydrogel lens wearing patient exhibiting vascular growth approximately 1mm past the inferior corneal limbus. This patient was subsequently refit into a silicone hydrogel material.
MANAGEMENT:
A hypoxic corneal environment appears to play a crucial role in the formation of neovascularization in contact lens wearers. New vessels that form are likely to have weak barriers and are prone to leakage of blood constituents such as lipid or cholesterol molecules (3). These substances can acquire an opaque appearance in the clear cornea, therefore deposits close to the visual axis will affect vision.
As mentioned previously, corneal neovascularization tends to occur in extended wear of low Dk/t soft hydrogel lens materials. Patients with a high ametropia may also be more prone to neovascular changes due to the increased lens thickness required; for example, aphakic patients or high myopes with a thicker lens periphery. A tight fitting soft lens may also predispose the cornea to neovascular changes due to an increased incidence of limbal vessel engorgement, hypermia and limited tear exchange which may promote the action of angiogenic factors upon limbal vessels (5). Due to the high Dk/t of silicone hydrogel lens materials, corneal vascularization is rarely observed with these lenses (6).
The incidence of neovascularization in gas permeable wearers is low due to the newer more oxygen permeable lens materials, the tear pump and the smaller lens diameter.
Soft Lens Wearers
For daily wear soft hydrogel contact wearers, if limbal hyperemia is present and a tight fitting lens is apparent, the base curve should be changed in order to promote more lens movement. If there is adequate movement with an optimal fit, the lens is not providing the necessary oxygen to the cornea. Refitting the patient in a silicone hydrogel lens will increase the oxygen to the cornea and decrease the hypoxia. Both limbal hyperemia and corneal vascularization have been found to improve upon refitting with a silicone hydrogel lens. (3, 5,10).
In extended soft hydrogel lens wearing patients, because of the inadequate amount of oxygen transmissibility in the lens material, these patients should be refit into a higher Dk/t silicone hydrogel lens material. Available silicone hydrogel lens options are FDA approved for extended wear either up to 6 nights and 7 days, or for 30 days continuous wear; therefore patients should be educated on these options. If there is apparent vessel growth, regression of these vessels will be seen after changing to a higher Dk/t material with a good prognosis for up to 4mm of in-growth. Ghost vessels will remain which have the capacity to fill with blood again if the cornea is subsequently subjected to a similar hypoxic environment. (5, 6)
GPs
Gas permeable wearers experiencing 3 and 9 staining and evidence of localized neovascular and fibrovascular changes due to a poorly fitting lens should be refit into a design that limits this condition. Recommended methods of preventing 3 and 9 staining and the subsequent neovascularization include the use of wettable fluoro-silicone/acrylate lens materials, improved lens centration, proper edge clearance and adequate corneal lubrication via proper blinking and use of lubricants. (7)
In both soft and GP contact lens wear, it is rare that with proper follow-up and annual evaluation, that neovascularization cannot be managed with the aforementioned changes. In extreme cases, with marked neovascularization creeping towards the visual axis and associated fibrovascular areas and lipid deposition all contact lens wear should be discontinued. Close follow-up care every 2 – 3 months should be initiated to monitor for any possible further detrimental changes and to watch for regression. Afterwards, these patients should be refit into high Dk/t silicone hydrogel or gas permeable lenses. If the opacified areas do not regress and there are areas of scarring and a poor visual outcome, then a corneal transplant may be indicated. (3)
Some clinicians advocate the use of a topical steroid in order to suppress active neovascularization. The steroid works to decrease blood vessel permeability and leakage in addition suppressing the recruitment of involved cells. (3)
No single cause has been identified as the sole trigger of corneal neovascularization, however it is believed that corneal hypoxia, especially in soft hydrogel extended wear patients, is the main culprit. Patient education plays an important role as many do not understand or are aware of the consequences that can result from lens over-wear or non-compliance to lens wear schedules. Given the multitude of lens options now available and a more appreciable knowledge of the changes and findings that can be observed, quick diagnosis and management will hopefully prevent any irreversible damage.
BEST REFERENCES:
Grohe RM and Lebow KA. Vascularized limbal keratitis. ICLC 1989;16(7&8): 197-208.
Weissman, BA and Yeung, KK Neovascularization, Corneal, CL-related: Treatment and Medication Nov 21, 2001 http://emedicine.medscape.com/article/1195886-treatment Accessed 02/11/2009
Swarbrick HA. Extended Wear: Physiologic Considerations In: Bennett ES, Weissman BA. eds. Clinical Contact Lens Practice, Philadelphia: Lippincott Williams and Wilkins, 2005:647-675.
Liesegang, TJ Physiologic Changes of the Cornea with Contact Lens Wear CLAO Journal 28(1): 12 – 27, 2002
OTHER REFERENCES:
Kanski, JJ. Cornea In: Kanski JJ, Clinical Ophthalmology – A Systemic Approach 5th Edition, London: Butterworth-Heinemann, 2003:95 - 143
Efron, N. Contact Lens Complications. London: Butterworth-Heinemann, pp:153 – 161, 2004
Weissman BA, Yeung KK Neovascularization, Corneal, CL-related: Treatment and Medication Nov 21, 2001 http://emedicine.medscape.com/article/1195886-treatment Accessed 02/11/2009
Swarbrick HA. Extended Wear: Physiologic Considerations In: Bennett ES, Weissman BA. eds. Clinical Contact Lens Practice, Philadelphia: Lippincott Williams and Wilkins, 2005:647-675.
Josephson, JJ and Caffery, BF Corneal Neovascularization In: Anterior Segment Complications of Contact Lens Wearers 2nd Edition, Butterworth-Heinemann pp:95 – 106, 2000
Fonn, D, MacDonald KE, Richter, D et al. The Ocular Response to Extended Wear of a High Dk Silicone Hydrogel Contact Lens Clin Exp Optom 85(3):176 – 182, 2002
Bennett ES, Scheid T. Gas-Permeable Len Problem Solving In: Bennett ES, Henry VA. eds. Clinical Manual of Contact Lenses 3rd Edition, Philadelphia: Lippincott Williams and Wilkins, 2009:183-208.
Liesegang, TJ Physiologic Changes of the Cornea with Contact Lens Wear CLAO Journal 28(1): 12 – 27, 2002
Dumbleton K, Jones, L Extended Wear In Bennett, ES and Henry, VA Clinical Manual of Contact Lenses 3rd Edition, Philadelphia: Lippincott Williams and Wilkins, 2009:410 – 443
Holden, BA, Mertz, GW Clinical Oxygen Levels to Avoid Corneal Edema for Daily and Extended Wear Contact Lenses Invest Ophthalmol Vis Sci 25(10): 1161 – 1167, 1984
Fonn, D. and Bruce, A.S. A Review of the Holden-Mertz Criteria for Critical Oxygen Transmission Eye Contact Lens Nov: 31(6): 247 – 251, 2005

Cornea and Contact Lens Living Library
Corneal Neovascularization

Authors:
Olivia K. Do, O.D.
Vinita Allee Henry, O.D., F.A.A.O. 

Reviewed by:
Julie Ott DeKinder, O.D., F.A.A.O.
Bruce W. Morgan, O.D., F.A.A.O.