Complications -- Part II
A continued investigation of contact lens complications. The second part of this series explores those complications pertaining to the cornea.
PAUL WHITE, O.D.
Part I of this two-part series appeared in the November 1999 issue and discussed contact lens complications related to the pre-ocular tear film, contact lens deposits and vascular changes. Part II explores the corneal complications of staining, hypoxia and ulceration.
Corneal staining is the most frequently observed contact lens related tissue complication. Its prevalence in rigid gas permeable (RGP) and soft contact lens wearers is about 60 percent.
The most common etiologic categories for contact lens related staining are drying, mechanical, toxic or allergic, physiologic and infectious.
Drying -- Part I of this series discussed 3 and 9 o'clock staining with RGPs, and binding of both rigid and soft lenses. Severe and deeper 3 and 9 o'clock staining can produce a localized corneal thinning or dellen. Dellen are saucer-like depressions that don't actively stain with fluorescein unless the overlying epithelium has been disrupted. Rupture of the corneal epithelium may lead to ulceration. Dellen are usually shallow, but may involve up to 75 percent of corneal thickness with scarring and vascularization in the area.
Pseudopterygia are very uncommon, superficial, vascularized lesions of the peripheral cornea as a sequelae to chronic and severe 3 and 9 o'clock staining. They appear as winged-shaped lesions with raised corneal epithelium, and conjunctival and limbel vessel hyperemia encroaching on the peripheral cornea. True pterygia are degenerative and hyperplastic, and the conjunctiva actively invades the cornea (Fig. 1).
FIG. 1: A pseudopteryguim on a long-term RGP lens wearer.
Incomplete closure of the palpebral aperture from lagophthalmos, or other eyelid or blinking abnormalities often result in drying and superficial punctate keratitis (SPK) of the inferior cornea. SPK is a diffuse corneal stain exhibiting small dot-like changes of the epithelium that temporarily hold fluorescein when the cells are damaged or missing. Drying is a cause of SPK, as are mechanical irritation, toxic and allergic reactions, hypoxia and infection. One type of desiccation SPK occurs with ultrathin high water content soft contact lenses, where lens dehydration leads to post-lens tear film drying and epithelial desiccation. The staining is seen as coarse punctates, usually toward the center or bottom third of the cornea (Fig. 2).
Small diameter or decentered soft lenses may leave part of the cornea uncovered. The exposed area may desiccate and stain in an arcuate shape, both from the drying and the mechanical trauma caused by the lens edge (Fig. 3).
FIG. 2: SPK from an ultrathin high water content soft lens.
FIG. 3: Arcuate stain from a decentered soft contact lens.
Mechanical irritants -- Foreign bodies or debris may flow or become trapped between the contact lens and the cornea, resulting in epithelial abrasion and staining. The pattern and severity varies depending on the size, shape, duration of pressure and flow pattern of the foreign body. Foreign bodies more frequently flow under RGPs than soft lenses, and the staining is usually superficial without long-term sequelae. Deeper abrasions cause discomfort, pain and photophobia, and may contribute to the development of recurrent corneal erosion, especially for patients with abnormal basement membranes. Lens imperfections, rips or tears, improper insertion or removal techniques, and fingernails are also mechanical irritants. Increased epithelial fragility from hypoxia may increase the propensity for abrasion (Fig. 4).
Dimple or "orange peel" staining is caused by air or carbon dioxide bubbles trapped under contact lenses, especially RGPs. The bubbles temporarily indent the epithelium, pooling fluorescein, especially centrally, with a steep base curve, or peripherally, with excessive secondary clearance. Steep secondary curves can cause indentation and staining from mechanical pressure (Fig. 5).
FIG. 4: A deep abrasion from a foreign body.
FIG. 5: After rigid lens removal, the peripheral indentation staining from steep secondary curves and the central dimple-type staining are seen.
Minute trapped bubbles may be one etiology of the "smile stain," which occurs with some flat fitting and more form holding soft contact lenses. "Smile stains" usually appear as an arcuate, concave-up configuration between the lower pupillary border and the lower limbus. Changing the base curve radius or using a more flexible soft lens material often resolves the problem (Fig. 6).
Epithelial splitting manifests as diffuse, scattered punctate dots in a linear or arcuate configuration on the superior cornea under the upper eyelid. The epithelium appears as an arcuate heaping with a central crack that holds fluorescein. Asymptomatic at first, progression often causes discomfort. Mechanical, drying and hypoxic factors probably contribute, and the lesion heals after several days or weeks of lens discontinuation. Superior limbal epithelial staining occurs with high water extended wear (EW) soft contact lenses, is less defined than epithelial splitting and is probably due to a sealing effect caused by the lens and the upper eyelid on the superior cornea (Fig. 7).
FIG. 6: Inferior "smile stain."
FIG. 7: Epithelial splitting.
Toxins and allergies -- To various degrees, all chemicals used for bacteriostatic or bacteriocidal purposes in contact lens solutions are potentially toxic and can cause tissue reactions and corneal staining. Although most current solutions establish a good balance between safety and efficacy, reactions still occur for some patients, especially with solution misuse.
Sensitivity reactions may occur with one instillation of a solution or they may take years of use. The reaction may have mild to severe symptomology and signs, including tearing, redness, infiltrates and staining. The staining is usually SPK, which is typically diffuse, bilateral and grade 1-4.
Severe epithelial disorder associated with solution toxicity and hypersensitivity can result in pseudodendrites that appear as raised, gray epithelial plaques with serpentine shapes and light staining. Superior limbic keratoconjunctivitis (SLK) is associated with the organic mercury thimerosal and manifests as an inflammatory reaction with bulbar conjunctival injection, small subepithelial opacites and infiltrates, a grayish thickening of the superior limbal and corneal epithelium, and punctate staining of the involved conjunctiva and cornea.
Many contact lens complications have resulted from hypoxia, which is contributed to by the patching effects of the contact lens and of the eyelid during sleep. For many years, RGPs have been available with Dk/ls large enough so that hypoxic tissue complications for both daily wear (DW) or extended wear (EW) have been minimized or eliminated. Until recently, this has not been true for EW soft lenses with their maximum Dk/l in the low 30s. Newer EW soft lens materials have a Dk/l three to four times this value, which should minimize or eliminate the hypoxic-induced tissue complications that will be described.
Krebs' Cycle -- The cornea's high rate of aerobic glycolysis is essential to its normal function. Corneal oxygen uptake is about 4.8µl/hr/cm. About 90 percent of the oxygen-related reactions occur in the epithelium. Histological changes from hypoxia tie in with the well-established Krebs' cycle.
Hypoxia (anaerobic glycolysis) oxidizes more pyruvic acid to form lactic acid and only two adenosine triphosphate (ATP) moles for each mole of glucose. Consequently, glycogen stored in epithelial basal cells is consumed to produce additional energy, and leaves nonmetabolized lactic acid. This lactic acid does not readily penetrate out of the epithelium, but rather diffuses through the stroma, Descemet's membrane and endothelium, and into the aqueous humor. Lactic acid accumulation makes the cornea relatively hypertonic, and relatively hypotonic fluid is drawn into the cornea (edema) to produce an osmotic equilibrium. That is, an increase of lactate or lactic acid in the stroma induces an osmotically driven influx of water into the tissue, which results in stromal swelling.
Lactic acid accumulation lowers the corneal pH, which influences cell growth and function, e.g., mitosis, glycolysis and epithelial ion secretion. Hypoxia and its resultant pH decrease could stress epithelial metabolism and also endothelial fluid transport, which accounts for most of the maintenance of stromal fluid. In essence, epithelial hypoxia leads to decreased stromal pH, which could compromise the endothelium.
Eyelid patch -- The atmospheric pressure is 760mm Hg, and its oxygen partial pressure at sea level is about 155mm Hg, i.e. 21 percent of 760mm Hg. With closed eyes, the oxygen pressure is about one-third of this, (i.e. about 55mm Hg), and is derived primarily by diffusion from the vasculature of the palpebral conjunctiva. This oxygen pressure, or oxygen tension, is the driving force for the rate of oxygen movement, or oxygen flux, through a tissue or contact lens material. Thus, oxygen flux is directly related to oxygen pressure.
Because oxygen pressure is decreased with eye closure, a relative hypoxic state results. This eyelid patching is the major cause of an average three to four percent corneal thickening upon awakening for non-contact lens wearers. Other factors also contribute. The pH of both the tears and the stroma are decreased from about 0.15 to 0.20 from eyelid patching during sleep. Precorneal fluid becomes relatively hypotonic (0.89 percent NaCl) during eye closure as compared to that with open eyes (0.97 percent). Additionally, metabolic products, CO2 accumulation (hypercapnia), desquamated epithelial cells and inflammatory cells are relatively stagnated with eye closure and lack of flushing.
Contact lens patch -- Sleeping with a contact lens in adds a second patch to the front of the eye which decreases oxygen flux. Consequently, the hypoxia increases edema and corneal thickness as measured by pachymetry.
The rate of oxygen movement (permeability) is indicated by the symbol Dk, in which "D" represents diffusion transfer and "k" represents solubility transfer, (i.e. oxygen dissolved in fluid). Historically, almost all of the permeability through a soft contact lens was by solubility, and through a rigid lens was by diffusion. The new high-Dk soft contact lenses achieve this with chemistry that combines both solubility and diffusion. Hypoxia from the contact lens patch depends upon the material's true permeability, the lens' thickness configuration and the area of corneal coverage. Practitioners should understand that Dk/l (oxygen transmissibility, wherein "l" is the lens center thickness) and Dk/l (average oxygen transmissibility, wherein "l" is an averaging of overall lens thickness gradient) are more important than Dk. Some standards now use "t" instead of "l."
Equivalent oxygen percentage -- Equivalent oxygen percentage (EOP) determines the oxygen tension in the precorneal fluid. As contrasted with the physical testing for the material Dk, EOP is a biological testing which tries to simulate the contact lens wearing situation, i.e. it reflects the natural interactions between the lens, tears and the cornea under open or closed eyelids. Dk/l and EOP are related, but not in a linear manner. To achieve the same increase in EOP, a greater increase of Dk/l is needed at higher Dk/l levels.
Earlier work indicated that a minimum of five percent EOP was required so that histological changes, such as an increase of lactic acid, a decrease of glycogen reserves and an increase of fluid (edema) did not occur. A seven to eight percent EOP level represents the closed eyelid situation. More recent work established 18 percent EOP as ideal for EW, 12 percent EOP as a tolerable level for EW, and 10 percent EOP as satisfactory for DW. These would correlate with a Dk/l of about 75 x 10-9 for EW and a Dk/l of about 25 x10-9 for DW. Again, this three-to-one ratio relates to the same ratio of oxygen partial pressure with open eyes (155mm Hg) versus with closed eyes (55mm Hg).
Upon awakening and eyelid opening, one of the two patches is removed and oxygen supply/pressure is increased three times - from seven percent (55mm Hg) during sleep to 21 percent (155mm Hg) from the atmosphere. Corneal deswelling occurs, but this is quicker and fuller with RGP lenses because they cover less of the cornea, move more and have about a 10 to 20 times greater tear pump than hydrogel lenses. Maximum deswelling with hydrogels is about eight percent. So, corneas that have swelling more than this overnight would have residual, continual daytime edema. Studies indicate that a Dk/l of 87x10-9 would limit overnight swelling to about four percent, i.e., the same as for a non-contact lens wearer, and 34x10-9 would produce an average of eight percent corneal swelling, i.e., the amount of deswelling that occurs with soft contact lens wearers after awakening.
Epithelium -- Epithelial microcysts are probably minute collections of dead cellular material that form at the epithelium's basement membrane and migrate to and through the epithelium's surface (Figs. 8 & 9). Microcysts are more common in the midperipheral cornea with hydrogel wear, and are about twice as numerous with lower water content than with higher water content (HWC) lenses. This is probably due to the relatively greater oxygen transmissibility through the midperipheral portion of HWC lenses. The microcyst number is significantly reduced when hydrogel EW is worn for two rather than for seven days continuously. Approved RGP EW has a very low incidence of microcysts, but only when the oxygen transmissibility is high. Microcysts increase over the first week of cessation of lens wear, but gradually dissipate over about six to eight weeks. Epithelial microcysts are often asymptomatic, but consequent rupturing of the epithelial surface may cause symptoms. Coalescing of ruptures disrupts epithelial surface integrity and allows a portal for infection and ulceration, which is exacerbated by concurrent decreases of epithelial adhesion, metabolism and mitosis. Maintenance of epithelial integrity is essential, and compromised epithelial metabolism and adherence are conducive to infection, especially in the presence of a bacteriologically contaminated contact lens.
FIG. 8: Microcysts within the epithelium.
FIG. 9: Microcysts that have migrated through the epithelium and demonstrate staining.
With polymethylmethacrylate (PMMA) or very low Dk/l RGP lenses, the edema from hypoxia is called central circular clouding (CCC), or gross circumscribed edema (Fig. 10). The higher Dk/l values of contemporary RGPs have eliminated this, just as the higher Dk/l values of newer soft lenses will minimize or eliminate hypoxia-induced tissue problems; CCC is an intercellular collection of fluid in the epithelium, centered in relation to the optic zone with primary fixation, appearing as a 2-4mm circular whitish gray area against the nonedematous portions of the cornea when viewed with the naked eye and split-limbal illumination. When CCC is moderate or severe, cellular integrity is reduced to a degree where corneal staining occurs in the area of CCC (Fig. 11).
FIG. 10: Grade 3 central circular clouding.
FIG. 11: Staining from severe central circular clouding.
With long-term PMMA lens wear, a corneal exhaustion syndrome may occur due to chronic hypoxia and hypercapnia. Patients become completely intolerant to contact lenses and manifest significant corneal distortion, spherical and astigmatic refractive changes. This should be differentiated from spectacle blur that can occur from RGP or soft lens wear. Spectacle blur with RGP lenses does not usually result in complete intolerance to wear, but mechanical pressure and physiological effects produce changes of spectacle refraction, altered keratometric mires and corneal shape topographic changes (i.e., epithelial corneal wrinkling). Spectacle blur with soft EW often involves an induced increase of minus or decrease of plus refractive power, both with the lenses on and off the eyes, often called "myopic creep."
Stroma -- Soft lens stromal edema is clinically detectable by the appearance of so-called striae when corneal thickness increases about six or seven percent. Posterior stromal striations are fine, grayish-white lines, which are probably refractile changes caused by fluid separation of the posterior stroma's fine collagen fibrils (Fig. 12). A 10 percent or greater corneal thickness increase probably buckles the posterior corneal layers, and folds appear as endothelial creasing when observed by specular reflection illumination (Fig. 13). Striations indicate a need for caution, but folds are unacceptable. Almost all EW patients awaken with at least seven percent corneal thickness increase, and many have 10 percent or greater. Therefore, almost all EW patients awaken with striations, and many of them have folds, whereas only a very small percentage of RGP or hydrogel DW contact lens wearers have striations or folds.
FIG. 12: Striae from hypoxia.
FIG. 13: Folds from hypoxia.
Stromal infiltrates may be caused by many factors, such as viral infections and toxic reactions. However, the overall effects of hypoxia can directly and indirectly contribute. Infiltrates appear as focal or diffuse, hazy, gray areas which are often near the limbus (Fig. 14). They are probably aggregations of inflammatory cells, such as polymorphonuclear leukocytes or monocytes, between the stromal collagen fibrils.
FIG. 14: Peripheral corneal infiltrates.
The adjacent conjunctiva is usually hyperemic, which suggests that the inflammatory cells may originate from the reticuloendothelial system of the limbal vessels. EW hydrogel contact lenses can bind around the limbus during sleep and trap debris and organisms. The trapped debris may decompose and release toxins that stimulate inflammatory cell migration from the limbal vessels. Infiltrate incidence is much less with RGP or hydrogel DW, and also with RGP and EW rather than with hydrogel EW. This is probably because RGP contact lenses don't patch the peripheral cornea or limbus, and rigid contact lenses have greater movement and pumping away of debris with open eyes.
Stromal neovascularization from EW is unclear in etiology and pathophysiology. It has been hypothesized that chronic peripheral corneal edema from hypoxia, induced by hydrogel EW, reduces stromal compactness, which allows for vessel ingrowth. But the stimulus for the neovascularization itself might be vasostimulating agents, perhaps enzymes. It has also been suggested that contact lens-induced neovascularization is subepithelial rather than stromal, and the hypoxic epithelial cells release vasogenic factors that stimulate neovascularization. Neovascularization extending 1-2mm beyond the normal corneal/limbal plexus is clinically unacceptable and requires intervention. Although contact lens-induced neovascularization is usually self-limiting and rarely extends to the pupillary area, it is obviously of great concern. Neovascularization occurs less with DW than with EW, especially less than with hydrogel EW.
Stromal pH is lowered consequent to epithelial hypoxia and reduced aerobic metabolism, and represents an increase of lactic acid from this and perhaps, from carbon dioxide trapped by the contact lens. This increased acidity appears in studies on endothelial blebs and the aqueous.
Noninvasive fluorescein studies confirm increased stromal acidity. A study with donor corneas further confirms this acid shift, and hypothesizes that hypoxia causes the epithelium to release a factor which changes the hydrogen ion balance in the stroma and results in endothelial stress.
Endothelium -- Endothelial blebs appear within minutes after contact lens insertion for almost all hydrogel contact lens patients. Blebs appear as black, non-reflecting areas that bulge toward the aqueous when viewed with a slit lamp biomicroscope using high magnification and specular reflection (Fig. 15). Some studies show that the bleb response peaks in about 25 minutes and then decreases to a low level after about 50 minutes. Blebs dissipate quickly after contact lens removal, and are of more concern as a manifestation of corneal stress in general than as a specific problem.
FIG. 15: Endothelial blebs.
Endothelial polymegethism is detected by specular microscopy, as determined by endothelial photography using a modified clinical biomicroscope or a specially designed endothelial camera. Only a small area (200 to 800 micrometers) can be photographed at one time, unless complex scanning systems are used. Polymegethism indicates an increased variance of endothelial cell size and an apparent decrease of cell density, which is probably due to a decreased pH (Fig. 16). The degree of hypoxia appears to be directly correlated with the degree of endothelial polymegethism, and highly transmissible silicone-elastomer lenses do not cause polymegethism. Such structural endothelial changes may decrease the endothelial metabolic pump function, increase corneal edema and decrease corneal deswelling capacity, however, this is not clearly established.
FIG. 16: A schematic illustrating a normal endothelium of a non-contact lens wearer and polymegathism of a soft lens EW.
It is more clearly established that cessation of contact lens wear either does not fully eliminate induced polymegethism or eliminates it over a long period of time. Polymegethism occurs less with DW than with EW. Polymegethistic morphologic changes of the endothelium are of most concern if these structural changes alter endothelial function in terms of the metabolic pump which maintains corneal deturgescence.
Contact lens-induced microbial keratitis is relatively rare, but the risk for corneal ulcers has been much greater with soft EW compared to with soft or RGP DW, or RGP EW. Corneal defense mechanisms are much less effective with eye closure during sleep. When not blinking, the pre-ocular tear film and the lacrimal outflow have reduced wiping, diluting and rinsing away of microorganisms and debris. Simultaneously, hypoxia may make the cornea more susceptible to infection. Coated contact lenses hold even more microbes than unused lenses.
The combined results of 11 studies done at different medical centers from 1984 to 1991 demonstrated 750 contact lens-induced ulcers of which 450 (60 percent) were culture positive ulcers (CPU) and 300 (40 percent) were culture negative peripheral ulcers (CNPU) or sterile ulcers. The bacterial organisms causing lens-induced CPUs were: Pseudomonas -54 percent, Staphylococcus -22 percent, other gram-negative bacteria-11 percent, and other gram-positive bacteria-10 percent. Only two percent of the ulcers were caused by fungi and one percent by amoeba, and the course of keratitis from those organisms is quite slow. Because most non-contact lens induced ulcers are associated with the toxic effects of staphylococcal bacteria, the very high incidence of contact lens induced pseudomonal ulcers should guide practitioners to assume pseudomonas as the cause until laboratory or clinical findings prove to the contrary.