Age-Related Changes in the Normal Cornea: Clinical Implications in Refractive Surgery
Guy M. Kezirian, MD
Age-related changes in a normal cornea present issues for potential refractive surgery patients of all ages. These issues include whether corneal-based procedures are safe in young people, if older patients respond differently to procedures, and whether changes in the cornea undermine the benefits of surgery over time.
Photorefractive keratectomy (PRK) and LASIK are not often performed in pediatric patients. Potential indications include children who are being treated with contact lenses for low-to-moderate refractive correction, such as anisometropic amblyopia and accommodative strabismus. Pediatric aphakic patients are not suitable candidates because the high plus correction needed exceeds the established range for LASIK and PRK. Epikeratophakia, which does not rely on photoablation and does not remove corneal tissue, has met with some acceptance in this population.1-4
Similarly, few patients over the age of 65 present for primary refractive correction. In most cases, the mean age of patients undergoing LASIK for the correction of myopia is approximately 40 years with a standard deviation of approximately 10 years.5 Ages are slightly higher for hyperopic corrections, with a reported mean of 52 6 7 years.6 However, recent advances in the understanding of aberrations suggest that more pseudophakes may undergo LASIK or other corneal procedures to improve astigmatism, coma, and spherical aberration. Additionally, the recent resurgence of corneal-based thermoplastic procedures for presbyopia may cause older patients to undergo corneal-based refractive procedures. For these reasons, it is worthwhile to consider whether age-related changes may affect the outcome of refractive procedures in older patients.
A valid concern among refractive surgeons is whether age-related changes may undermine the benefits of correcting higher-order aberrations as a patient ages. Understanding the expected aging changes may allow the surgeon to provide the refractive correction that will best serve a patient over time.
Age-related changes in the cornea can be classified in the following four categories:
Other authors7 have selected alternate categories, which are also valid. An anatomic classification is selected here because of its relevance to surgery.
Most of the age-related changes listed are well understood. When considered in the context of refractive surgery, their effects can be anticipated. The literature contains recent studies that describe the optical changes using aberrometry, providing additional insight into the aging process.8-13
The corneal surface plays a critical role in the quality of vision after refractive surgery and is significantly affected by the tear film. Tear film quality decreases with age and can be affected by conditions such as Sjögren's syndrome, and diabetes, and smoking. The epithelium becomes thinner, the epithelial basement membrane becomes thicker, and the hemi-desmosome attachments to Bowman's layer become less adherent with age.7,14,15 Re-epithelialization occurs slowly in older eyes. Finally, corneal sensitivity decreases with age,16 which may increase the tendency for surface-related problems after LASIK and other tissue ablating procedures.17
In the absence of scarring or degeneration, stromal clarity is unaffected with aging.18 However, a general reduction in cellular activity occurs with age, with decreased responsiveness14 to inflammation, infection, or other insult. Collagen quality diminishes and increased intramolecular and interfibrillar spacing, probably due to increased protein glycation, has been reported.19,20 This may underlie the tendency for the increased effect of radial keratotomy in older eyes.21
Stimulated apoptosis of anterior stromal keratocytes after surface procedures plays a role in corneal healing after refractive surgery.22 With cellular senescence, this response may be diminished as keratocyte function decreases linearly with age.23 The implication for refractive surgeons is that the tendency for regression may be less in older eyes. In addition, age has not been shown to correlate with the formation of haze following PRK.24
Decreased corneal endothelial cell counts25 and other changes26 lead to decreased endothelial function with age. Development of guttata and Fuchs' dystrophy can lead to complications such as corneal scarring after excimer ablations.27
Age is not a primary determinant of ablation rates for excimer-based procedures28; however, decreased endothelial cell counts and decreased endothelial cell function can result in increased stromal thickness and higher water content in older eyes. The effects of higher water content on laser ablation rates are dependent on the laser fluence level and, therefore, the effect of age-related increased water content varies. In most series, the effect is not detectable. Moreover, since presbyopic patients do not tolerate postoperative hyperopia well, most LASIK and PRK nomograms include age adjustments that decrease the ablation amount in older patients. This effect usually outweighs any adjustments to increase the ablation amount to overcome increased corneal water content in older eyes.
An aging cornea develops steeper keratometric readings and shifts from with-the-rule to against-the-rule astigmatism.8,9 Recent studies show that overall ocular aberrations in general,10 and corneal coma in particular, increase with age.11 Overall, spherical aberration also increases, but seems to occur in the lens, not the cornea,12 especially after the age of 50.13
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A comparison of topography and aberrometry images provides clinical information regarding the source of higher-order aberrations (Slide 1). When aberrations originate from the lens, the topography and aberrometry should appear as if they are mirror images of each other. Aberrations that originate from the lens may show a smooth topography with distorted aberrometry (Slide 2).
Physiologic age-related degenerations of the cornea, such as farinata, arcus senilis, crocodile shagreen, and Hassall-Henle bodies, may be visible at the slit lamp. Most do not affect refractive outcomes unless they interfere with the ability to obtain aberrometry.
LASIK and PRK in the pediatric population have been reported,29-33 but remain controversial.34,35 Most studies focus on adolescents as opposed to young children. Concerns exist about corneal stability, regression, predictability, haze formation, progression of the underlying refractive error, and preclusion of subsequent contact lens use.
Refractive surgeons performing corneal procedures in the older patient should assess the ability of the tear film and ocular surface to withstand surgery. Epithelial defects and slower epithelial healing may be expected. Preexisting dry-eye conditions in adults can be exacerbated by LASIK and other procedures more than in the younger population due to poorer quality of the tear film prior to surgery and the decreased corneal sensitivity found in older eyes.
Decreased endothelial pump function may lead to a greater tendency for older eyes to develop edema and this may affect the adhesion of LASIK flaps.
Decreasing keratocyte activity with age may cause the response to thermal keratoplasty procedures, which depend on collagen shrinkage, to vary. Since these procedures are often performed in presbyopic eyes, this may explain some of the refractive variability that has been reported with this procedure.36
Whether the age-related optical changes of the cornea undermine the utility of correcting higher-order aberrations, or even the lower-order (spherocylinder) aberrations, is a matter of judgment. In the absence of pathology such as lenticular changes, age is not a contraindication to refractive surgery. However, lens changes resulting in optical aberrations have been observed to increase sharply after the age of 50,11 even in the absence of clinical cataract formation. This tendency should be considered when planning refractive surgery in this age group.
Corneal optical changes related to aging include gradual steepening, tendency toward against-the-rule astigmatism, and increasing coma. Since these changes occur in the context of other optical changes (eg, increasing spherical aberration in the lens) the decision as to whether to proceed with any refractive correction is best left to the surgeon and patient. The decision involves consideration of the overall health of the eye, the potential need for other procedures in the future, and the many other considerations that influence the decision to have surgery.
