On the structural origin of refractive instability and corneal haze after excimer laser keratectomy for myopia

Refractive errors are due to an improper relationship between the refractive power of the cornea and lens, the depth of the anterior chamber, and the length of the eye globe. Myopia represents the most common refractive disorder with a prevalence of approximately 20–25% for Europeans, 50–70% for Chinese, and less than 10% for Eskimos. Despite intense research efforts, the etiology and pathogenetic mechanism(s) responsible for development of myopia, and for the exceedingly wide variation among ethnic groups, remain elusive. Traditionally, refractive errors have been corrected with spectacles or corneal contact lenses. However, the idea of obtaining maximal visual acuity without corrective eyewear has motivated a search for surgical alternatives to manipulate the ocular refraction permanently and predictably. The prime focus has been the cornea that represents the main refractive element of the eye. The anterior corneal surface has a refractive power of approximately 49 diopters (D) as compared to −6 D of the posterior corneal surface. Thus, of the eye's total refractive power of about 60 D, approximately 43 D or 72% is located in the cornea. Alteration of the anterior corneal curvature therefore offers a good opportunity for surgical correction of visual refractive errors. For the treatment of myopia, the overall intention has been to induce a controlled flattening of the central cornea (and a steepening of the periphery), and still maintain a smooth and optically transparent surface. During the last 25 years, many keratorefractive surgical procedures have been designed and tested based on various incisional, lamellar, and thermal principles. However, since the introduction of non-thermal, ultraviolet excimer laser photoablation, the field of refractive corneal surgery has widely expanded. In biophysical terms, excimer laser photoablation is based on ultraviolet radiation from an ‘excited dimer’ of argon and fluorine gas molecules, which exists transiently before dissociating with intense emission of energetic photons with a wavelength of 193 nm. The emitted photons are absorbed within a thin layer of the treated surface and have sufficient energy to break intermolecular bonds leading to ablative decomposition of the tissue into minor fragments that are ejected. Currently, there are two main treatment approaches: (1) photorefractive keratectomy (PRK), where the apical corneal epithelium initially is removed (by manual debridement or by transepithelial photoablation) followed by ablation of the denuded stromal surface (anterior stromectomy); (2) laser in situ keratomileusis (LASIK), where the photoablation is performed in the mid-stroma following temporary displacement of a 130–160 µm hinged (epithelial and stromal) tissue flap, formed with a microkeratome (intracorneal stromectomy). To reduce the anterior corneal convexity and correct 1·00 D of myopia, both procedures require removal of a stromal lenticule shaped as a biological contact lens with a central thickness of approximately 13 µm for a 6-mm diameter optical zone and 9 µm/D for a 5-mm diameter ablation zone (Munnerlyn et al. 1988; Colliac et al. 1994). The predictability of excimer laser surgery for myopia has so far never been comparable to that of corrective eyewear including spectacles and contact lenses. Today as well as in the past, the refractive outcomes of both PRK and LASIK have shown an exceedingly wide variation, with 70–100% of low myopes, 40–85% of moderate myopes, and 20–67% of high myopes being within ±1·00 D of intended refraction by 1 year post-surgery (Dutt et al. 1994; Epstein et al. 1994; Maguen et al. 1994; Talley et al. 1994; Seiler et al. 1994; Sher et al. 1994; Piebenga et al. 1995; McCarty et al. 1996; Schallhorn et al. 1996; Hersh et al. 1998; Tuunanen & Tervo 1998; Shah et al. 1998; Han et al. 2000). There appears to be two main sources of variation to account for this low predictability. Firstly, there is no precise control of the actual photoablation depth during surgery in each individual patient (i.e. the exact amount of stromal tissue removed). Secondly, there is no precise control of the that to the refractive correction by of of The for photoablation of the corneal is about energy for and for et al. no ablation a relationship exists between ablation and energy with µm removed the energy in most excimer et al. 1994; et al. However, the is on tissue a energy have tissue removed laser to less tissue removed laser to et al. 1994). corneal tissue to treatment and for and of of leading to variation in the photoablation in the of et al. 1994). there variation in the tissue (and tissue of the leading to in the actual photoablation are is to that the actual laser most is to based on the of the ablative on a of be an of Thus, the photoablation depth on the excimer laser to treatment (i.e. the is and based on Currently, no exists for the of individual photoablation in There is therefore a to an corneal to the laser treatment has the The refractive excimer laser photoablation a following treatment for myopia, the patient is with an to account for the of treatment During the year both PRK and the refraction a D less and following (Dutt et al. 1994; Epstein et al. 1994; Maguen et al. 1994; Seiler et al. 1994; Sher et al. 1994; Talley et al. 1994; Piebenga et al. 1995; McCarty et al. 1996; et al. et al. 1998; et al. 1998; Hersh et al. 1998; Tuunanen & Tervo 1998; Han et al. 2000). For this excimer laser with correction to account for the of treatment et al. However, are based on of corneal are from the refractive of the of the is and since the refractive among the the patient or There is no of refractive the refractive to 1 of both PRK and LASIK have a for with et al. 1994; et al. et al. Tuunanen & Tervo 1998; Han et al. that corneal is in and require to be the and of excimer laser procedures are Despite the high and of refractive following PRK and there has been a of of the pathogenetic The from of and corneal from the of is is that both and stromal the refractive correction by of tissue in the Thus, many of have an and most of the corneal epithelium to µm in and as compared to µm in et al. et al. et al. et al. et al. 1994; et al. 1996; et al. of various and (i.e. stromal has been et al. et al. et al. et al. et al. et al. 1995; et al. 1996; et al. However, of have or on the stromal as and have for in a have central corneal both PRK & et al. and LASIK et al. 1998; et al. in both and with the and leading to central corneal However, the and of and stromal have due to a of corneal be that of the tissue stromal or has been as a of following both PRK & and LASIK et al. 1998; Seiler to the relationship between correction and keratectomy the of the stromal be of following high Currently, the for the thickness of the is µm et al. 1998; Seiler et al. 1998; Seiler which to the of laser correction without stromal and refractive of the mechanism(s) in the development of following both PRK and LASIK be to to to control and the refractive surgical outcomes of is therefore to an in for and in of and stromal thickness to the of tissue in refractive excimer laser refractive surgery laser PRK the transparent cornea to of optical and and within the et al. 1994; Maguen et al. 1994; Seiler et al. 1994; Sher et al. 1994; Talley et al. 1994; McCarty et al. 1996; et al. 1996; Schallhorn et al. 1996; Hersh et al. et al. LASIK a of the the optical of LASIK is due to including or et al. 1998; et al. et al. on the the is following about and during the following During this visual and low visual acuity et al. McCarty et al. 1996; Shah et al. in the optical of of following However, there is no for have an and be with the of a have been appears that the and of is to the maximal photoablation with (i.e. being with corneal & & 1995; McCarty et al. 1996; Shah et al. 1998; et al. there appears to be no with the of refractive et al. et al. 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et al. 1998; et al. and in & Tervo and in the epithelium et al. the of excimer laser correction on to and manipulate corneal in individual to the predictability and of the is that excimer have a for visual acuity et al. a of the has been corneal refractive surgery never and visual and refractive for µm et et et µm for excimer laser photoablation, 193 ultraviolet PRK LASIK in situ 130–160 µm for to central 13 µm for (D) 9 laser For excimer laser et For −6 D D −6 excimer laser excimer laser et variation D, to PRK laser PRK 9 variation have et for excimer laser (1) (2) excimer laser for for in PRK stromal photoablation excimer laser for for excimer laser for PRK et PRK laser et central µm central stromal stromal to to (1) (2) for for