Ординатура / Офтальмология / Английские материалы / Hyperopia and Presbyopia_Tsubota, Boxer Wachler, Azar_2003

we may observe patients with corneal curvature values of 46 D who show good visual acuity, while others with, for example, 45 D do not enjoy such good vision. In a patient with 46 D and normal eccentricity, there is no marked peripheral flattening and visual acuity will be good. Another patient, with a keratoconus and a corneal curvature within normal values, such as 45 D, will inevitably show a high eccentricity and therefore a marked (e.g., spherical) optical aberrations, a very small homogeneous optical zone, and reduced vision quality.

Highly positive eccentricity values (above 1.0 to 1.2) are typical of keratoconus and some cases of hyperopic ablations. A whitish scar may occur in the stroma following PRK or LASIK. This scar correspond topographically to the point of maximal corneal curvature (Figs. 12 and 13). In these cases there is always a high eccentricity value. At present, the etiology of this scar remains uncertain; there is an inhomogeneous tear film as well as lid trauma to the centrally steepened area. For photorefractive treatments, the scar was believed to be the result of denervation of the central corneal area due to the depth of the peripheral ablation. This hypothesis is no longer held, however, because the scar is observed at the point of greatest corneal curvature and not at that of maximal corneal ablation. Furthermore, the scar is not observed with a greater frequency in LASIK eyes, where central corneal denervation is more complete. However, a similar scar is present in posttraumatic corneal leukomas, always at the point of greatest corneal curvature. In these cases of corneal leukoma, topographic analysis may very often be misleading due to problems with the elaboration of the map. Keratoscopy must always be obtained and examined.

Correction of hyperopia with LASIK is more successful, even in the presence of high e values. As a matter of fact, the flap does not follow the new shape of the stromal bed, perfectly thus reducing the eccentricity created by the ablation. In PRK, corneal epithelium follows the newly imparted morphology faithfully. However, above certain values of eccentricity, even LASIK fails.

Retreatment with PTK of these fibrotic areas in hyperopia leads to limited or no result at all, if corneal eccentricity remains positive (e 1.0 1.5), with recurrence of

Figure 12 Keratoscopy of an eye with a subepithelial (PRK) whitish scar, corresponding topographically to the point of maximal corneal curvature.

Figure 13 Topography of same eye as in Figure 12.

the scar at the point of greatest corneal curvature. On the other hand, when eccentricity is decreased, as with corneal excimer laser smoothing, recurrence is prevented. A key point of hyperopic ablation is thus to maintain a corneal eccentricity as much as possible close to physiological values.

Corneal topography offers the advantage of an accurate evaluation of the quality of hyperopic ablation. A wide, homogeneous central area is necessary for improved visual quality, and the surgeon must strive to achieve it as well as to monitor the result topographically. The aberrometric map allows evaluation of central corneal dioptrical homogeneity as well as detection of irregularities that may generate aberrations. The wider the central treatment, the less important is the second, peripheral part of the transition zone (Figs. 1 and 2). Our experience with the Nidek OPD aberrometer shows that, with good topographical indexes, we have a satisfactory aberrometric map: more than 80% of optical aberrations are caused by the first corneal surface.

The future is represented by a larger optical zone (in relation to corneal diameter), of 6.5 mm or greater, with a first, more smooth and homogeneous transition zone up to 9 mm, and a second, limbal transition zone, of more than 9 mm. Let us remember that the corneal periphery offers also the advantage of a greater thickness (Fig. 14).

corneal burns were made in a radial pattern with eight rows and comprised of three or four applications, each up to a premarked optical zone. Trials with radial thermokeratoplasty showed limited clinical benefit because of regression of refractive effect and poor predictability (13–15). Like previous methods of thermokeratoplasty, there were also reports of endothelial damage, corneal decompensation, and corneal necrosis.

Improvement in laser technology has led to advancement in thermokeratoplasty techniques. Prior to the use of infrared laser sources, the complications with thermokeratoplasty techniques were partly related to nonuniform heating of corneal stroma at high temperatures. Laser thermokeratoplasty (LTK) allows for controlled delivery of heat to the corneal stroma while preventing excessive injury to the epithelium and endothelium.

Several lasers have been investigated to induce stromal injury. The carbon dioxide laser (CO2, wavelength: 10.6 m) leads only to superficial retraction of collagen, with early regression of effect (16,17). The yttrium-erbium-glass laser (Yt-Er-glass, wavelength: 1.54 m) allows for deep penetration of corneal stroma with good refractive results, but its use may lead to corneal tissue necrosis and iris damage (18). The cobalt:magnesium fluoride laser (wavelength: 1.85 to 2.25 m) and the continuous-wave hydrogen fluoride chemical laser (wavelength: 2.61 m) have also been evaluated in animal studies, with stable results (19,20).

Initial trials with a pulsed holmium:yttrium-aluminum-garnet laser (Ho:YAG, wavelength: 2.06 m) in human eyes resulted in a hyperopic shift of up to 5 D, which remained stable for 4 months (21). The advantages of the Ho:YAG laser include a corneal stromal penetration depth of about 400 to 450 m and a cone-shaped profile. Unlike the cylindrical profile of thermal probes, the Ho:YAG laser produces a cone-shaped coagulation, allowing for greater shrinkage of anterior stromal collagen compared to the posterior stroma (22). Controlling the magnitude and depth of stromal coagulation allows for greater refractive effect and increased stability of results. In addition, the Ho:YAG laser uses solid-state technology, which is relatively inexpensive to manufacture and maintain.

B. MECHANISM

The basic mechanism of thermokeratoplasty involves change in corneal curvature through heat-induced injury of stromal collagen. Stringer and Parr first reported that the temperature required to shrink corneal collagen is 55 to 58 C (23). Heating above 65 to 70 C causes collagen relaxation, while even higher temperatures lead to stromal collagen necrosis (24). Refractive outcome with LTK is based on optimal corneal stromal shrinkage, determined by the following parameters (25):

1.Temperature. Collagen shrinkage without destruction of collagen fibrils occurs in a narrow temperature range between 55 and 58 C. When the corneal stroma is heated to 55 to 60 C, the tropocollagen helical structure collapses due to dissociation of interpeptide hydrogen bonds, unwinding of the triple helix, crosslinkage between tropocollagen molecules, and dehydration of the stroma. This causes the corneal collagen to shrink maximally, to one-third of its original size. The temperature threshold increases with age due to a greater number of thermally stable cross-linked hydrogen bonds (26). Increasing the temperature to 78 C or more leads to relaxation of contracted collagen and loss of tissue elasticity (24).

2.Tissue elasticity. The refractive effect is dependent on tissue resistance to collagen shrinkage (24). In younger patients, rigid corneal tissue will lead to limited initial response; greater elasticity of corneal tissue will increase regression of effect (25).

3.Keratocyte response. Keratocyte injury occurs when stromal collagen is heated to 79 C, which induces wound healing, including extracellular matrix remodeling and keratocyte activation (27). These changes contribute to postoperative regression of induced refractive effect.

4.Stability of corneal collagen. Normal replacement of treated collagen by newly synthesized collagen may also contribute to regression of refractive effect. Collagen turnover in the cornea is very slow, with a half-life of 10 years; the stability of corneal collagen after LTK is unknown (28,29).

C.CONTACT AND NONCONTACT LTK

The Ho:YAG laser delivery system can be used with a contact probe (Summit Technology, Waltham, MA, and Technomed, Baesweiler, Germany) or a noncontact device (Sunrise Technologies, Fremont, CA) (22,30). The contact probe allows for sequential delivery of laser pulses into premarked spots using a fiberoptic handpiece brought into direct contact with the cornea. The spot size is variable and dependent on the diameter of the fiber optic handpiece (Summit Technology, Waltham, MA, 0.7 mm; Technomed, Baesweiler, Germany, 0.55 mm). Depending on the degree of hyperopia, rings of eight spots are applied with a treatment zone of 6.5 and 9.0 mm, 7.0 and 9.0 mm, and 7.5 mm with the Summit Ho:YAG LTK and 6, 7, or 8 mm with the Technomed Ho:YAG LTK.

The noncontact Ho:YAG laser device allows for simultaneous delivery of eight laser pulses using a slit-lamp, with a fixed spot size of 0.60 mm. One, two or three radial or staggered concentric octagonal rings are placed at 6-to 8-mm ring diameters. This technology can be coupled with real-time wavefront measurements to minimize the unpredictability of the surgery.

D. PATIENT SELECTION

The noncontact Ho:YAG laser (Hyperion, Sunrise Technologies, Freemont, CA) was approved by the U.S. Food and Drug Administration (FDA) in June 2000 for the temporary reduction of hyperopia in patients with the following indications:

1.Age 40 years

2.Manifest refraction spherical equivalent of 0.75 to 2.5 diopters

3.Cylindrical correction 0.75 diopters

4.Stable refraction 6 months prior to the procedure

LTK is contraindicated in patients:

1.During pregnancy or while nursing

2.With keratoconus

3.With clinically significant corneal dystrophy or scarring in the 6-or 7-mm central zone

4.With a history of herpetic keratitis

5.With an autoimmune disease, collagen vascular disease, clinically significant atopic syndrome, insulin-dependent diabetes or an immunocompromised state

Patient evaluation includes visual assessment with both uncorrected and best-cor- rected visual acuity with cycloplegic refraction. Intraocular pressure should be measured to exclude narrow-angle glaucoma in hyperopic patients. A poor LTK effect is observed in patients with high intraocular pressure (31). Corneal topography is performed to determine

presence of irregular astigmatism. Pachymetry is helpful, because thinner corneas have greater effect with LTK. Systemic anti-inflammatory medications should be avoided 2 months preoperatively and 3 months postoperatively due to their contribution to regression of refractive effect. Wavefront-guided LTK studies are underway, but have not been approved as of yet by the FDA.

E. SURGICAL PROCEDURE

1. Contact LTK

With the contact Ho:YAG laser (Summit Technology, Waltham, MA, and Technomed, Baesweiler, Germany), energy is delivered through a quartz fiberoptic probe handpiece and focused by a disposable tip at the corneal surface with a cone angle of 120 (32). Preoperatively, patients are given topical tetracaine anesthesia and the pupil is constricted with 1% pilocarpine. The optical zone center is located using coaxial fixation and marked over the center of the pupil. Probe placement is guided by using a specially designed marker with radial and arcuate marks. The probe tip is applied perpendicular to the corneal surface at the intersection of the radial and arcuate marks. The laser energy is set at 19 mJ per pulse for 25 pulses, pulse duration of 300 ms, with a repetition rate of 15 Hz. The patients receive either 8 or 16 spots at variable optical zones. Loose epithelium is debrided with a weck-cell sponge from the treatment areas after and the eye is patched after administering antibiotic/steroid ointment. Postoperatively, patients receive tobramycin 0.3%/dexamethazone 0.1% ointment five times daily until re-epithelialization.

2. Noncontact LTK

The noncontact Ho:YAG laser (Hyperion, Sunrise Technologies, Fremont, CA) is a solidstate, pulsed laser connected to a slit-lamp delivery system (Nikon) capable of projecting eight uniform beams in an octagonal ring (33). Each beam has an individual shutter with adjustable optical zone diameters, allowing for different treatment patterns. The laser energy is set from 21 to 25 mJ per pulse for 5 to 10 pulses with a repetition rate of 5 Hz applied over several seconds. Two HeNe laser beams are used for alignment, centration, and coaxial focusing. Preoperatively, topical anesthetic drops (0.5% proparacaine solution) are administered, starting 20 min before treatment, for a total of four drops. A lid speculum is inserted to allow the eyelids to be held open for 3 min before laser application to dry the tear film. This helps standardize the effects of epithelial swelling and corneal hydration on delivery of laser energy to the corneal stroma. The patient is instructed to fixate on a flickering red light during laser application. The ring diameter and number of rings applied depends on the desired correction. Postoperatively, patients are given 0.3% tobramycin and diclofenac sodium drops four times daily until the epithelium is healed. Patients may also take acetaminophen or acetaminophen with codeine for pain management. In realtime wavefront-guided LTK, the energy per pulse can be adjusted to improve the surgical outcomes.

F. VISUAL OUTCOMES

1. Contact LTK

The safety of contact Ho:YAG LTK was initially established in 33 human cadaver and 4 blind human eyes (21). Sixteen coagulations on two concentric rings, with diameters of 6 and 9 mm, were applied. This resulted in central corneal steepening with a refractive

change that increased with the applied pulse energy above a threshold of 10 mJ per pulse, remaining constant between 15 and 35 mJ per pulse. Hyperopic shifts of up to 5.00 D were obtained, decreasing linearly with increasing diameter of treatment zone, which remained stable for 4 months.

Durrie et al. conducted FDA phase I and II trials for contact Ho:YAG LTK for low to moderate hyperopia (32). Patients in phase I had a mean spherical equivalent of 4.17 D ( 2.25 to 6.62 D). However, because of limited efficacy with higher refractive corrections, phase II included patients with a mean spherical equivalent of 1.50 D (0.00 to 4.25 D). One or two ring treatments with eight spots were applied at 7.0, 7.5, 7.0, and 9.0 and 6.5 and 9.0 mm. No patients saw J2 or better preoperatively, and 75% saw J2 or better 6 months postoperatively. In phase II, 79% of patients were within 1 D of emmetropia, and 89% of patients had uncorrected visual acuity of 20/40 or better at 1 year follow-up. After initial regression, the refractive results were stable at the 6-month follow-up for patients in both phase I and phase II. The phase I patients were followed for 1 year with further regression of effect. Tutton et al. treated 22 eyes by placing two rings with eight laser spots at 6.5 and 9.0 mm to produce a 4-D correction (34). Only 25% of patients were within 1.00 D of intended correction. In addition, 1.25 to2.50 D astigmatism was induced with 50% regression of refractive effect at 2 years postoperatively. Eggink et al. treated 55 hyperopic eyes with one ring of eight spots with a treatment diameter of 6, 7, or 8 mm (35). The 6- and 7-mm-diameter treatments were more effective than the 8-mm-diameter treatment zone. Twelve-month follow up did not show stability, and there was limited additive effect of retreatment.

Contact Ho:YAG LTK has also been used for correction of astigmatism (36–38). Corneal coagulation produces flattening in the peripheral cornea, accompanied by central steepening. This can be an effective treatment for steepening the flat axis in astigmatism. There is also a myopic shift in the spherical equivalent equal to one-half the steepening of the flat axis. Thompson et al. treated 30 eyes with four coagulation treatments with two spots placed on either side of an 8.5-mm ablation zone in the flat axis of the cylinder (38). The preoperative cylinder ranged from 1.50 to 4.00 D, with the average astigmatic correction obtained being 1.69 D ( 0.4 to 3.98 D). Uncorrected distance visual acuity improved by two or more lines in 18 eyes and remained unchanged in the other 8 eyes. There was a trend toward more astigmatic correction with increasing age as well as a trend toward a myopic shift in spherical equivalent. With limited efficacy of results and a high rate of regression of refractive effect, the FDA trials for contact LTK were discontinued.

2. Noncontact LTK

The safety of noncontact Ho:YAG LTK was initially established in humans with poorly sighted eyes. Ariyasu et al reported no evidence of endothelial cell loss, corneal thinning or neovascularization, persistent epithelial defects or change in intraocular pressure. (39) Table 1 summarizes the clinical trials conducted for noncontact Ho:YAG LTK. In the United States, the FDA phase II trial for low hyperopic correction by noncontact Ho:YAG LTK was conducted with 1-year follow-up (40). Twenty-eight patients with a preoperative spherical equivalent of 2.21 0.89 D (0.5 to 3.88 D) were treated with either one or two symmetrical staggered rings of eight spots per ring, with a diameter of 6 mm (one ring) or 6 and 7 mm (two rings). Ten pulses of laser light were applied at 5-Hz pulse frequency, with pulse energy ranging from 208 to 242 mJ. At 1 year postoperatively,

uncorrected distance visual acuity improved in all patients. The mean change in spherical equivalent was 0.55 0.33 D (one-ring treatment) and 1.64 0.61 D (two-ring treatment). After initial regression, there was good stability of refractive effect after 6 months. The mean induced refractive astigmatism was 0.25 0.29 D (1 ring) and 0.470.53 D (two rings). The extent of refractive change in each group was correlated with the amount of laser pulse energy using the following algorithms: for one-ring treatment, change in spherical equivalent (diopters) 3.20 0.0171 pulse energy; for two-ring treatment, change in spherical equivalent (diopters) 14.47 0.0685 pulse energy. Corneal topographic changes confirm peripheral corneal flattening and central corneal steepening, with a greater change in curvature being produced with two-ring treatment.(41) Two-year follow-up of low hyperopic treatment with eight spots at a 6 mm diameter revealed stable refractive effect, similar to the 1-year data (42). Eighteen-month follow up of low hyperopia treatment with two octagonal staggered rings at 6- and 7-mm diameter also confirmed stability of refractive results (43).

Two-ring treatments may be performed with radial or staggered rings of eight spots. Vinciguerra et al. compared the effects of the two treatment patterns in the correction of hyperopia with Ho:YAG LTK (44). The treatment consisted of 24 spots in three concentric rings of eight spots each, with ring diameters of 6, 7, and 8 mm. Each spot received seven pulses of laser energy. One eye of each patient received the radial ring pattern, while the fellow eye was treated with the staggered ring pattern. The radial and staggered patterns effectively corrected low hyperopia, and both were subject to regression. However, the radial pattern produced faster postoperative recovery of spectacle-corrected visual acuity and demonstrated greater refractive stability.

Histopathological studies of rabbit and human corneas have shown a direct correlation between the amount of pulse radiant energy and resulting acute tissue injury (25,45). These studies have shown that Ho:YAG laser irradiation produces acute epithelial and stromal tissue changes, which stimulate a brisk wound-healing response. The wound healing response has been correlated to rapid early regression of refractive effect. In order to determine whether regression correlates to initial pulse energy, a clinical trial was conducted using five pulses of laser light (1.2 J of total energy compared to 2.35 J with 10 pulses) for treatment of low to moderate hyperopia (46). Thirty-nine eyes with preoperative spherical equivalent of 2.95 0.97 D (1.50 to 4.75 D) were treated with two radial rings of eight spots with diameters of 5 and 6 mm (Group A), 6 and 7 mm (Group B), or 6.5 and 7.5 mm (Group C). Uncorrected distance visual acuity improved in all three groups at 1-year follow-up. The mean change in spherical equivalent was 2.08 1.13 D for Group A, 1.83 0.88 D for Group B and 1.22 0.88 D for Group C. In comparing the 10-pulse with the 5-pulse Ho:YAG treatment, there was less initial refractive effect with the 5-pulse treatment. However, there was also less regression, with increased stability of refractive effect. In addition, the duration of treatment for five pulses is reduced to 1 s, which is more comfortable for patients and less likely to produce irregular effects due to motion. Group C also showed reduced refractive effect when compared to groups A and B because of reduction in areal energy density with peripheral treatment. The induced refractive cylinder was greatest with group A, corresponding to the proximity of treatment spots to the central visual axis.

Regression of initial refractive effect can be large with Ho:YAG LTK. Alio et al. demonstrated a direct relationship between refractive regression, age, and measurements of central corneal thickness (47). In this study, 57 eyes, with a mean preoperative spherical equivalent of 3.80 0.22 D (1.50 to 5.00 D), were treated with Ho:YAG LTK, applying