Management of keratoconus with Intacs

Methods 

In this prospective nonrandomized clinical trial, 26 keratoconus patients (33 eyes), 17 males (65%) and 9 females (35%), 21 to 51 years (mean age was 32 ± 9.7 years) were included. All patients had clear central corneas and contact lens intolerance, whereas patients were excluded if any of the following criteria applied after the preoperative examination: previous intraocular or corneal surgery; history of herpes keratitis; diagnosed autoimmune disease; and systemic connective tissue disease.

All patients were appropriately informed before their participation in the study, and gave their written informed consent in accordance with institutional guidelines, according to the Declaration of Helsinki.

A complete ophthalmologic examination was performed preoperatively to exclude other ocular disease, and the preoperative as well as postoperative follow-up evaluation included uncorrected visual acuity (UCVA; decimal scale), best corrected visual acuity (BCVA; decimal scale), manifest refraction, keratometric data, and corneal topography. Postoperative visits were scheduled for days 1, 3, 15, and 30, and every 3 months thereafter.

Surgical procedure 

Operations were performed by two surgeons (C.S.S., I.G.P.). The surgical procedure was done under topical anesthesia. Two Intacs segments of 0.45-mm thickness were inserted so as to embrace the steepest keratoconus meridian, according to the topographic image, aiming at maximal flattening.

There were 19 eyes (57%) with topographically inferior corneal ectasia and 14 eyes (43%) with central corneal ectasia. In the first group two Intacs segments (0.45 mm) were inserted superiorly–inferiorly (embracing the steep axis; Figure 1), whereas in eyes with central keratoconus Intacs (0.45 mm) were inserted in the location used for low myopia procedure (nasally–temporally).

View Large Image Download to PowerPoint

FIGURE 1. Preoperative illustration: (A) Intacs position of insertion indicated (top right) and 12-month postoperative (B) topographies of a case of left eye keratoconus.

The corneal thickness was measured intraoperatively at the incision site and peripherally in the cornea along the ring placement markings with ultrasonic pachymetry (Sonogage, Cleveland, Ohio, USA). Using a diamond knife, set at 70% of the thinnest corneal measurement, a 0.9-mm radial incision was formed, and corneal pockets were created using two Sinskey hooks and a Suarez spreader. Two corneal tunnels were then formed using clockwise and counterclockwise dissectors under suction created by a vacuum-centering guide. The two polymethyl methacrylate (PMMA) segments (0.45-mm thickness) were implanted in the respective corneal tunnels, maintaining a space of approximately 2.0-mm between their ends and 1.5 mm between the opposite edge of each segment and the edge of the incision.

The incision site was sutured using a single 10/0 nylon stitch. All procedures were uneventful. Postoperatively, all eyes received antibiotic/corticosteroid combination eye drops four times daily for 2 weeks. In addition, all patients were instructed to avoid rubbing and to use preservative-free artificial tears frequently. The sutures were removed 2 weeks after surgery.

Results 

Intacs were successfully implanted in all eyes, although in one eye they were removed after 3 months because of their improper (superficial) placement. In addition, one patient’s Intacs were removed after 3 months of follow-up due to patient’s dissatisfaction, followed by a subsequent penetrating keratoplasty 3 months later. The mean follow-up was 11.3 ± 6.5 months (range, 1–24 months).

Visual acuity 

The mean UCVA significantly improved after Intacs implantation from 0.13 ± 0.14 (range, CF-0.50) to 0.39 ± 0.27 at the last follow-up (range, CF-1.00) (P < .01, paired t-test). Of 33 eyes, 2 eyes lost 1 line of UCVA, and 3 eyes maintained the preoperative UCVA, whereas the rest (28 eyes) experienced 1- to 10- line gain. The mean difference between preoperative and postoperative UCVA was a gain of 2.5 lines (range, loss of 1 line to a gain of 10 lines, FIGURE 2, FIGURE 3).

View Large Image Download to PowerPoint

FIGURE 2. Change in (A) uncorrected visual acuity (UCVA) and (B) best-corrected visual acuity (BCVA) (lines in decimal scale) between preoperative and the last postoperative follow-up.

View Large Image Download to PowerPoint

FIGURE 3. Mean (A) uncorrected visual acuity (UCVA) and (B) best-corrected visual acuity (BCVA) (decimal scale) after Intacs implantation. The error bars indicate 95% confidence intervals for the means.

Best-corrected visual acuity also significantly changed from 0.47 ± 0.31 (range, CF-1.00) to 0.64 ± 0.26 (range, 0.10-1.00) (P < .01, paired t-test). Of 33 eyes, 4 eyes experienced a 1- to 2-line loss of BCVA and 4 eyes maintained the preoperative BCVA, whereas the rest (25 eyes) experienced a 1- to 6-line gain. The mean difference between preoperative and last follow-up BCVA was a gain of 1.7 ± 1.9 lines (range, loss of 2 lines to gain of 6 lines; FIGURE 2, FIGURE 3). In parallel, the correlation between preoperative and last follow-up BCVA indicates a sufficiently invariable improvement (observable as the offset on the horizontal axis) (rsq = 0.62), while no similar effect was observed for the UCVA (rsq = 0.13; Figure 4A and 4B).

View Large Image Download to PowerPoint

FIGURE 4. Correlation between preoperative and postoperative (A) uncorrected visual acuity (UCVA) and (B) best-corrected visual acuity (BCVA).

Topographic findings (keratometric values 

A significant reduction in keratometric values was found at the last follow-up examination. Mean preoperative keratometry from 50.86 diopters ± 6.62 diopters (range, 41.67 diopters–71.00 diopters) significantly changed to 47.63 diopters ± 5.41 diopters (range, 37.54–57.56 diopters; P < .01) at last follow-up with a mean reduction of 1.94 diopters ± 3.51 diopters (range, + 4.56 diopters to −13.75 diopters; Figure 5A). The preoperative mean keratometric astigmatism was 3.33 ± 2.10 and the postoperative one was 3.06 ± 2.14. These differences were not statistically significant (P = .44)

View Large Image Download to PowerPoint

FIGURE 5. Changes in mean (A) keratometric indications and (B) spherical equivalent refraction during the follow-up period. The error bars indicate 95% confidence intervals for the means.

Visual acuity versus site of Intacs placement 

There were no statistically significant differences in changes of UCVA and BCVA between patients with central (temporally and nasally placed segments) and inferior cone (superiorly and inferiorly placed segments) after Intacs implantation (UCVA: gain 3.50 ± 3.03 vs 2.16 ± 2.04 lines, P = .19; BCVA: gain 2.50 ± 1.70 vs 1.36 ± 1.88 lines, P = .08; Figure 6A and B).

View Large Image Download to PowerPoint

FIGURE 6. Correlation between changes in (A) uncorrected visual acuity (UCVA), (B) best-corrected visual acuity (BCVA), and Intacs placement (according to the area of cone; mean ± SD).

Adverse effects and postoperative complications 

In one eye, 6 months after Intacs implantation, a significant decrease in UCVA (from 0.4 to CF) and BCVA (from 0.8 with contact lens to 0.2) and increases in topographic irregularity were observed (Figure 7A and B). We decided to remove the superior segment and to advance the inferior segment to further embrace the keratoconus area. Three months later, the patient had a remarkable and unexpected increase in UCVA (0.8), BCVA (0.9) and in the topographic findings, which remained stable at the last follow-up 10 months later (Figure 7C and D).

View Large Image Download to PowerPoint

FIGURE 7. (A) Preoperative topography illustration. Postoperative topographies: (B) 2 weeks after two Intacs segments insertion; (C) 10-months after upper segment removal; (D) an illustration of right eye keratoconus where the upper segment was removed.

In another eye (with central cone), due to superficial placement of one segment and lack of improvement of the patient’s data, we decided to remove the segments after 3 months of follow-up. No significant alterations in the preoperative data were found after this manipulation.

In one eye, because of patient’s dissatisfaction, Intacs were removed followed by a PKP after 3 months. Penetrating keratoplasty was uneventful, and after 6 months of follow-up there was no evidence of any postoperative complications.

At 6 months the majority of eyes demonstrated mild channel deposits at the inner edge of the segments. In one eye superficial mild wound site neovascularization was found after 2 months, which remains stable during the follow-up of 11.3 months and without any changes in visual acuity or topographic findings.

Discussion 

The procedure of PKP for keratoconus has significantly improved during the past few decades. Currently, PKP results in moderate regular and irregular astigmatism, which is easily managed by various surgical techniques.17, 18 The complication rate (such as corticosteroid side effects and allograft reactions) has decreased during the last decade.19

In the year 2000, Colin and associates15 first published an article about their preliminary results regarding the management of keratoconus with Intacs. One year later, the same authors published a series of 10 keratoconic patients 1-year after Intacs implantation20 where they support that Intacs reduced the corneal steepening and astigmatism, while visual acuity was improved in almost all eyes. The surgical procedure was similar to that for low myopia correction, except the Intacs segment thickness and location of incision site. The authors used a temporal incision in all patients while a 0.45-mm thickness segment was inserted inferiorly and a 0.25-mm segment superiorly to counterbalance and flatten the overall anterior corneal surface.

In our study we used a different surgical approach, in which two same-thickness segments (0.45-mm) were inserted in all eyes. We used this approach because we believe that the intended tectonical changes in the disarray keratoconic cornea should have the maximum effect. Despite the differences between the two methods, it seems that Intacs improve UCVA, BCVA, refraction, and topographic findings in keratoconic patients. In addition, in our study there were 14 keratoconic eyes with central keratoconus. In these patients Intacs were implanted in the same position as in the low myopia procedure (nasally–temporally) without significant differences in the effect of Intacs between these eyes and those implanted superiorly–inferiorly.

An important finding was that there were a few patients who did not show improvement of UCVA (3 eyes, 9%) and BCVA (4 eyes, 12%), whereas in another group of patients a reduction in UCVA (2 eyes, 6%) and BCVA (4 eyes, 12%) was observed. Loss of lines or unchanged BCVA did not necessarily correlate with patient dissatisfaction, because some of these patients experienced a significant gain of UCVA. Regarding UCVA, however, a statistically significant increase in preoperative mean spherical equivalent refraction and an increase in mean average keratometric values were found in eyes that Intacs implantation did not change or decreased UCVA in comparison with eyes with post-Intacs implantation improvement. It seems that Intacs have less effect in more advanced stages of disease, while encouraging results were found in early stages.

An advantage of this method is that Intacs are removable. One patient underwent Intacs removal, followed by PKP after 3 months (estimated by the authors to be sufficient period of time) without any complications. This one patient, however, certainly cannot eliminate the concern for the effect on the success rate of PKP after Intacs removal.

Several questions arise from complicated cases. We were surprised by the significant improvement in the patient who underwent superior segment removal. These findings support that we are indeed unable to predict the effect of Intacs in keratoconic patients.

Even though the sample of eyes that completed a 2-year follow-up is small (4 eyes), it seems that the major changes in visual acuity, refraction, and topographic findings took place during the first 9 months, while a trend for stable results was observed after this period. These results are in controversy with the results of Intacs implantation in low myopia patients, where stability in refraction and visual acuity after the third month are observed.14 This is very important when Intacs are used for keratoconus, where more time must probably be given to come out with final conclusions about the effect of Intacs in these eyes. How much time that will be, is a question to which the authors have no answer for to date.

The question that arises from our results and those of other investigators is whether Intacs can replace in selected cases PKP. We believe that the results of Intacs implantation are very preliminary, and despite the initial enthusiasm, as long as we do not have sufficient concrete data regarding patient selection and predictability of the procedure, Intacs could be considered as a new alternative minimally invasive method that is under investigation and, at the present time, cannot replace the importance of PKP in the treatment of these patients. Indeed, the assumption that Intacs can stabilize keratoconus and prevent its progression is at this point anecdotal. Additionally, to rationalize the keratoconus patients’ expectations and to protect this new method, the patients must be informed that Intacs are a new promising alternative therapy that has come to complement the keratoconic patients’ treatment and not to replace PKP (at least for the present). This is essential because this method is under investigation with preliminary results. The possibility of not satisfying the exceeding patients’ expectations could lead to a negative and mistrustful approach to any other therapeutic method.

In conclusion, after a mean follow-up of 11.3 months, Intacs seem to offer a minimally invasive alternative treatment before PKP for keratoconus patients with clear corneas and contact lens intolerance, especially in early stages of the disease with less topographic irregularities.