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Biomechanical and morphological corneal response to placement of intrastromal corneal ring segments for keratoconus
ARTICLE
Biomechanical and morphological corneal response to placement of intrastromal corneal ring segments for keratoconus Caroline Dauwe, David Touboul, MD, Cynthia J. Roberts, PhD, Ashraf M. Mahmoud, Julien Ke´rautret, MD, Pierre Fournier, MD, Franc¸ois Malecaze, MD, Joseph Colin, MD
PURPOSE: To evaluate the biomechanical and morphological changes in keratoconic corneas after Intacs intrastromal corneal ring segment (ICRS) implantation. SETTING: Department of Ophthalmology, National Reference Center for Keratoconus, Bordeaux University, Bordeaux, France. METHODS: Keratoconic eyes were retrospectively analyzed after ICRS implantation; preoperative and 6-month postoperative evaluation were done using the Ocular Response Analyzer (ORA) and the Orbscan II topographer. Biomechanical parameters included corneal hysteresis (CH), the corneal resistance factor (CRF), and other parameters extracted from the signal curves. Morphological parameters included simulated keratometry and the cone location magnitude index from the axial map (aCLMI) and tangential map (tCLMI). Parameters were extracted using software designed to read and process topographic maps. RESULTS: There were no significant differences between preoperatively and postoperatively in mean CH (7.7 mm Hg G 1.4 [SD] versus 7.4 G 1.4 mm Hg) or mean CRF (6.6 G 1.8 mm Hg versus 6.1 G 1.4 mm Hg). Only 2 ORA signal parameters were significantly different. Topographic parameters with significant decreases were minimum central keratometry (K) (mean change 5.8 G 2.9 diopters [D]) (P<.001), minimum central K (mean change 5.8 G 2.3 D) (P<.001), mean aCLMI (9.6 G 2.7 preoperatively versus 7.7 G 2.5 postoperatively) (P<.009), and mean tCLMI (18.9 G 2.8 versus 12.9 G 4.4) (P<.002). The only significant correlation between biomechanical and topographic parameters was postoperative ORA infrared signal peak 1 and postoperative aCLMI. CONCLUSIONS: Intrastromal corneal ring implantation significantly decreased corneal curvature, with preoperative values predicting magnitude of change. However, it did not alter the viscoelastic biomechanical parameters of CH and CRF. J Cataract Refract Surg 2009; 35:1761–1767 Q 2009 ASCRS and ESCRS
With a prevalence of 1 in 2000 persons in the general population, keratoconus is considered a rare disease.1,2 This idiopathic corneal dystrophy is characterized by progressive bulging and thinning of the stromal layer of the cornea, so-called corneal ectasia. The treatment for mild to moderate cases of keratoconus consists of wearing glasses and/or contact lenses. Most patients wear rigid gas-permeable contact lenses and have satisfactory tolerance to the lenses.3 Eyes with a severe stage of the disease, patients with contact lens intolerance, and cases in which vision remains insufficient because of apical opacities may require corneal surgery. When the cornea is still transparent, intrastromal corneal ring segments (ICRS) can Q 2009 ASCRS and ESCRS Published by Elsevier Inc.
be used to flatten the central cornea. When the cornea is very deformed or is opaque in the center, a corneal graft is the only option.4 The aim of ICRS implantation is to reshape the corneal surface to avoid or delay the need for penetrating keratoplasty. Intacs (Addition Technology, Inc.) were initially used in 1987 to correct low myopia by flattening the central cornea. In 1998, Colin et al.5 proposed using these ICRS in eyes with keratoconus. Implantation of ICRS is an additive technique. The ICRS reinforces the cornea and thus decreases asymmetrical astigmatism and the convexity of the cone, which improves visual acuity, with or without correction, in most cases.6,7 0886-3350/09/$dsee front matter doi:10.1016/j.jcrs.2009.05.033
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The major changes in refraction and topographic findings after ICRS implantation usually take place in the early postoperative period. However, results should only be evaluated 6 months after the surgery because keratoconic corneas require time to stabilize because of their viscoelastic nature.8 The morphologic effect of ICRS implantation in eyes with keratoconus is well known; however, the effect on the biomechanical properties of tissue has not been reported. The purpose of this study was to evaluate the difference in corneal biomechanical parameters before and after placement of ICRS in eyes with keratoconus and to correlate these parameters with morphological parameters measured by topography. PATIENTS AND METHODS This retrospective study comprised 1 eye of consecutive patients diagnosed with keratoconus by an experienced clinician. All patients were examined at the Reference National Centre for Keratoconus (CRNK). Indications for ICRS implantation included keratoconus and intolerance to contact lenses. Patients were excluded if the central cornea was not clear, the peripheral pachymetry was less than 450 mm, or the maximum central keratometry was more than 60.00 diopters (D). The same surgeon (J.C.) performed all ICRS implantations using topical anesthesia, as described by Colin et al.5 Two 0.45 mm thick Intacs segments were inserted to embrace the steepest keratoconus meridian according to the measured topography, with the goal of maximum flattening. Preoperatively and 6 months postoperatively, all patients had a complete ocular examination. The examination included medical history, visual acuity with and without correction, slitlamp evaluation, and refraction obtained by corneal topography (Orbscan II, Bausch & Lomb) or autokeratometry (Speedy K, Nidek, Inc.). All eyes were also evaluated with an ocular response analyzer (ORA) (Ocular Response Analyzer, Reichert), which dynamically measures the cornea’s biomechanic response to an air pulse.9,10 The air pulse is applied over the central cornea to illicit inward and outward applanation events
Submitted: January 29, 2009. Final revision submitted: April 29, 2009. Accepted: May 5, 2009. From the Departments of Ophthalmology, Reference National Centers for Keratoconus, Bordeaux University (Dauwe, Touboul, Ke´rautret, Colin), Bordeaux, and Toulouse University (Malecaze), Toulouse, France; the Departments of Ophthalmology and Biomedical Engineering (Roberts, Mahmoud), Ohio State University, Columbus, Ohio, USA. No author has a financial or proprietary interest in any material or method mentioned. Corresponding author: David Touboul, MD, Reference National Center for Keratoconus (CRNK), CHU Bordeaux, Pellegrin, Pr. Joseph Colin Department of Ophthalmology, Place Ame´lie RabaLe´on, 33000, Bordeaux, France. E-mail: [email protected].
and thus characterize the cornea’s viscoelastic response to the pressure curve of the applied air. The collimated air pulse causes the cornea to move inward and become slightly concave. Immediately after applanation, the air pump shuts off and the pressure continues to increase due to inertia in the piston, before it declines in a smooth fashion. As the pressure decreases, the cornea begins to return to its normal configuration. In the process, it again passes through an applanated state. However, because of its viscoelastic characteristics, the cornea resists the dynamic force of the air pulse, causing a pressure delay between the inward and outward applanation, resulting in 2 pressure values. The applanation detection system monitors the cornea throughout the process, which takes milliseconds. This measurement provides 4 numerical parameters. The first is corneal hysteresis (CH), which is defined as the difference between the inward and outward applanation pressures. It is considered a numerical characterization of the corneal tissue’s viscoelastic response to a dynamic deformation. The CH is the result of energy being absorbed or dissipated in the corneal tissue. The second is the corneal resistance factor (CRF), which is calculated using a linear combination of inward and outward applanation pressures. It was empirically determined with the goal of generating the maximum correlation with central corneal thickness (Luce D. IOVS 2006; 47:ARVO E-Abstract 2266). Therefore, it is weighted by elasticity but still represents a viscoelastic parameter. Keratoconus is usually associated with lower CH and CRF values than in normal eyes and with an abnormal profile shape9,11 (Mahmoud AM, et al. IOVS 2007; 48:ARVO E-Abstract 1843). The third is the cornealcompensated intraocular pressure (IOPcc), which was designed to compensate for the effect of the cornea on the IOP measurement process. The IOPcc was also empirically determined by Luce. The fourth, the Goldmann-correlated IOP, is the average of the 2 applanation pressure values. For the subset of eyes with both ORA and Orbscan II topographic data, the ORA signals and the topographic maps were further analyzed using purpose-designed software for topographic data12 and ORA data13 (Mahmoud AM, et al. IOVS 2000; 41:ARVO Abstract 3599; Rouse EJ, et al. IOVS 2007; 48:ARVO E-Abstract 1247). From the ORA signal, the following parameters were extracted: peak 1 and peak 2 (maximum heights of the corresponding infrared signal peaks), time 1 and time 2 (timing of the corresponding infrared signal peaks), FWHM 1 and FWHM 2 (full width at half maximum of the corresponding infrared signal peaks), slope 1 and slope 2 (slopes of the pressure curve at the time of the corresponding infrared applanation peaks), Pmax (maximum value of the air pressure curve), Tpmax (time of maximum air pressure), P1 and P2 (air pressure corresponding to infrared signal peaks). From the Orbscan II topographic maps, the following indices were determined: CLMI (cone location and magnitude index)14 and Mt (maximum tangential curvature overlying the cone) (Mahmoud AM, et al. IOVS 2001; 42:ARVO Abstract 4825). The CLMI is a relative index calculated by using a search routine to locate the 2.0 mm region of greatest curvature on the map; that region is compared with a corresponding 2.0 mm region 180 degrees away to check for asymmetry and an area-corrected difference with the average curvature of the remaining area of the map is determined. The CLMI can be calculated on the axial map (aCLMI) in general practice for keratoconus-screening purposes. The CLMI on the tangential map (tCLMI) is used in eyes with diagnosed keratoconus to track disease
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progression. The Mt represents an absolute index describing the mean value inside the 2.0 mm diameter region of greatest curvature on the tangential map overlying the cone in keratoconus.
Table 1. Intrastromal corneal ring measurements and surgical characteristics.
RESULTS The study evaluated 18 eyes of 18 patients (10 men, 8 women) with a mean age of 31.3 years (range 13 to 50 years). The keratoconus was bilateral in 16 patients and unilateral in 2 patients. Keratometry was obtained by corneal topography in 15 eyes and by autokeratometry in 3 eyes. Table 1 shows the ICRS measurements and surgical characteristics by patient. The mean central corneal thickness was 483 mm; the mean peripheral corneal thickness, 596 mm; and the mean incision depth, 397 mm. The ICRS were implanted successfully in all eyes. There were no perioperative or postoperative surgical complications. Table 2 shows the preoperative and 6-month postoperative CH, CRF, IOPcc, maximum central K, and minimum central K as well as the change in K. There were no statistically significant differences between preoperatively and postoperatively in mean CH (7.7 mm Hg G 1.4 [SD] versus 7.4 G 1.4 mm Hg), mean CRF (6.6 G 1.8 mm Hg versus 6.1 G 1.4 mm Hg), or the difference parameter CH–CRF (PO.05). In 2 parameters extracted from the ORA signal, the
Pt
Eye
Central CCT (mm)
Peripheral PCT (mm)
Incision Depth (mm)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
R L L R R L L R R L L L L R L R R L
460 440 482 570 360 485 NA 480 480 480 460 550 528 480 465 520 480 488
580 570 590 660 560 581 579 580 640 600 590 610 560 640 605 620 570 600
386 380 393 440 373 387 386 386 426 400 393 406 373 426 403 413 380 400
CCT Z central corneal thickness; NA Z not available; PCT Z peripheral corneal thickness; Pt Z patient
difference between the preoperative and postoperative measurements was statistically significant. The mean maximum height of the infrared signal at the
Table 2. Preoperative and postoperative CH, CRF, maximum central K, and minimum central K and the change in K.
Preoperative
Preop to Postop Change
Postoperative
Pt
Eye
CH
CRF
Kmax
Kmin
CH
CRF
Kmax
Kmin
Kmax
Kmin
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
R L L R R L L R R L L L L R L R R L
7.7 6.9 6.9 11.2 9.1 6.9 8.5 9.7 7.7 6.0 7.1 7.1 5.9 6.6 7.4 9.1 7.6 7.0
5.6 7.4 5.4 10.7 8.1 5.6 6.8 10.7 5.2 4.9 6.4 6.9 5.3 5.6 5.9 7.7 5.6 4.5
NA 58.1 51.7 55.3 58.2 51.7 52.2 54.6 49.1 NA 61.8 48.7 47.3 56.0 58.2 53.9 48.2 53.9
NA 51.6 47.0 43.3 55.7 49.0 47.7 44.6 44.1 NA 47.5 43.5 40.6 47.9 51.2 48.3 41.6 52.0
9.2 5.5 7.2 11.2 8.8 8.0 5.9 6.4 8.4 6.4 6.6 7.5 6.5 7.5 7.7 7.7 7.3 6.2
7.3 4.3 6.3 9.5 6.7 7.3 4.5 5.8 5.5 7.2 5.6 6.9 4.6 5.6 6.9 6.6 6.1 3.6
59.6 NA 48.7 48.2 50.0 47.2 51.2 46.1 43.9 NA 52.3 46.5 45.0 50.7 51.3 47.1 41 50.3
50.8 NA 40.6 35.9 44.2 44.6 45.7 39.1 38.9 NA 38.9 42.8 37.9 42 44.3 43.6 37.3 41.9
NA NA 3.0 7.1 8.2 4.5 6.8 8.5 5.2 NA 9.5 2.2 2.3 5.3 6.9 6.8 6.5 3.6
NA NA 6.4 7.4 11.5 4.4 3.3 5.5 5.2 NA 8.6 0.7 2.7 5.9 6.9 4.7 3.4 10.1
CH Z corneal hysteresis; CRF Z corneal resistance factor; Kmax Z maximum central keratometry; Kmin Z minimum central keratometry; NA Z not available; Pt Z patient
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Figure 1. Preoperative ORA profile showing CH (App Z applanation; CCT Z central corneal thickness; CRF Z corneal resistance factor; IOPcc Z corneal-compensated intraocular pressure; IOPg Z Goldmann-correlated intraocular pressure).
Figure 2. Postperative ORA profile showing CH (App Z applanation; CCT Z central corneal thickness; CRF Z corneal resistance factor; IOPcc Z corneal-compensated intraocular pressure; IOPg Z Goldmann-correlated intraocular pressure).
second outward applanation event (peak 2) decreased from 376 G 128 signal intensity units to 270 G 100 signal intensity units (P!.002). However, the decreased infrared signal peak did not affect the pressure (P2) at which the applanation event occurred; thus, CH was unaffected. Also, the width of the infrared peak during the first applanation event (FWHM 1) decreased from 12.3 G 3.0 milliseconds to 10.3 G 2.8 milliseconds (P!.046). In none of the remaining signal parameters was the difference between the preoperative and postoperative measurements statistically significant; that is, the ORA signal shape was similar at the 2 time periods. There was a trend toward decreased applanation curve oscillations postoperatively. Figure 1 and Figure 2 show ORA signals of the same cornea before surgery and after surgery, respectively. Corneal topography showed a mean minimum central K value of 47.2 D (range 40.6 to 55.7 D) and a mean maximum central K value of 53.7 D (range 47.3 to 61.8 D). After surgery, the means were 41.8 D (range 35.9 to 50.8 D) and 48.7 D (range 41.0 to 59.6 D), respectively. Both mean K values decreased more than 5.0 D after ICRS implantation (Table 3); the decreases were statistically significant (P!.0001). One patient was excluded from the corneal topography subset analysis because of poor peripheral
coverage, which affected calculation of the indices. Figures 3 and 4 show examples of aCLMI and tCLMI maps. The Mt index (mean curvature in 2.0 mm area over the cone) decreased significantly (mean 4.6 D) after surgery (P!.001). The decrease was significantly predicted by the preoperative magnitude of the cone (P!.007, r2 Z 0.43), with a greater preoperative conecurvature producing greater induced flattening (Figure 5). The decrease in the aCLMI and tCLMI relative indices from preoperatively to postoperatively was also statistically significant (mean 9.6 G 2.7 versus 7.7 G 2.5 [P!.009] and 18.9 G 2.8 versus 12.9 G 4.4 [P!.002], respectively). The decrease in tCLMI was significantly predicted by preoperative tCLMI (P!.011, r2 Z 0.38), with a greater preoperative tCLMI producing a greater decrease (Figure 6). The only statistically significant correlation between biomechanical parameters and topographic parameters was between postoperative ORA peak 1 and postoperative aCLMI (P!.022, r2 Z 0.32) (Figure 7); a lower aCLMI (less severe keratoconus) was associated with a higher peak 1, indicating a stiffer cornea and that more severe keratoconus produces a smaller or nonuniform area of applanation, reducing the infrared peak. Preoperatively, the correlation was not significant, perhaps because the range of CLMI values was too low to produce a significant relationship. A postoperative reduction in CLMI led to an increased range, showing a significant correlation.
Table 3. Mean decrease in maximum and minimum central and 95% confidence intervals. 95% CI Parameter Kmax Kmin
Mean Decrease (D) G SD
Lower
Upper
5.8 G 2.3 5.8 G 2.9
1.3 0.1
10.3 11.5
CI Z confidence interval; Kmax Z maximum central keratometry; Kmin Z minimum central keratometry
DISCUSSION The goal of ICRS implantation is to stabilize and reinforce the ectatic cornea rather than weaken the structural integrity through an incision or ablation. The maximum and minimum central topographic K values as well as aCLMI, tCLMI, and Mt decreased postoperatively, which confirms that Intacs implantation
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Figure 3. Preoperative axial map (left) and tangential map (right) of cone location and magnitude index (CLMI).
can reduce the corneal steepening and astigmatism associated with keratoconus. It takes approximately 6 months for ICRS implantation to show an effect on the cornea and improve the visual acuity because of the viscoelastic nature of the cornea. In our study, which had a 6-month follow-up, it was still too early in the postoperative period to consider the changes in uncorrected distance visual acuity and corrected distance visual acuity.7,8 The goal of our study was to correlate the morphological topography changes in keratoconus with biomechanical parameters from the ORA. We did not find significant changes in the CH and CRF values between preoperatively and postoperatively and found only 2 significant changes in the ORA signal. The decrease in peak 2 and FWHM 1 may have been because a smaller area of the cornea was available for deformation by the artificial limbus created by the segments. Although the ORA measurement area is defined by the device’s manufacturer as the central 3.0 mm, a larger region of the cornea is likely involved in the deformation process, which would be limited by
ICRS placement. This would result in less infrared light impinging on the detector and a lower recovery peak in the infrared signal. The smaller infrared peak 2 did not affect the outward applanation pressure (P2) at which it occurred. Thus, neither CH nor CRF were affected. The decrease in FWHM 1 indicates that the cornea deformed more rapidly postoperatively than preoperatively, which also may be due to a more limited area for corneal deformation after ICRS placement (consistent with Glass DH, et al. IOVS 2008; 49:ARVO E-Abstract 646). Therefore, these changes are probably not due to modification of the biomechanical properties themselves but are rather an indication of greater corneal stability. The qualitative reduction in signal oscillation postoperatively is further evidence of this stability. Corneal hysteresis and the CRF are not correlated with keratometry but rather with IOP and central pachymetry11 (Luce D. IOVS 2006; 47:ARVO E-Abstract 2266). In our study, both IOP and central pachymetry remained stable postoperatively and thus played a role in the lack of a significant change in CH and
Figure 4. Postoperative axial map (left) and tangential map (right) of cone location and magnitude index (CLMI).
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Figure 5. Preoperative Mt versus induced change in Mt (Mt Z maximum tangential curvature overlying the cone).
Figure 6. Preoperative tCLMI versus induced change in tCLMI (tCLMI Z tangential cone location and magnitude index).
CRF values. We hypothesize that because of the lamellar structure of the cornea, the ICRS segments might reshape the center of the cornea (biometry) without changing the fundamental biomechanical properties of the corneal tissue, at least in the short-term postoperative period. It would be interesting to compare Intacs segments with smaller intracorneal rings such as Ferrara rings. According to our preliminary surgical results, Ferrara rings may be more powerful in reshaping because of the higher slope between the center of the cornea and the edges of the implanted rings. We noticed that ORA profiles had only minor differences before and after Intacs implantation. We thus conclude that the segments do not interfere with ORA measurements. To our knowledge, this is the first study that shows that Intacs placement changes the morphological characteristics of the cornea but not the biomechanical viscoelastic response parameters, such as CH and CRF. The changes in the ORA infrared signal likely
correspond to greater stability of the cornea, including fewer oscillations, greater speed of deformation, and a lower recovery peak 2. However, our study is preliminary. A study with more cases and a longer follow-up is necessary to determine the effect of Intacs implantation on CH and CRF in patients with keratoconus. A long-term study would help draw conclusions about the evolution of keratoconus and corneal biomechanical properties after ICRS implantation.
Figure 7. Postoperative peak 1 versus postoperative aCLMI (aCLMI Z axial cone location and magnitude index).
REFERENCES 1. Kaya V, Utine CA, Altunsoy M, Oral D, Yilmaz OF. Evaluation of corneal topography with Orbscan II in first-degree relatives of patients with keratoconus. Cornea 2008; 27:531–534 2. Nichols JJ, Steger-May K, Edrington TB, Zadnik K. The relation between disease asymmetry and severity in keratoconus; the CLEK study group. Br J Ophthalmol 2004; 88:788–791. Available at: http://www.pubmedcentral.nih.gov/picrender.fcgi? artid=1772171&blobtype=pdf. Accessed June 20, 2009 3. Nepomuceno RL, Boxer Wachler BS, Weissman BA. Feasibility of contact lens fitting on keratoconus patients with INTACS inserts. Contact Lens Anterior Eye 2003; 26:175–180 4. Barr JT, Wilson BS, Gordon MO, Rah MJ, Riley C, Kollbaum PS, Zadnik K. Estimation of the incidence and factors predictive of corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study; the CLEK Study Group. Cornea 2006; 25:16–25 5. Colin J, Cochener B, Savary G, Malet F. Correcting keratoconus with intracorneal rings. J Cataract Refract Surg 2000; 26:1117–1122 6. Akaishi L, Tzelikis PF, Raber IM. Ferrara intracorneal ring implantation and cataract surgery for the correction of pellucid marginal corneal degeneration. J Cataract Refract Surg 2004; 30:2427–2430 7. Zare MA, Hashemi H, Salari MR. Intracorneal ring segment implantation for the management of keratoconus: safety and efficacy. J Cataract Refract Surg 2007; 33:1886–1891 8. Kymionis GD, Siganos CS, Tsiklis NS, Anastasakis A, Yoo SH, Pallikaris AI, Astyrakakis N, Pallikaris IG. Long-term follow-up of Intacs in keratoconus. Am J Ophthalmol 2007; 143:236–244 9. Luce DA. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg 2005; 31:156–162
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10. Kirwan C, O’Keefe M, Lanigan B. Corneal hysteresis and intraocular pressure measurement in children using the Reichert Ocular Response Analyzer. Am J Ophthalmol 2006; 142:990–992 11. Touboul D, Roberts CJ, Ke´rautret J, Garra C, Maurice-Tison S, Saubusse E, Colin J. Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry. J Cataract Refract Surg 2008; 34:616–622 12. Mahmoud AM, Roberts C, Lembach R, Herderick EE, McMahon TT. Simulation of machine-specific topographic indices for use across platforms; the CLEK Study Group. Optometry Vis Sci 2006; 83:682–693 13. Kerautret J, Colin J, Touboul D, Roberts C. Biomechanical characteristics of the ectatic cornea. J Cataract Refract Surg 2008; 34:510–513
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14. Mahmoud AM, Roberts CJ, Lembach RG, Twa MD, Herderick EE, McMahon TT. CLMI; the cone location and magnitude index; the CLEK Study Group. Cornea 2008; 27:480–487
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First author: Caroline Dauwe Department of Ophthalmology, Reference National Center for Keratoconus, Bordeaux University, Bordeaux, France
Biomechanical and morphological corneal response to placement of intrastromal corneal ring segments for keratoconus Caroline Dauwe, David Touboul, MD, Cynthia J. Roberts, PhD, Ashraf M. Mahmoud, Julien Ke´rautret, MD, Pierre Fournier, MD, Franc¸ois Malecaze, MD, Joseph Colin, MD
PURPOSE: To evaluate the biomechanical and morphological changes in keratoconic corneas after Intacs intrastromal corneal ring segment (ICRS) implantation. SETTING: Department of Ophthalmology, National Reference Center for Keratoconus, Bordeaux University, Bordeaux, France. METHODS: Keratoconic eyes were retrospectively analyzed after ICRS implantation; preoperative and 6-month postoperative evaluation were done using the Ocular Response Analyzer (ORA) and the Orbscan II topographer. Biomechanical parameters included corneal hysteresis (CH), the corneal resistance factor (CRF), and other parameters extracted from the signal curves. Morphological parameters included simulated keratometry and the cone location magnitude index from the axial map (aCLMI) and tangential map (tCLMI). Parameters were extracted using software designed to read and process topographic maps. RESULTS: There were no significant differences between preoperatively and postoperatively in mean CH (7.7 mm Hg G 1.4 [SD] versus 7.4 G 1.4 mm Hg) or mean CRF (6.6 G 1.8 mm Hg versus 6.1 G 1.4 mm Hg). Only 2 ORA signal parameters were significantly different. Topographic parameters with significant decreases were minimum central keratometry (K) (mean change 5.8 G 2.9 diopters [D]) (P<.001), minimum central K (mean change 5.8 G 2.3 D) (P<.001), mean aCLMI (9.6 G 2.7 preoperatively versus 7.7 G 2.5 postoperatively) (P<.009), and mean tCLMI (18.9 G 2.8 versus 12.9 G 4.4) (P<.002). The only significant correlation between biomechanical and topographic parameters was postoperative ORA infrared signal peak 1 and postoperative aCLMI. CONCLUSIONS: Intrastromal corneal ring implantation significantly decreased corneal curvature, with preoperative values predicting magnitude of change. However, it did not alter the viscoelastic biomechanical parameters of CH and CRF. J Cataract Refract Surg 2009; 35:1761–1767 Q 2009 ASCRS and ESCRS
With a prevalence of 1 in 2000 persons in the general population, keratoconus is considered a rare disease.1,2 This idiopathic corneal dystrophy is characterized by progressive bulging and thinning of the stromal layer of the cornea, so-called corneal ectasia. The treatment for mild to moderate cases of keratoconus consists of wearing glasses and/or contact lenses. Most patients wear rigid gas-permeable contact lenses and have satisfactory tolerance to the lenses.3 Eyes with a severe stage of the disease, patients with contact lens intolerance, and cases in which vision remains insufficient because of apical opacities may require corneal surgery. When the cornea is still transparent, intrastromal corneal ring segments (ICRS) can Q 2009 ASCRS and ESCRS Published by Elsevier Inc.
be used to flatten the central cornea. When the cornea is very deformed or is opaque in the center, a corneal graft is the only option.4 The aim of ICRS implantation is to reshape the corneal surface to avoid or delay the need for penetrating keratoplasty. Intacs (Addition Technology, Inc.) were initially used in 1987 to correct low myopia by flattening the central cornea. In 1998, Colin et al.5 proposed using these ICRS in eyes with keratoconus. Implantation of ICRS is an additive technique. The ICRS reinforces the cornea and thus decreases asymmetrical astigmatism and the convexity of the cone, which improves visual acuity, with or without correction, in most cases.6,7 0886-3350/09/$dsee front matter doi:10.1016/j.jcrs.2009.05.033
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BIOMECHANICAL AND MORPHOLOGICAL CORNEAL RESPONSE TO INTRASTROMAL CORNEAL RINGS
The major changes in refraction and topographic findings after ICRS implantation usually take place in the early postoperative period. However, results should only be evaluated 6 months after the surgery because keratoconic corneas require time to stabilize because of their viscoelastic nature.8 The morphologic effect of ICRS implantation in eyes with keratoconus is well known; however, the effect on the biomechanical properties of tissue has not been reported. The purpose of this study was to evaluate the difference in corneal biomechanical parameters before and after placement of ICRS in eyes with keratoconus and to correlate these parameters with morphological parameters measured by topography. PATIENTS AND METHODS This retrospective study comprised 1 eye of consecutive patients diagnosed with keratoconus by an experienced clinician. All patients were examined at the Reference National Centre for Keratoconus (CRNK). Indications for ICRS implantation included keratoconus and intolerance to contact lenses. Patients were excluded if the central cornea was not clear, the peripheral pachymetry was less than 450 mm, or the maximum central keratometry was more than 60.00 diopters (D). The same surgeon (J.C.) performed all ICRS implantations using topical anesthesia, as described by Colin et al.5 Two 0.45 mm thick Intacs segments were inserted to embrace the steepest keratoconus meridian according to the measured topography, with the goal of maximum flattening. Preoperatively and 6 months postoperatively, all patients had a complete ocular examination. The examination included medical history, visual acuity with and without correction, slitlamp evaluation, and refraction obtained by corneal topography (Orbscan II, Bausch & Lomb) or autokeratometry (Speedy K, Nidek, Inc.). All eyes were also evaluated with an ocular response analyzer (ORA) (Ocular Response Analyzer, Reichert), which dynamically measures the cornea’s biomechanic response to an air pulse.9,10 The air pulse is applied over the central cornea to illicit inward and outward applanation events
Submitted: January 29, 2009. Final revision submitted: April 29, 2009. Accepted: May 5, 2009. From the Departments of Ophthalmology, Reference National Centers for Keratoconus, Bordeaux University (Dauwe, Touboul, Ke´rautret, Colin), Bordeaux, and Toulouse University (Malecaze), Toulouse, France; the Departments of Ophthalmology and Biomedical Engineering (Roberts, Mahmoud), Ohio State University, Columbus, Ohio, USA. No author has a financial or proprietary interest in any material or method mentioned. Corresponding author: David Touboul, MD, Reference National Center for Keratoconus (CRNK), CHU Bordeaux, Pellegrin, Pr. Joseph Colin Department of Ophthalmology, Place Ame´lie RabaLe´on, 33000, Bordeaux, France. E-mail: [email protected].
and thus characterize the cornea’s viscoelastic response to the pressure curve of the applied air. The collimated air pulse causes the cornea to move inward and become slightly concave. Immediately after applanation, the air pump shuts off and the pressure continues to increase due to inertia in the piston, before it declines in a smooth fashion. As the pressure decreases, the cornea begins to return to its normal configuration. In the process, it again passes through an applanated state. However, because of its viscoelastic characteristics, the cornea resists the dynamic force of the air pulse, causing a pressure delay between the inward and outward applanation, resulting in 2 pressure values. The applanation detection system monitors the cornea throughout the process, which takes milliseconds. This measurement provides 4 numerical parameters. The first is corneal hysteresis (CH), which is defined as the difference between the inward and outward applanation pressures. It is considered a numerical characterization of the corneal tissue’s viscoelastic response to a dynamic deformation. The CH is the result of energy being absorbed or dissipated in the corneal tissue. The second is the corneal resistance factor (CRF), which is calculated using a linear combination of inward and outward applanation pressures. It was empirically determined with the goal of generating the maximum correlation with central corneal thickness (Luce D. IOVS 2006; 47:ARVO E-Abstract 2266). Therefore, it is weighted by elasticity but still represents a viscoelastic parameter. Keratoconus is usually associated with lower CH and CRF values than in normal eyes and with an abnormal profile shape9,11 (Mahmoud AM, et al. IOVS 2007; 48:ARVO E-Abstract 1843). The third is the cornealcompensated intraocular pressure (IOPcc), which was designed to compensate for the effect of the cornea on the IOP measurement process. The IOPcc was also empirically determined by Luce. The fourth, the Goldmann-correlated IOP, is the average of the 2 applanation pressure values. For the subset of eyes with both ORA and Orbscan II topographic data, the ORA signals and the topographic maps were further analyzed using purpose-designed software for topographic data12 and ORA data13 (Mahmoud AM, et al. IOVS 2000; 41:ARVO Abstract 3599; Rouse EJ, et al. IOVS 2007; 48:ARVO E-Abstract 1247). From the ORA signal, the following parameters were extracted: peak 1 and peak 2 (maximum heights of the corresponding infrared signal peaks), time 1 and time 2 (timing of the corresponding infrared signal peaks), FWHM 1 and FWHM 2 (full width at half maximum of the corresponding infrared signal peaks), slope 1 and slope 2 (slopes of the pressure curve at the time of the corresponding infrared applanation peaks), Pmax (maximum value of the air pressure curve), Tpmax (time of maximum air pressure), P1 and P2 (air pressure corresponding to infrared signal peaks). From the Orbscan II topographic maps, the following indices were determined: CLMI (cone location and magnitude index)14 and Mt (maximum tangential curvature overlying the cone) (Mahmoud AM, et al. IOVS 2001; 42:ARVO Abstract 4825). The CLMI is a relative index calculated by using a search routine to locate the 2.0 mm region of greatest curvature on the map; that region is compared with a corresponding 2.0 mm region 180 degrees away to check for asymmetry and an area-corrected difference with the average curvature of the remaining area of the map is determined. The CLMI can be calculated on the axial map (aCLMI) in general practice for keratoconus-screening purposes. The CLMI on the tangential map (tCLMI) is used in eyes with diagnosed keratoconus to track disease
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progression. The Mt represents an absolute index describing the mean value inside the 2.0 mm diameter region of greatest curvature on the tangential map overlying the cone in keratoconus.
Table 1. Intrastromal corneal ring measurements and surgical characteristics.
RESULTS The study evaluated 18 eyes of 18 patients (10 men, 8 women) with a mean age of 31.3 years (range 13 to 50 years). The keratoconus was bilateral in 16 patients and unilateral in 2 patients. Keratometry was obtained by corneal topography in 15 eyes and by autokeratometry in 3 eyes. Table 1 shows the ICRS measurements and surgical characteristics by patient. The mean central corneal thickness was 483 mm; the mean peripheral corneal thickness, 596 mm; and the mean incision depth, 397 mm. The ICRS were implanted successfully in all eyes. There were no perioperative or postoperative surgical complications. Table 2 shows the preoperative and 6-month postoperative CH, CRF, IOPcc, maximum central K, and minimum central K as well as the change in K. There were no statistically significant differences between preoperatively and postoperatively in mean CH (7.7 mm Hg G 1.4 [SD] versus 7.4 G 1.4 mm Hg), mean CRF (6.6 G 1.8 mm Hg versus 6.1 G 1.4 mm Hg), or the difference parameter CH–CRF (PO.05). In 2 parameters extracted from the ORA signal, the
Pt
Eye
Central CCT (mm)
Peripheral PCT (mm)
Incision Depth (mm)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
R L L R R L L R R L L L L R L R R L
460 440 482 570 360 485 NA 480 480 480 460 550 528 480 465 520 480 488
580 570 590 660 560 581 579 580 640 600 590 610 560 640 605 620 570 600
386 380 393 440 373 387 386 386 426 400 393 406 373 426 403 413 380 400
CCT Z central corneal thickness; NA Z not available; PCT Z peripheral corneal thickness; Pt Z patient
difference between the preoperative and postoperative measurements was statistically significant. The mean maximum height of the infrared signal at the
Table 2. Preoperative and postoperative CH, CRF, maximum central K, and minimum central K and the change in K.
Preoperative
Preop to Postop Change
Postoperative
Pt
Eye
CH
CRF
Kmax
Kmin
CH
CRF
Kmax
Kmin
Kmax
Kmin
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
R L L R R L L R R L L L L R L R R L
7.7 6.9 6.9 11.2 9.1 6.9 8.5 9.7 7.7 6.0 7.1 7.1 5.9 6.6 7.4 9.1 7.6 7.0
5.6 7.4 5.4 10.7 8.1 5.6 6.8 10.7 5.2 4.9 6.4 6.9 5.3 5.6 5.9 7.7 5.6 4.5
NA 58.1 51.7 55.3 58.2 51.7 52.2 54.6 49.1 NA 61.8 48.7 47.3 56.0 58.2 53.9 48.2 53.9
NA 51.6 47.0 43.3 55.7 49.0 47.7 44.6 44.1 NA 47.5 43.5 40.6 47.9 51.2 48.3 41.6 52.0
9.2 5.5 7.2 11.2 8.8 8.0 5.9 6.4 8.4 6.4 6.6 7.5 6.5 7.5 7.7 7.7 7.3 6.2
7.3 4.3 6.3 9.5 6.7 7.3 4.5 5.8 5.5 7.2 5.6 6.9 4.6 5.6 6.9 6.6 6.1 3.6
59.6 NA 48.7 48.2 50.0 47.2 51.2 46.1 43.9 NA 52.3 46.5 45.0 50.7 51.3 47.1 41 50.3
50.8 NA 40.6 35.9 44.2 44.6 45.7 39.1 38.9 NA 38.9 42.8 37.9 42 44.3 43.6 37.3 41.9
NA NA 3.0 7.1 8.2 4.5 6.8 8.5 5.2 NA 9.5 2.2 2.3 5.3 6.9 6.8 6.5 3.6
NA NA 6.4 7.4 11.5 4.4 3.3 5.5 5.2 NA 8.6 0.7 2.7 5.9 6.9 4.7 3.4 10.1
CH Z corneal hysteresis; CRF Z corneal resistance factor; Kmax Z maximum central keratometry; Kmin Z minimum central keratometry; NA Z not available; Pt Z patient
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Figure 1. Preoperative ORA profile showing CH (App Z applanation; CCT Z central corneal thickness; CRF Z corneal resistance factor; IOPcc Z corneal-compensated intraocular pressure; IOPg Z Goldmann-correlated intraocular pressure).
Figure 2. Postperative ORA profile showing CH (App Z applanation; CCT Z central corneal thickness; CRF Z corneal resistance factor; IOPcc Z corneal-compensated intraocular pressure; IOPg Z Goldmann-correlated intraocular pressure).
second outward applanation event (peak 2) decreased from 376 G 128 signal intensity units to 270 G 100 signal intensity units (P!.002). However, the decreased infrared signal peak did not affect the pressure (P2) at which the applanation event occurred; thus, CH was unaffected. Also, the width of the infrared peak during the first applanation event (FWHM 1) decreased from 12.3 G 3.0 milliseconds to 10.3 G 2.8 milliseconds (P!.046). In none of the remaining signal parameters was the difference between the preoperative and postoperative measurements statistically significant; that is, the ORA signal shape was similar at the 2 time periods. There was a trend toward decreased applanation curve oscillations postoperatively. Figure 1 and Figure 2 show ORA signals of the same cornea before surgery and after surgery, respectively. Corneal topography showed a mean minimum central K value of 47.2 D (range 40.6 to 55.7 D) and a mean maximum central K value of 53.7 D (range 47.3 to 61.8 D). After surgery, the means were 41.8 D (range 35.9 to 50.8 D) and 48.7 D (range 41.0 to 59.6 D), respectively. Both mean K values decreased more than 5.0 D after ICRS implantation (Table 3); the decreases were statistically significant (P!.0001). One patient was excluded from the corneal topography subset analysis because of poor peripheral
coverage, which affected calculation of the indices. Figures 3 and 4 show examples of aCLMI and tCLMI maps. The Mt index (mean curvature in 2.0 mm area over the cone) decreased significantly (mean 4.6 D) after surgery (P!.001). The decrease was significantly predicted by the preoperative magnitude of the cone (P!.007, r2 Z 0.43), with a greater preoperative conecurvature producing greater induced flattening (Figure 5). The decrease in the aCLMI and tCLMI relative indices from preoperatively to postoperatively was also statistically significant (mean 9.6 G 2.7 versus 7.7 G 2.5 [P!.009] and 18.9 G 2.8 versus 12.9 G 4.4 [P!.002], respectively). The decrease in tCLMI was significantly predicted by preoperative tCLMI (P!.011, r2 Z 0.38), with a greater preoperative tCLMI producing a greater decrease (Figure 6). The only statistically significant correlation between biomechanical parameters and topographic parameters was between postoperative ORA peak 1 and postoperative aCLMI (P!.022, r2 Z 0.32) (Figure 7); a lower aCLMI (less severe keratoconus) was associated with a higher peak 1, indicating a stiffer cornea and that more severe keratoconus produces a smaller or nonuniform area of applanation, reducing the infrared peak. Preoperatively, the correlation was not significant, perhaps because the range of CLMI values was too low to produce a significant relationship. A postoperative reduction in CLMI led to an increased range, showing a significant correlation.
Table 3. Mean decrease in maximum and minimum central and 95% confidence intervals. 95% CI Parameter Kmax Kmin
Mean Decrease (D) G SD
Lower
Upper
5.8 G 2.3 5.8 G 2.9
1.3 0.1
10.3 11.5
CI Z confidence interval; Kmax Z maximum central keratometry; Kmin Z minimum central keratometry
DISCUSSION The goal of ICRS implantation is to stabilize and reinforce the ectatic cornea rather than weaken the structural integrity through an incision or ablation. The maximum and minimum central topographic K values as well as aCLMI, tCLMI, and Mt decreased postoperatively, which confirms that Intacs implantation
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Figure 3. Preoperative axial map (left) and tangential map (right) of cone location and magnitude index (CLMI).
can reduce the corneal steepening and astigmatism associated with keratoconus. It takes approximately 6 months for ICRS implantation to show an effect on the cornea and improve the visual acuity because of the viscoelastic nature of the cornea. In our study, which had a 6-month follow-up, it was still too early in the postoperative period to consider the changes in uncorrected distance visual acuity and corrected distance visual acuity.7,8 The goal of our study was to correlate the morphological topography changes in keratoconus with biomechanical parameters from the ORA. We did not find significant changes in the CH and CRF values between preoperatively and postoperatively and found only 2 significant changes in the ORA signal. The decrease in peak 2 and FWHM 1 may have been because a smaller area of the cornea was available for deformation by the artificial limbus created by the segments. Although the ORA measurement area is defined by the device’s manufacturer as the central 3.0 mm, a larger region of the cornea is likely involved in the deformation process, which would be limited by
ICRS placement. This would result in less infrared light impinging on the detector and a lower recovery peak in the infrared signal. The smaller infrared peak 2 did not affect the outward applanation pressure (P2) at which it occurred. Thus, neither CH nor CRF were affected. The decrease in FWHM 1 indicates that the cornea deformed more rapidly postoperatively than preoperatively, which also may be due to a more limited area for corneal deformation after ICRS placement (consistent with Glass DH, et al. IOVS 2008; 49:ARVO E-Abstract 646). Therefore, these changes are probably not due to modification of the biomechanical properties themselves but are rather an indication of greater corneal stability. The qualitative reduction in signal oscillation postoperatively is further evidence of this stability. Corneal hysteresis and the CRF are not correlated with keratometry but rather with IOP and central pachymetry11 (Luce D. IOVS 2006; 47:ARVO E-Abstract 2266). In our study, both IOP and central pachymetry remained stable postoperatively and thus played a role in the lack of a significant change in CH and
Figure 4. Postoperative axial map (left) and tangential map (right) of cone location and magnitude index (CLMI).
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Figure 5. Preoperative Mt versus induced change in Mt (Mt Z maximum tangential curvature overlying the cone).
Figure 6. Preoperative tCLMI versus induced change in tCLMI (tCLMI Z tangential cone location and magnitude index).
CRF values. We hypothesize that because of the lamellar structure of the cornea, the ICRS segments might reshape the center of the cornea (biometry) without changing the fundamental biomechanical properties of the corneal tissue, at least in the short-term postoperative period. It would be interesting to compare Intacs segments with smaller intracorneal rings such as Ferrara rings. According to our preliminary surgical results, Ferrara rings may be more powerful in reshaping because of the higher slope between the center of the cornea and the edges of the implanted rings. We noticed that ORA profiles had only minor differences before and after Intacs implantation. We thus conclude that the segments do not interfere with ORA measurements. To our knowledge, this is the first study that shows that Intacs placement changes the morphological characteristics of the cornea but not the biomechanical viscoelastic response parameters, such as CH and CRF. The changes in the ORA infrared signal likely
correspond to greater stability of the cornea, including fewer oscillations, greater speed of deformation, and a lower recovery peak 2. However, our study is preliminary. A study with more cases and a longer follow-up is necessary to determine the effect of Intacs implantation on CH and CRF in patients with keratoconus. A long-term study would help draw conclusions about the evolution of keratoconus and corneal biomechanical properties after ICRS implantation.
Figure 7. Postoperative peak 1 versus postoperative aCLMI (aCLMI Z axial cone location and magnitude index).
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10. Kirwan C, O’Keefe M, Lanigan B. Corneal hysteresis and intraocular pressure measurement in children using the Reichert Ocular Response Analyzer. Am J Ophthalmol 2006; 142:990–992 11. Touboul D, Roberts CJ, Ke´rautret J, Garra C, Maurice-Tison S, Saubusse E, Colin J. Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry. J Cataract Refract Surg 2008; 34:616–622 12. Mahmoud AM, Roberts C, Lembach R, Herderick EE, McMahon TT. Simulation of machine-specific topographic indices for use across platforms; the CLEK Study Group. Optometry Vis Sci 2006; 83:682–693 13. Kerautret J, Colin J, Touboul D, Roberts C. Biomechanical characteristics of the ectatic cornea. J Cataract Refract Surg 2008; 34:510–513
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First author: Caroline Dauwe Department of Ophthalmology, Reference National Center for Keratoconus, Bordeaux University, Bordeaux, France