To analyze the outcomes of intracorneal ring segment (ICRS) implantation for the treatment of keratoconus based on preoperative visual impairment.
Multicenter, retrospective, nonrandomized study.
A total of 611 eyes of 361 keratoconic patients were evaluated. Subjects were classified according to their preoperative corrected distance visual acuity (CDVA) into 5 different groups: grade I, CDVA of 0.90 or better; grade II, CDVA equal to or better than 0.60 and worse than 0.90; grade III, CDVA equal to or better than 0.40 and worse than 0.60; grade IV, CDVA equal to or better than 0.20 and worse than 0.40; and grade plus, CDVA worse than 0.20. Success and failure indices were defined based on visual, refractive, corneal topographic, and aberrometric data and evaluated in each group 6 months after ICRS implantation.
Significant improvement after the procedure was observed regarding uncorrected distance visual acuity in all grades ( P < .05). CDVA significantly decreased in grade I ( P < .01) but significantly increased in all other grades ( P < .05). A total of 37.9% of patients with preoperative CDVA 0.6 or better gained 1 or more lines of CDVA, whereas 82.8% of patients with preoperative CDVA 0.4 or worse gained 1 or more lines of CDVA ( P < .01). Spherical equivalent and keratometry readings showed a significant reduction in all grades ( P ≤ .02). Corneal higher-order aberrations did not change after the procedure ( P ≥ .05).
Based on preoperative visual impairment, ICRS implantation provides significantly better results in patients with a severe form of the disease. A notable loss of CDVA lines can be expected in patients with a milder form of keratoconus.
Keratoconus is an ectatic debilitating corneal disorder characterized by a progressive corneal thinning that results in corneal protrusion, irregular astigmatism, and decreased vision. A variety of options have been described for the management of this pathologic condition, such as rigid gas-permeable contact lenses, corneal collagen cross-linking, intracorneal ring segment implantation, or keratoplasty.
In a number of studies intracorneal ring segments (ICRS) have been demonstrated to be effective in improving visual acuity and reducing the refractive error and the mean keratometry in selected cases of keratoconic eyes. Such a positive therapeutic effect is considered to be based on the induction of a remodeling of the corneal anterior and posterior surface’s topography, which improves the optical quality of the cornea and reduces the optical aberrations, with consequent improvement in best-corrected visual acuity.
Although in the healthy cornea, the sectorial arcuate addition to the corneal local volume caused by these implants at the corneal midperiphery induces a flattening of the central cornea in an arc-shortening effect, with the consequence of a decrease in myopic spherical equivalent attributable to the overall reduction in the optical power of the cornea, such corneal modeling effect may be different in structurally abnormal corneas such as in keratoconus.
Even though the effectiveness of ICRS in the correction of keratoconus has been the subject of a number of studies and investigations, most reported evidence is based on the study of limited case series and may reflect only the experience of 1 surgeon or a limited and specific study group. Taking into consideration how diverse is the clinical condition of keratoconus in terms of anatomic severity and impact on the visual function, the reported results may be easily biased by the patient selection criteria, the degree of ectasia, the surgical technique employed, and the length of the follow-up, and thus may not reflect the general standards of the outcomes obtained with ICRS in the correction of keratoconus.
We report herein the outcomes of ICRS in the surgical correction of different levels of severity of keratoconus obtained in a large multicenter series of cases analyzed based on a common definition of success regarding the visual outcomes.
Patients and Methods
This multicenter, retrospective, interventional study comprised a total of 611 consecutive keratoconic eyes of 357 patients treated with ICRS implantation; 213 were male and 144 were female, ranging in age from 10 to 73 years (mean age: 35.15 ± 11.62 years). Before surgery each patient was exhaustively informed about the surgical procedure, its risks, and its benefits, and patients signed an informed consent in accordance with the Helsinki Declaration where they agreed that their clinical data may be included in scientific studies. The ethical board committee of Vissum Corporacion Oftalmologica Alicante approved the retrospective revision of the medical chart where were included the clinical data of the patients for developing this investigation. All patients were included after a retrospective review of all cases with the diagnosis of keratoconus in 6 different ophthalmologic centers that belong to the Spanish Network of Research in Ophthalmology (Red Tematica de Investigacion Cooperativa en Salud: Patologia Ocular del enevejecimiento, Calidad visual y Calidad de Vida, RD07/0062): 4 centers from the Vissum Corporation (Alicante, Madrid, Albacete, and Sevilla, all in Spain); the Barraquer Ophthalmological Center, Barcelona (Spain); and the Coimbra University Hospital (Portugal). All patients were included following the same protocol for data recording and analysis. Data recording was retrospective and was based on the review of all cases operated with ICRS implantation for correction of keratoconus in all participant centers from May 2000 to October 2011. Table 1 shows the contribution of each participating center in the current study. In those centers where more than 1 surgeon was involved in the surgical decision of the procedure, the number of surgeons involved is also mentioned.
|Vissum Corporation, Alicante, Spain||296 (6 surgeons)|
|Coimbra University Hospital, Coimbra, Portugal||112 (2 surgeons)|
|Vissum Corporation, Madrid, Spain||93 (2 surgeons)|
|Centro de Oftalmologia Barraquer, Barcelona, Spain||59 (3 surgeons)|
|Vissum Corporation, Albacete, Spain||30 (1 surgeon)|
|Vissum Corporation, Sevilla, Spain||21 (1 surgeon)|
Only keratoconus cases implanted with ICRS (KeraRing; Mediphacos, Belo Horizonte, Brazil; and Intacs; Addition Technology Inc, Fremont, California, USA) using either femtosecond laser technology or mechanical corneal dissection were included in this investigation. Patients with previous ocular surgery or an active ocular disease other than keratoconus were excluded from the study. Keratoconus diagnosis was based on corneal topography and slit-lamp observation. In all cases, preoperative findings characteristic of keratoconus were confirmed: corneal topography revealing an asymmetric bowtie pattern with or without skewed axes or keratoconus sign on slit-lamp examination, such as localized stromal thinning, conical protrusion of the cornea at the apex, Fleischer ring, Vogt striae, or anterior stromal scar. In all cases ICRS implantation was indicated because of confirmed keratoconus diagnosis, poor motivation of the patient to wear contact lenses, or the existence of contact lens intolerance.
Grading System According to the Level of Visual Limitation
Patients were divided into 5 different groups according to the grading system based on the limitation of preoperative visual acuity.
Grade I included patients with spectacle-corrected distance visual acuity (CDVA) (decimal notation) of 0.90 or better; grade II, patients with CDVA equal to or better than 0.60 and worse than 0.90; grade III, patients with CDVA equal to or better than 0.40 and worse than 0.60; grade IV, patients with CDVA equal to or better than 0.20 and worse than 0.40; and grade plus, patients with CDVA worse than 0.20.
A comprehensive ophthalmologic examination was performed in all cases, which included uncorrected distance visual acuity (UDVA), CDVA, manifest refraction (sphere and cylinder), slit-lamp biomicroscopy, Goldmann tonometry, fundus evaluation, ultrasonic pachymetry, and corneal topographic analysis. As topographic data were collected from 6 different centers, a total of 3 different corneal topography systems were used for corneal examination: the CMS 100 Topometer (G. Rodenstock Instrument GmbH, Ottobrunn, Germany), CSO (CSO, Firenze, Italy), and Orbscan IIz system (Bausch & Lomb, Rochester, New York, USA). The first 2 devices are Placido-based systems and the Orbscan IIz is a combined scanning-slit and Placido-disc topography system. Although the agreement between these specific devices has not been reported, Orbscan and Placido-based devices have been proven to provide similar accuracy and precision on calibrated spherical test surfaces. The following topographic data were evaluated and recorded with the 3 corneal topographic devices: corneal dioptric power in the flattest meridian for the 3-mm central zone (K1), corneal dioptric power in the steepest meridian for the 3-mm central zone (K2), and mean corneal power in the 3-mm zone (KM).
Corneal aberrometry was recorded and analyzed only for those patients examined with the CSO topography system (279 eyes), because this device was the only one with the capability to calculate directly this specific information. This topography system analyzes a total of 6144 corneal points of a corneal area enclosed in a circular annulus defined by an inner radius of 0.33 mm and an outer radius of 10 mm with respect to corneal vertex. The software of the CSO, the EyeTop2005 (CSO), automatically performs the conversion of corneal elevation profile into corneal wavefront data using the Zernike polynomials with an expansion up to the seventh order. In this study, the aberration coefficients and root mean square (RMS) values were calculated for a 6-mm pupil in all cases. The corresponding RMS values were calculated for the following types of aberrations: higher-order (RMS HOA), coma-like (RMS coma-like) (computed for third-, fifth-, and seventh-order Zernike terms), and spherical-like (RMS sph-like) (computed for fourth- and sixth-order Zernike terms).
The patients wearing contact lenses were instructed in all cases to discontinue their use for at least 2 weeks before each examination for soft contact lenses and at least 4 weeks before each examination for rigid gas-permeable contact lenses.
All the clinical information from the ophthalmologic examinations was extracted from histories and recorded in a standardized database by 6 experienced optometrists following the same protocol.
Surgical procedures were performed by different surgeons, depending on each participating center in the study. In all cases an antibiotic prophylaxis consisting of topical ciprofloxacin was prescribed and taken every 8 hours for 2 days before surgery. All procedures were performed under topical anesthesia.
The mechanical surgical procedure was initiated by marking a reference point for centration (pupil center) and performing a radial incision of approximately 1.8 mm in length. After this, a calibrated diamond knife was set at approximately 70% of the mean corneal thickness, determined by ultrasonic pachymetry. From the base of the incision, pocketing hooks were used to create corneal pockets on each side of the incision, taking care to maintain a uniform depth. A device containing a semi-automated suction ring was placed around the limbus, guided by the previously marked reference point on the cornea. Two semicircular dissectors were then placed sequentially into the lamellar pocket to be steadily advanced by a rotational movement (counterclockwise and clockwise dissectors). In the femtosecond laser–assisted surgical procedure the suction ring was applied, and then the disposable glass lens of the laser system was applied first in order to applanate the cornea, fixate the eye, and help maintain a precise distance from the laser head to the focal point. Then, a continuous circular stromal tunnel was created at approximately 80% of corneal depth. The 60-kHz IntraLase femtosecond system was always used (IntraLase Corp, Irvine, California, USA).
A total of 464 eyes (75.80%) were operated with the femtosecond laser–assisted technique, whereas operations of the remaining 147 eyes (24.20%) were performed with the mechanical dissection.
Regarding the ICRS type, Intacs (Addition Technology, Inc) were implanted in a total of 314 eyes (51.45%), whereas KeraRings (Mediphacos) were implanted in 297 eyes (48.55%).
The selection of the number (1 or 2), arc length, and thickness of ICRS was performed following the nomogram defined by the manufacturer.
Postoperatively, topical tobramycin and dexamethasone eye drops (TobraDex; Alcon Laboratories Inc, Fort Worth, Texas, USA) were used every 6 hours for 1 week and then stopped. Topical lubricants were also prescribed every 6 hours for 1 month (Systane; Alcon Laboratories Inc).
In order to carry out a more precise analysis of the results from the general series under study, a homogenous sample was taken where we included only the patients that underwent surgery with the femtosecond laser and were implanted with KeraRing ICRS, with selection criteria and surgery planning performed by the same experienced surgeon from the same specific center (J.L.A., Vissum, Alicante, Spain). This group comprised 114 eyes and was defined as the “best-case group.” A statistical comparison of the variables under investigation between the general series and the “best-case group” was carried out in order to evaluate the representativeness of the population under study and the reliability of the results.
Definition of Success and Failure Indices
The following criteria were defined for success and failure in order to evaluate the efficacy of the surgical procedure. Success was defined as those cases that showed 1 of the following characteristics 6 months after the procedure: (1) an improvement in 1 or more lines of uncorrected or corrected distance visual acuity, (2) a decrease in 2 or more diopters of spherical equivalent, (3) a decrease of at least 1 µm of the RMS corneal higher-order or coma-like aberrations.
Failure was considered when 1 of the following criteria was found 6 months after the procedure: (1) a loss of 1 or more lines of uncorrected or corrected distance visual acuity, (2) an increase in 2 or more diopters of spherical equivalent, (3) an increase in 1 µm or more in the RMS corneal higher-order or coma-like aberrations.
Patients who did not fulfill the change criteria outlined above were considered as remaining without significant change after the surgical procedure.
Data from the preoperative visit, the first postoperative day, and months 1, 3, and 6 were taken for the analysis of the results. On the first postoperative day, UDVA measurement and slit-lamp examination (intracorneal ring position and corneal integrity) were performed. Snellen chart UDVA and CDVA measurement, manifest refraction, slit-lamp examination, and corneal topography were performed in the rest of the postoperative examinations. A total of 268 eyes completed the 6-month follow-up evaluation.
Complications after ICRS implantation for the treatment of keratoconus were not within the scope of the variables analyzed in the current investigation. Nevertheless, segments explanted for different reasons (segment migration, recurrent corneal erosion, corneal melting, corneal perforation, infectious keratitis, or patients unsatisfied because of poor refractive outcome) were observed in 38 of the 611 cases (6.21%) under investigation. All these cases were excluded from the statistical analysis to avoid biased results and are the subject of an independent study previously published by our research group.
The statistical analysis was performed using the SPSS software for Windows (version 15.0.1; SPSS Inc, Chicago, Illinois, USA). The mean values and standard deviations were calculated for every parameter during the follow-up. Normal distribution of all data samples was first checked by means of Kolmogorov-Smirnov test. If a parametric analysis was possible, the Student t test for paired data was performed for comparisons between data obtained in the preoperative and postoperative examinations or consecutive postoperative visits. When a parametric analysis was not possible, the Wilcoxon rank sum test was applied to assess the significance of differences between preoperative and postoperative data, using in all instances the same level of statistical significance ( P < .05).
Regarding the comparisons among groups, the 1-way analysis of variance with the Bonferroni post hoc comparison procedure was used when parametric analysis was possible. If variances were not homogeneous (checked by the Levene test), the Tamhane post hoc analysis was used. When parametric analysis was not possible, the Kruskal-Wallis test was used, again using the same level of statistical significance ( P < .05). For post hoc analysis, the Mann-Whitney test with Bonferroni adjustment was used in order to avoid the experimental error rate in these cases.
Main Outcomes Measures
Main outcome measures were visual acuity (UDVA, CDVA), manifest refraction, corneal topography, anterior corneal higher-order aberrations, and success and failure indices as described above.
This study comprised a total of 611 consecutive keratoconic eyes of 357 patients treated with ICRS; 213 were male and 144 were female, ranging in age from 10 to 73 years (mean age: 35.15 ± 11.62 years). A total of 268 eyes had a full ophthalmologic examination 6 months after the primary implantation of ICRS. According to the degree of visual limitation, of these 268 eyes, 37 eyes (13.80%) were classified as grade I, 87 eyes (32.46%) as grade II, 74 eyes (27.61%) as grade III, 43 eyes (16.04%) as grade IV, and 27 eyes (10.07%) as grade plus.
There was no statistically significant difference when the results from the “best-case group” were compared with the results from the general series. Preoperatively, again, there was no statistically significant difference in terms of age ( P = .06), UDVA ( P = .83), spherical equivalent ( P = .57), CDVA ( P = .89), keratometry ( P > .05), and corneal aberrometry between groups ( P > .05). In addition, when we compared the postoperative outcomes of the variables mentioned above, among the subgroups defined according to the degree of visual limitation, we did not find any significant difference ( P > .05).
Patients classified as keratoconus grade I showed an increase in UDVA, from a preoperative mean value of 0.36 ± 0.26 to 0.45 ± 0.24 postoperatively ( P = .04). CDVA decreased significantly from a mean preoperative value of 0.97 ± 0.06 to a mean postoperative value of 0.86 ± 0.18 ( P < .01). In this group, 37.8% (14/37) of patients lost 2 or more lines of CDVA ( Table 2 ). In patients with keratoconus grade II, UDVA significantly improved from a mean preoperative value of 0.27 ± 0.21 to a postoperative value of 0.44 ± 0.24 ( P < .01). CDVA also increased from a preoperative mean value of 0.71 ± 0.08 to 0.75 ± 0.22 postoperatively ( P = .04). In this group, 20.6% (18/87) of patients lost 2 or more lines of CDVA ( Table 2 ). In patients with keratoconus grade III, UDVA and CDVA increased significantly from a preoperative mean level of 0.16 ± 0.14 and 0.45 ± 0.53, respectively, to a postoperative mean level of 0.24 ± 0.16 and 0.57 ± 0.22, respectively ( P < .01). In this group, 9.45% (7/74) of patients lost 2 or more lines of CDVA ( Table 2 ). Patients with keratoconus grade IV also showed a statistically significant improvement of both UDVA and CDVA from preoperative values of 0.13 ± 0.09 and 0.27 ± 0.05, respectively, to a postoperative level of 0.20 ± 1.55 and 0.50 ± 0.22, respectively ( P < .01). In this group 4.65% (2/43) of patients lost 2 or more lines of CDVA ( Table 2 ). Finally, patients classified as keratoconus grade plus are the ones that showed the largest increase in CDVA. Preoperatively these patients had a mean CDVA of 0.09 ± 0.05, which improved to a postoperative value of 0.38 ± 0.26 ( P < .01). UDVA also increased significantly from a preoperative 0.05 ± 0.04 to postoperative 0.14 ± 0.14 ( P = .03). In grade plus, only 3.7% (1/27) of patients lost 2 or more lines of CDVA ( Table 2 ).
|Keratoconus Grade||Lost ≥2 lines CDVA|
Comparison of the eyes with the least advanced keratoconus (grades I and II) and eyes with the most advanced keratoconus (grades IV and plus) showed statistically significant difference in relation to the cases that lost 2 or more lines of CDVA ( P < .01). Thus, 25.8% (32/124) of patients with CDVA 0.6 or better (grades I and II) presented a loss of 2 or more lines of CDVA, whereas just 4.2% (3/70) of patients with CDVA 0.4 or worse (grades IV and plus) showed a loss of 2 or more lines of CDVA ( Table 3 ).
|Visual Acuity||Gained ≥1 Line CDVA||Lost ≥1 Line CDVA||Lost ≥2 Lines CDVA|
|CDVA ≥0.6 grade I + II||37.90%||36.29%||25.80%|
|CDVA ≤0.4 grade IV + plus||82.85%||10.00%||4.28%|
Spherical Equivalent and Keratometry
Analysis of the mean spherical equivalent (SE) showed a statistically significant reduction in all grades of keratoconus 6 months after the primary surgery ( P ≤ .02). Patients in grade I showed a decrease from a preoperative mean SE of −2.86 ± 2.68 to a mean postoperative SE of −1.76 ± 2.57 ( P < .01). In grade II, preoperative SE was −3.88 ± 3.58, decreasing to a postoperative level of −2.07 ± 2.68 ( P < .01). Patients in grade III presented a reduction from a preoperative mean value of −5.25 ± 4.33 to a postoperative mean SE of −2.82 ± 4.06 ( P < .01). In grade IV, SE decreased from a preoperative mean value of −6.35 ± 5.04 to a postoperative value of −4.18 ± 5.42 ( P < .01), and in grade plus, patients showed a reduction from preoperative −7.43 ± 6.10 to postoperative −3.93 ± 5.63 ( P = .02). Patients with the most advanced form of the disease (grades IV and plus) showed the largest reduction in terms of spherical equivalent in comparison with patients with the least advanced form of keratoconus (grades I and II) ( P = .04).
A statistically significant reduction of the flattest, steepest, and mean keratometry readings was also observed in all grades ( P ≤ .01) ( Table 4 ). Patients classified as grade I showed a reduction in the mean keratometry of 1.55 diopters (D). In grade II, reduction of the mean keratometry was 1.72 D. Patients in grade III exhibited a decrease of 2.84 D in the mean keratometry. Patients grouped under grade IV showed a reduction in the mean keratometry of 4.01 D. Finally, the largest reduction was observed in the more advanced cases (grade plus), where patients showed a decrease of 5.61 D in the mean keratometry.
|Keratoconus Grade||K1 Pre||K1 6M||P Value||K2 Pre||K2 6M||P Value||KM Pre||KM 6M||P Value|
|I||43.75 ± 2.95 (36.22-49.10)||41.95 ± 2.13 (35.50-46.10)||<.01||45.91 ± 3.87 (36.00-58.82||44.71 ± 2.20 (41.56-49.38)||<.01||44.90 ± 2.96 (35.65-54.96)||43.35 ± 1.69 (38.63-47.45)||<.01|
|II||45.09 ± 4.44 (34.07-56.00)||43.17 ± 4.47 (33.46-53.94)||<.01||47.41 ± 5.42 (34.10-65.09)||46.08 ± 5.25 (34.10-59.23)||<.01||46.24 ± 4.13 (34.57-59.10)||44.52 ± 4.41 (34.32-56.10)||<.01|
|III||48.10 ± 6.00 (33.37-74.69)||44.56 ± 4.90 (32.45-54.49)||<.01||49.88 ± 6.71 (37.25-83.67)||47.68 ± 5.68 (32.75-64.06)||<.01||48.93 ± 5.67 (36.25-78.80)||46.09 ± 5.07 (32.60-59.52)||<.01|
|IV||51.41 ± 6.69 (31.50-69.40)||45.94 ± 4.62 (38.00-58.02)||<.01||51.89 ± 6.69 (33.80-74.48)||49.34 ± 5.74 (41.76-62.20)||<.01||51.65 ± 6.06 (32.65-72.70)||47.64 ± 4.87 (39.88-60.11)||<.01|
|Plus||53.13 ± 8.10 (32.20-79.08)||47.73 ± 4.97 (35.37-59.10)||<.01||55.68 ± 9.15 (38.10-85.51)||50.24 ± 5.11 (40.40-61.93)||<.01||54.40 ± 8.00 (38.48-82.62)||48.81 ± 4.39 (39.54-57.34)||<.01|