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May 2007

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Peer-Reviewed Literature: Intacs for Keratoconus

Editor: Ming Wang, MD, PhD
Reviewer and Co-Editor: Tracy Swartz, OD, MS
Panel Members: Helen Boerman, OD, FAAO; Wei Jiang, MD; Lisa Martén, MD; Gregory J. McCormick, MD; Jason Noble, MD; Jay S. Pepose, MD, PhD; Renée Solomon, MD; Elizabeth Yeu, MD

In January 2005, I reviewed the literature regarding Intacs (Addition Technology, Inc., Des Plaines, IL) for keratoconus. I sought to revisit this issue to further evaluate the safety, efficacy, and techniques used for the placement of Intacs in eyes with keratoconus. The following papers were reviewed for clarification of the issues of long-term follow-up, complications, the rings' placement, and the channels' creation:

  1. Alió JL, Shabayek MH, Artola A. Intracorneal ring segments for keratoconus correction: long-term follow-up. J Cataract Refract Surg. 2006;32:978-985.
  2. Kymionis GD, Siganos CS, Tsiklis NS, et al. Long-term follow-up of Intacs in keratoconus. Am J Ophthalmol. 2007;143:236-244.
  3. Colin J. European clinical evaluation: use of Intacs for the treatment of keratoconus. J Cataract Refract Surg. 2006;32:747-755.
  4. Kanellopoulos AJ, Pe LH, Perry HD, Donnenfeld ED. Modified intracorneal ring segment implantations (Intacs) for the management of moderate to advanced keratoconus. Cornea. 2006;25:29-33.
  5. Ly LT, McCulley JP, Verity SM, et al. Evaluation on intrastromal lipid deposits after Intacs implantation using in vivo confocal microscopy. Eye Contact Lens. 2006;32:211-215.
  6. Samimi S, Leger F, Touboul D, Colin J. Histopathological findings after intracorneal ring segment implantation in keratoconic human corneas. J Cataract Refract Surg. 2007;33:247-253.
  7. Pokroy R, Levinger S. Intacs adjustment surgery for keratoconus. J Cataract Refract Surg. 2006;32:986-992.
  8. Rabinowitz YS, Li X, Ignacio TS, Maguen E. Intacs inserts using the femtosecond laser compared to the mechanical spreader in the treatment of keratoconus. J Refract Surg
    9. . 2006;22:764-771.
  9. Ertan A, Bahadir M. Intrastromal ring segment insertion using a femtosecond laser to correct pellucid marginal corneal degeneration. J Cataract Refract Surg. 2006;32:1710-1716.
  10. Alió JL, Shabayek MH, Belda JI, et al. Analysis of results related to good and bad outcomes on Intacs implantation for keratoconus correction. J Cataract Refract Surg. 2006;32:756-761.

LONG-TERM FOLLOW UP
Several studies reported the results of Intacs' implantation with follow-up in excess of 1 year. Alió et al1 reported data on 13 eyes and six eyes, 36 and 48 months following the implantation of Intacs, respectively. No significant differences in BSCVA and inferior-superior asymmetry were noted in any of the patients between their 6- and 36-month visits. Average keratometric values did not remain stable during the 36-month period, however, and increased by 1.67 D. No differences were noted between eyes receiving single versus double segments.

Kymionis et al2 reported on 15 patients (17 eyes) 5 years following the implantation of Intacs. The investigators found no significant change in spherical equivalent during the 5-year follow-up period. Mean keratometric values increased from 45.20 to 48.02 D during the investigation due to a lack of stability in eyes that preoperatively showed more advanced stages of keratoconus. The investigators suggested that, despite improvement in BCVA and refraction, the possibility of chronic corneal stromal remodeling from keratoconus' progression exists. They additionally reported that, in patients with low keratometric values (less than 47.00 D) and earlier stages of disease, the mean keratometric values and topographic astigmatism remained stable. This was not the case, however, for eyes with more severe disease.

COMPLICATIONS
Serious complications are generally rare with Intacs. Postoperative complications may include foreign body sensation, mild discomfort, photophobia, and optical aberrations. According to Colin,3 patients' dissatisfaction with their postoperative vision necessitated the removal of Intacs in 12% of eyes compared with 8.3% in the study by Kymionis et al.2 Kanellopoulos et al4 encountered a large percentage of postoperative complications (35%), however, including six cases in which the segments moved and became exposed through the axial wound 3 to 6 months after their implantation. There was a case of corneal melt and a significant infiltrate in one eye that necessitated the segment's removal 7 months postoperatively.

Deposits in the channel were reported in several studies, including those by Alió et al1 (four of 13 eyes) and Colin3 (no numbers were specified). Kymionis et al2 reported needle-shaped keratocytes and tortuous subnasal nerves in one patient; microdeposits, stretched keratocytes, and mild fibrosis were observed in all 15 patients in the study.

Ly et al5 evaluated six eyes using confocal microscopy 5 years after the implantation of Intacs. The investigators did not note any activation of keratocytes, but diffuse haze surrounding the segments was observed in all eyes. Shiny crystalline or amorphous deposits were noted in all eyes under confocal microscopy and in five eyes at the slit lamp. According to the data, lipid deposits may have resulted from alterations in lipid synthesis or metabolism by activated keratocytes during the initial postoperative healing period.

Samimi et al6 reported on eight eyes of patients who underwent penetrating keratoplasty (PKP) with the removal of Intacs due to a poor refractive outcome or the segments' extrusion. Histological evaluation found focal hypoplasia immediately above the Intacs' tunnel in five eyes. The keratocytes' density was lower in areas above and below the channel. Each one's epithelium appeared normal centrally, and six had a break in their Bowman's membrane, which is characteristic of advanced keratoconus. Haze in the channel at a depth of 50% to 75% was noted in seven eyes.

Pokroy and Levinger7 reported on seven eyes (out of a cohort of 58 eyes) that required an adjustment of their Intacs. The investigators defined an adjustment as the removal, exchange, addition, or shifting (or combination thereof) of a segment to improve the refractive outcome. The indications for an adjustment included surgically induced astigmatism, an overcorrection resulting in hyperopia, and an undercorrection. Six of seven corrective adjustments left eyes with a single segment. The investigators therefore recommended initially placing Intacs through a temporal incision to allow the easy removal of the superior segment if required. They also noted that the two eyes that did not improve following an adjustment in the segment's position were more advanced cases that had manifest astigmatism of at least 6.00 D, keratometric astigmatism equal to or greater than 10.00 D, reduced BSCVA, and little spherical myopia. According to the investigators, the aforementioned parameters suggest a poor prognosis with Intacs.

RINGS' PLACEMENT
Earlier studies suggested the horizontal placement of Intacs with asymmetrical sizes when double segments were implanted as being advantageous.4 Most studies used topography to direct the placement of the segments. The insertion of a single segment was performed when the cone's location was inferior or limited to half of the corneal surface. Two segments were placed when the cone's size exceeded more than half of the corneal surface, as seen on topography.1,8,9

Pokroy and Levinger7 found that centering the inferior segment in the steepest meridian on topography, adjacent to the cone, was helpful in reducing astigmatism. Kymionis et al,2 based on topography, used two 0.45-mm segments to flatten the steepest meridian. Rabinowitz et al8 used two 0.35-mm segments for maximal flattening in all patients.

Kanellopoulos et al4 used asymmetric rings with the thinner segment in the upper cornea and the thicker in the lower cornea, and they adjusted the rings' center according to the cone's location. The center of the virtual circle of the rings was moved in the direction of the cone rather then centered on the visual axis. This centration flattened the cone and resulted in a possible deviation toward the visual axis, as seen on topography.

Colin3 used a more complex nomogram based on the shape of the cone. An eye with an asymmetrical cone received a thicker Intacs segment inferiorly and a thinner superiorly. An eye with a global and central cone received double segments of equal thickness. Using this nomogram, the investigators obtained a gain of two to eight lines of BSCVA in 62% of eyes at 6 months postoperatively, 32% experienced no change, and 3.5% lost two lines of BSCVA.

Alió et al10 analyzed the postoperative visual outcomes in two groups of eyes that received Intacs. Group A comprised 20 eyes that achieved an increase of three or more lines of BSCVA. Group B was composed of five eyes that lost at least one line of BSCVA. The researchers reported that group B had a mean sphere 3.90 D higher than group A, a cylindrical dioptric power of 1.46 D more, and a mean keratometry reading that was 6.91 D higher than in group A. The investigators concluded that the greater the cone's protrusion, the lower the ability of Intacs to provide keratoconic correction. They further concluded that better outcomes might be anticipated in eyes with mean keratometry readings of 53.00 D or less and a relatively low spherical equivalent. Advanced keratoconus with mean keratometry readings of at least 55.00 D should not be expected to benefit from Intacs.

Rabinowitz et al8 also suggested that Intacs should not be considered in patients with contact lens intolerance who have keratometry readings above 57.00 D. Other contraindications include a corneal thickness lower than 450 µm at the 7-mm optical zone, central stromal scarring, and patients' unrealistic expectations for visual outcome following the implantation of Intacs.

THE CHANNEL'S CREATION
All studies discussed thus far utilized manually made channels to accommodate the Intacs segment. These channels were made using a diamond blade set to 70% of the corneal pachymetry to create a 1.5- to 2.0-mm incision at the location of insertion. Using a semi-automated device, the stromal dissection was performed at the full depth of the incision. The device uses a suction ring to stabilize the cornea, thus allowing two semicircular lamellar dissectors to be placed sequentially in the lamellar pocket, which was steadily advanced by a rotational movement. The device creates two 180° semicircular dissections into the stroma with an approximate diameter of 7.5 mm.9

The femtosecond laser has a unique capability of programming channels at a predetermined depth with a high degree of accuracy. Rabinowitz et al8 compared the outcomes of Intacs' implantation using the femtosecond laser versus a mechanical method. Ten eyes received Intacs via the manual channel technique. Two 0.35-mm segments were placed in each eye, followed by a 10Ð0 nylon suture at 100% depth, which was removed 1 month postoperatively. One of the segments extruded after being placed too superficially, and it was removed. Another patient elected to have his segments removed due to continued visual fluctuation up to 1 year postoperatively, and he underwent PKP in both eyes. Significant epithelial defects with moderate-to-severe discomfort on postoperative day 1 were experienced by 50% of patients undergoing Intacs using the manual channel technique.

A femtosecond laser created the channels in the other 20 eyes. The channel's depth was set to 400 µm. The entry incision's length was 1.4 mm with a width of 1.0 mm. The channel's inner diameter was 6.6 mm, and the outer diameter was 7.4 mm, which effectively created a 0.4-mm channel for the 0.35-mm segment. Entry sites were closed using 10Ð0 nylon sutures, and the eyes were covered with bandage contact lenses.

Fifteen of these eyes received double 0.35-mm segments. Single 0.35-mm segments were inserted in four eyes. In one eye, a 0.25-mm segment was placed superiorly with a 0.35-mm segment inferiorly. Postoperatively, one patient developed a gram-positive infection after the suture loosened, and the patient refused a replacement. The segments had probably moved because the patient rubbed his eyes. The infection was controlled after the segment was removed and fortified antibiotics were administered. Two patients suffered from advanced keratoconus. These individuals could not tolerate gas permeable contact lenses and elected to undergo PKP after the successful removal of the segments.

Only 15% of the 20 eyes that received Intacs with use of the femtosecond laser to create the channels had significant epithelial defects and experienced moderate-to-severe discomfort on the first postoperative day. Narrow channels enhanced the flattening effect but also made the segments' insertion more difficult. The investigators found that a single Intacs may be just as effective as two segments for mildly-to-moderately asymmetric cones.

THE BOTTOM LINE
Better outcomes can be anticipated in eyes with mean keratometry readings not exceeding 53.00 D and with a relatively low spherical equivalent. Eyes with advanced keratoconus and mean keratometry readings of at least 55.00 to 57.00 D should not be expected to benefit from Intacs. Although an improvement in BSCVA of as much as 10 lines can be expected with Intacs in eyes with keratoconus, the implants rarely reduce the BSCVA by as much as two lines. Because the results with the segments can vary, patients should be educated appropriately. Approximately 3.00 D of flattening on keratometry can be expected. Although gains in BSCVA and UCVA appear to last for several years after implantation, the keratometry may increase over the same time intervals.

Reviewer and Co-Editor
Tracy Swartz, OD, Educational Director at the Wang Vision Institute in Nashville, Tennessee. Dr. Swartz acknowledged no financial interest in the products or companies mentioned herein. She may be reached at (615) 321-8881; drswartz@wangvisioninstitute.com.

Panel Members
Helen Boerman, OD, FAAO, is Assistant Clinical Operations Manager at the Wang Vision Institute in Nashville, Tennessee, and Staff Optometrist and Adjunct Faculty at the Indiana University School of Optometry in Bloomington. She acknowledged no financial interest in the product or company mentioned herein. Dr. Boerman may be reached at (615) 321-8881; drboerman@wangvisioninstitute.com
Wei Jiang, MD, is a general ophthalmologist practicing in Kaiser, California. She acknowledged no financial interest in the product or company mentioned herein. Dr. Jiang may be reached at (925) 847-5065; wjiang70@yahoo.com.
Lisa Martén, MD, is a corneal fellow at the Wang Vision Institute in Nashville, Tennessee. She acknowledged no financial interest in the product or company mentioned herein. Dr. Martén may be reached at (615) 321-8881; drmarten@wangvisioninstitute.com.
Gregory J. McCormick, MD, is a corneal and refractive surgeon in Burlington, Vermont. He acknowledged no financial interest in the product or company mentioned herein. Dr. McCormick may be reached at (802) 864-2010; mccormick_greg@hotmail.com.
Jason Noble, MD, is a resident physician at the Department of Ophthalmology and Vision Sciences at the University of Toronto. He acknowledged no financial interest in the product or company mentioned herein. Dr. Noble may be reached at (416) 844-5477; jason.noble@utoronto.ca.
Jay S. Pepose, MD, PhD, is Professor of Clinical Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis. He acknowledged no financial interest in the product or company mentioned herein. Dr. Pepose may be reached at (636) 728-0111; jpepose@peposevision.com.
Renée Solomon, MD, is working at the Ophthalmic Consultants of Long Island in New York. She acknowledged no financial interest in the product or company mentioned herein. Dr. Solomon may be reached at reneeoph@yahoo.com.
Elizabeth Yeu, MD, is Resident Physician at the Rush University Medical Center in Chicago. She acknowledged no financial interest in the product or company mentioned herein. Dr. Yeu may be reached at (312) 942-5315; elizabeth_yeu@rush.edu.

Editor
Ming Wang, MD, PhD, Clinical Associate Professor of Ophthalmology at the University of Tennessee and Director of the Wang Vision Institute in Nashville, Tennessee. Dr. Wang acknowledged no financial interest in the products or companies mentioned herein. He may be reached at (615) 321-8881; drwang@wangvisioninstitute.com.