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Clinical characteristics of lamellar channel deposits after implantation of Intacs

Ruckhofer, Josef MDa,b,*; Twa, Michael D. ODa; Schanzlin, David J. MDa

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Journal of Cataract & Refractive Surgery: October 2000 - Volume 26 - Issue 10 - p 1473-1479
doi: 10.1016/S0886-3350(00)00575-7
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Abstract

Intrastromal corneal ring segments (Intacs, KeraVision), which were approved for commercial use by the United States Food and Drug Administration in April 1999, were designed to achieve a reversible refractive adjustment that leaves the center of the cornea without biomicroscopically visible changes.1–7 Intacs are placed in the midperipheral cornea between the stromal lamellae in a semicircular channel at two-thirds stromal depth. The devices reduce myopia by flattening the central corneal curvature while maintaining a prolate aspheric shape in the central optical zone. Intacs consist of 2 hexagonal poly(methyl methacrylate) (PMMA) segments, each 150 degrees in arc length, with an inner diameter of 6.8 mm and an outer diameter of 8.1 mm. Three different thicknesses (0.25, 0.30, and 0.35 mm) are available to correct myopia ranging from −1.0 to −3.0 diopters (D) in eyes with less than 1.0 D of astigmatism. The segments can be removed or exchanged if the patient's needs change, the refractive goal is not achieved, or other problems arise.8

After implantation of Intacs, an extracellular intrastromal substance, visible on biomicroscopic examination, may accumulate in the lamellar channel around the segments (Figures 1 and 2). These deposits have been described,6,7 but their origin and composition are unknown. The presence of this material has not resulted in alteration of the optical performance of Intacs or any detected anatomical or physiological corneal deterioration. They resolve after removal of the segments.7 We report the frequency, location, and severity of these deposits in a multicenter phase III clinical trial in the U.S.

Figure 1.
Figure 1.:
(Ruckhofer) Cross-section of corneal model with implanted Intacs segment showing channel space of the segment centrally and peripherally.
Figure 2.
Figure 2.:
(Ruckhofer) Intacs segment with channel haze and lamellar channel deposits inside the curvature.

Patients and Methods

Study Protocol

Ten investigational sites and 359 patients participated in the trial, which began in December 1996. The investigational review board of each site approved the study protocol, and informed consent was obtained from each patient before enrollment. The trial was intended to provide the final safety and efficacy data required before the commercial release of Intacs in the U.S.9

Enrollment Criteria

Patients enrolled were required to have healthy, normal eyes with best spectacle-corrected visual acuity (BSCVA) of at least 20/20, spherical equivalent refractive error between −1.0 and −3.0 D, and less than 1.0 D of astigmatism. Corneal diameter had to be greater than 10.0 mm and corneal curvature, from 40.0 to 46.0 D. Patients with a central corneal thickness of less than 480 μm or peripheral corneal thickness of less than 570 μm were excluded from the study. Contraindications to surgery included pregnancy, any active systemic disease that might complicate surgical recovery (eg, diabetes or autoimmune disease), a history of ophthalmic disease or degeneration (eg, keratoconus or herpes simplex keratitis), prior ophthalmic surgery, and intraocular pressure of less than 10 mm Hg or greater than 21 mm Hg.

Evaluations

Baseline testing was performed preoperatively. Postoperative evaluations were scheduled for 1 and 7 days and 1, 2, 3, 6, 9, 12, 18, and 24 months. At each evaluation, the presence or absence of deposits observed on slitlamp examination was noted. A standardized scale was used to grade the severity (density) of the deposits, ranging from 0 (no deposits) to 4 (severe deposits), as shown in Table 1 and Figure 3.

Table 1
Table 1:
Standardized scale for grading lamellar channel deposits.
Figure 3.
Figure 3.:
(Ruckhofer) Lamellar channel deposits: A, Grade 1; B, Grade 2; C, Grade 3; D, Grade 4.

Statistical Analysis

The incidence of lamellar channel deposits among the 3 thickness groups was compared using the Fisher exact test, and the severity of the deposits among these groups was compared using the Kruskal–Wallis test. Statistical significance was defined as P ≤ .05. Statistical analysis was performed using SAS Version 6.12 (SAS Institute, Inc.).

Results

In the 359 patients who received Intacs in 1 eye, the 0.25 mm device was implanted in 119 eyes, the 0.30 mm device in 120, and the 0.35 mm device in 120. The mean patient age was 39.4 years (range 22 to 65 years); 48% of patients were men. Sixty-one percent of the patients wore contact lenses. The device was explanted or exchanged prior to 24 months in 44 patients, and 24 month data were not available for an additional 25 patients who were lost to follow-up, missed the examination, or whose data have not been reported. Thus, data for 290 eyes were available at the 24 month examination.

Incidence of Lamellar Channel Deposits

The incidence of lamellar channel deposits with all Intacs thicknesses during the first 24 months after implantation is shown in Figure 4. There was an increase at all times over the first 18 months, with a steep rise between 1 and 6 months and a less steep slope between 6 and 18 months. At 24 months, 213 eyes (74%) had deposits. The incidence of deposits increased with ring thickness (Figure 5). At 24 months, 63 of 103 eyes (61%) in the 0.25 mm group, 74 of 102 (73%) in the 0.30 mm group, and 76 of 85 (89%) in the 0.35 mm group had deposits. The difference in the incidence of lamellar channel deposits among the 3 groups was significant at 6, 12, 18, and 24 months (all P < .001, Fisher exact test). There was no correlation with patients' age (P = .528, Kruskal–Wallis test).

Figure 4.
Figure 4.:
(Ruckhofer) Presence of deposits at study time points, all thicknesses.
Figure 5.
Figure 5.:
(Ruckhofer) Presence of deposits at study time points by segment thickness.

Severity of Deposits

Figure 6 shows the severity ratings for the deposits at 6, 12, and 24 months. None of the eyes had reached grade 3 at 6 months, and none reached grade 4 over the first 24 months. A shift toward higher severity grades occurred at 12 and 24 months. The difference in severity among the 3 thickness groups was evaluated at 24 months (Figure 7). The greatest proportion of eyes with high severity ratings occurred in eyes with 0.35 mm Intacs and the lowest proportion in eyes with 0.25 mm Intacs. The severity of the deposits increased with device thickness, and this difference was significant at 6, 12, and 24 months (all P < .001, Kruskal–Wallis test).

Figure 6.
Figure 6.:
(Ruckhofer) Severity of deposits with all segment thicknesses at 6, 12, and 24 months.
Figure 7.
Figure 7.:
(Ruckhofer) Severity of deposits by segment thickness at 24 months.

Location

Lamellar deposits occurred in the channel along the inner curvature of the segments (Figure 8,A), along the outer curvature (Figure 8,B), along the inner and outer curvatures (Figure 8,C) in a combination of locations (eg, inner curvature and anterior, Figure 8,D), and anterior to the segments. A location posterior to the segments was not reported. The most frequent location at 12 months was along the inner curvature of the segment, which occurred in 95% of eyes (inner curvature alone or in combination with outer curvature and anterior; Table 2).

Figure 8.
Figure 8.:
(Ruckhofer) Location of deposits: A, along the inside of the segment curvature; B, along the outside of the segment curvature; C, along the inside and outside of the segment curvature; D, along the inside of the curvature and anterior to the segment.
Table 2
Table 2:
Location of lamellar channel deposits, all thicknesses, 12 months after implantation (n = 215).

Morphology

The appearance of lamellar channel deposits varied from white to gray, tan, chalky, or translucent. The white–gray chalky form was much more common than the translucent form.

Discussion

Lamellar channel deposits occurred frequently. Channel haze, a separate finding, should be differentiated from lamellar channel deposits. Channel haze may be caused by the physical separation of stromal lamellae that occurs when the lamellae are dissected to create a channel for placing Intacs. The peripheral loss of stromal transparency represented by lamellar haze has no visual significance for the patient. In some instances, this gray translucent haze can be difficult to differentiate from lamellar channel deposits. That lamellar deposits were reported at 1 and 7 days presumably represents improper classification by some investigators of channel haze as deposits, since in several other studies the earliest appearance of deposits was reported at a mean of 1 month after surgery.7,10–14

The incidence of lamellar channel deposits increased steeply between 1 and 6 months, less steeply between 6 and 18 months, and appeared to decrease between 18 and 24 months. However, the disappearance of deposits in patients with Intacs in situ has not been reported. The small apparent decline (<4%) at 24 months may be a statistical artifact associated with a reduced number of patients with available data at that time. Ongoing follow-up of the patients may clarify this issue.

The incidence and severity (density) of deposits increased with increasing segment thickness. Deposit density also tended to increase over time. Most eyes with deposits had trace or grade 1 deposit levels, and none had a grade 4 level within the first 24 months. Future follow-up may determine whether the frequency of deposits continues to increase after 24 months. The lamellar channel deposits were most commonly located along the inner curvature of the segments, less often along both the inner and outer curvatures, and even less frequently along the outer curvature only. No deposits were observed posterior to the Intacs. The deposits were most commonly white–gray and chalky in appearance.

The presence of this material has not resulted in alteration of the optical performance of Intacs or detected anatomical or physiological corneal deterioration. When the segments were removed, the deposits slowly disappeared.7 Although the origin and composition of the material are unknown, the material appears to fill in any space in the lamellar channel that is not occupied by the Intacs segment. This space is larger with thicker segments, which would account for the association of increasing density with increasing segment size.

Our studies with confocal microscopy have shown that the material in these lamellar deposits appears to be extracellular and contains no degenerated keratocytes.15 Quantock and coauthors used electron microscopy to investigate stromal healing 8 months after explantation of intrastromal corneal ring segments (ICRS) from a nonfunctional human eye16 and also examined the material within the positioning holes of 4 ICRS explanted from nonfunctional human eyes.17 The authors reported no deposits in the cornea 8 months after explantation.16 The substance in the positioning holes was identified as amorphous material interspersed with curved cellular processes, collagen fibrils with various diameters, and proteoglycan macromolecules.17

Parks and coauthors18 found lipid crystals in 11 of 49 monkeys 21 to 150 days after implantation of a hydrogel lenticule. The crystals were adjacent to the lenticule (posterior to the implant in 7 cases, anterior to the implant in 3 cases, and posterior and anterior in 1 case). They were identified as cholesterol crystals by specular microscopy.

Rodrigues et al.19 used histochemical and immunofluorescent staining to identify whitish crystalline deposits that appeared in a monkey posterior to a 5 mm PMMA intracorneal lens (placed in the deep posterior stroma) 6 months after lens implantation. The material was composed of lipid and dissolved cholesterol crystals. Additional homogeneous extracellular deposits anterior and posterior to the implant could not be identified. Parks and coauthors18 and Rodrigues et al.19 concluded that stromal keratocytes produce lipids as a nonspecific response to stress. A more thorough histological and chemical analysis will be required to determine the origin and composition of these lamellar channel deposits after Intacs implantation.

References

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© 2000 by Lippincott Williams & Wilkins, Inc.