Two-year outcomes of intrastromal corneal ring segments for the correction of myopia.

OBJECTIVE: To evaluate the safety and efficacy of Intrastromal Corneal Ring Segments (ICRS) for the correction of myopia. DESIGN: Nonrandomized, comparative trial. PARTICIPANTS: Patients enrolled in the United States Food and Drug Administration phase II and phase III clinical trials of the ICRS had best spectacle-corrected visual acuity (BSCVA) of 20/20 or better, myopia of -1.00 to -3.50 diopters (D), and a cylindrical correction of 1.00 D or less as measured by manifest refraction. INTERVENTION: Surgical correction of myopia with an ICRS. MAIN OUTCOME MEASURES: Efficacy was assessed by predictability of refractive outcome (deviation from predicted cycloplegic refraction spherical equivalent), stability of refractive effect, and postoperative uncorrected visual acuity. Safety was assessed by adverse events, maintenance or loss of preoperative BSCVA, and induced manifest refraction cylinder. RESULTS: Four hundred fifty-two patients were enrolled at 11 investigational sites in both studies. Of the 454 surgical attempts, 449 received an ICRS in one eye (0.25, 0.30, and 0.35 mm in 148, 151, and 150 eyes, respectively). First surgeries were attempted in 452 patients. An ICRS was successfully implanted in 447 initial eyes, and 5 surgeries were discontinued. Of the five discontinued surgeries, three patients subsequently exited from the study, and two patients went on to have the ICRS implanted in the second eye, bringing the total number of successful implants to 449 patient eyes. Month 24 postoperative follow-up was completed on 358 patients (80%). At month 24, 328 of 354 eyes (93%) were within +/-1.00 D of predicted refractive outcome. Refraction changed by 1 D or less in 97% of eyes (421/435) between 3 and 6 months after implantation and in 99% (343/348) between months 18 and 24. Before surgery, 87% of eyes (390/448) saw worse than 20/40 uncorrected; 24 months after surgery, 55% of eyes (196/358) saw 20/16 or better, 76% (271/358) saw 20/20 or better, and 97% (346/358) saw 20/40 or better. Although two eyes (2/358; 0.5%) lost two or more lines of BSCVA at 24 months; visual acuity in both was 20/20 or better. Intraoperative complications included anterior corneal surface perforation (three eyes) and anterior chamber perforations (two eyes, one during an attempted exchange procedure); all healed spontaneously without suturing and without loss of BSCVA. The ICRS was repositioned in five eyes to increase correction. Postoperative complications in one eye each were infectious keratitis, shallow segment placement, and loss of two lines of BSCVA at two or more consecutive examinations (subsequently regained). CONCLUSIONS: The ICRS safely, predictably, and effectively reduced or eliminated myopia of -1.00 to -3.50 D. The refractive effect was stable over time.

Intrastomal corneal ring segments: reversibility of refractive effect.

PURPOSE: To evaluate the reversibility of refractive effect following removal of the ICRS (intrastromal corneal ring segments; Intacs). METHODS: Data from 34 eyes from which ICRS were removed during United States FDA Phase II and III clinical trials were evaluated with regard to segment size, loss or change of best spectacle-corrected visual acuity (BSCVA), any change of uncorrected visual acuity (UCVA), manifest spherical equivalent refraction, manifest cylinder refraction, stability of manifest cylinder refraction, and subjective visual symptoms. RESULTS: Out of 725 initial or contralateral eyes placed with the ICRS during Phase II and III clinical trials, segments were removed from 34 eyes (4.7%). Other than one (1/725, 0.1%) safety related ICRS removal, 30/725 (4.1%) were due to visual symptoms. ICRS removal was accomplished under topical anesthesia without complications in all eyes. The mean length of time the segments remained in the cornea after initial surgery was 10.3 +/- 5.4 months. At 3 months after ICRS removal, 21 eyes had monitored data available and were within +/-1 line or 10 letters of their preoperative BSCVA. Twenty eyes (20/21, 95%) returned to within +/-1.00 D of their preoperative manifest spherical equivalent refraction. All eyes had a stable refraction at the 3-month examination after removal, and a manifest spherical equivalent refraction within +/-1.00 D of their 1-month examination after removal. Nineteen eyes (19/21, 90%) returned to within +/-2 lines and 16 eyes (16/21, 76%) returned to within +/-1 line of preoperative UCVA. CONCLUSION: The ICRS (Intacs) was easily and safely removed, and eyes returned to preoperative refractive status within 3 months.

Two-incision radial keratotomy for low myopia with astigmatism.

PURPOSE: To evaluate the effectiveness of two-incision radial keratotomy (RK) in correcting low-magnitude refractive myopic astigmatism. SETTING: Two clinical study sites, one in St. Louis, Missouri, USA, the other in Caracas, Venezuela. METHODS: Fifty-seven eyes of 43 patients with low-magnitude myopic astigmatism had two-incision RK at one of two clinical study sites. In the initial phase of this series, 10 eyes with amblyopia at the 20/30 level had surgery at one center. Refractive keratotomy was performed with the radial incision placed in the plus cylinder axis of refraction. This axis was verified as the meridian of greatest corneal curvature by standard keratometry and computer-assisted corneal topographic analysis. Two eyes received a second operation (enhancement). RESULTS: Mean follow-up was 11.1 months (range 6 to 12 months). Mean preoperative and postoperative myopic spherical equivalent measured -1.42 diopters (D) +/- 0.51 (SD) and -0.14 +/- 0.39 D, respectively; the mean reduction was 1.28 +/- 0.59 D (P = .0001). Mean preoperative and postoperative refractive astigmatism was 1.41 +/- 0.45 D and 0.48 +/- 0.33 D, respectively (P = .0001). Mean preoperative and postoperative keratometric astigmatism was 1.26 +/- 0.54 D and 0.31 +/- 0.35 D, respectively, a mean reduction of 0.95 D (P = .0001). The surgical meridian was flattened by an average of 2.06 D by keratometry and the orthogonal meridian, by an average of 1.10 D. Preoperative uncorrected visual acuity (UCVA) was 20/40 or better in five (9%) eyes (range counting fingers to 20/40). Postoperative UCVA acuity was 20/40 or better in all eyes (mean acuity 20/25). In the nonamblyopic subgroup mean postoperative UCVA was 20/24. CONCLUSIONS: A limited number of radial incisions placed in the topographically confirmed axis of greatest curvature are effective in the treatment of low-magnitude myopic astigmatism.

Organization of collagen in the lyophilized cornea.

PURPOSE: To investigate the organization of collagen fibrils in the lyophilized cornea. METHODS: Freshly harvested porcine corneas (n = 10) were lyophilized and examined by synchrotron x-ray diffraction and transmission electron microscopy. RESULTS: Collagen fibrils are highly compacted in lyophilized corneas. They become more widely spaced when the tissue is rehydrated, however, the distribution of imbibed water throughout the stroma is not necessarily homogeneous within an individual cornea, nor is it always similar in specimens that have been rehydrated to similar levels. In lyophilized corneas, the mean center-to-center interfibrilar spacing of the regularly arranged collagen reaches levels found in freshly thawed porcine corneas (between 74% and 78% water by weight) when between 74.3% and 81.6% of the rehydrated lyophilized cornea's weight is water. CONCLUSION: Regularly arranged collagen fibrils are able to reapproximate their original spacings if lyophilized corneal tissue is rehydrated, although the manner in which imbibed water is distributed is somewhat unpredictable.

Macular corneal dystrophy type II: multiple studies on a cornea with low levels of sulphated keratan sulphate.

We investigated an individual macular corneal dystrophy (MCD) type II cornea from a 42-year-old woman with markedly reduced antigenic keratan sulphate levels. A characteristic 4.6 A X-ray reflection was evident, and the mid-stroma contained 30% less sulphur than normal. Close packing of collagen was restricted to the superficial stroma. Abnormally large proteoglycan filaments were noted throughout the extracellular matrix and Descemet's membrane's posterior non-banded zone, but not its anterior banded zone. Small, collagen-associated stromal proteoglycans were susceptible to digestion with chondroitinase ABC, but not keratanase I or N-glycanase. On occasion, collagen fibrils ranged in size from 20 nm to 58 nm, with preferential diameters of 34 nm and 42 nm. Corneal guttae were evident, as were numerous endothelial inclusions, most probably due to intracellular fibrillogranular vacuoles similar to those found in the stroma. The endothelium expressed reduced anti-keratan sulphate labelling.

The combined (Genesis) technique of radial keratotomy. A prospective, multicenter study. Refractive Keratoplasty Study Group.

PURPOSE: A prospective, multicenter, clinical study to evaluate a standardized surgical (Genesis) protocol which includes combined-technique radial incisions in patients seeking reduction of their physiologic myopia. The combined incisions were designed to incorporate the safety of the centrifugal incision technique with the efficacy of the centripetal incision technique. METHODS: A total of 375 eyes undergoing radial keratotomy procedures performed in six different clinical centers were analyzed. All procedures were performed in accordance with the Genesis nomograms. The Genesis protocol called for using preoperative screening pachymetry to guide central clear zone size selection, incising the thinnest corneal quadrant first, suturing corneal perforations, and discouraged more than one enhancement procedure, when indicated. Globe fixation technique served as a study variable. RESULTS: Mean follow-up was 6.2 months (range, 1.5-12 months). Mean residual cycloplegic refraction was -0.48 +/- 0.61 diopters (D) (range, -2.50 to +1.50 D); 92% of eyes were within 1 D of the planned goal of -0.50 D and 85% were within 1 D of emmetropia; 14% were myopic; and 1% was hyperopic by more than 1 D. Uncorrected visual acuity was 20/40 or better in 95% of eyes; the remaining 5% retaining myopic refractive errors. A single procedure was performed in 73% of eyes, and 99% received less than two enhancements. Of eyes with no enhancements, 97% had uncorrected visual acuity of 20/40 or better. One study eye (0.3%) had a two-line loss of spectacle visual acuity. There were no invasions of the central clear zone. Globe fixation was a significant predictor for enhancement incidence (P < 0.001) but not for perforation incidence (P = 0.06). Incision sequence was predictive for perforation incidence (P < 0.0002). CONCLUSION: The combined-technique of radial keratotomy, coupled with the Genesis surgical protocol, affords centrifugal incision safety with centripetal incision efficacy. The Genesis nomograms, with a built in refractive outcome goal of -0.50 D provide an acceptable degree of accuracy and predictability while guarding against hyperopic overcorrection.

Accuracy and precision of the corneal analysis system and the topographic modeling system.

Two computer-assisted topographic analysis systems were evaluated with calibrated spherical surfaces and normal human corneas. The Topographic Modeling System-1 (TMS-1) was found to be statistically more accurate in determining the power of calibrated spheres near the apex and at 1 mm from the apex than the Corneal Analysis System (CAS). The CAS, however, was statistically more accurate at 3 mm from the apex with each calibrated sphere. The small differences in accuracy between the two instruments, however, are unlikely to be of clinical significance. The topographic patterns on color-coded maps from 22 normal corneas of 11 subjects were similar with the two instruments. Simulated keratometry values with the CAS more accurately identified the keratometer-determined major cylinder axis compared with the TMS-1. Conversely, the TMS-1 was more accurate than the CAS at determining the level of corneal astigmatism.

Fate of lyophilized xenogeneic corneal lenticules in intrastromal implantation and epikeratophakia.

The antigenicity of intrastromal and epikeratophakia xenografts of lyophilized corneal tissue was evaluated in nonimmune and immune recipients. Lyophilized feline lenticules were implanted into intrastromal pockets in unsensitized rabbits and rabbits sensitized to the donor cat. In both cases, the grafts remained clear. Sensitized rabbits with clear intrastromal grafts received fresh tissue penetrating keratoplasty grafts from the same donor cat, placed adjacent to the intrastromal grafts. The fresh tissue penetrating keratoplasty grafts were rapidly rejected, while the lyophilized intrastromal grafts remained clear. Cats sensitized to rabbits received lyophilized and rehydrated epikeratophakia grafts shaped from rabbit cornea; these lyophilized grafts also remained clear for the 3-month period of the study. The results indicate that lyophilized and rehydrated corneal stroma, which is devoid of living cells, is not antigenic and is not subjected to immunologic attack, even in cases where the donor and host are of different species and the host has been previously immunized to the donor.

Peripheral corneal disorders.

The peripheral cornea is anatomically and physiologically distinct from its central counterpart. The major differences relate to the gradual transition of corneal tissues to those of the conjunctiva, episclera, and sclera; furthermore, the vascular structures, lymphatics, and inflammatory cells from these neighboring structures are intimately associated with the limbus and periphery of the cornea. The peripheral cornea is thereby predisposed to three main classes of disorders which do not normally involve the central cornea. First, local conditions affecting the sclera and conjunctiva may secondarily spread to involve the limbus and peripheral cornea. These include several infectious diseases, as well as hypersensitivity conditions, mass lesions, and degenerations. Second, due to the associated blood vessels and lymphatics, the peripheral cornea may be involved in a variety of systemic diseases, including vasculitides, autoimmune disorders, and abnormal metabolic conditions. Finally, there are several conditions, such as the noninflammatory peripheral degenerations, which primarily affect the peripheral cornea without associated ocular or systemic changes. In this review, we present a classification and discussion of the various disorders which may involve the peripheral cornea.

Five year follow-up of epikeratophakia in children.

Epikeratophakia alters the anterior curvature of the cornea by the addition of a machine-carved donor lenticule. Since March 1980, 88 patients under eight years of age have had epikeratophakia, with at least six months of follow-up. Eighty percent of the original surgeries were successful; some failed grafts were replaced successfully, so that in all, 89% of the patients had successful grafts. The average increase in curvature of the cornea was 14.7 diopters, and the average spectacle overcorrection was +0.56 diopters. In these growing eyes, we documented a myopic shift of 1.5 diopters per year. Visual acuity results varied with the timing of refractive surgery, density of the amblyopia, and the parents' ability to maintain the patching schedule. The largest group of children were those who had unilateral traumatic cataracts. In this group, 7 of 15 patients who had surgery under 4 years of age had final verbal acuities of 20/40 or better. Long-term follow-up has demonstrated that epikeratophakia safely and successfully corrects refractive errors in aphakic children either as a primary procedure, or as a secondary procedure after cataract extraction.

Antibody response following implantation of xenogenic lenticules.

Rabbits underwent implantation of either lyophilized or fresh porcine lenticules into the central or peripheral cornea. All animals were followed for up to four months by slit-lamp examination and macrophotography to determine implant rejection. Serum antibody levels to soluble porcine cornea extract were determined by an enzyme-linked immunosorbant assay. Only those animals receiving lenticules into the peripheral cornea experienced a rejection and developed an antibody response to the porcine cornea extract. The production of antibody preceded the appearance of vascularization of the implanted lenticules. Thus, the site of lenticule implantation, not the type of tissue preparation, determined the outcome of the graft.

Keratophakia with lyophilized cornea lathed at room temperature: new techniques and experimental surgical results.

A modified method of prelathing lyophilized corneal tissue at room temperature for refractive keratoplasty is described. This method allows perfect centration of a lyophilized corneal button on the plastic base and thus more accurate lathing. Keratophakia was performed with lenticules prepared in this fashion on a series of eight cats which were followed for 30 weeks postoperatively. All lenticules were clear ten weeks following surgery and the final optical correction obtained varied +/- 2.5 D from the intended correction.