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.

Corneal surface topography and associated visual performance with INTACS for myopia: phase III clinical trial results. The INTACS Study Group.

OBJECTIVE: To characterize corneal topography with INTACS (KeraVision, Inc., Fremont, CA) an ophthalmic device designed to correct myopia, and relate findings to visual performance. DESIGN: Prospective nonrandomized self-controlled comparative intervention study. PARTICIPANTS/INTERVENTION: Patients were participants in the INTACS FDA phase III clinical trials. MAIN OUTCOME MEASURES: Preoperative and postoperative month 6 videokeratographic corneal topography (EyeSys, Houston, TX) was analyzed for 165 eyes from eight clinical sites. Topographic flattening, asphericity, and surface characteristics were statistically evaluated for relationship to visual acuity, refractive data, contrast sensitivity, and subjective visual symptoms. RESULTS: Corneal radius of curvature flattening was aspheric in nature and increased incrementally and significantly for progressively thicker INTACS (P < 0.05). Comparative stratification analyses suggest potential interactions between existing preoperative asphericity and myopia, postoperative asphericity, and visual performance outcomes. Qualitative symmetric and asymmetric toric topography patterns were related to the postoperative self-reported visual symptoms of "double images" (P < or = 0.05) and "halos" (P < or = 0.10), respectively. CONCLUSIONS: The anterior corneal surface is aspherically flattened (prolately) with INTACS, whereas postoperative corneal asphericity is significantly more prolate than preoperative. Specific qualitative postoperative topography patterns were associated with subjective clinical visual performance.

Characterization of the aspheric corneal surface with intrastromal corneal ring segments.

PURPOSE: Anterior corneal surface asphericity was examined in eyes of Phase II clinical trial participants, before and after intrastromal corneal ring segments (ICRS, Intacs) refractive surgery, and surveyed for relationship to clinical visual performance. METHODS: Aspheric test objects with surface asphericity (Q) ranging from -0.01 Q to -1.44 Q and base radius of curvatures ranging from 7.5 mm to 9.0 mm were measured topographically using videokeratography. Radius of curvature asphericity profile plots were produced for test objects and compared to similar plots created for trial participant eyes (n=25) to quantify corneal asphericity. The potential effects of different amounts of corneal asphericity were assessed using measurement of uncorrected and spectacle-corrected visual acuity and photopic contrast sensitivity. RESULTS: Preoperative corneal asphericity ranged from -0.01 Q to -0.81 Q and postoperative from -0.01 Q to -1.44 Q. Preoperative uncorrected visual acuity was significantly related to corneal asphericity; more myopic eyes tended to have more prolate corneal asphericity. Corneal asphericity was not significantly related to spectacle-corrected visual acuity or photopic contrast sensitivity, before or after surgery. CONCLUSION: Postoperative corneal asphericity values demonstrated that intrastromal corneal ring segments (Intacs) produced a prolate aspheric surface for myopic correction from -1.00 D to -6.00 D. This study indicated that the range of corneal asphericity measured in these 25 eyes, before and after surgery, provided good visual acuity and normal contrast sensitivity.

Topographic predicted corneal acuity with intrastromal corneal ring segments.

PURPOSE: To evaluate predicted optical quality of the central anterior corneal surface before and after the intrastromal corneal ring segment (ICRS) refractive procedure using a clinical videokeratoscope and software index developed for that purpose. METHODS: Predicted corneal acuity, a topographically derived index provided with the EyeSys System 2000 videokeratscope, representing potential optical quality of the cornea, was assessed preoperatively and at postoperative month 3 in 94 eyes that received an ICRS to treat -1.00 to -6.00 D of myopia. Predicted corneal acuity was calculated by determining the difference between a measured cornea and its best-fit ellipses for reflected ring circumferences within the central 3 mm diameter zone. RESULTS: Preoperative predicted corneal acuity was 20/10 in 92 of 94 eyes (98%). At month 3 after the ICRS procedure, 48 (51%) of moderately myopic eyes were corrected to 20/20 or better, 96% (90 eyes) were corrected to 20/40 or better, and 98% of eyes (92 eyes) had a predicted corneal acuity of 20/10. For the eyes with a predicted corneal acuity of 20/10, spectacle-corrected visual acuity was normally distributed between 20/10 and 20/25. CONCLUSION: Predicted corneal acuity did not change significantly from baseline in eyes with an ICRS. This suggests that topographic irregularities in the central 3 mm of the cornea detectable by predicted corneal acuity software were not induced in the central cornea with the ICRS.

Lamellar intrastromal corneal tattoo for treating iris defects (artificial iris)

PURPOSE: Defects in the iris are associated with clinically significant optical anomalies, such as glare and peripheral light scatter; however, current artificial-iris technology remains inadequate. The purpose of this study was to explore the practicality of a lamellar intrastromal tattoo technique as a treatment modality to correct optical and cosmetic defects resulting from simulated iris abnormalities in eye-bank eyes. METHODS: Simulated iris defects (abnormally large pupil, sector iridectomy, iridodialysis, and aniridia) were produced in a series of eye-bank eyes. Depending on the simulated iris defect, one or two lamellar channel(s) were created at 50% depth of the cornea via a peripheral incision (1.8 mm) with specialized proprietary instruments (KeraVision, Inc., Fremont, CA, U.S.A.). Commercially available tattoo pigment was inserted through the lamellar channel(s) and blended into the defective region of the iris. RESULTS: The tattoo treatment was relatively simple to perform. Tattoo pigment was inserted uniformly through the small incision, and adequate color blending to match the recipient iris was achieved. The intrastromal tattoo effectively obscured light. CONCLUSION: The lamellar intrastromal tattoo technique appeared to be efficacious for treating different types of iris defects in eye-bank eyes. Further investigation of this technique in nonsighted patient eyes is warranted.

Intrastromal corneal ring technology: results and indications.

Intracorneal ring technology has shown rapid development in the past 10 years, and clinical results are confirming outstanding results for the correction of low to moderate refractive myopias. Two of these device designs, the Intrastromal Corneal Ring and the Intrastromal Corneal Ring Segments (both manufactured by KeraVision, Inc., Fremont, CA) are currently undergoing rigorous investigation in US Food and Drug Administration-regulated clinical trials. Results to date indicate the surgical procedure is safe and easily performed, the visual results are excellent (preserving best spectacle-corrected visual acuity), and the procedure provides stable and predictable correction through several years postoperatively. Preliminary results show that enhancements can be easily performed by device exchange, and the device can be removed, reversing the refractive effect.

Corneal asphericity in eye bank eyes implanted with the intrastromal corneal ring.

OBJECTIVE: To evaluate the effects of the intrastromal corneal ring, a device developed to reduce myopia, on corneal asphericity in a large set of eye bank eyes. METHODS: Forty-one deturgesced eye bank eyes were implanted with intrastromal corneal rings of five different thicknesses, ranging from 0.25 mm to 0.45 mm. Corneal asphericity, before and after implantation, was examined using two different metrologies. Corneal asphericity profiles were produced from dioptric power data collected from videokeratography. To statistically assess the corneal asphericity differences between exam times for each intrastromal corneal ring thickness, dependent sample confidence intervals (95%) were calculated for the mean differences between preoperative and postoperative measures for each topographic diameter zone. Laser holographic interferometry was used to inspect corneal asphericity in one eye bank eye case study for four intrastromal corneal ring sizes. Wave unit map and geometric zonal spot ray tracing analyses derived from laser holographic interferometry topography were surveyed. RESULTS: Videokeratographic analysis suggested that preoperative corneal shape was prolate, i.e., flattened from central to paracentral cornea. Corneal shape became more prolate with intrastromal corneal ring implantation for all intrastromal corneal ring thicknesses. Laser holographic interferometry demonstrated that prolate asphericity was preserved with the intrastromal corneal ring sizes tested and that optical collection efficiency of the cornea was not diminished. CONCLUSION: Using two different measurement techniques, this eye bank eye study demonstrated that intrastromal corneal rings maintain prolate corneal asphericity.

The intrastromal corneal ring segments. Phase II results for the correction of myopia.

OBJECTIVE: The purpose of the study was to evaluate the safety and efficacy of the intrastromal corneal ring segments (ICRS) for the correction of myopia. DESIGN: A 2-year phase II clinical trial of ICRS was initiated in May 1995. The investigational plan specifies that 150 patients with sighted eyes, requiring myopic corrections from -1.00 to -6.00 diopters (D), will each receive ICRS in 1 eye. The patient population will be divided into approximately five patients per ICRS thickness (0.25, 0.30, 0.35, 0.40, and 0.45 mm) per site. Six investigational sites are participating in the trial. PARTICIPANTS: Fifty-nine men and 43 women requiring myopic corrections were enrolled at four U.S. investigational sites. These 102 patients each received the ICRS product in 1 eye. INTERVENTION: Correction of myopia. MAIN OUTCOME MEASURES: Efficacy of ICRS was assessed with respect to the trial endpoints of predictability of refractive effect, uncorrected visual acuity (UCVA), stability of UCVA, maintenance of best spectacle-corrected visual acuity and stability of refractive effect. RESULTS: As shown by the available month-3 data (99 patients; all device thicknesses), 95 (96%) of 99 patients had a UCVA of 20/40 or better. Ninety-eight (99%) of 99 patients were within 2 lines of their preoperative best spectacle-corrected visual acuity. The average change (with standard error) in cycloplegic refraction (spherical equivalent) achieved by ICRS thickness was -1.27 +/- 0.09 D (0.25 mm), -2.13 +/- 0.16 D (0.30 mm), -2.56 +/- 0.15 D (0.35 mm), -3.77 +/- 0.37 D (0.40 mm) and -4.16 +/- 0.24 D (0.45 mm). Seventy-seven percent (76/99) of the patients were within +/-1.00 D of their intended correction. When the ICRS was removed in two cases, both patients returned to within 0.75 D of their preoperative manifest refraction. CONCLUSIONS: The ICRS appears to be a viable and effective alternative for the treatment of myopia. Additionally, as indicated by the explant data, the ICRS's refractive effect may be reversible upon removal of the device.

Intrastromal corneal ring: 12-month sighted myopic eyes.

BACKGROUND: To evaluate the efficacy, predictability, and stability of the refractive effect produced by the Intrastromal Corneal Ring (ICR), the authors completed a 12-month study on 10 myopic eyes. METHODS: Ten patients with preoperative refractive errors ranging from -2.63 diopters (D) to -4.25 D (mean, -3.30 D) participated in the study. The attempted correction was -2.50 D for a 7.0-mm diameter, 0.3-mm thick ICR. One eye of each patient received an ICR. RESULTS: The average change in spherical equivalent at 12 months was -2.25 D (SD 0.54 D; range, -1.62 to -3.25 D). All patients maintained a spectacle-corrected visual acuity of 20/20 or better during the 12-month study period, with the exception of patient no. 6 who saw 20/30 at the 6-month examination. Her spectacle-corrected visual acuity returned to 20/20 a few days after the ICR was explanted and remained stable throughout the study. Uncorrected visual acuity had improved to 20/40 or better in all patients on postoperative day 1 and remained in this range for the 9 eyes (90%) during the 12 months of follow up. At postoperative month 12, 9 of 9 eyes (100%) had an uncorrected visual acuity of 20/40 or better with 3 of 9 eyes (33%) seeing 20/20 or better. The remaining patient, no. 6, experienced a tear in Descemet's membrane during the procedure and required explantation of the ring after 6 months due to induced astigmatism and deterioration of uncorrected visual acuity. Two patients developed infiltrates that resolved with the use of antibiotics. The most common postoperative ocular findings were peripheral corneal haze in all eyes that diminished over time, minute lamellar channel deposits (7 of 10 eyes, 70%), deep stromal neovascularization (5 of 10 eyes, 50%), and pannus (5 of 10 eyes, 50%). CONCLUSION: This preliminary study shows that implantation of an intrastromal corneal ring of this dimension (0.3-mm thick) can reduce approximately 1.50 to 3.00 D of myopia and maintain spectacle-corrected visual acuity.

Flattening of central corneal curvature with intrastromal corneal rings of increasing thickness: an eye-bank eye study.

Intrastromal Corneal Rings (ICRs) have been demonstrated to flatten human corneas when implanted into peripheral intrastromal corneal channels. To study the flattening effect, ICRs of increasing thickness, 0.26, 0.31, 0.36, 0.41, and 0.46 mm, were placed into oversized (approximately 70% depth) intrastromal channels in 38 eye-bank eyes. Each of 33 eyes received one ICR; the mean change in dioptric data was obtained for four meridians using an intraoperative photokeratoscope. Intrastromal corneal rings of increasing thickness resulted in corneal flattening of 3.8 +/- 1.1, 4.9 +/- 0.6, 5.2 +/- 1.1, 5.3 +/- 1.9, and 7.3 +/- 1.6 diopters, respectively, for keratoscope mire 2. One of each size ICR was placed into one of five additional eye-bank eyes; the degree of flattening measured by laser holographic interferometry was 1.8, 2.9, 5.5, 4.7, and 10.1 diopters, respectively, for the central 6 mm corneal zone. These results indicate that the ICR provides a fairly linear flattening relationship over the range of thicknesses tested. Additionally, laser holographic interferometry wave unit maps of preoperative and postoperative corneas demonstrated that the ICR tends to preserve positive corneal asphericity if present preoperatively.

Optisol corneal storage medium.

We compared the safety and efficacy of Optisol (Chiron Ophthalmics, Irvine, California), a new corneal storage medium, with McCarey-Kaufman and Dexsol corneal storage media (Chiron Ophthalmics, Irvine, California) and K-Sol corneal storage medium (Cilco, Huntington, West Virginia). Optisol contains dextran, 2.5% chondroitin sulfate, vitamins, and precursors of adenosine triphosphate (adenosine, inosine, and adenine). In in vitro studies, rabbit and human corneas stored in Optisol were thinner after 12 to 14 days at 4 C than tissue stored in other media. Thymidine uptake showed increased mitotic activity in human corneal endothelial cells cultured in Optisol, compared to Dexsol. Specular microscopic fields showed larger are-as of visibly intact endothelial cells and ultrastructural examination disclosed fewer structural changes in endothelial cells stored in Optisol, compared to tissue stored in Dexsol. In vivo, no clinical signs of epithelial toxicity or histologic evidence of intraocular inflammation were observed in rabbit eyes in which Optisol drops were instilled four times a day for 14 days. Finally, 51 patients undergoing penetrating keratoplasty with tissue stored in Optisol for one to six days (mean, 3.6 days) were enrolled in an uncontrolled, open-label clinical study. The percentage of clear grafts (93%, 41 of 44 patients examined at three months; and 98%, 42 of 43 patients examined at six months) and endothelial cell loss (5.0% and 11.5% at three and six months, respectively) were comparable to data from previous studies that used tissue stored in other short-term and intermediate-term media. The results suggest that Optisol storage preserves corneal endothelial cells for up to two weeks at 4 C, thereby permitting flexibility in the use of donor tissue for corneal transplantation, and that Optisol storage yields thinner tissue, which may allow for more accurate evaluation and more effective surgical manipulation.

Effects of intrastromal corneal ring size and thickness on corneal flattening in human eyes.

Intrastromal corneal rings can flatten the human cornea, providing a potential new method of keratorefractive surgery. We investigated the effect of implanting various ring sizes of a given thickness in 8.50-mm intrastromal channels dissected in human eye bank corneas. A new intraoperative corneal topography device was used to obtain serial data. Smaller rings with no expansion pressure on the channels were found to induce corneal flattening presumably due to the ring thickness alone. Rings of increasing diameters produced high degrees of corneal flattening at progressively declining rates; this suggests that shear stresses may have expanded the channel due to mechanical stresses placed by our particular experimental technique. Implantation techniques that minimize stress on the outer channel lamellae appear advisable. New ring designs should take ring thickness into consideration along with outer edge configurations that minimize shear stresses on the lamellar channels.

Esterase isozymes in a solitary bee, Megachile rotundata (Fab.): characterization, developmental multiplicity, and adult variability.

This study describes the biochemical characterization and genetic variation of cytosolic esterases in the alfalfa leafcutting bee, Megachile rotundata (Fab.). Esterase isozymes were separated by nondenaturing polyacrylamide gel electrophoresis and isoelectric focusing and characterized by inhibition with eserine sulfate, EDTA, paraoxon, and p-hydroxymercuribenzoate. Based on inhibition patterns and substrate specificity, there are major differences between adults and immature forms and more subtle differences between male and female adults. M. rotundata esterases are largely organophosphate sensitive and the two major adult allozymes were highly variable within the population examined. Differences in esterase expression between life stages with respect to niche and the occurrence of diploid males are discussed.

Expression of two molecular forms of the complement decay-accelerating factor in the eye and lacrimal gland.

Complement is present in ocular fluids, but the molecular mechanism(s) restricting its activation to exogenous targets and not to autologous ocular cells are currently unknown. To clarify how this control is achieved, monoclonal antibody (mAb)-based techniques were used to examine the eye, the lacrimal gland, and ocular fluids for the decay-accelerating factor (DAF), a membrane regulatory protein which protects blood cells from autologous complement activation on their surfaces. Immunohistochemical staining of tissue sections revealed DAF antigen on corneal and conjunctival epithelia, corneal endothelium, trabecular meshwork, and retina, as well as on lacrimal gland acinar cells and in adjacent lumens. By flow cytometry, cultures of conjunctival epithelium exhibited the highest DAF levels and levels on corneal epithelium greater than corneal endothelium greater than conjunctival fibroblasts. Biosynthetic labeling of corneal endothelium yielded de novo DAF protein with an apparent molecular weight (Mr) of 75 kD, approximating that of blood cell DAF protein, and digestions of conjunctival epithelium with phosphatidylinositol-specific phospholipase C (PI-PLC), an enzyme which cleaves glycoinositolphospholipid membrane anchors, released approximately 70% of the ocular surface DAF protein similar to leukocyte surface DAF protein. Quantitations of DAF by radioimmunometric assay employing mAbs against two DAF epitopes revealed 325 ng/ml (n = 12), 4.8 ng/ml (n = 10), and 22.0 ng/ml (n = 8) of soluble DAF antigen in tears, aqueous humor, and vitreous humor, respectively. Western blot analyses of the tear DAF antigen revealed two DAF forms, one with an apparent Mr of 72 kD resembling membrane DAF forms in other sites, and a second with an apparent Mr of 100 kD, which is previously undescribed. Since DAF activity is essential physiologically in protecting blood cells from autologous complement attack, the identification of DAF on the ocular surface, intraocularly, in the lacrimal gland, and in tears suggests that DAF-mediated control of complement activation is also required in these locations.

A computerized recall system for clinical trials.

A major difficulty facing investigators involved in clinical studies is ensuring the timely follow-up of patients involved in the investigations. Two microcomputer programs are described that create a follow-up calendar for each subject, list patients due to appear for any given month, and generate printouts of subjects who have missed key follow-up appointments. These programs were formulated using dBASE II (Ashton Tate, California), a widely used data base management package suitable for International Business Machines-compatible microcomputers. The programming concept used in formulating these programs can be adapted to most other data base management software systems. These programs are currently enhancing the follow-up of patients enrolled in a prospective ophthalmic surgical protocol and are potentially useful to any investigator involved in prospective studies who has access to a microcomputer.

Impact of routine inquiry legislation in Oregon on eye donations.

Routine inquiry legislation can significantly affect procurement of donor eye tissues. Oregon Revised Statute (ORS) 97.268 was the first legislation of this type passed in the United States. In the first 12 months under this legislation, the Oregon Lions Eye Bank obtained, 2,312 eyes, sustaining a 135% increase in donor eye procurement over the yearly average for 1984-1985. During the first 12 months of routine inquiry, 484 corneas suitable for penetrating keratoplasty were obtained versus an annual average of 291 corneas for 1984-1985. Tissues for other transplant purposes and for research have similarly become more available. Age of donor tissue appears to be increasing slightly due to the disproportionate increase of donor eyes from the 70-or-over population. The Oregon Donor Program, the public and professional education coalition of the transplant programs in the state of Oregon, has played an invaluable role in making this penalty-free law a success.