EpiSmart Crosslinking for Keratoconus: A Phase 2 Study.

PURPOSE: The aim of this study was to assess changes in visual acuity after epithelium-on ("epi-on") corneal crosslinking after a diagnosis of keratoconus. METHODS: Subjects with corneal ectatic diseases were enrolled in a prospective, randomized, controlled, open-label, multicenter trial. Subjects were randomized to 1 of 3 treatment groups and treated with an epi-on crosslinking system including riboflavin/sodium iodide and pulsed UVA exposure (EpiSmart, CXL Ophthalmics, Encinitas, CA). The UVA treatment groups were 2.4 J/cm 2 over 20 minutes, 3.6 J/cm 2 over 20 minutes, and 3.6 J/cm 2 over 30 minutes. The primary end point was logarithm of the minimum angle of resolution corrected distance visual acuity (CDVA). Secondary end points were logarithm of the minimum angle of resolution uncorrected distance visual acuity (UCVA), maximum corneal curvature (Kmax), and minimum corneal thickness. Data were assessed 6 and 12 months post-operatively, using t -tests for differences from baseline. RESULTS: Two thousand two hundred twenty-eight subjects were treated with epi-on crosslinking. One thousand nine hundred twenty-two subjects had a diagnosis of keratoconus; other treated eyes had postsurgical and other ectasias. At 6 and 12 months, the subjects with keratoconus demonstrated significant improvements in CDVA, UCVA, and Kmax; minimum corneal thickness was unchanged. One hundred ninety-five subjects (8.7%) reported at least 1 adverse event (AE). A mild corneal epithelial defect was reported in 31 cases (1.4%) and was the only AE reported in >1% of subjects. There were no serious AEs related to the treatment. CONCLUSIONS: EpiSmart epi-on crosslinking resulted in mean improvements in CDVA, UCVA, and Kmax at both 6 and 12 months and an excellent safety and efficacy profile in subjects with keratoconus, with few significant side effects. Differences between UVA treatment groups were not significant.

Pachymetric Assessment After EpiSmart® Epithelium-on Cross-Linking for Keratoconus and Post-Surgical Ectasia.

Purpose: To assess the change in corneal pachymetry after a novel epithelium-on (EpiSmart®) corneal crosslinking procedure (CXL). Methods: Eyes treated as part of the open-label, non-controlled arm of the study "Collagen Crosslinking with Ultraviolet-A in Asymmetric Corneas" (NCT01097447) were examined at baseline, 3-, 6- and 12-months post-CXL. Thinnest pachymetry readings based on Pentacam (OCULUS GmbH, Wetzlar, Germany) were recorded. Results: A total of 101 eyes met the study inclusion criteria. Thinnest pachymetric readings at baseline averaged 451 ± 50 microns. The mean (± SD) minimum thickness was 450 ± 46 microns at 3 months, 452 ± 47 microns at 6 months, and 451 ± 48 microns at 12 months post-CXL. The changes from baseline (mean ± SE) at 3, 6, and 12 months post-CXL were -1.2 ± 1.5 microns, 0.5 ± 1.6 microns, and 0.4 ± 1.6 microns, respectively. Student's t-tests showed no statistically significant change in pachymetry from baseline for any exam period. Conclusion: This study demonstrated that, after EpiSmart® epithelium-on CXL, there was no substantial corneal thinning observable on Scheimpflug tomography out to 12 months.

Transepithelial crosslinking retreatment of progressive corneal ectasia unresponsive to classic crosslinking.

A 41-year-old man presented 10 years after uneventful laser in situ keratomileusis (LASIK) with symptomatic post-LASIK ectasia. He had treatment with the classic Dresden epithelium-off technique and presented 4 years later with progression of the ectasia. He was subsequently retreated with conductive keratoplasty (CK) followed by a new proprietary epithelium-on corneal collagen crosslinking (CXL) procedure using a proprietary transepithelial riboflavin formulation and delivery system on the following day. One year after retreatment, the patient noted stable vision in the treated eye with a corrected distance visual acuity (CDVA) of 20/60+. Thus, epithelium-on CXL, if performed with appropriate formulations and delivery technology as well as careful attention to appropriate riboflavin loading of the stroma, can stabilize an ectatic cornea. In addition, when performed prior to CXL, CK can induce a significant, lasting improvement in corneal shape and CDVA. This technique merits further study.

Clostridium perfringens endophthalmitis after penetrating keratoplasty with contaminated corneal allografts: a case series.

PURPOSE: To report the postoperative clinical course of 3 patients who underwent corneal transplantation with corneal allografts contaminated with Clostridium perfringens and to evaluate the risk factors for anaerobic contamination in 2 donors. METHODS: Patient records and adverse reaction reports from a single eye bank related to cases of posttransplant C. perfringens endophthalmitis were reviewed. Records regarding the mated corneas, donor autopsy reports, and other pertinent data were also reviewed. RESULTS: Three adverse reactions associated with transplantation of corneal allografts contaminated with C. perfringens were reported. Two cases were from mated corneas. Both patients developed fulminant endophthalmitis after undergoing uncomplicated penetrating keratoplasty and required subsequent enucleation. Another isolated case (with no adverse reaction in the mate cornea) developed hypopyon postoperatively that resolved with intravitreal and topical antibiotics. Possible risk factors for anaerobic tissue contamination in the donors included illicit drug use in the first donor and exposure to sewage at the time of death in the second donor. CONCLUSIONS: Clostridial endophthalmitis is an aggressive rapidly progressive infection with potentially poor visual outcomes that can be transmitted from infected corneal allografts. Further investigation is needed to clarify the role of anaerobic donor rim cultures and the donor risk factors associated with recovering corneal allograft tissue contaminated with C. perfringens.

A new system, the LipiFlow, for the treatment of meibomian gland dysfunction.

PURPOSE: To evaluate the safety and effectiveness of the LipiFlow System compared to the iHeat Warm Compress (WC) for adults with meibomian gland dysfunction (MGD). METHODS: This was a non-significant risk, prospective, open-label, randomized, crossover multicenter clinical trial. One hundred thirty-nine subjects were randomized between LipiFlow (n=69) and WC control (n=70). Subjects in the LipiFlow group received a 12-minute LipiFlow treatment and were reexamined at 1 day, 2 weeks and 4 weeks. Control subjects received a 5-minute iHeat treatment with instructions to perform the same treatment daily for 2 weeks. At 2 weeks, they crossed over (LipiFlow Crossover) and received the LipiFlow treatment. Effectiveness parameters: meibomian gland (MG) assessment, tear break-up time (TBUT) and dry eye symptoms. Safety parameters: adverse events, ocular health exam, ocular surface staining, intraocular pressure, visual acuity and discomfort. RESULTS: LipiFlow resulted in significant improvement (P < 0.05) in MG secretion at 2 and 4 weeks (mean ± standard deviation at baseline = 6.3 ± 3.5; 2 weeks = 14.3 ± 8.7; 4 weeks = 16.7 ± 8.7); and TBUT at 2 and 4 weeks: (at baseline = 5.5 ± 2.9; 2 weeks = 6.9 ± 5.0; 4 weeks = 7.4 ± 5.5). There was no significant change in MG secretion or TBUT in the control group. LipiFlow resulted in a greater significant reduction in dry eye symptoms than the iHeat WC. The crossover group demonstrated similar significant improvement 2 weeks post-treatment with the LipiFlow. There was no significant difference between groups in the incidence of non-serious, device-related adverse events. CONCLUSION: The LipiFlow System was significantly more effective than iHeat WC. These results support its safety and effectiveness in the treatment of MGD and dry eye symptoms.

Successful treatment of recurrent epithelial ingrowth associated with interface fluid syndrome, flap necrosis, and epithelial defects following LASIK.

PURPOSE: to report the successful treatment of two patients who developed flap necrosis preceded by recurrent epithelial ingrowth and interface fluid syndrome after LASIK. METHODS: patient 1 was treated with epithelial debridement and flap suturing. Patient 2 was initially treated with epithelial debridement and flap suturing, but developed recurrent epithelial ingrowth in the right eye and 2 weeks later in the left eye. RESULTS: patient 1 developed diffuse interface fluid accumulation in the left eye after epithelial debridement and flap suturing and was treated with timolol meleate 0.5% solution and methazolamide. The interface fluid resolved and the cornea and flap became clear. Slit-lamp examination identified a small area of epithelial ingrowth recurrence, which has remained stable for 3 years. Patient 2 was successfully retreated with epithelial debridement followed by fibrin tissue adhesive application. Five months after debridement and fibrin tissue adhesive, no recurrence of epithelial ingrowth or interface fluid accumulation was noted. CONCLUSIONS: epithelial ingrowth and interface fluid syndrome may be associated with secondary flap necrosis following LASIK, which can be effectively treated with debridement and flap suturing or fibrin tissue adhesive application.

Reduced application time for prophylactic mitomycin C in photorefractive keratectomy.

OBJECTIVE: To determine whether the duration of mitomycin C (MMC) 0.02% application affects visual outcome or the incidence of subepithelial haze in patients undergoing photorefractive keratectomy (PRK) with prophylactic administration of MMC. DESIGN: Retrospective, comparative case series. PARTICIPANTS: Two hundred sixty-nine eyes undergoing PRK. METHODS: This was a retrospective comparative case series that included 269 eyes that underwent PRK with prophylactic MMC application for 120 seconds (group 1, n = 74), 60 seconds (group 2, n = 36), or 12 seconds (group 3, n = 159). The mean preoperative spherical equivalent was -6.49 diopters (D) in group 1, -6.77 D in group 2, and -7.10 D in group 3. Photorefractive keratectomy was performed using a modified nomogram. All eyes received a single intraoperative application of MMC (0.02%) after laser ablation for the above specified durations. MAIN OUTCOME MEASURES: Best-corrected visual acuity and corneal haze score. RESULTS: Best-corrected visual acuity was 20/23 in group 1, 20/20 in group 2, and 20/21 in group 3. The mean haze score+/-standard deviation (scale, 0.00-4.00) was 0.11+/-0.31 in group 1, 0.14+/-0.28 in group 2, and 0.07+/-0.20 in group 3 throughout a mean follow-up of 31 months in group 1, 16 months in group 2, and 10 months in group 3. No eyes had a haze score of more than 1.00. CONCLUSIONS: There was no statistically significant difference in postoperative best-corrected visual acuity or haze scores among the 3 groups. Administration of prophylactic MMC 0.02% for 12 seconds after PRK seems to be equally efficacious for haze prophylaxis when compared with longer application times of 60 and 120 seconds.

Culture-positive endophthalmitis after implantation of intraocular Collamer lens.

We report a case of culture-positive bacterial endophthalmitis following implantation of a Staar intraocular Collamer lens (ICL). The patient presented 4 days after uneventful sutureless surgery with decreased visual acuity, redness, and photosensitivity. Inflammation increased over the next 24 hours, which prompted a tap for culture and intravitreal injection of antibiotic agents. Vitreous culture was positive for coagulase-negative Staphylococcus epidermidis. One year postoperatively, the uncorrected distance visual acuity was 20/20; persistent anterior vitreous opacities were the only observable sequelae. Bacterial endophthalmitis is a potential complication of ICL implantation. It can be successfully diagnosed and treated if a high degree of suspicion is maintained and if appropriate diagnostic and treatment modalities are used.

Effect of mitomycin C on the corneal endothelium when used for corneal subepithelial haze prophylaxis following photorefractive keratectomy.

PURPOSE: To evaluate the potential effect of topical mitomycin C (MMC) on the corneal endothelium of myopic patients undergoing photorefractive keratectomy (PRK). METHODS: Sixteen eyes with a planned ablation depth >75 microm underwent PRK followed by 0.02% MMC applied for 12 seconds using a methylcellulose sponge. Endothelial specular microscopy was performed with the Keeler-Konan specular photomicroscope in 16 eyes before and at least 1 year after surgery. Mean follow-up was 18 months (range: 12 to 24 months). Mean cell density, coefficient of variation of mean cell area, and percentage of hexagonal cells were measured and calculated using computerized morphometric analysis. RESULTS: Mean endothelial cell densities before and after surgery were 2882 +/- 783 cells/mm2 (range: 1511 to 4022 cells/mm2) and 2867 +/- 588 cells/mm2 (range: 1638 to 3881 cells/mm2), respectively (P > .05). Mean coefficient of variation before and after surgery was 0.30 +/- 0.07 (range: 0.23 to 0.49) and 0.26 +/- 0.04 (range: 0.22 to 0.33), respectively (P=.06). Mean percentage of hexagonal cells before and after surgery was 61% +/- 6.8% (range: 47% to 70%) and 66% +/- 6.7% (range: 54% to 75%), respectively. CONCLUSIONS: Administration of MMC for haze prophylaxis following PRK did not have a significant effect on quantitative endothelial cell density or qualitative morphometric parameters in this study.

Noninvasive diagnosis of epithelial downgrowth after penetrating keratoplasty using immunohistochemical analysis of resected corneal buttons.

PURPOSE: To describe a noninvasive technique that can be used to support a clinically suspected diagnosis of epithelial downgrowth in patients who have previously undergone penetrating keratoplasty (PK). METHODS: Previously resected corneal buttons of 14 patients who developed signs suggestive of epithelial downgrowth after PK were examined retrospectively using immunohistochemical analysis to determine if occult epithelial cells were in fact present on the posterior surface of the cornea. Many of these patients were diagnosed with pseudophakic corneal edema or graft failure and had undergone multiple intraocular surgical procedures. In all cases, the initial histopathologic evaluation did not disclose the presence of epithelial cells using light microscopy after standard handling and staining techniques. Fourteen age- and diagnosis-matched control specimens were also examined. RESULTS: Thirteen of 14 specimens (92.9%) exhibited positive staining with anti-keratin AE1/AE3 markers, indicating that epithelial cells were already present on the endothelial surface at the time of the original PK. None of the control specimens displayed positive staining of the retrocorneal surface. CONCLUSION: Retrospective immunohistochemical analysis of corneal specimens can establish the diagnosis of epithelial downgrowth in a noninvasive manner. Early diagnosis may allow for this condition to be treated more successfully if aggressive intervention is undertaken. Alternatively, it may spare the patient from additional (and potentially futile) intraocular surgery. In the clinical setting of suspected epithelial downgrowth, ophthalmic pathologists should re-evaluate PK specimens from patients initially diagnosed with pseudophakic corneal edema or graft failure.

Corneal ectasia after laser in situ keratomileusis in patients without apparent preoperative risk factors.

PURPOSE: To evaluate patients who developed ectasia with no apparent preoperative risk factors. METHODS: Potential cases of patients who developed ectasia without apparent risk factors were identified by contacting participants in the Kera-Net (n = 580), ASCRS-Net (n = 450), and ISRS/AAO ISRS-Net (n = 525) internet bulletin boards from April to October 2003. Cases were included if ectasia developed after laser in situ keratomileusis in the absence of apparent preoperative risk factors. Reported cases were excluded for the following reasons: (1) calculated residual stromal bed less than 250 microm, (2) preoperative central pachymetry less than 500 microm, (3) any keratometry reading greater than 47.2 diopters (D), (4) a calculated inferior-superior value greater than 1.4, (5) more than 2 retreatments, (6) attempted initial correction greater than -12.00 D, (7) an Orbscan II "posterior float" (if obtained) greater than 50 microm, and (8) surgical/flap complications. RESULTS: A total of 27 eyes of 25 patients were submitted for consideration. Eight eyes (8 patients) met our inclusion criteria. Mean age was 27.7 years (range, 18-41 years). Preoperative manifest refraction spherical equivalent was -4.61 D (range, -2.00 to -8.00 D); steepest keratometric reading was 43.86 D (range, 42.50-46.40 D); keratometric astigmatism was 0.93 D (range, 0.25-1.90 D); and preoperative central pachymetry was 537 microm (range, 505-560 microm). The mean calculated ablation depth was 82.8 microm (range, 21-125.4 microm), and mean calculated residual stromal bed was 299.5 microm (range, 254-373 microm). Mean time to recognition of ectasia onset was 14.2 months (range, 3-27 months) postoperatively. At the time of ectasia diagnosis, the mean manifest refraction spherical equivalent was -1.23 D (range, +0.125 to -3.00) with a mean of 2.72 D (range, 0.75-4.00 D) of astigmatism. CONCLUSIONS: Ectasia can occur after an otherwise uncomplicated laser in situ keratomileusis procedure, even in the absence of apparent preoperative risk factors.