Mediators of Corneal Haze Following Implantation of Presbyopic Corneal Inlays.

Purpose: To identify protein mediators of corneal haze following presbyopic corneal inlay surgery. Methods: Tears were collected from eyes with corneal haze following surgery with a shape-changing corneal inlay. Samples were subjected to quantitative proteomic analysis using iTRAQ and proteins significantly increased or decreased (1.3-fold or more) in haze eyes relative to fellow eyes were identified. Expression ratios were compared to postoperative eyes without corneal haze to identify proteins selectively increased or decreased in corneal haze eyes. Results: Inlay-associated haze occurred in 35% of eyes (6 of 17). Of 1443 unique tear proteins identified, eight proteins were selectively reduced in tears from postoperative haze eyes and one protein selectively increased. Proteins reduced in haze eyes included complement 4a (level relative to nonhaze eyes 0.464, P = 0.037), complement factor H (0.589, P = 0.048), immunoglobulin kappa variable 2-29 (0.128, P = 0.006), immunoglobulin kappa variable 2D-28 (0.612, P = 0.025), immunoglobulin lambda variable 7-46 (0.482, P = 0.007), S100 calcium binding protein A4 (0.614, P = 0.048), Shootin-1 (0.614, P = 0.048), and tissue inhibitor of metalloproteinase-1 (0.736, P = 0.023). The Xaa-Pro aminopeptidase 1 was increased in haze eyes relative to nonhaze eyes (1.517, P = 0.023). Conclusions: Corneal haze following corneal inlay surgery is associated with reduction in levels of known inflammatory and immune mediators. These findings represent a starting point for elucidation of pathways involved in corneal haze following synthetic inlay implantation and may enable development of targeted therapies that modulate the haze response.

Keratoprosthesis surgery for end-stage corneal blindness in asian eyes.

PURPOSE: To establish a multidisciplinary surgical program for osteo-odonto-keratoprosthesis (OOKP) surgery in Asia and to evaluate efficacy and preliminary safety of this keratoprosthesis in end-stage corneal and ocular surface disease. DESIGN: Prospective noncomparative case series. PARTICIPANTS: Sixteen adults of Asian ethnic origin, bilaterally blind with end-stage corneal blindness from Stevens-Johnson syndrome, or severe chemical or thermal burns. METHODS: Osteo-odonto-keratoprosthesis surgery involves 2 procedures-in stage 1, an autologous canine tooth is removed, modified to receive an optical polymethyl methacrylate cylinder, and implanted into the cheek. The ocular surface is denuded and replaced with full-thickness buccal mucosa. Stage 2 surgery, performed 2 to 4 months later, involves retrieval of the tooth-cylinder complex and implanting it into the cornea, after reflection of the buccal mucosal flap, corneal trephination, iris and lens removal, and anterior vitrectomy. Concurrent glaucoma and vitreoretinal procedures are also performed at either stage, as required. MAIN OUTCOME MEASURES: Visual acuity (VA), field of vision, anatomical integrity and stability, and ocular and oral complications related or unrelated to the OOKP device. RESULTS: Osteo-odonto-keratoprosthesis surgery was performed on 15 patients, with a mean follow-up of 19.1 months (range, 5-31). Intraoperative complications included expulsive hemorrhage (keratoprosthesis device not implanted), tooth fracture (n = 1), oronasal fistula (n = 1), and mild inferior optic tilt (n = 1). Anatomical stability and keratoprosthesis retention has been maintained in all eyes, with no dislocation, extrusion, retroprosthetic membrane formation, or keratoprosthesis-related infection. Other complications not directly related to device insertion included retinal detachment (RD) related to silicone oil removal (n = 1) and endophthalmitis related to endoscopic cyclophotocoagulation performed 1 year after OOKP surgery (n = 1). Eleven patients (73.3%) attained a stable best spectacle-corrected VA of at least 20/40 or better, whereas 9 (60%) attained stable 20/20 vision. Four patients achieved their best visual potential, ranging from 20/100 to counting fingers vision, related to preexisting glaucomatous optic neuropathy or previous RD. CONCLUSIONS: Establishment of our OOKP program suggests that OOKP surgery has the potential to restore good vision to the most severe cases of corneal blindness in an Asian setting, with minimal device-related complications. Longer follow-up of these cases is currently underway.

Compressive C-shaped lamellar keratoplasty: a surgical alternative for the management of severe astigmatism from peripheral corneal degeneration.

OBJECTIVE: To describe a compressive lamellar surgical technique for treating severe astigmatism in peripheral corneal ectasia. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Four eyes of 3 patients with either pellucid or Terrien's marginal corneal degeneration were included in this series. METHODS: C-shaped lamellar keratoplasty using multiple trephines of different sizes, with deliberate undersizing of the donor graft for a controlled compressive effect, was performed on these patients. MAIN OUTCOME MEASURES: Visual acuity outcome and refraction were measured at different intervals at up to 40 months of follow-up. RESULTS: All eyes achieved Snellen visual acuity of 20/40 or better and stable astigmatism ranging from 0 to -2.75 diopter cylinder within 6 months, with no recurrence of corneal thinning or peripheral corneal vascularization. CONCLUSIONS: Compressive C-shaped lamellar keratoplasty is able to reduce severe corneal astigmatism in peripheral corneal ectasia and can result in good visual and refractive outcomes with early visual rehabilitation.

Pharmacokinetic and toxicity study of an intraocular cyclosporine DDS in the anterior segment of rabbit eyes.

PURPOSE: To establish the safety and pharmacokinetic efficacy of an Oculex Drug Delivery System (DDS; Oculex Pharmaceuticals, Inc., Sunnyvale, CA) containing cyclosporin A (CsA) in the anterior segment of the rabbit eye. METHODS: The Oculex DDS is an intraocular, sustained-release, drug delivery system comprising a biodegradable lactic acid-glycolic acid copolymer. A controlled prospective study was performed that involved implanting a DDS containing 0.5 mg of CsA into the anterior chamber (AC) of the right eyes of 16 New Zealand White rabbits. A placebo DDS was implanted into the left eyes of these same rabbits as the control. Slit lamp examinations and AC taps were performed serially, and the rabbits were killed and the globes removed at 2, 4, 8, and 12 weeks for histology and determination of CsA drug levels. Analysis of CsA levels was performed with high-performance liquid chromatography-mass spectrometry. RESULTS: High concentrations of CsA were detectable in all layers of the cornea (epithelium, corneal stroma and endothelium) throughout the 3-month period. Low CsA levels were detected in the aqueous, whereas no CsA was detectable in the blood. There were no adverse reactions observed. CONCLUSIONS: The Oculex DDS CsA device is effective in delivering long-term levels of CsA to corneal tissues, without adverse effects. Further studies in an animal model of corneal transplant rejection should be performed to determine the potential of this device in the prophylaxis and treatment of corneal transplant rejection in humans.

Microsporidial keratoconjunctivitis in healthy individuals: a case series.

PURPOSE: To present a series of 6 cases of microsporidial keratoconjunctivitis in healthy, nonimmunocompromised individuals. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Six individuals with unilateral keratoconjunctivitis. METHODS: Cornea epithelial scrapings were taken and evaluated by modified trichome staining. Blood was taken for human immunodeficiency virus (HIV) enzyme-linked immunosorbent assay in all cases and for CD4 and CD8 T-lymphocyte counts in 5 cases. MAIN OUTCOME MEASURES: The individuals were evaluated based on symptoms, visual acuity, slit-lamp biomicroscopy, and pathologic examination of the corneal scrapings. RESULTS: All cases occurred in men whose ages ranged from 16 to 37 years. Initial symptoms included unilateral pain and redness. All experienced subsequent worsening of symptoms and blurring of vision after using topical steroids prescribed by general practitioners. Slit-lamp biomicroscopy revealed coarse, multifocal, punctate epithelial keratitis in all 6 cases, anterior stromal infiltrates in 2 cases, with accompanying conjunctivitis in all cases. Modified trichrome staining of corneal epithelial scrapes revealed pinkish to red spores characteristic of microsporidia in all cases. Results of an HIV enzyme-linked immunosorbent assay were negative in all cases, and CD4 and CD8 T-lymphocyte counts and ratios were normal in all 5 tested cases. On diagnosis, topical steroid therapy was stopped in all cases. Treatment with topical Fumidil B (bicyclohexylammonium fumagillin; Leiter's Park Ave Pharmacy, San Jose, CA) together with oral albendazole was given in 3 cases, oral albendazole alone in a single case, and broad-spectrum antibiotic treatment with topical norfloxacin or chloramphenicol in two cases. Two cases had keratic precipitates with mild cellular activity in the anterior chamber and one such case was restarted subsequently on topical steroids. All six cases showed resolution of epithelial keratitis but with residual visually inconsequential subepithelial scars by the end of 1 month of treatment. CONCLUSIONS: Microsporidial keratoconjunctivitis can occur more commonly than expected in healthy, nonimmunocompromised individuals. Topical steroids seem to contribute to the persistence of this infection and may be a predisposing factor in these cases by creating a localized immunocompromised state. The clinical course is variable and may be self-limiting with cessation of topical steroid use.