The Effect of Topical Substance-P Plus Insulin-like Growth Factor-1 (IGF-1) on Epithelial Healing After Photorefractive Keratectomy in Rabbits.

PURPOSE: To determine whether topical Substance-P (SP) plus insulin-like growth factor-1 (IGF-1) can improve corneal healing after photorefractive surface ablation in a rabbit. METHODS: After a 9.0-mm corneal de-epithelialization using a combination of chemical (18% alcohol) and mechanical debridement, excimer photorefractive surface ablation was performed bilaterally in eight rabbits (16 eyes) with an 8.0-mm ablation zone and 70-µm depth. The right eye was treated with SP (250 µg/mL) and IGF-1 (25 ng/mL) in hyaluronic acid, one drop twice a day, and the other eye treated with only hyaluronic acid. The epithelial healing process was documented photographically twice a day until healing was complete. Six rabbits were sacrificed 6 weeks after photorefractive keratectomy (PRK) and corneas examined histologically. RESULTS: Seven of eight rabbit eyes treated with SP/IGF-1 healed in a shorter time than the untreated eye. For rabbit #6, both eyes healed at the same time. The average healing time (total time until wound closure) for the treated eyes was 99 hours, while the average healing time for the untreated eyes was 170 hours (P = 0.0490). A persistent epithelial defect was found in two of the nontreated eyes but none in the treated eyes. Corneal pathology showed some degree of epithelial separation in the central corneal wound in three out of six nontreated eyes and in just the treated eye of rabbit #6. CONCLUSION: Topical SP plus IGF-1 increases the epithelial healing rate after PRK. There may have been beneficial effects upon cell adhesion as well. TRANSLATIONAL RELEVANCE: Better and faster healing.

Time- and temperature-dependent stability of growth factor peptides in human autologous serum eye drops.

PURPOSES: To develop a step-by-step production method for human autologous serum (AS) eye drops that was broadly compliant with US Food and Drug Administration requirements for reinjection of processed biological substances. To determine optimum storage conditions for AS eye drops by measuring the concentration of growth factor peptides (GFP) as a function of storage temperature and storage duration. METHODS: AS derived from the blood of 3 healthy male volunteers was produced using a closed, vacuum-driven, cascade-filtration system under sterile, low-pyrogen conditions. In-process controls included methods for monitoring protein electrophoretic mobility and degradation rate and the content of free hemoglobin and endotoxin. Stability of transforming growth factor beta1, substance P, nerve growth factor, calcitonin gene-related peptide, insulin-like growth factor 1, and epidermal growth factor was evaluated at -15 degrees C, +4 degrees C, +25 degrees C, +37 degrees C, and +42 degrees C at different time intervals (hours to weeks). The main outcome measures were the concentrations of GFP, endotoxin, and lipid peroxidation by-products (a proxy measure for protein degradation) in dilute AS. RESULTS: The stability of GFP varies: transforming growth factor beta1, nerve growth factor, epidermal growth factor, and insulin-like growth factor 1 were more temperature and time resistant, but substance P and calcitonin gene-related peptide significantly degraded at +4 degrees C in 24 hours. Endotoxin and lipid peroxidation by-products were not significantly increased by processing. CONCLUSIONS: This pilot study developed a closed, cascade-filtration system that was an effective method for the production of high-quality, low-pyrogen AS. The processing method broadly complied with Food and Drug Administration requirements for reinjection of biological substances. Variable GFP stability was observed at +4 degrees C and above. For clinical use, AS should be packaged in daily-use containers, which should be stored frozen; the container in active use should be refrigerated between doses.

Serum growth factor analysis in dry eye syndrome.

BACKGROUND: To perform a comprehensive serum growth factor analysis in dry eye syndrome patients and to compare this with matched controls. METHODS: Six female dry eye syndrome patients and six age- and gender-matched controls were recruited. Whole blood was collected, allowed to clot and then centrifuged. Serum was extracted by using sterile technique. Enzyme-linked immunosorbent assays were performed to quantify serum growth factor levels. RESULTS: Levels of transforming growth factor-beta 1 and 2 (TGF-beta1 and beta2), nerve growth factor (NGF), insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), acidic and basic fibroblast growth factor (FGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor-AA, AB and BB (PDGF-AA, AB and BB), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and glial cell line-derived neurotrophic factor (GDNF) were quantified, and statistical analysis was performed by using the Mann-Whitney U-test with the Bonferroni correction. CONCLUSIONS: No significant difference was found between serum growth factor levels in dry eye syndrome patients versus controls. Our study provides comprehensive analysis of serum growth factor levels in autologous serum eye drops produced from ocular surface disease patients. A knowledge of growth factor levels in serum may be important because of the increasing use of autologous serum eye drops in refractory ocular surface diseases and for an understanding of how topical serum may provide benefit.

Descemet's stripping automated endothelial keratoplasty in intraoperative floppy-iris syndrome: suture-drag technique.

Descemet's stripping automated endothelial keratoplasty avoids a full-thickness corneal procedure and provides rapid visual rehabilitation. Success depends on positioning the graft successfully while minimizing intraoperative donor endothelial trauma. Previously described techniques for graft insertion may be problematic in patients with intraoperative floppy-iris syndrome, anatomically shallow or unstable anterior chambers, or increased intraoperative posterior vitreous pressure. We describe an alternative called the suture-drag technique that may facilitate lamellar endothelial graft insertion in these special circumstances.

Continuous intraocular pressure recordings during lamellar microkeratotomy of enucleated human eyes.

PURPOSE: To analyze the course of intraocular pressure (IOP) during lamellar microkeratotomy (LMK) in enucleated human eyes using 3 microkeratome systems. SETTING: Department of Ophthalmology, Texas Tech University Health Sciences Center, Lubbock, Texas, U.S.A. METHODS: Sixteen enucleated human globes were cannulated through the optic nerve, and IOP was recorded continuously while the eyes had standard LMK flap creation. Three microkeratomes were used: Carriazo-Barraquer (Moria Inc.), Innovatome (Innovative Optics Inc.), and Hansatome (Bausch & Lomb). RESULTS: During the vacuum affixation phase, the IOP reached a mean plateau of 97.9 mm Hg with the Hansatome, 135.8 mm Hg with the Innovatome, and 150.0 mm Hg with the Carriazo-Barraquer. During applanation and cutting, the IOP rose to mean plateau of 154.7 mm Hg, 151.8 mm Hg, and 175.8 mm Hg, respectively. Statistical analysis using Kruskal-Wallis testing suggested a difference in mean IOP elevation between the 3 microkeratomes during the vacuum affixation phase (P = .0394) but no difference during the applanation and cutting phase (P = .506). CONCLUSION: The IOP during LMK was higher than previously reported, and this may increase the risk for complications in certain patient groups.

Successful treatment of resistant ocular fusariosis with posaconazole (SCH-56592).

PURPOSE: To describe the successful treatment with systemic posaconazole of a series of Fusarium ocular infections refractory to other antifungal agents. DESIGN: Retrospective, interventional case series. METHODS: We identified three patients from three different centers who received diagnoses of Fusarium keratitis and who received systemic posaconazole after their infections failed to respond to maximal tolerated medical and surgical therapy. All patients received multiple systemic, intracameral, and topical antifungal agents, which were ineffective in controlling their infection. RESULTS: Two patients were contact lens wearers. Two patients developed endophthalmitis. The infections of all three patients failed to respond to systemic and/or topical voriconazole treatment. One patient could not tolerate systemic voriconazole, and another experienced no marked improvement. The third discontinued treatment for both reasons. All patients were treated with oral posaconazole and experienced rapid reduction of intraocular inflammation and pain, as well as resolution of the infection without additional intervention. CONCLUSIONS: Deep Fusarium keratitis is difficult to treat and carries a high risk of progression to endophthalmitis. Posaconazole, which exhibits excellent tissue penetration and demonstrates efficacy in the treatment of systemic Fusarium infection, was successful in treating three cases of pan-resistant keratitis and/or endophthalmitis.

Pseudallescheria boydii keratitis.

A case of Pseudallescheria boydii keratitis is presented. The patient was successfully treated with topical natamycin and systemic itraconazole in conjunction with penetrating keratoplasty, leading to visual acuity of 20/40.

Visual field changes after laser in situ keratomileusis.

PURPOSE: To determine whether laser in situ keratomileusis (LASIK) affects the central 30-degree visual field. SETTING: University-based ophthalmology practice. METHODS: This nonrandomized clinical trial comprised 14 normal patients (27 eyes) scheduled to have LASIK for myopia or myopic astigmatism. Automated static perimetry was performed before and 6 months after surgery using the Octopus 1-2-3 perimeter and the Dynamic-32 test strategy. Patient data included sex, age, preoperative and postoperative refractive errors, preoperative and postoperative best corrected visual acuity, preoperative corneal thickness, programmed optical zone, programmed total ablation diameter, and duration of microkeratome suction. All surgery was performed using the same Alcon LADARVision 4000 excimer laser. The main outcome measures were the mean sensitivity (MS) change in the central 15-degree visual field and the MS change in the 15- to 30-degree visual field. A multivariate analysis of the MS change as a function of preoperative clinical parameters was performed. RESULTS: There was no significant change in the MS in the central 15-degree visual field; between 15 and 30 degrees, there was a statistically significant decrease of -0.82 dB +/- 1.40 (SD) (P=.01, 2-tailed t test). The decline in MS was positively correlated with refractive error and corneal thickness; it was negatively correlated with the programmed optical zone diameter. CONCLUSIONS: Automatic static perimetry can detect decreased sensitivity in the midperipheral visual field after myopic LASIK. It may be a useful quantitative subjective test for measuring the effects of future improvements in surgical technique on vision quality.

Endophthalmitis caused by non-perfringens Clostridium species.

The role of other non-perfringens Clostridium species in endophthalmitis infections has not been analyzed. We describe a case of non-perfringens Clostridium endophthalmitis and review prior cases in the literature. Fulminant clinical presentations and poor visual outcomes are the rule, but a combined aggressive medical and surgical approach may conserve vision.

The effect of daily use of brimonidine tartrate on the dark-adapted pupil diameter.

PURPOSE: To investigate the effect of daily brimonidine tartrate 0.15% on the dark-adapted pupil diameter. DESIGN: Observational case series. METHOD: Ten normal volunteers administered brimonidine to their right eyes once daily. Four to six hours later, infrared pupil photographs were taken after dark adaptation. Measurements were performed at baseline; on treatment days 1, 5, 11, and 18; and on washout days 1 and 2. RESULTS: One subject had no response. The nine responding subjects showed an average maximum antimydriatic effect of -1.63 mm (range, -0.57 mm--2.30 mm); all subjects experienced tachyphylaxis. Five subjects showed rebound mydriasis (mean maximum rebound +0.87 mm larger than baseline; range 0.50 mm-1.22 mm). The untreated pupil also responded, showing antimydriasis (two subjects), rebound mydriasis (two subjects), or paradoxical direct mydriasis (one subject). CONCLUSIONS: Once-daily use of brimonidine tartrate to prevent dark-induced pupil dilation can lead to tachyphylaxis and rebound mydriasis.