Antioxidant properties of amniotic membrane : novel observations from a pilot study

Objective Amniotic membrane (AM) is used to manage various debilitated ocular surface conditions. The impact of oxidative stress and free radicals on the ocular surface is increasingly being recognized. Hyaluronic acid (HA) has anti-inflammatory properties and is abundantly present in AM. In this in vitro pilot study, we investigated the potential of AM for intrinsic free radical scavenging properties. Methods Strips of AM were incubated in sealed tubes with hydrogen peroxide (H2O2). After being sonicated, uptake of reactive oxygen species (ROS) was measured by the Amplex Red Hydrogen Peroxide/Peroxidase assay. For comparison, 1630 kDA HA was used. Results There was uptake of ROS by all AM samples, which decreased with increasing concentrations of H2O2. Mean ROS uptake for 5 different AMs at 1 hour was significantly greater for 50 μM (83%; SD 11.7, SEM 5.23) compared with 100 μM (67%; SD 20.48, SEM 9.16; p = 0.028; 95% CI 2.8-29.2). The HA comparison group showed similar uptake and trend. Conclusion This pilot study demonstrates that AM is able to remove ROS from its environment. Demonstrating total antioxidant capacity in AM provides evidence for use as a free radical scavenger. The antioxidant properties of AM and the contribution from HA require more research

Management and Clinical Outcome of Penetrating Keratoplasty for Long-Term Corneal Changes in Sympathetic Ophthalmia

Purpose. To report the visual outcome of penetrating keratoplasty performed on the sympathizing eye in three cases of sympathetic ophthalmitis. Methods. Interventional case series of three patients, diagnosed with sympathetic ophthalmitis, with corneal changes in the form of band keratopathy and decompensation underwent penetrating keratoplasty to the sympathizing eye. They had each sustained penetrating trauma as a child and had undergone previous cataract surgery and superficial keratectomy. Two patients had undergone lamellar keratoplasty prior to this procedure. One patient had undergone trabeculectomy for glaucoma, and she was on antiglaucoma medication. The preoperative visual acuity was 1/60 in the affected eye of each patient. Penetrating keratoplasty was performed in the sympathizing eye and the donor graft size was 7.50 mm, and the host graft size was 7.25 mm. Our patients were immunosuppressed prior to the procedure to help prevent graft rejection. Result. At one year follow-up, a BCVA of 6/36 or better was achieved in all three patients. Postoperative examination of the fundus showed peripheral chorioretinal atrophy with pigmentary changes at the macula, accounting for the limited vision. The grafts remain clear to date, and there has been no recurrence of uveitis or rejection. Conclusion. Penetrating keratoplasty can be considered as a surgical option to restore useful vision in a stable sympathizing eye in sympathetic ophthalmitis, and this depends on the extent of the pathology. However, these cases require treatment with immunosuppressives to prevent graft rejection and to prolong graft survival

Patients' attitudes towards the potential use of stability tape to minimize head movements during cataract surgery

Introduction: Head stabilization may reduce intra-operative risk during cataract surgery, but could be misinterpreted as "restraint." We wanted to establish patients' attitudes towards the potential use of stability-tape. Materials and Methods: One-hundred consecutive patients attending for local-anaesthetic cataract surgery were asked to complete a pre-operative questionnaire. This explored patient concerns and views regarding intra-operative head movement and the potential use of stability-tape. Results: All 100-patients completed the questionnaire. The median head movement concern score was 2 out of 10 (range 1–9, IQR 1–5). Eighty-four percent felt stability tape should be offered to all patients and 97% would consent for its' use. Only 6% voiced concern about the use of stability-tape (95% CI 2.2%, 12.6%). Conclusion: Patients had low concern for moving their head during surgery. The concept of stability-tape to minimize head movements during cataract surgery was viewed positively by most patients. This strategy may promote safer surgery in selected cases

Modelling floppy iris syndrome and the impact of phenylephrine on iris buckling

Abnormal iris movement (floppy iris syndrome) during intraocular surgery is associated with an increased risk of intraoperative complications. We have previously investigated this scenario with respect to intracameral air in corneal endothelial transplantation, and described the concept of iris buckling. As a number of clinical interventions are recommended for addressing floppy iris syndrome, we wished to evaluate the impact of intracameral phenylephrine on iris buckling and so refine our mathematical model. We considered the stability of an iris structure under a uniform pressure loading. We performed mathematical and computational simulations to demonstrate iris buckling, and then altered the parameters to assess the impact of phenylephrine on the model. We elucidated a number of buckled iris configurations which become unstable as the intraocular pressure increased, for transversely isotropic iris material properties, and identified a positive correlation between the critical pressure and the iris stiffness. A mechanical analysis with a dilated pupil (mimicking phenylephrine use) was also conducted, and demonstrated a significant increase in the critical pressure required to induce iris buckling. We have shown that iris buckling can arise at lower pressures when the iris stiffness is reduced, as in floppy iris syndrome. The use of phenylephrine was shown to prevent iris movement (buckling) by increasing the required critical pressures. This refined model demonstrates the positive effectiveness of phenylephrine in the management of floppy iris syndrome and gives evidence to the clinical practice of using this as a preventative measure

Modelling floppy iris syndrome and the impact of pupil size and ring devices on iris displacement

INTRODUCTION:The aim of this paper was to further develop a previously described finite element model which equates clinical iris billowing movements with mechanical buckling behaviour, simulating floppy iris syndrome. We wished to evaluate the impact of pupil dilation and mechanical devices on normal iris and floppy iris models. METHODS:Theoretical mathematical modelling and computer simulations were used to assess billowing/buckling patterns of the iris under loading pressures for the undilated and dilated normal iris, the undilated and dilated floppy iris, and additionally with a mechanical ring device. RESULTS:For the normal iris, billowing/buckling occurred at a critical pressure of 19.92 mmHg for 5 mm pupil size, which increased to 28.00 mmHg (40.56%) with a 7 mm pupil. The Malyugin ring device significantly increased critical initiating buckling pressures in the normal iris scenario, to 34.58 mmHg (73.59%) for 7 mm ring with boundary conditions I (BC I) and 34.51 mmHg (73.24%) with BC II. For the most floppy iris modelling (40% degradation), initiating buckling value was 18.04 mmHg (-9.44%), which increased to 28.39 mmHg (42.52%) with the 7 mm ring. These results were much greater than for normal undilated iris without restrictive mechanical expansion (19.92 mmHg). CONCLUSION:This simulation demonstrates that pupil expansion devices inhibit iris billowing even in the setting of floppy iris syndrome. Our work also provides a model to further investigate the impact of pupil size or pharmacological interventions on anterior segment conditions affected by iris position

Phase 2 randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis

Purpose: To evaluate the safety and efficacy of topical recombinant human nerve growth factor (rhNGF) for treating moderate-to-severe neurotrophic keratitis (NK), a rare degenerative corneal disease resulting from impaired corneal innervation. Design: Phase 2 multicenter, randomized, double-masked, vehicle-controlled trial. Participants: Patients with stage 2 (moderate) or stage 3 (severe) NK in 1 eye. Methods: The REPARO phase 2 study assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 μg/ml, 20 μg/ml, or vehicle. Treatment was administered 6 drops per day for 8 weeks. Patients then entered a 48- or 56-week follow-up period. Safety was assessed in all patients who received study treatment, whereas efficacy was by intention to treat. Main Outcome Measures: Corneal healing (defined as <0.5-mm maximum diameter of fluorescein staining in the lesion area) was assessed by masked central readers at week 4 (primary efficacy end point) and week 8 (key secondary end point) of controlled treatment. Corneal healing was reassessed post hoc by masked central readers using a more conservative measure (0-mm staining in the lesion area and no other persistent staining). Results: At week 4 (primary end point), 19.6% of vehicle-treated patients achieved corneal healing (<0.5-mm lesion staining) versus 54.9% receiving rhNGF 10 μg/ml (+35.3%; 97.06% confidence interval [CI], 15.88–54.71; P < 0.001) and 58.0% receiving rhNGF 20 μg/ml (+38.4%; 97.06% CI, 18.96–57.83; P < 0.001). At week 8 (key secondary end point), 43.1% of vehicle-treated patients achieved less than 0.5-mm lesion staining versus 74.5% receiving rhNGF 10 μg/ml (+31.4%; 97.06% CI, 11.25–51.49; P = 0.001) and 74.0% receiving rhNGF 20 μg/ml (+30.9%; 97.06% CI, 10.60–51.13; P = 0.002). Post hoc analysis of corneal healing by the more conservative measure (0-mm lesion staining and no other persistent staining) maintained statistically significant differences between rhNGF and vehicle at weeks 4 and 8. More than 96% of patients who healed after controlled rhNGF treatment remained recurrence free during follow-up. Treatment with rhNGF was well tolerated; adverse effects were mostly local, mild, and transient. Conclusions: Topical rhNGF is safe and more effective than vehicle in promoting healing of moderate-to-severe NK

Phase I trial of recombinant human nerve growth factor for neurotrophic keratitis

Neurotrophic keratitis/keratopathy (NK), a rare degenerative corneal disease, lacks effective pharmacologic therapies.1 Because NK pathology involves trigeminal nerve damage and loss of corneal innervation, nerve growth factor (NGF) is surmised to promote healing of NK.2 Preliminary studies with murine NGF demonstrated efficacy for treating corneal neurotrophic ulcers;3 however, the complex tertiary structure of NGF has complicated the production of recombinant human NGF (rhNGF) suitable for clinical development. To this end, we developed an Escherichia coli–derived rhNGF formulation that demonstrated to be well tolerated and safe for topical ophthalmic use in a phase I study in healthy volunteers.4 We report phase I results of topical rhNGF for patients with moderate-to-severe NK

Assessing the accuracy of intracameral phenylephrine preparation in cataract surgery

Purpose: Unpreserved phenylephrine is often used as an off-licence intracameral surgical adjunct during cataract surgery to assist with pupil dilation and/or stabilise the iris in floppy iris syndrome. It can be delivered as a neat 0.2 ml bolus of either 2.5 or 10% strength, or in a range of ad-hoc dilutions. We wished to assess the accuracy of intracameral phenylephrine preparation in clinical practice. Methods: Phenylephrine 0.2 ml was analysed both neat (2.5 and 10%) and in diluted form (ratio of 1:1 and 1:3). Samples were analysed using the validated spectrophotometric method. Results: A total of 36 samples were analysed. The standard curve showed linearity for phenylephrine (R2 = 0.99). Wide variability was observed across all dilution groups. There was evidence of significant differences in the percentage deviations from intended results between dilutions (p &lt; 0.001). Mean percentage deviation for 1:3 dilution was significantly greater than neat (p = 0.003) and 1:1 dilution (p = 0.001). There was no evidence of a significant difference between 1:1 and neat (p = 0.827). Conclusions: Current ad-hoc dilution methods used to prepare intracameral phenylephrine are inaccurate and highly variable. Small volume 1 ml syringes should not be used for mixing or dilution of drug. Commercial intracameral phenylephrine products would address dosage concerns and could improve surgical outcomes in cases of poor pupil dilation and/or floppy iris syndrome

Allogeneic Ex Vivo Expanded Corneal Epithelial Stem Cell Transplantation: A Randomized Controlled Clinical Trial

APPEAL FROM THE DECREE OF DIVORCE EXECUTED AND ENTERED BY THE THIRD JUDICIAL DISTRICT COURT. IN AND FOR SALT LAKE COUNTY. STATE OF UTAH. THE HONORABLE FRANK G. NOEL. PRESIDIN