Frank Larkin

Errors leading to unexpected pseudophakic ametropia.

Purpose Determination of the reasons for clinically significant unplanned ametropia following cataract surgery and the results of management of the ametropia.Methods Retrospective review of 11 consecutive cases of tertiary referral for management of pseudophakic ametropia to the authors. Corrective surgery involved either lens implant exchange or LASIK refractive surgery. Final outcome was assessed by uncorrected and best spectacle corrected visual acuity and manifest refractive outcome.Results Five cases (45%) were due to significant error in axial length determination at pre-surgery biometry. Six cases (55%) were due to surgeon or surgical team error, where the surgeon implanted a lens of power at variance with that specified pre-operatively. Nine patients elected to undergo refractive surgery to correct the ametropia and 2 elected to wear a spectacle lens. Seven underwent lens implant exchange and 2 patients underwent LASIK keratorefractive surgery. Eight of nine patients were within 1 dioptre of intended spherical equivalent after refractive surgery and 1 patients was —1.5 dioptre myopic.Conclusions Most cases of serious unintended ametropia after cataract surgery are avoidable. Care should be taken with the biometry and procedural checks to minimise error. When lens implant exchange or LASIK was performed the final refractive results were satisfactory.

31. EncorStat®: A Human Donor Cornea Genetically Engineered To Resist Rejection in High Risk Patients

Corneal transplantation is one of the most successful transplant procedures because of the relatively immune-privileged status of the eye and the avascularity of the cornea. However, normal corneal immune privilege can be eroded by neovascularization by providing a route of entry for immune-mediating cells, leading to subsequent irreversible immunological rejection of the corneal graft, the most common reason for graft failure. In high risk patients, which account for >20% of the 100,000 transplants carried out worldwide each year, the rejection rate can be very high (50-90%), particularly if there is pre-existing vascularization of the recipient corneal bed. In these patients the prognosis is extremely poor, with grafts failing at an accelerating rate to the point where patients are no longer considered suitable for further transplants and are left blind, despite an otherwise healthy eye. It is therefore not surprising that neovascularization (both pre- and post-grafting) is a significant risk factor for corneal graft failure. Neovascularization is thus an attractive target to prevent corneal graft failure due to rejection.EncorStat® is a human donor cornea modified prior to transplant by the ex vivo delivery of the genes encoding secretable forms of the angiostatic human proteins, endostatin and angiostatin, by a lentiviral vector, derived from the Equine Infectious Anaemia Virus (EIAV), which prevents subsequent rejection by suppressing neovascularization.Modified rabbit corneas have been evaluated in two different models of corneal graft rejection, a highly aggressive model in which rejection is driven by the retention of thick graft sutures, and a less aggressive model in which rejection is driven by pre-vascularizing the recipient corneal bed prior to surgery. In this latter model thin sutures are used to secure the graft that are removed two weeks following surgery, which is more analogous to the clinical setting. The process to generate EncorStat® corneas has been optimized to secrete substantial and persistent levels of angiostatic proteins with very little shedding of residual vector. These corneas substantially suppress corneal neovascularization, opacity and subsequent rejection in both rabbit models of cornea graft rejection.The non-clinical data to be presented support the evaluation of EncorStat® corneas in a First-in-Man trial. With support from the UK Technology Strategy Board (Innovate UK), this trial will be conducted in 2016, following completion of non-clinical safety studies and GMP vector manufacture this year. An outline of this clinical trial design will also be presented.