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Acute Reversible Corneal Endothelial Changes Associated With Selective Laser Trabeculoplasty Andrew J. White1,2, Achyut Mukherjee1, Inderraj Hanspal1, Nicholas Sarkies1, Humma Shahid1, Madhavan Rajan1,3, Keith R. Martin1,2, Peter Shah4,5. 1Ophthalmology, Cambridge University Teaching Hospitals NHS Foundation Trust, Cambridge, United Kingdom; 2NIHR Biomedical Research Centre, University of Cambridge, Cambridge, United Kingdom;3Anglia Ruskin University, Cambridge, United Kingdom 4Ophthalmology, NIHR BRC for Ophthalmology, Moorfields Eye Hospital & UCL Institute of Ophthalmology, London, United Kingdom; 5Ophthalmology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom. Changes Are Seen Across the Cornea Background • • • Central Cornea Peripheral Cornea Selective Laser Trabeculoplasty (SLT) is an increasingly popular treatment for glaucoma and ocular hypertension using Q switched YAG laser pulses applied to the trabecular meshwork applied via a gonioscopic lens In vitro and cadaveric studies have largely focussed on changes induced in the trabecular meshwork 1-4 There has been very little published on changes induced in the cornea by SLT with the exception of a few isolated case reports 5,6 1:Alvarado JA, et al. Am J Ophthalmol. 2010;150:254-64. 2:Cvenkel B, et al. Lasers Surg Med. 2003;33:204-8. 3:Kramer TR, et al. Ophthalmology. 2001 Apr;108(4):773-9. 4:Wood JP, et al. Lasers Surg Med. 2010;42:326-37. 5:Holz H, et al. J Cataract Refract Surg. 2010;36:847-9. 6:Moubayed SP, et al. Ophthalmol. 2009;44:337-8. SLT at Addenbrooke’s Hospital • Over 140 patients treated in the last 12 months • Standard protocol is: – – – – – – – – Figure 5: Representative confocal images of central cornea and peripheral cornea 3mm from the visual axis in the same patient taken approximately 30 minutes post SLT documenting endothelial changes across the cornea. 30 No Morphological Changes On Specular Microscopy 25 Pilocarpine 2% Apraclonidine 1% Proxymetacaine anaesthesia Ellex Tango YAG/SLT with Latina lens (previously Goldmann) 180 degrees treatment Power 0.6-1.0mJ (Latina Lens) No preoperative or postoperative steroid Routine followup at 6 weeks 20 Preoperative IOP 15 (mmHg) 6 Week Followup 10 5 0 PreSLT 6 weeks 6 9 12 months months months Figure 1: IOP drop with SLT for 129 eyes in 129 patients Postoperative Confocal Postoperative Figure 6: Specular microscopy images of central corneal endothelium taken immediately pre treatment, approximately 1hour post treatment and 6 weeks post treatment. Confocal microscopy images taken of the same region of cornea in the same patient approximately 1 hour post SLT treatment. A Clinically Apparent Finding • Subtle endothelial changes noticed at 2 centres immediately post SLT treatment • One centre routinely pre treated with dexamethasone (Birmingham), one did not (Cambridge). • Differing machines • Ellex (Cambridge) • Coherent (Birmingham) • Changes appeared to resolve within 24hrs Central Specular Microscopy Counts Figure 7: Mean specular endothelial counts, average cell size and corneal thickness taken immediately pre treatment, 1hour post treatment and 6 weeks later. Error bars represent standard deviation. Figure 2: Subtle endothelial changes (arrow) noted approximately 30 minutes post SLT Further Investigation • • • • • Routinely booked patients at one centre (Cambridge) consented to have additional imaging pre and post SLT and at routine followup (n=9) Patients to have preoperative confocal microscopy and endothelial cell counts with specular microscopy Standard treatment and followup Confocal and specular imaging immediately postoperatively (within 30-60 mins) and at routine 6 week followup Local IRB approval granted What is Causing This? • • • • Confocal Images Pre and Post SLT • Preoperative Postoperative Human donor cornea obtained from Bristol Eye Bank unusable for transplant Study covered by Eye Bank ethical approval Mounted in artificial anterior chamber filled with Balanced Salt Solution (BSS) Confocal imaging of endothelium either: – Removed from chamber and direct SLT laser applied to endothelium (0.9mJ) – 10% fresh blood with BSS washout – 2mM hydrogen peroxide 30mins Remounted in anterior chamber and re- imaged 6 Week Followup Donor Cornea Prior to Treatment Donor Cornea 0.9mJ Laser Donor Cornea 10% Blood Donor Cornea 2mM Peroxide Figure 3: Confocal imaging of corneal endothelium immediately pre SLT. Imaging of the same patient approximately 30 minutes post SLT and 6 weeks post SLT A Spectrum of Post SLT Changes Figure 4: Patient age ranged from 66-84. Four patients had PXF, four had previous cataract surgery and one had previous retinal detachment surgery. The was no change in visual acuity post proceedure (0.14 logMAR units, (range -0.2 – 0.7, n =16 eyes)). Changes observed post SLT ranged from very mild (top left) to marked and diffuse changes (bottom right). Only 2 (12%) eyes showed no obvious abnormality post SLT. Figure 8: Human donor cornea prior to exposure and following direct exposure to laser, 10% blood and 30 mins of 2mM hydrogen peroxide. The direct laser produced a crircular region of endothelial destruction surrounded by increased endothelial blebs (white arrow). A different cornea exposed to blood showed increased patches of hyperreflectivity on the endothlium (red arrow) and the final cornea exposed to peroxide showed a widening of intracellular spacing (blue arrow) Summary • SLT appears to cause transient endothelial changes immediately postoperatively that appear to resolve within a few days and do not affect vision • The cause is unknown but we are investigating potential mechanisms • Endothelial changes do not appear to be caused by direct laser damage • Further study is required to investigate this finding Acknowledgements We also acknowledge Guy Negretti and Anja Nessman for help auditing our SLT outcomes and Elena Novitskya and George Voyatzis for help with imaging of the donor cornea