Evaluation of Corneal Graft Profile Following Deep Anterior and Posterior Lamellar Keratoplasty Procedures by Fourier-Domain Optical Coherence Tomography Miss Tarang Gupta MB BS MRCOphth Mr Dipak Parmar BSc (Hons), MB BS(london) FRCOphth (UK) There are no financial disclosures for this study

Introduction Recent emergence of lamellar graft techniques allows selective removal of only diseased tissue Deep anterior lamellar keratoplasty (DALK) 1 Retains host Descemet’s membrane and endothelium Eliminates endothelial rejection Enhances long term graft survival Descemet’s stripping endothelial keratoplasty (DSEK) targets only abnormal endothelium 2 Benefits include: Intra operative closed globe surgery Preserved corneal integrity and tensile strength Rapid visual recovery Fourier domain OCT allows for faster A scan acquisition rate 65 times faster than time domain systems Less variability with patient movement Depth resolution of 5µm Useful for allowing measurement of separate lamellar components 2. Price FW, Price MO. Descemet’s stripping with endothelial keratoplasty in 200 eyes: early challenges and techniques to enhance donor adherence. J CataractRefract Surg. 2006;32(3): BA Noble et al Deep Anterior Lamellar Keratoplasty (DALK) Visual Outcome and Complications for a Heterogeneous Group of Corneal Pathologies Cornea 2007;26:59–64

Method Purpose To quantify changes in host and donor corneal profile after lamellar procedures using Fourier domain OCT Method Prospective case series of patients undergoing lamellar graft procedures between Jan 09 to Dec 09 All patients underwent complete biomicroscopy and fundus examination. DALK was performed with big bubble of Anwar technique 1, utilizing manual dissection of host and donor tissue (on an artificial anterior chamber) DSEK donor graft was prepared manually with 3 DORC blades (Zuidland, The Netherlands) on an artificial anterior chamber employing Melles technique 2. Measured variables included best spectacle VA (logMAR), refractive spherical equivalent, anterior corneal keratometric values and OCT findings OCT scans were taken at week 1, 1 month, 3 months and 6 months All patients received post operative topical steroids and antibiotics QDS for 1 month. Statistics Student paired T-test and regression analysis was used. P value <0.05 considered significant 1.Anwar M, Teichmann KD. Big-bubble technique to bare Descemet’s membrane in anterior lamellar keratoplasty. J Cataract Refract Surg 2002;28:398–403 2.Melles GRJ, Lander F, Rietveld FJR, et al. A new surgical technique for deep stromal anterior lamellar keratoplasty. Br J Ophthalmol. 1999;83: 327–333.

OCT measurements The interface between host stroma and graft tissue was identified by direct visualisation Corneal lamellar thickness was measured using the callipers provided by OCT software. All OCT images were of sufficient quality to be analysed. All measurements were made by one investigator Corneal thickness measurements were taken at the vertex (centrally) and peripheral scans 2mm nasal and temporal to the vertex -2.0mm +2.0mm 0.0mm

9 patients included BCVA better than 6/12 (logMAR 0.30) in 67% (2/3) Mean BCVA 0.42 (6/15) Mean keratometric value changed from 2.56 pre op to 3.02D post operatively (P= 0.58 Mean anterior lamellar thickness changed from 641µm (±48) to 546 µm (±21)(P> 0.05) Mean posterior lamellar thickness (DM/endothelium) changed from 46.7 µm(±12) to 27 µm (±5) (P>0.05) Average final post op total central corneal thickness was µm (range – ) CharacteristicNumber (%) Age years (mean ± SD)52.2 ± 21.7 Follow up months (mean ± SD) 12.3 ± 7.8 Male/female3/6 (33/66) Right/left eye6/3 (66/33) Diagnosis Keratoconus3 (33) HSK keratitis3 (33) Macular dystrophy2 (22) Central clouding dystrophy of Francois 1 (12) Graft size 8.25mm2 (22) 8.5mm7 (78) Suturing Continuous1 (12) Interrupted8 (88) Table 1 illustrates DALK patient characteristics DALK RESULTS DALK RESULTS

Graph 1 illustrates the change in best spectacle correct visual acuity (BSCVA) between pre operative and last post operative evaluation P=0.07 P=0.08 DALK RESULTS DALK RESULTS Graph 2 shows the change in corneal lamellar thickness over time No of Patients

complicationRateAction Descemets micro- perforation 2 (22%)Conservative Graft rejection (suture vascularisation only) 1 (11%)Topical steroids – resolved Graft detachment 2 (22%)Air reinjection. 1 failed 1 resolved Double AC1 (11%)Air reinjection corneal massage – resolved Epithelial defect1 (11%)BCL Loose suture3 (33%)Suture removal Gaping corneal cataract wound following suture removal 1 (11%)Wound re- sutured Steroid response (raised IOP) 1 (11%)Switch to alternative topical steroid Pre op OCT Increased stromal reflectivity in the herpetic scar 1 week post op OCT Integrated graft. Small change in optical density identifying host/donor junction 3 month post op OCT Reduced junctional reflectivity Homogenous stroma Serial OCTs of a patient with a central herpetic scar undergoing DALK Table 2 illustrating complications and management

DSEK Results 4 patients All women & right eyes Mean age at surgery 75.2 (SD ± 6.7) Underlying aetiology Pseudophakic Bullous Keratopathy n= 3 Fuchs Endothelial Dystrophy n=1 Mean BCSVA (logMAR) 1.23 (± 0.33) pre op improved to mean of 0.83 (± 0.36) at last post operative visit (P=0.06) Mean difference between pre and post op BSCVA was gain of 2 lines Snellen acuity

Central graft thickness (µm ± SD) Central total thickness (µm ± SD) Peripheral graft thickness (µm ± SD) Peripheral total thickness (µm ± SD) Epithelial thickness (µm ± SD) Week 1175 (± 64.7)763.5 (± 93.4)495.5 (±279) (±344.4)53.75 (±30.9) Month 1153 (± 76)230.7 (±56.5) (±84)962.5 (±141.4)67.0 (±28.0) Month 3103 (±28.8) (±78.1)181 (±29.9) (±90.3)55.25 (±23.3) P value DSEK Results  Peripheral graft thickness appears to decrease faster than central measurements (p=0.09)  Peripheral graft rates changed most during 1 st month  Peripheral graft thinning rate was 104.8µm/month compared to 24.1µm/month centrally (p<0.01) Graph 3 illustrates change in various corneal lamellae with time Table 3 comparing mean change in lamellar thickness with time

DSEK Results Pearson correlation coefficient r = 0.54 Correlation between a) central corneal thickness and best spectacle corrected visual acuity (BSCVA) 6 months after DSEK and b) between peripheral thickness and BSCVA Pearson correlation coefficient r = 0.39 Day 1 Week 1 Month 1 Month 3 Serial change in DSEK lamella with time

Benefits of OCT Imaging High IOP 2 days post uncomplicated DSEK Thought to be due to migrating air bubble behind iris causing pupil block OCT showed material occluding angle ?sequestered viscoelastic Patient underwent synechiolysis Post procedure OCT confirms clear angle – IOP normal Patient undergoing re-do DALK. Day 1 post op graft looks attached clinically OCT shows showed residual interface material (retained viscoelastic) Washout in theatre Adherent graft post op Viscoelastic in angle Clear angle post washout/synechiolysis

Discussion We have demonstrated the benefits of Fourier domain OCT in imaging corneal layers following lamellar graft procedures. In particular they allowed Day 1 post operative non contact assessment of graft apposition and serial measurements during follow up Epithelial layer measurements, Assessment of graft host interface with greater clarity Assessment of anterior chamber angle crowding Assessment of graft dislocation and donor apposition (especially when corneal oedema precludes direct visualisation) In our study we have demonstrated similar findings of preferential peripheral graft thinning as other authors Pascuale et al showed peripheral graft may continue to thin and remodel beyond 6 months post operatively. Changes in peripheral graft thickness have been correlated with the induced hyperopic shift. 2 Thickened peripheral graft may increase risk of anterior chamber angle crowding LIMITATIONS: Measurements are taken by visually assessing the transition of lamellae Optical density and reflectivity are qualitative measures – it remains to be seen whether these methods are reproducible and accurate 2. Yoo et al One-Year Results and Anterior Segment Optical Coherence Tomography Findings of Descemet Stripping Automated Endothelial Keratoplasty Combined With Phacoemulsification Arch Ophthalmol. 2008;126(8): Pascuale et al Corneal Deturgescence after Descemet Stripping Automated Endothelial Keratoplasty Evaluated by Visante Anterior Segment Optical Coherence Tomography Am J Ophthalmol 2009;148:32–37.