Manuscript - Revision 2 Prevalence of foveolar lucency with different gas tamponades 1 2 3 in surgically closed macular holes assessed by spectral 4 5 6 domain optical coherence tomography 7 8 9 10 11 Javier Zarranz-Ventura, MD, PhD, FEBO,1,2,5 Abdallah A. Ellabban, MD,1,3 12 13 5 5 14 Dawn A. Sim, PhD, FRCOphth, Pearse A. Keane, MD, FRCOphth, James 15 16 N. Kirkpatrick, MD, FRCOphth,1 Ahmed A. B. Sallam, PhD, FRCOphth1,4 17 18 1Vitreo-Retinal Service, Cheltenham General Hospital, Gloucestershire Hospitals NHS Trust, 19 20 Cheltenham, United Kingdom 21 22 2Vitreo-Retinal Unit, Institut Clínic d´Oftalmologia (ICOF), Hospital Clínic, Barcelona, Spain 23 24 3 25 Department of Ophthalmology, Suez Canal University, Ismailia, Egypt 26 4 27 Jones Eye Institute, University of Arkansas for Medical Science, Arkansas, USA 28 5 29 NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS 30 31 Foundation Trust, London, United Kingdom 32 33 34 35 Correspondence and reprint requests: 36 37 38 Javier Zarranz-Ventura, Vitreo-Retinal Service, Cheltenham General Hospital, Sandford 39 40 Road, Gloucestershire Hospitals NHS Trust, Cheltenham, United Kingdom 41 42 ([email protected]). 43 44 Tel: +34 660008417 45 46 47 48 Acknowledgements: 49 50 This work is dedicated to the memory of Rob Johnston, Vitreo-Retinal Consultant (1966-2016), 51 52 53 who played a major role in designing this study and passed away weeks before the submission 54 55 of this paper. Rest in peace Rob. 56 57 58 59 60 61 62 63 64 1 65 Disclosure: 1 2 3 None of the authors have any conflict or proprietary interest in any of the 4 5 devices mentioned in this article. 6 7 8 9 10 11 Running Head: 12 13 Foveolar lucency and gas tamponade 14 15 16 17 18 Keywords: 19 20 21 Ellipsoid 22 23 Foveolar lucency 24 25 26 Foveal lucency 27 28 Gas 29 30 31 Macular hole 32 33 Neurosensorial 34 35 36 Optical coherence tomography 37 38 Subretinal fluid 39 40 Tamponade 41 42 43 Vitrectomy 44 45 46 47 48 Summary statement: 49 50 51 Temporary foveolar lucency is a highly prevalent feature in successfully 52 53 closed macular holes at month 1, which seems to be related to the gas 54 55 56 tamponade type employed and does not affect the final visual outcome. 57 58 59 60 61 62 63 64 2 65 Abstract: 1 2 3 4 5 6 Purpose: To evaluate the prevalence of foveolar lucency (FL) in surgically 7 8 closed macular holes by spectral domain optical coherence tomography (SD- 9 10 OCT). 11 12 13 Methods: 142 eyes of 132 patients underwent pars plana vitrectomy (PPV), 14 15 internal limiting membrane (ILM) peeling and gas tamponade in a 60 months’ 16 17 18 time frame. Anatomical success and FL rates assessed by SD-OCT, mean 19 20 preoperative and postoperative best-measured visual acuity (BMVA) and 21 22 23 surgical details were retrospectively analyzed. 24 25 Results: SD-OCT confirmed closed holes with FL in 33.7% (34/101) of eyes 26 27 at 1 month, 7.3% (9/123) at 3 months, 4.6% (6/129) at 6 months and 3% 28 29 30 (4/133) at 12 months. Prevalence of FL in closed holes at month 1 was lower 31 32 in C3F8-treated eyes (9.5%, 2/21) compared to C2F6 (40.9%, 18/44, p = 33 34 35 0.03) and SF6-treated eyes (38.9%, 14/36, p = 0.05). No differences were 36 37 observed at month 3. No differences in BMVA change were observed 38 39 40 between closed holes with or without FL at month 1 (-0.14 ± 0.19 vs. -0.11 ± 41 42 0.23, p = 0.48) or any of the other time points. 43 44 45 Conclusions: Temporary FL is a highly prevalent feature in successfully 46 47 closed macular holes. Eyes treated with C3F8 gas had lower rates of FL at 48 49 month 1 than C2F6 and SF6-treated eyes. The presence of FL in closed holes 50 51 52 does not appear to have any effect on the visual outcomes. 53 54 55 56 57 58 59 60 61 62 63 64 3 65 INTRODUCTION: 1 2 3 4 5 6 Idiopathic full-thickness macular hole (IFMH) is characterized by a full 7 8 thickness defect in the fovea that causes a central scotoma, metamorphopsia 9 10 and reduced visual acuity.1 It represents a common vitreo-retinal pathology 11 12 2 13 with an estimated incidence of 8.6 cases/100,000 population/year and is the 14 15 indication for surgery in almost 10% of all pars plana vitrectomy (PPV) 16 17 3 18 operations performed in the United Kingdom (UK). The surgical treatment of 19 20 IFMH with PPV combined with intravitreal gas tamponade has been proven 21 22 4, 5 23 effective in randomized controlled trials for stage II, III and IV holes, 24 25 resulting in good long-term visual and anatomical outcomes.6 More recently, 26 27 the results of a prospective registry-based study from New Zealand and 28 29 30 Australia demonstrated that peeling of the internal limiting membrane (ILM) 31 32 increased the anatomical closure rate 7, although this was not always 33 34 8 35 associated with better visual acuity outcomes. 36 37 The use of optical coherence tomography (OCT) has refined the clinical 38 39 40 description of success (open or closed) to include analysis of the status of the 41 42 outer retinal layers in ophthalmoscopically closed holes.9, 10 In particular the 43 44 45 presence of foveolar lucency (FL) – a hyporeflective space underlying the 46 47 fovea with continuity of the inner retinal layers after surgery - and/or disruption 48 49 of outer retinal layers such as the ellipsoid layer or the external limiting 50 51 52 membrane have been described in the course of the macular hole closure 53 54 healing process.9-12 Given the descriptive nature of these studies in small 55 56 57 cohorts of patients, the prevalence of these findings remains uncertain. 58 59 60 61 62 63 64 4 65 The primary aim of the study was to determine the prevalence of FL in eyes 1 2 with closed macular holes after vitrectomy surgery at different time points in a 3 4 5 large series of patients. Secondary aims were to explore the influence of the 6 7 type of intraocular gas tamponade on this OCT feature and its effect on post- 8 9 10 operative visual acuity at different time points. 11 12 13 14 15 METHODS: 16 17 18 19 20 21 Study Eyes 22 23 This study included 142 eyes from 132 patients with idiopathic macular hole 24 25 operated in the vitreo-retinal unit of Gloucestershire Hospitals NHS 26 27 28 Foundation Trust by 3 consultant teams and followed up with spectral domain 29 30 optical coherence tomography (SD-OCT) over a 60 months’ period (2007- 31 32 33 2012). All clinical data for these patients were prospectively entered during 34 35 routine clinical practice into an electronic medical record (EMR) system 36 37 38 (Medisoft Ophthalmology, Medisoft Limited, Leeds, UK). Data were extracted 39 40 and anonymized as part of a non-interventional retrospective audit and on this 41 42 basis formal ethics approval was not required. All patients underwent 20 or 43 44 45 23G pars plana vitrectomy (PPV), ILM peel and gas tamponade. In all cases 46 47 ILM peeling was performed with trypan blue and brilliant blue (TB-BB) 48 49 50 (Membraneblue-Dual, DORC, Zuidland, The Netherlands). The gas 51 52 tamponade employed was determined by consultant choice rather than 53 54 55 macular hole grade with one consultant favouring sulfahexafluoride (SF6), 56 57 another favouring hexafluoroethane (C2F6) and a third perfluoropropane 58 59 60 (C3F8). All cases were given the same posturing advice: to avoid lying supine 61 62 63 64 5 65 for the first week regardless of macular hole stage or gas tamponade 1 2 employed, patients were not instructed to adopt face down positioning. 3 4 5 Macular holes secondary to previous retinal surgery, uveitis, diabetes or 6 7 trauma were excluded from this study. 8 9 10 11 12 Clinical Data 13 14 15 Clinical and demographic data extracted from the EMR included: age, gender, 16 17 stage of macular hole, type of tamponade, preoperative phakic status, 18 19 secondary cataract surgery rate, anatomical success rate and FL prevalence 20 21 22 by SD-OCT images at 1, 3, 6, 12 and 24 months post-surgery, preoperative 23 24 and postoperative best measured visual acuity (BMVA) at 1, 3, 6, 12 and 24 25 26 27 months after surgery. Visual acuity was measured in either logarithm 28 29 minimum angle of resolution (LogMAR) or Snellen notation and converted to 30 31 32 LogMAR for analyses. 33 34 35 36 SD-OCT Image Acquisition Protocol 37 38 39 All SD-OCT image sets included in this study were acquired on the Cirrus HD- 40 41 OCT (Carl Zeiss Meditec, Dublin, California) during routine clinical practice 42 43 44 using the Macular Cube protocol. The Macular Cube protocol consists of 128 45 46 horizontally oriented B-scans acquired in a continuous, automated sequence 47 48 49 and covers a 6 mm × 6 mm area. Each B scan is 6 mm in length and 50 51 composed of 512 equally spaced transverse sampled locations. 52 53 54 55 56 SD-OCT Qualitative and Quantitative Analysis Criteria: 57 58 59 60 61 62 63 64 6 65 SD-OCT images were analyzed for macular hole closure postoperatively at 1 2 different time points (Figures 1 and 2).