Eye (2011) 25, 149–153 & 2011 Macmillan Publishers Limited All rights reserved 0950-222X/11 $32.00 www.nature.com/eye 1 1 2 Comparing fixation E Pearce , S Sivaprasad and NV Chong CLINICAL STUDY location and stability in patients with neovascular age-related macular degeneration treated with or without Ranibizumab Abstract fixation. Majority (84.6%) of the patients in the untreated group had predominantly eccentric Purpose To compare fixation location and fixation. Fixation stability was significantly stability in patients with neovascular age- better in the ranibizumab-treated group as related macular degeneration (AMD) treated compared with the untreated group, using with or without ranibizumab. both the software provided by the MP1 Methods Patients were recruited from the machine (v2 21.8, P 0.0001) and the mean log Macular Clinic of the King’s College Hospital o bivariate contour ellipse area calculated from in London. Two groups of patients with the raw data obtained from the machine neovascular AMD with at least 12 months of (3.64 vs 4.39 in treated and untreated group follow-up were included in the study. The respectively, P 0.0001). treated group was treated with ranibizumab o Conclusion Low vision rehabilitation while the untreated group did not have any strategy for this group of patients in the treatment. Best corrected visual acuity (BCVA) ranibizumab era will be very different from 1 with modified ETDRS chart, fixation location Laser and Retinal Research those used in untreated patients with dense Unit, King’s College and stability as measured with Nidek MP1, central scotoma. Further studies on the visual Hospital, University of central retinal thickness as measured by Zeiss rehabilitation in the ranibizumab-treated London, London, UK Cirrus SD-optical coherent tomography patients should consider fixation (OCT), and lesion size as measured by Topcon 2Oxford Eye Hospital, characteristics of the patients. TRC-50IX camera were analysed and University of Oxford, Eye (2011) 25, 149–153; doi:10.1038/eye.2010.167; correlated. Oxford, UK published online 19 November 2010 Results In total, 102 eyes were included in Correspondence: the study with 76 in the ranibizumab-treated Keywords: age-related macular degeneration; NV Chong, Oxford Eye group and 26 in the untreated group. There Hospital, Headley Way, ranibizumab; fixation; eccentric; visual were no significantly demographic differences Oxford, OX3 9DU, UK. rehabilitation; low vision between the two groups. However, as Tel: 01865 236736; expected, the treated group has significantly Fax: 01865 236515; E-mail: [email protected] better vision (48.5 vs 15.5 letters, Po0.0001) and smaller lesions (10.8 vs 18.3 mm2, Introduction Received: 30 April 2010 P ¼ 0.004), the central macular thickness as Accepted in revised form: measured by OCT also showed a trend of Neovascular age-related macular degeneration 31 August 2010; normalised macular thickness (252 vs 282 (AMD) causes decreased visual acuity and Published online: 19 microns, P ¼ 0.07). The location of fixation was morphological changes in the posterior pole of November 2010 significantly more central in the ranibizumab- the fundus that are mainly characterised by the Presentation: Part of the 2 treated group (v 17.9, Po0.0001) with over presence of subretinal haemorrhage, intra- and data was presented in ARVO 50% of eyes with predominantly central subretinal fluid and/or pigment epithelial 2009 and Euretina 2009 Fixation location and stability in neovascular MAD E Pearce et al 150 detachment (PED) which can be visualised by optical Ranibizumab treatment regimen coherent tomography (OCT). Without treatment, most All included patients received three intravitreal patients develop a disciform scar with destruction of the injections with ranibizumab at monthly intervals. foveal retinal tissue. Decision to re-treat after three injections was based on the Over time, many patients develop an eccentric area of following criteria: (1) recurrence of any subretinal fluid fixation, there is evidence to suggest that eccentric or intra-retinal fluid on OCT in a previously dry macula; viewing training might improve reading ability of these (2) persistent subretinal fluid or intra-retinal fluid on patients. Indeed, the Macular Disease Society in the OCT; (3) new-onset haemorrhages on fundus United Kingdom has reported their programme of examination; (4) decrease of five letters or more eccentric viewing training by trained members of the associated with fluid on OCT or (5) new classic CNV. society was a success. The numerical changes in central retinal thickness and Ranibizumab (Novartis, Basel, Switzerland) is a the presence of serous PED alone without fluid were not recombinant, humanised, monoclonal antibody antigen- taken into account to decide re-treatment. binding fragment that inhibits all the known isoforms of vascular endothelial growth factor (VEGF-A). Pivotal phase III trials on treatment of neovascular AMD with Visual acuity measurement monthly intravitreal injections of ranibizumab have shown average improvement in visual acuity with a BCVA for each eye was measured using standard ETDRS decrease in central macular thickness.1,2 protocol at 2 m distance with a modified ETDRS distance There is some evidence to suggest patients with chart by a certified examiner on the day of the fixation neovascular AMD in the ranibizumab era might be test. Visual acuity was scored as the total number of different from those who were previously untreated. ETDRS letters read correctly. In this study, we compared these two groups of patients formally. Assessment of location and stability of fixation using MP-1 microperimetry The Nidek microperimeter (MP-1, Nidek Instruments, Materials and methods Padova, Italy) was used to measure fixation with a white fixation cross of height 31 presented on a dark The study was performed in the Laser and Retinal background on the LCD screen of the MP-1. The fixation Research Unit at King’s College Hospital. All the cross was presented at the maximum luminance of the measurements adhered to the tenets of the Helsinki MP-1. Subjects were asked to look toward the centre of agreement; the study was approved by the Clinical the cross and were encouraged to use peripheral retina if Effectiveness department and the Local Ethics needed. Once subjects had located the cross, fixation was Committee. measured for a period of 30 s. Eye position was recorded by tracking a retinal landmark at 25 Hz throughout the fixation assessment. The pattern of fixation was classified based on location Inclusion criteria and stability using the MP-1 software as recommended Consecutive patients aged 55 years or older with at least by Fujii et al.3 In brief, the location of fixation is defined as 12 months follow-up for ranibizumab therapy for the position of fixation with respect to the centre of the neovascular AMD were included in this study as the foveal avascular zone, and stability of fixation is defined treated group. The best corrected visual acuity (BCVA) at as the ability of the eye to maintain a stable fixation in the baseline of the ranibizumab-treated eye ranged between preferred retinal locus (PRL). 24 and 73 ETDRS letters. All lesion subtypes were The location of fixation was defined as predominantly included. Exclusion criteria were CNVs because of central fixation (PC) when more than 50% of the causes other than AMD, previous photodynamic therapy preferred fixation points were located within 21 of the or any other anti-VEGF therapy, vitrectomy or fovea; poor central fixation (POC) when less than 50% submacular surgery. The untreated eyes had never but more than 25% of the preferred fixation points were received any treatment for neovascular AMD. Treatment within 21 of fovea and predominantly eccentric fixation was not initiated in the latter group because of non- (PE) when less than 25% of the preferred fixation points availability of the drug at the time of presentation or the were located within the 21 circle of the fovea. presenting vision was already too poor to be considered The stability of fixation was based on the variation of for treatment or the lesion was inactive. the PRL. The location of fixation was defined as stable Eye Fixation location and stability in neovascular MAD E Pearce et al 151 fixation when more than 75% of the fixation points were Table 1 Patient characteristics located within a pre-determined limit area of variation of Untreated Ranibizumab treated P-value a21-diameter circle centred in the gravitational centre of (n ¼ 26) (n ¼ 76) all fixation points, regardless of the position of the foveal centre. The location of fixation was classified as relatively Mean age in years 80.2 79.5 P ¼ 0.64 Males in % 38.5 31.6 P ¼ 0.52 unstable fixation when less than 75% of the fixation Mean BCVA in 15.5 48.5 Po0.0001 1 points were located within a 2 -diameter circle, but more letters than 75% of the fixation points were located within a Mean lesion size in 18.3 10.8 P ¼ 0.004 41-diameter circle. The location of fixation was classified mm2 as unstable fixation when less than 75% of the fixation Mean CMT in 282.2 252.2 P ¼ 0.07 microns points were located within a 41-circle. Abbreviations: BCVA, best corrected visual acuity; CMT, central macular thickness. Calculation of bivariate contour ellipse area (BCEA) Crossland et al4 reported that quantifying fixation Table 2 Location of fixation in the untreated and ranibizumab- stability by calculating a BCEA that encompasses 68% treated group of fixations is a more powerful and accurate tool than the Untreated Ranibizumab treated P-value in-built fixation software of MP-1 for patients with (n ¼ 26) (n ¼ 76) macular diseases. The log BCEA correlated well with Fixation location as measured by MP1 reading speed in patients with AMD.