The Association Between Ocular Surface Measurements with Visual Field Reliability Indices and Gaze Tracking Results in Preperime
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Downloaded from http://bjo.bmj.com/ on August 28, 2017 - Published by group.bmj.com BJO Online First, published on August 1, 2017 as 10.1136/bjophthalmol-2017-310309 Clinical science The association between ocular surface measurements with visual field reliability indices and gaze tracking results in preperimetric glaucoma Takahiro Arai, Hiroshi Murata, Masato Matsuura, Tomohiko Usui, Ryo Asaoka Department of Ophthalmology, ABSTRACT when the patient fails to respond to a more intense The University of Tokyo, Tokyo, Background/aims To investigate the relationship stimulus than one previously perceived at the Japan between gaze tracking (GT) results and ocular surface same location. All three VF reliability indices are condition in glaucoma. important clinical markers. Elevated FLs can mask Correspondence to 1 Dr Ryo Asaoka, Department of Method The Humphrey 24–2 visual field (VF) asw early scotoma, increased FP errors indicate ‘trig- Ophthalmology, The University measured in 34 eyes of 30 patients with open-angle ger-happy’ patients, while a high FN rate may of Tokyo, Graduate School of glaucoma without VF damage. Tear break-up time, suggest patient inattention or fatigue during the Medicine, Tokyo, 113-8655, Schirmer’s test, tear meniscus volume (TMV) and 2 Japan; rasaoka- tky@ umin. ac. jp VF examination. Previous studies have reported presence of superficial punctate keratopathy (SPK) were the usefulness of these indices3; however, their Received 7 February 2017 also measured in order to describe the condition of the limitations have also been reported in more recent Revised 8 June 2017 ocular surface. Various GT parameters were calculated: studies. For instance, FLs can be increased by Accepted 2 July 2017 the average frequency of eye movements per stimulus mislocalisation of the blind spot,4 and fixational between 1° and 2° (move ), the average frequency of 1-2 instability can be experienced even in well-trained eye movements per stimulus between 3° and 5° (move 5 3- examinees. Furthermore, a high FN rate is signifi- ), the average frequency of eye movements per stimulus 5 cantly associated with the amount of field loss, more than 6° (move ), the average tracking failure ≥6 rather than threshold reproducibility,6 and there- frequency per stimulus (TFF) and the average blinking fore this index is no longer used in the HFA. frequency. The relationship between GT parameters, reliability indices and ocular surface measurements was We have investigated the usefulness of gaze tracking (GT) in assessing the reproducibility7 and investigated using linear mixed modelling. 8 9 Results SPK was positively associated with high rates overestimation/underestimation of the VF. GT is of move (coefficient=0.12 for SPK+, p=0.003) and a record of eye movement monitored throughout 3-5 the VF measurement.10 Currently, the GT results move≥6 (coefficient=0.052 for SPK+, p=0.023). High TMV was significantly related to TFF (coefficient=0.37, are represented as a printed line diagram at the p=0.023). Fixation losses, false-positives and false- bottom of the VF printout and can only be subjec- negatives were not significantly associated with any GT tively evaluated by clinicians. In our prior studies, parameters or ocular surface measurements. GT results were evaluated objectively and quanti- Conclusion SPK is associated with increased frequency tatively.7–9 However, GT uses a record of infrared video recording of the fixation stimulus (corneal of eye movements (move3-5 and move≥6). In addition, large TMV is associated with increased rate of TFF. reflex), and hence it may be largely influenced by Careful attention should be paid when interpreting GT the scattering of light associated with the condi- parameters in patients with SPK or a large TMV. tion of the corneal surface, such as superficial punctate keratopathy (SPK) and an abnormal tear film state. Indeed, examples of poor GT due to dry eye have been reported11; however, no study has INTRODUCTION quantitatively analysed the relationship between Reliable visual field (VF) results are imperative GT and dry eye. Thus, the purpose of the current for the accurate diagnosis of glaucoma and early study is to investigate the relationship between GT detection of disease progression. Fixation losses results and ocular surface condition in patients (FLs), false-positives (FPs) and false-negatives with glaucoma. The purpose of the current (FNs) are measures of reliability implemented study was to investigate the effect of dry eye to in the Humphrey Field Analyzer (HFA, Carl GT parameters in glaucomatous eyes and not in Zeiss Meditec, Dublin, California, USA). FLs are normative subjects. However, as GT parameters recorded when the patient perceives a stimulus that are significantly related to VF deterioration,8 9 is presented in the physiological blind spot. FPs were traditionally measured using catch trials, and only glaucomatous eyes — with no measurable VF a FP would be recorded when the patient reported damage — were analysed in the current study. We To cite: Arai T, Murata H, seeing a stimulus when one was not presented; recently reported that, even if a VF criterion for Matsuura M, et al. however, in the Swedish Interactive Threshold VF damage is not satisfied, VFs of glaucomatous Br J Ophthalmol Published 12 Algorithms (SITA), FPs are measured through the eyes are different from those from normal eyes. Online First: [please include 13 Day Month Year]. use of ‘listening windows’. These windows are Thus, only ‘preperimetric’ glaucomatous VFs doi:10.1136/ intervals between stimulus presentations when no were included in the current study to mitigate the bjophthalmol-2017-310309 patient response is anticipated. FNs are recorded effects of obvious VF deterioration. Arai T, et al. Br J Ophthalmol 2017;0:1–6. doi:10.1136/bjophthalmol-2017-310309 1 Copyright Article author (or their employer) 2017. Produced by BMJ Publishing Group Ltd under licence. Downloaded from http://bjo.bmj.com/ on August 28, 2017 - Published by group.bmj.com Clinical science average blinking frequency (BF), the average frequency of eye movement per stimulus between 1° and 2° (denoted by move1- 2), 3° and 5° (denoted by move3-5) and more than 6° (denoted by move≥6). Total magnitude of eye movement was calculated as the movement degree × the average frequency of eye movement (denoted by total move). Ocular surface condition measurements Prior to VF measurements, SPK was assessed by fluorescein staining.15 The area of SPK was estimated in four gradations: 0 (no SPK), 1 (less than one-third of cornea), 2 (between one-third and two-thirds of cornea) and 3 (larger than two-thirds of cornea). The density of SPK was graded as 0 (no SPK was present), 1 (SPK was sparse), 2 (moderately dense) and 3 (SPK was high and the lesions overlapped). As the current study included only Figure 1 Illustrated gaze tracking record. An upward bar in the mild dry eye cases (only one eye had an area score larger than 2 chart indicates fixation disparity and the length of the bar represents and only three eyes had density scores larger than 2), SPK was the magnitude of disparity. A short downward bar represents tracking defined in a binary fashion: SPK− (SPK area and density scores failure, while a long downward bar indicates eyelid closure. Gaze were 0) or SPK+ (SPK area or density score was >0). Then, tracking parameters were calculated as follows: average TFF per tear break-up time (TBUT) was measured three times and the stimulus, the average frequency of eye movement per stimulus between average value was calculated. Alcon Schirmer Standard Tear Test Strips (Fort Worth, Texas, USA) were used to assess anaesthe- 1° and 2° (denoted by move1-2), 3° and 5° (denoted by move3-5) and tised tear secretion. In addition to these measurements, after the more than 6° (denoted by move≥6). BF, blinking frequency; TFF, tracking failure frequency. VF test, tear meniscus volume (TMV) was measured using ante- rior segment optical coherence tomography (SS-1000; Tomey, Tokyo, Japan), following our previous reports.16–18 Details of METHODS the TMV measurement are described elsewhere.16–18 In short, The study was approved by the Research Ethics Committee of the TMV value was calculated automatically with the integrated the Graduate School of Medicine and Faculty of Medicine at tear meniscus area values of the consecutive central 11 images, The University of Tokyo. Written consent was given by patients where the TM area value was defined as an inferior triangular for their information to be stored in the hospital database and TM area formed by the corneal anterior boundary, the anterior used for research. This study was performed according to the boundary of the lower eyelid and the anterior borderline of the tenets of the Declaration of Helsinki. TM. Subjects Statistical analysis Thirty-four eyes of 30 patients with open-angle glaucoma (16 The relationships between GT measurements, FLs FPs and FNs male and 14 female) were prospectively included in the study. and ocular surface measurements were first analysed using the All patients visiting the glaucoma clinic at The University of Wilcoxon test for comparing numeric values between two groups Tokyo Hospital during the period of February 2016–July 2016 and also Spearman test for analysing the relationship between who fulfilled the following criteria were included in the current two numerical values. Linear mixed modelling, whereby eyes study: (1) glaucomatous changes in the optic nerve head with or were nested in each patient,