Purpose To describe a new combined myopia and glaucoma visual field classification system in order to report the visual field defects in a population of mostly young Chinese high myopes aged 7–70 years.
Methods A total of 1434 visual fields (including confirmatory repeats of abnormal defects) from 487 high myopes (sphere ≤−6.0 D) were analysed from the prospective Zhongshan Ophthalmic Center–Brien Holden Vision Institute (ZOC–BHVI) High Myopia Registry Study. The predefined classification definitions covering high myopia and glaucoma categories were: normal, enlarged blind spot, abnormal suspect and abnormal with nine subtypes. Two independent graders reviewed the first 150 of 1434 fields for initial grading calibration and the remaining 1284 fields were used to assess intergrader agreement. For the percentage distribution of visual fields, the repeats and unreliable fields were excluded, leaving 894 fields.
Results The intergrader agreement of this combined classification system was a κ value of 0.61 (95% CI 0.59 to 0.63). Among the 894 unique fields, the most common visual field was normal at 33.7% followed by enlarged blind spot at 25.6%. The per cent of ‘arcuate-like’ field defects (combining nasal step, early arcuate and advanced arcuate) was 16.1% with advanced arcuate at 3.4%.
Conclusions A proposed combined visual field classification for high myopia and glaucoma demonstrates acceptable intergrader agreement. A total of 16.1% of defects in young high myopes were found to mimic classic glaucomatous defects. These subjects are being followed prospectively to assess which ones will progress to differentiate myopic from glaucomatous field defects.
- Field of vision
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
Myopia morbidity continues to increase substantially worldwide,1 especially in East Asians.2 Myopia can be corrected by spectacles, contact lens, or various intraocular or laser refractive surgeries to achieve good vision. However, in high myopia, defined as worse than or equal to −6 dioptres sphere and also known as degenerative myopia, sight-threatening complications increase with many potentially blinding conditions, such as myopic degenerative retinopathy, macular scars, increased primary open-angle glaucoma (POAG) and more frequent retinal detachment.3 Unlike cataract or age-related macular degeneration, which mainly affect the elderly population, high myopia also affects many young adults of working age; thus myopia is rapidly becoming a major public health problem.4
The relationship between high myopia and POAG has been explored extensively in prior studies.5 However, accurate diagnosis of glaucoma in the setting of high myopia is a challenge in clinical practice for two major reasons: (1) High myopia can cause tilted optic discs, large peripapillary atrophy obscuring the disc edge and shallow cupping without shifting of the vessels nasally, making the subjective interpretation of glaucomatous excavation more difficult. (2) Although the diagnosis of glaucoma relies upon characteristic optic nerve cupping with associated progressive visual field loss, myopic degeneration can also cause similar glaucomatous-like visual field defects.6 ,7 Therefore, patients need to be followed over time to confirm true glaucoma progression.8 There is little information in the literature describing the overall clinical characteristics of high myopes with visual field defects or any prospective data on how or if myopic defects change over time. We were interested in determining how often Chinese myopes have visual field defects that mimic glaucoma, particularly since many of those defects in young myopes may be minimally progressive and not glaucomatous.9
In the present study, we first propose a broader combined classification system of visual field defects in high myopes to include both high myopia and glaucoma types. After reporting the intergrader agreement, we describe the baseline percentages of each field defect type in a large group of Chinese high myopes aged 7–70 with a median age of 17.4 years. The data collected, including visual fields, is part of an ongoing ZOC–BHVI High Myopia Registry Study that is designed to understand the natural history and pathogenesis of myopic retinopathy, initiated in November 2011 in Guangzhou, China.
Ethics approval was obtained from the Zhongshan Ophthalmic Center Ethics Review Board. The study was conducted in accordance with the tenets of the World Medical Association's Declaration of Helsinki. Written informed consent was obtained from all participants, or their parents or legal guardians if their age was <18 years.
A longitudinal observational high myope registry study was initiated in Guangzhou in 2011 and is expected to run until 2021. Subjects with high myopia, defined as worse than or equal to −6 dioptres sphere (not spherical equivalent) in both eyes, were recruited from both optometric clinic and a previous community screening population study in order to have more subjects older than 50 years.10 At baseline, a total of 895 participants were eligible and enrolled in the registry. However, only 487 subjects had visual field data.
Baseline data collected in the high myopia registry included: cycloplegic refraction, best-corrected visual acuity, ocular biometry, external motility and slit lamp exam, lens opacity by the Lens Opacities Classification System (LOCS III) grading scale, intraocular pressure (IOP) measurement by Goldmann applanation, standard automatic perimetry, B-scan ultrasound, digital stereo fundus photography (Canon CX-1), autofluorescence (Heidelberg Spectralis) and spectral domain optical coherence tomography (SD-OCT Optovue). Refraction was performed with an autorefractor (Topcon KR-8800) after cycloplegia. Ocular biometric parameters including axial length were obtained by optical low-coherence reflectometry (Lenstar LS-900, Haag-Streit AG).
Visual field examination
A total of 487 subjects underwent bilateral standard automatic perimetry (Zeiss Humphrey Visual Field 750i, Carl Zeiss Meditec, Dublin, California, USA) on a separate return visit, using the 24-2 Swedish interactive threshold algorithm (SITA) fast, white-on-white, performed on a single machine. All visual fields were conducted in a single dark room without distraction (ambient light <5 lux) with a trained technician who explained to all subjects how to complete the test reliably. Each subject had a short demonstration test before commencing the official examination. During the test, the technician also monitored the subject's eye movement, and made adjustments as necessary to maintain proper fixation. Unreliable fields, defined as reach one of three criteria: false positive ≥15%, false negative ≥33% and fixation loss ≥33%, were repeated immediately (up to two times) as well as any abnormal fields. From November 2011 to August 2012, a total of 1434 visual fields (including repeats of abnormals) from 487 patients were available for our current visual field analysis, the outline of the recruitment was shown in figure 1.
Visual field classification system and grading
In order to include visual field defect types associated with high myopia, new visual field grading criteria were drafted, consisting of four major types: normal, enlarged blindness spot (at least two abnormal edge point around the blind spot), suspicious for abnormal (minimum criteria for a defect but no pattern) and definitely abnormal (figure 2). The grading criteria for glaucomatous defects were adapted from the Ocular Hypertension Treatment Study visual field criteria: nasal step, early arcuate, advanced arcuate with additional myopic related defects added including generalised (widespread) sensitivity loss, paracentral defect, central defect, rim artefacts, tilted disc (crosses at least two outer rims crossing vertical and horizontal midlines) and cecocentral defect. We used the first 150 of 1434 visual fields to train two grading ophthalmologists to reach the final assessment shown in figure 2, and the visual field grading schematic depicted in figure 3.
Minus the calibration training set of 150 fields, 1284 visual fields were independently graded by two ophthalmologists (XD and RTC) for calculating the intergrader agreement. When the agreement estimation was completed, all visual fields were pooled and the ones in disagreement were readjudicated with the established criteria to determine final percentages reported from the unique 894 fields in which repeat or unreliable fields had been removed. A total of 167 unreliable fields (13%) were removed. If the original and repeat field were both reliable, then the field with fewer false positives was chosen or fewer fixation losses if the false positives were the same. Thus, 167 unreliable and 373 repeat visual fields were removed, arriving at the 894 visual field total for analysis (figure 1).
Median, range and 25th–75th percentile were used to describe the non-normal distribution parameters. The agreement between two graders was assessed by κ, whose values of >0.7 are generally considered excellent and between 0.4 and 0.7 are considered as moderate. p<0.05 was considered statistically significant. All statistics were performed using STATA (V.12.0, Stata, College Station, Texas, USA).
Among the 487 participants, 229 (47.0%) were male and 258 (53.0%) were female. The median age was 17.4 years, range 7–70 years, the 25% percentile was 13.3 years and 75% percentile was 28.1 years. The median refraction was −8.6 D, range −6 to −35 D, 25% and 75% percentiles were −7.4 and −11.0 D, respectively. The median axial length was 27.2 mm, range 23.8–32.0 mm and the 25% and 75% percentiles were 26.3 and 28.1 mm, respectively (table 1).
Of the 1284 visual fields available for the reader agreement analysis, the κ index of agreement before adjudication was 0.61 (95% CI 0.59 to 0.63). Given that the agreement would be higher with a higher percentage of normal visual fields, after removing the fields both graders read as normal, the κ value was 0.56 (95% CI 0.54 to 0.58) revealing moderate correlation.11
Of the 1434 visual fields, 540 were removed due to unreliability (167) or repeats (373), leaving 894 unique visual fields used for distribution description. Table 2 displays the percentage distribution of visual field defects in high myopes, the most common one being normal, which accounted for 33.7% (95% CI 30.6% to 36.9%). Based on our definitions, the next most common defects were enlarged blind spots at 25.6% (95% CI 22.8% to 28.6%) and generalised reduction in sensitivity at 23.4% (95% CI 20.6% to 26.3%). The arcuate-like visual field defects, grouped together as either nasal step (5.1%), early arcuate (7.6%) and advanced arcuate (3.4%), contributed up to 16.1% (95% CI 13.8% to 18.9%). Relatively rarer types were: paracentral defect at 5.9% (95% CI 4.4% to 7.7%), rim artefacts at 2.5% (95% CI 1.5% to 3.7%), tilted disc defects at 1.6% (95% CI 0.8% to 2.6%) and central defects at 1.0% (95% CI 0.4% to 1.9%), with the least common being cecocentral defect which only accounted for about 0.3% (0.0% to 0.9%).
Classically, nasal step, early arcuate and advanced arcuate defects are strongly associated with glaucoma, and we found 16.1% of all field defects in our young high myopic population had this pattern. To assess this group further in terms of glaucoma risk, baseline clinical data on IOP, central corneal thickness (CCT), fundus photos and SD-OCT were reviewed for these 144 subjects. Elevated IOP (>21 mm Hg, with adjustment for CCT), as well as glaucomatous optic nerve appearances in fundus photos (including optic nerve notching, retinal nerve fibre layer (RNFL) defect, optic haemorrhage, enlarged cup–disc ratio and asymmetry between two eyes) were considered as signs of high risk glaucoma suspects when correlated with the field defects. RNFL map and quadrant values provided by SD-OCT helped to localise areas of RNFL loss when reviewing the fundus photos. Nineteen (2.1%) eyes in this young population were finally categorised as high-risk glaucoma suspect, and the others appeared lower risk but would need follow-up testing to assess for progression. Two typical cases with high and low risk of glaucoma suspects were shown in the online supplementary materials.
The ZOC–BHVI Myopia Registry Study was initiated to observe the natural history of high myopia and to explore the potential risk factors for visual acuity damage. This current analysis of the visual field data from 487 young high myopes derived from the ZOC–BHVI study has led to proposing an updated visual field classification system for high myopia and glaucoma. While this study is a retrospective review of a cross-sectional sample, longitudinal prospective data is still being collected and will be reported in the future. Approximately 16.1% had repeatable arcuate-like field defects with 2.1% eyes judged to be at high risk of glaucoma after IOP, CCT, fundus photos and OCT were also reviewed and correlated. There is much interest in this area because young high myopes may be at risk for normal tension glaucoma (NTG) but diagnosing glaucoma in this setting can be a challenge given the overlap in structural and functional testing. The high myopes with arcuate-like visual fields will be followed to watch for visual field progression over the next 10 years. Those results may be able to confirm the natural history of a previously reported small series of young Chinese high myopes followed over 7 years who had minimally progressive visual field defects.9
When designing the visual field classification, we decided not to use mean deviation (MD) since the MD significantly decreases as the degree of myopia increases. A study by Aung et al of 146 patients with an average refraction of −6.4±3.7 D (range −0.5 to −14.0 D) using a regression model, found that when myopia increased by 1 dioptre, the MD decreased by about 0.2 dB.12 This relationship held for high myopia alone, and also for glaucoma with myopia. In Mayama's study,13 the mean refraction was −2.4±3.5 D (range +4.0 to −13.0 D) and, similarly, more negative spherical equivalent was associated with greater visual defects in advanced stage both POAG and NTG in central 10° field. Similar results were also found in a Japanese cohort of high myopes in Araie's study.14 In a retrospective analysis conducted by Perdicchi et al15 exploring the effect of various degrees of myopia on glaucoma visual field progression over a study duration from 24 to 64 months, the results of 110 patients revealed a significant decrease of MD in highly myopic patients. Thus, a new pattern-based visual field defect classification system helps to describe more accurately the distribution of abnormal points for pathological myopia combined with glaucomatous defects.
To the best of our knowledge, this is the first comprehensive visual field classification in high myopes. In a study carried out by Fledelius and Goldschmidt,16 the authors used Goldmann Kinetic perimetry with a large test stimulus (V/4e) to explore the visual field characteristics in high myopia in a sample size of 52 eyes (31 patients), using three defined types: significant visual field defects, marginal peripheral constriction and normal without further descriptive details. There were also several visual field defect categories, but they were specifically designed for staging glaucoma or glaucoma suspects, so the defect types did not match those commonly found in high myopia. For the enhanced glaucoma staging system (GSS-2) classification,17 the stage (stage 0–5) and type (localised, generalised and mixed defects) was totally based on MD and corrected pattern SD or corrected loss variance, but did not include various field defect distribution patterns. In the Ocular Hypertension Treatment Study (OHTS) visual field classification,11 the defects were divided into three major types: glaucoma-related defects, neurological defects and artefacts. We did reference the glaucoma-related defects, such as: nasal step, early arcuate, advanced arcuate, paracentral defect, generalised reduction sensitivity, rim artefacts, but we also added some classic myopic field defects, such as: enlarged or off-set blind spot, tilted disc defect and cecocentral defect.
All subjects had undergone 24-2 SITA fast testing strategy. The 24-2 pattern covers the central 24° visual field and is comparable to the 30-2 pattern in diagnosing glaucoma,18 and the 24-2 pattern is expected to have fewer lens rim artefacts. SITA strategy has become the most commonly used in glaucoma diagnosis due to its time saving without reducing its effectiveness.19 Two studies20 ,21 indicated that SITA standard strategy was less variable and more precise than SITA fast in patients with glaucoma, but only for low sensitivity spots. Most of the high myopes were normal, so SITA fast was a better choice. Furthermore, in a study conducted among inexperienced glaucoma and normal subjects to explore the sensitivity and specificity of SITA fast versus SITA standard on glaucoma diagnosis, the authors found both strategies had similar results.22
The intergrader agreement κ value in our study was 0.61, which was similar to OHTS,11 whose agreement among three graders was 0.64–0.66, but the agreement between two graders was better than ours. The κ in our study was not significantly better than OHTS because our classification allowed up to two categories for each field (ie, generalised depression and arcuate), and we did not analyse the upper and lower hemifield separately.
The most common defect was an enlarged blind spot, which is more likely in high myopes due to elongation of the eye and resultant displacement of the optic nerve insertion. Several epidemiological studies have found that the tilted disc (structural changes) is very high, about 50%–70% in myopia or high myopia23 ,24 and only about 10% in emmetropic individuals.24 The enlarged blind spot may be due to the peripapillary atrophy25 or elongated axial length with a tilted optic nerve insertion that maps outside of the normal blind spot on static perimetry. Peripapillary atrophy was reported to be as high as 80% in the high myopia study (SE≤−6.0 D) by Chang et al23 in which subjects were enrolled from three population-based investigations, age 40 years and older and the peripapillary atrophy was based on fundus photos using Curtin and Karlin classification.26
The main strength of this study is the large number and a priori systematic description of the visual pattern of visual field defects in high myopic patients validated with acceptable agreement between independent readers. Although the classification appears complicated, it encompasses both myopic and glaucomatous common categories with specific subtypes.
Nonetheless, several limitations should be noted. First, the patients were mostly recruited from specialised outpatient clinics lacking the random distribution of prospective population-based study designs. Second, although we were selecting from a large sample size of over 1000 subjects enrolled in the high myopia registry, only about half of them had visual fields tested at baseline, so the percentage may not be representative of the entire group. Third, the number of first time test takers was not recorded, but this effect was minimised by having unreliable exams repeated. Fourth, our classification scheme for abnormal defects produced a κ of 0.61, which may have been higher if we had fewer categories where subjects could have two subtypes. For example, if we only focus on glaucomatous defect (adding categories 4A–4C together), then the κ improves to 0.74. Fifth, the high myopia registry study had chosen 24-2 SITA fast testing strategy which may be a possible limitation for those who use 24-2 SITA standard. However, it is unlikely as a study by Saunders21 demonstrated that SITA fast and SITA standard result differences were similar and only small differences were found at low sensitivity values. Thus having used SITA fast would not significantly affect our classification system.
In conclusion, we have defined and validated a comprehensive visual field defect classification system for high myopia combined with glaucomatous defects. We have reported on a new finding of the percentage of arcuate-like visual field defects that need to be followed because of the risk of NTG. Finally, we plan to review serial fields from the ZOC–BHVI subjects who have high risk of glaucoma.
↵† Deceased 27 July 2015
Correction notice The author affiliation information for the authors Brien A Holden and Mingguang He has been updated since this paper was first published online.
Contributors XD: collected the data, conducted the analysis, organised the writing and compiled the initial draft. RTC: collected the data, organised the writing and compiled the initial draft. XG: collected the data and organised the writing. XL: reviewed the literatures. CAJ: reviewed the literatures. BAH: conceived and designed the study. MH: conceived and designed the study and organised the writing.
Funding The study was supported by the Fundamental Research Funds of the State Key Laboratory in Ophthalmology, the National Natural Science Foundation of China (81125007) and a research grant from the Brien Holden Vision Institute. The funding sources had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Ethics approval Ethics approval was provided by the Zhongshan Ophthalmic Center Ethics Review Board.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.