Several studies have been conducted in an attempt to establish maps relating VF regions to sectors of the optic disc.
24 25 26 27 28 29 The most complete map was reported by Garway-Heath et al.
28 They established the anatomic relationship between VF test points in the Humphrey SAP test grid and regions of the ONH relating to RNFL defects evaluated with monochromatic photographs. Although their study offers a sound approach, the nonquantitative method of RNFL photograph evaluation (and absence of related functional data) makes it necessary to validate the results with studies that actually measure visual function and relate visual function measurements to the RNFL thickness determined quantitatively.
Recently, other investigators
5 47 48 have used objective and highly reproducible techniques for RNFL measurement, such as OCT,
10 11 12 13 14 15 16 to study the structure–function relationship in glaucoma. Harwerth et al.
47 investigated this association in rhesus monkeys and found that SAP sensitivity and RNFL thickness measured with the OCT are correlated measures of the underlying populations of retinal ganglion cells. Hood et al.
5 48 developed a linear model to relate the loss in RNFL thickness measured with OCT to the loss in SAP sensitivity; they based their analysis on the Garway-Heath map,
28 and whereas there was a good fit between structure and function in glaucomatous VFs, in their model there was a very weak correlation between RNFL thickness and SAP sensitivity in healthy individuals. Although they concluded that SAP sensitivity in control subjects does not depend on RNFL thickness, the weak correlation may simply reflect the small range and imprecision of measurements among normal subjects. Several other studies
21 49 50 51 52 have demonstrated good correlations between OCT-measured RNFL thickness and VF sensitivity in glaucoma, even in the early stages of the disease. Strouthidis et al.
53 have also demonstrated a high level of association between the strength of correlation between the sensitivity of pairs of VF points and their relative location in the peripheral retina and the relative proximity of their respective RNFL bundle locations at the ONH. Our study validates the results of these previous studies and also introduces a new map obtained completely from objective analyses. This map can be used as a reference for developing future studies of the structure–function relationship in glaucoma.
After the current definitions that glaucoma is an acquired optic neuropathy,
1 2 we took optic disc morphology into account to identify glaucomatous eyes. Intraocular pressure is considered a risk factor, and therefore eyes were selected for the study regardless of intraocular pressure. Also, because we were evaluating the relationship between SAP and OCT, we did not include abnormal SAP or OCT as a criterion for a diagnosis of glaucoma. Consequently, as we chose ONH appearance as the reference standard used to distinguish patients with the target condition (glaucoma) from those without it, the maps obtained from this sample allow us to assess the structure–function relationship for glaucomatous optic neuropathy without introducing bias from preconceived structure–function relationships.
54
Based on the anatomic distribution of the RNFL bundles in the retina,
42 43 44 45 46 the superior hemifield areas are represented in the inferior RNFL bundles, and inferior hemifield areas are represented in the superior RNFL bundles; thus, the upper regions of the VF correlated with lower peripapillary RNFL thickness, and vice versa. We assumed that the degree of reduced visual sensitivity in a region of the VF was proportional to the amount of loss of ganglion cells in the corresponding area of the retina,
55 56 57 58 and therefore to the RNFL thickness in that region.
47 Our results are consistent with those in previous studies,
24 25 26 27 28 29 in which the distribution of the VF regions for the superior and inferior hemifields was reported to be asymmetric. Our findings were also in agreement regarding the poor representation of the temporal RNFL area (9 o’clock position) in the 24-2 Humphrey test. This area represents the papillomacular bundle in the neuroretinal rim at the ONH, which may be less sensitive for detecting early glaucomatous changes.
59 60 61 The superior and inferior poles of the ONH may be more commonly affected at early stages of glaucoma.
17 18 51 59 60 61 62 Thus, classically, the vertical cup-to-disc ratio is one of the best clinical parameters for glaucoma diagnosis.
35 63 64 Neither the 4- nor the 9-o’clock positions correlated with any VF region. Identification of change in OCT RNFL measurements in the horizontal meridian is more difficult because changes are numerically smaller, the lower the normal RNFL thicknesses.
The strongest correlations between superior VF regions and RNFL segments were observed for the 6- and 7-o’clock segment thicknesses, which, according to the normal distribution of the RNFL bundles (ISNT rule),
17 18 51 62 are the thicker segments. These clock-hour positions correlated better with the upper VF region number 1, where a cluster of depressed points is more likely to be found. The same is true of the inferior hemifield. Nevertheless, the VF sampling may introduce some bias. These segments, corresponding to the poles of the ONH, match with the best subserved VF areas. The VF regions corresponding to the vertical meridian of the ONH are more densely tested by the perimeter, and consequently the most easily recognized VF loss is more likely to relate to those RNFL bundles. There is also unequal sampling of the VF with respect to the peripapillary sectors. The arcuate regions (e.g., VF region 1) contained many more test points than other VF regions. The consequence is that the VF regions containing the higher number of tested points had greater signal averaging, and therefore, a greater signal-to-noise ratio. Hence, when these VF regions were correlated to the RNFL sectors, it resulted in stronger correlations.
The map derived from this study shows good agreement with other maps.
24 25 28 The differences between them arise from the differences in methods, samples, and statistical procedures used in the studies. With respect to the Garway-Heath map,
28 factor analysis generated 1 VF region more for each hemifield. As RNFL thickness measured with the OCT is divided into 12 clock-hour positions, we initially selected six possible factors to correlate with the 6 clock-hour positions of each hemifield. Statistical analysis determined that five factors was the optimal number for each hemifield.
There was not a one-to-one correspondence between RNFL sector and VF region. Within sectors of the RNFL, there was an overlap in the representation of VF regions. In general, most VF regions correlated well with various OCT segments, although every VF region had a segment in the peripapillary bundles, which had the best correlation. For the upper hemifield, the strongest correlations were observed between 6-o’clock segment thickness and VF region 1, 5-o’clock segment thickness and VF regions 2 and 4, and 7-o’clock segment thickness and VF regions 3 and 5. In the lower VF regions, the strongest correlations were found between the 11-o’clock segment thickness and VF regions 1, 3, 4 and 5 and the 2-o’clock segment thickness and VF region 2. However, the implication of the strongest correlation requires consideration. The RNFL sectors are not completely independent, so that if one sector is damaged, the likelihood of an adjacent sector’s being damaged is greater than that of a sector farther away. Moreover, some of the RNFL sectors may have been more likely to be damaged, and/or have a greater range of measurements, than others. Therefore, the strongest correlations may be expected in RNFL sectors that are thickest in undamaged eyes and are thin in the glaucomatous eye. This fact may explain why the 11-o’clock sector maps to most of the VF regions in the lower hemifield.
Factor analysis has limitations. Some disadvantages are that factor analysis is only as good as the data allow and cannot identify causality.
65 66 Factor analysis can classify factors with distant points within each hemifield. In our study, most VF regions obtained by factor analysis comprised contiguous points, although this statistical test does not necessarily provide that result, as occurred in region 2 of the inferior hemifield.
The high variability of normal human ONH morphology and the intertest variability of SAP limit the generalization of a structure–function map. Other limitations of the study are that RNFL thickness measured with the OCT mainly contained the axons of the retinal ganglion cells, glial cells, and blood vessels. Particularly, the distribution of blood vessels in the peripapillary RNFL may have influenced interindividual measurement variation and the range of measurements. Other sources of variability in structure–function correspondence may be the position and tilt of the ONH in relation to the fovea,
28 and must be taken into account in clinical practice.
The mild to moderate correlations observed between the VF regions and the RNFL thickness measurements obtained with the OCT in glaucomatous optic discs indicate a reasonable level of agreement in measuring different aspects of the same disease. In our analysis, we were forced to use the data as they were provided by the currently available techniques. On the one hand, Humphrey perimetry tests visual field points on a grid that is not arranged according to the anatomy of the nerve fiber bundle paths. On the other hand, peripapillary RNFL thickness measured with OCT is divided into 12 equal sectors independent of the anatomic distribution of the RNFL bundles around the optic disc. This fact and the anatomic differences between individuals contribute to the difficulties in developing structure–function relationship studies with the present technology. The suggested map shows the expected association between ONH locations and portions of the retina represented in the typical person, provides evidence of previously proposed hypothetical maps, and may help to elucidate the concordance between the structural and functional findings in patients with glaucoma.