Validity of definition of CFF laterality
Table 1 presents the characteristics of the non-affected and affected groups. There was no significant difference in patient background. Moreover, the affected group had more patients with abnormal visual function and larger tumors than the non-affected group. Furthermore, the difference between the left and right sides of the CFF was larger (p = 0.0008) and more number of patients had a difference of ≥3 Hz in the affected group than in the non-affected group (p < 0.0001).
The relationship between the mass effect on chiasma and the CFF or the difference of CFL was determined using the ROC curve. In the present study, at the cut-off CFF of 35.0 Hz (lower normal limit for an instrument developed at the Kinki University), an extremely high sensitivity was found (i.e., 95.7% sensitivity, 37.9% specificity, AUC = 0.77154, data not shown). Conversely, the optimal cut-off value of the difference in CFL was 3 Hz, and a slightly lower sensitivity but a higher specificity than CFF decline was found (i.e., 91.3% sensitivity, 52.8% specificity, AUC = 0.71118, Figure 2). Therefore, the combination of these two parameters (CFF abnormality) led to a high diagnostic accuracy to detect the mass effect on the optic chiasm.
Therefore, we have added positivity for CFL as one of the abnormal visual functions, such as visual acuity decline, visual field defect, and CFF decline, in the present study.
Characteristics of patients with abnormal visual function in the affected group
Table 2 lists the characteristics of patients with visual acuity decline, visual field defect, CFF decline, and CFL positivity. Visual acuity decline was seen in 24.7% of the patients, visual field defect in 47.1%, and CFF decline in 37.7%. CFL positivity was observed in 52.2% of the patients and was most sensitive to the presence of compressive Pit-NETs. Median tumor volume was lowest in CFL positive patients compared to those with visual acuity decline or visual field defect. Figure 3 compares median tumor height (95% CI) in patients with visual acuity decline, visual field defect, CFF decline, and CFL positivity. Tumor height was significantly lower in CFL positive patients compared to those with visual acuity decline (p = 0.0009) or visual field defect (p = 0.0076).
CFF decline and CFF laterality in the affected group
Assessment of the relationship between tumor volume and CFF showed that CFF decreased as the tumor volume increased (R2 = 0.1729, p < 0.0001; CFF = −0.7526 × tumor height + 40.51). Similarly, we found that CFF decreased as tumor height increased (R2 = 0.4358, p < 0.0001, CFF = −1.5950 × tumor height + 51.82). The correlation coefficient for tumor height was greater than that for tumor volume, indicating that tumor height at the suprasellar section is more correlated with the CFF values than tumor volume.
We also evaluated the relationship between tumor height and the difference value between CFF values for the left and the right eye (laterality value), and found that this difference value increased with tumor height (R2 = 0.1734, p < 0.0001; laterality value = 0.6643 × tumor height −0.0410). On the other hand, as the tumor height increases, the CFF in both eyes tends to decrease and the CFF laterality value in some patients tends to decrease. Therefore, the correlation coefficient with tumor height was higher in the CFF value than in the CFF laterality value.
Table 3 lists the characteristics of patients with and without CFF abnormality. There were no significant differences in age, sex, and the prevalence of diabetes mellitus. Compared to those without CFF abnormality, both Median logMAR visual acuity and median tumor height were significantly higher in patients with CFF abnormality (p < 0.0001 for both). The ratio of Knops 0–2 was comparable (p = 1.0000), and the prevalence of cystic tumors tended to be lower in patients with CFF abnormality (6.3% vs. 15.4%, p = 0.0656).
Table 4 shows the results of logistic regression analysis of factors associated with CFF abnormality, and only tumor height (OR = 1.21, 95% CI: 1.11–1.33, p < 0.0001) displayed a strong association.
Abnormal test findings classified by tumor height
Figure 4 shows the prevalence of each abnormal test finding classified according to tumor height. Neither visual acuity decline nor CFF decline were seen at tumor height of <3.5 mm, but their prevalence rose with increasing height. CFF decline was more prevalent than visual acuity decline at almost all tumor height values analyzed. Further, among the three preoperative tests, the prevalence of CFF decline was equivalent to that of visual field defect at a tumor height of 9.4 mm or below, and visual field defect showed the highest prevalence at a tumor height of >9.5 mm.
CFL positivity showed a relatively high prevalence even at low tumor height; specifically, at a height of 5.5–7.4 mm, visual acuity decline was found in only 1 patient (4.0%), while CFF decline was found in 4 patients (16.0%), visual field defect in 5 patients (20.0%), and CFL positivity was seen in 11 patients (44.0%). Moreover, above a tumor height of >9.5 mm, CFL positivity was found in more than 50% of the patients.
We evaluated the clinical value of CFF abnormality by classifying tumors into four groups based on tumor height and comparing values between visual acuity decline and visual field defect (Figure 5). The prevalence of abnormal results was highest for CFF abnormality in the small and middle groups, suggesting a higher sensitivity of CFF measurements toward small Pit-NETs compared to other preoperative assessments. Nevertheless, patients with no abnormalities in any of the assessments were higher in the small group (n = 20, 57.1%) compared to the middle group (n = 23, 52.3%) or the moderate group (n = 10, 23.8%); all patients in the large group showed abnormal results in the preoperative tests.