Discussion
Predicting visual outcome following surgery for pituitary macroadenomas, while useful in preoperative patient counselling, is difficult. Age of the patient, duration of symptoms, disc pallor, volume of the tumour and preoperative visual parameters are some of the documented predictors.1 2 5 7 8 15 16 However, deterioration of vision due to intraoperative and postoperative complications, although rare, is reported and cannot be predicted. In this unpredictable scenario, parameters other than preoperative visual function that might predict visual improvement in a simple yet consistent manner need to be explored. Although preoperative RNFL thickness has been shown to correlate with severity of preoperative field defects,17 it has an unclear correlation with visual outcome. This formed the basis for our investigation.
RNFL thickness and preoperative visual function
Reductions in RNFL thickness and papillomacular bundle have been shown to correlate well with degree of temporal hemianopia and central field defects, respectively.17–20 These correlations have been drawn by mapping optic nerve head sectors with the VFD values in the corresponding areas of the field map. Most studies have analysed visual field while correlations with visual acuity are scarce. Monteiro et al17 used segmented macular thickness and demonstrated that macular RNFL and ganglion cell layer correlated with visual field loss as well as band atrophy. The correlation was reportedly better than peripapillary RNFL. In our study, peripapillary RNFL was significantly thicker in all quadrants in those with normal visual acuity and normal visual field compared with those with impaired acuity and fields (table 2). Hence, RNFL may possibly be substituted for field analysis in those who are unable to perform field analysis due to reliability issues or severe visual impairment. We also found that RNFL was significantly thinner in those with disc pallor. This is useful, as early optic disc pallor is a rather subjective finding and has been found to be an inconsistent predictive factor of visual recovery.21
RNFL thickness and visual field following surgery
The preoperative visual parameters in our subjects were comparable with the findings of a meta-analysis22 including 19 studies that showed that eyes with normal RNFL had a greater likelihood of achieving approximately normal visual fields.15 21 23 24 Danesh-Meyer et al15 had determined that with similar severities of VFD the thicker RNFL group had better improvement in the postoperative visual field. Meyer et al,25 in a later publication, reported a faster visual field recovery and a greater chance of improvement to normal fields in the group with thicker RNFL at final follow-up (81% vs 37%, p<0.001). When they plotted the RNFL of those who improved and those who did not against the degree of improvement, a rough RNFL cut-off of about 80 μm seemed to differentiate between the two groups. Our ROC analysis estimated the cut-off for improvement in visual fields as 81 μm (AUC 0.7), with 73.1% sensitivity and 62.5% specificity. Garcia et al26 in a retrospective study using time domain OCT reported nasal RNFL thickness of 68.50 µm as being predictive, but with poor sensitivity and specificity of 61% and 50%, respectively. Our study demonstrated an OR of about 1.1 for improvement in VFD for every 1 μm of mean RNFL thickness, which was in agreement with the OR of about 1.29 reported by Jacob et al.24 In addition, they also did not find preoperative MD to be predictive of visual outcome as in our study. Although better preoperative logMAR visual acuity and smaller tumour volume may be associated with better visual field outcome as seen in our univariate analysis, it did not show statistical significance in the multivariate analysis.
Danesh-Meyer et al15 had divided their subjects into two groups based on RNFL thickness into normal and thin based on 97.5% of age-matched normative data, which is higher than the default of 95% used in routine practice. Nonetheless, 15% of those grouped into the thin RNFL group had normal preoperative visual fields. The concept of preperimetric compressive optic neuropathy was described based on these data. This was also explained in theory by Sun et al.23 In the 15-month follow-up data published by Meyer et al,25 both preoperative and postoperative RNFL thickness were thinner in patients who had VFD that improved to normal postoperatively compared with those with normal preoperative fields that remained normal. This suggests that RNFL thinning is a permanent structural change due to chronic compression and irreversible retrograde degeneration, even if there is potential for visual recovery. It may be slow and ongoing and can continue even for 3–6 months following visual field recovery.27 On the other hand, not all eyes with significant VFD exhibit RNFL thinning. This could be due to the acuteness of compression, such as in pituitary apoplexy, and functional recovery could be attributed to restoration of axonal transport through decompression.25 28 Hence RNFL thickness is a significant investigative tool regardless of visual fields. The challenge is to identify retinal microstructure parameters that can differentiate between reversible and irreversible conduction block.29
RNFL thickness and visual acuity following surgery
Variable rates of improvement of visual outcome, from 44% to 93%, have been reported in the literature.1–5 7 8 The study by Danesh-Meyer et al15 reported improvement in visual acuity to more than 6/12 in 97% of eyes with thick RNFL and 72% of eyes with thin RNFL in 6 weeks (p=0.02). The mean preoperative RNFL thickness in their patients was 89.7±20.1 µm, which was similar to our study (89.02 µm, SD: 25.63). Meyer et al25 later reported that improvement in visual acuity to 6/6 had evened out over 15 months between the thick and thin RNFL groups (73.4% vs 67.6%, p=0.53). In our study, 75% of the eyes showed an improvement in visual acuity, but there was no significant difference in the RNFL thickness between those who had improvement in acuity and those who did not. Additionally, we found that preoperative MD and VFI were worse in those with postoperative improvement in visual acuity compared with those without (table 4). Therefore, combining visual acuity and fields into a composite score to predict visual outcome in chiasmal compressions might not be prudent as they are probably independent physiological functions.
Arrangement of RNFL versus visual function
Jacob et al24 have shown that temporal RNFL shows the maximum amount of thinning in patients with pituitary adenoma, which is also in keeping with the temporal pallor we often see in chiasmal compressions. However, they did not find temporal RNFL to be predictive of visual field improvement. Interestingly, we found that RNFL was significantly thicker in all quadrants, except the temporal in eyes that had improvement in visual fields compared with those that did not. It is likely that temporal RNFL, being mostly composed of papillomacular fibres, is more important for visual acuity than visual fields. Wang et al,30 in a larger study, found inferior RNFL to be associated with higher odds of visual field recovery, superior RNFL to be associated with higher odds of visual acuity recovery, and that the visual improvement occurred in the first 6 weeks following surgery with no improvement thereafter. In our study, as there was no significant difference in RNFL thickness among those who had improvement in visual acuity versus those who did not, we further hypothesise that the potential for recovery of acuity might be unrelated to RNFL thickness and that other factors might be involved.
Alternative markers of visual function like RNFL thickness are all the more relevant in children where the former is unreliable. In a study by Parrozzani et al,31 the best RNFL cut-off that discriminated between normal and abnormal preoperative visual acuity in children with optic nerve glioma was 76.25 μm, which is close to the RNFL cut-off we have obtained in our study, although for predicting visual field outcome. This may suggest a possible range of RNFL thickness that could predict favourable visual outcome in tumours that affect the visual pathway. An ad-hoc analysis of a subset of 30 eyes of 15 patients, in whom data on postoperative RNFL thickness were available at 3–6 months, showed a postoperative decrease in average RNFL thickness compared with preoperative thickness by 2.37 μm (p<0.001). This suggests that RNFL thinning due to compression may be an ongoing process even after the compression is relieved; however, the sample is small to comment conclusively.
Limitations and strengths of the study
The principal strength of this study is that it is prospective. While earlier studies included chiasmal lesions other than pituitary adenomas, including meningiomas and craniopharyngiomas, operated by various routes,21 32 we included only pituitary macroadenoma operated trans-sphenoidally. We also used swept-source OCT, which has better resolution, takes faster scans per second and is more sensitive as compared with time domain OCT used in prior studies.33 34 A limitation was that most of our subjects were international patients; hence, the follow-up time was variable. Postoperative visual fields may have been performed better by patients due to the learning effect and this could bias the results. A prospective study with larger sample size might be able to determine a cut-off for RNFL thickness with better sensitivity and specificity. We also did not study the ganglion cell layer complex (GCC), which has been reported to show thinning earlier than RNFL in cases of chiasmal compression.35 36 However, the advantage of using GCC over RNFL to predict visual outcome is not clear. Further studies comparing both parameters might help understand this better.