We examined the effect of mydriasis on IOP and of trabeculectomy on mydriasis-induced IOP fluctuations in patients with NTG who were followed up during medical treatment and after surgical treatment, yielding over 40 IOP records for more than 5 years before and after the surgery. A significant increase in IOP was observed after mydriasis; however, after filtration surgery, the IOP change was no longer significant. Although mydriasis after surgery differs from physiological mydriasis, the results suggest that filtration surgery can suppress the post-mydriatic IOP changes. Eyes with NTG have been shown to exhibit IOP fluctuations in daily life (24), perhaps because the pupil diameter affects aqueous humor dynamics. After successful filtration surgery, continuous filtration might eliminate small IOP changes.
We evaluated only long-term follow-up (≥ 10 years) data because many variables affect IOP fluctuations, which are difficult to capture using short-term data. Diurnal and seasonal IOP fluctuations are likely to be the highest in eyes with open-angle glaucoma with higher IOP (25). Therefore, we included only open-angle eyes with NTG; we thought that such effects would be minimal in such eyes.
The relationship between physiological mydriasis (a change in pupil diameter) and IOP changes is difficult to study; thus, we explored how pharmacological mydriasis affected IOP changes. The IOP increase after pharmacological mydriasis has been attributed to ciliary muscle paralysis caused by parasympathetic blockers (7). The ciliary muscles control the tension of the trabecular meshwork; when these muscles relax, traction is reduced and aqueous humor outflow decreases, increasing IOP. Harris et al. (7) reported an increase in IOP after the application of 1% (w/v) cyclopentolate to 2% of normal eyes and 23% of eyes with open-angle glaucoma. Sympathomimetics also appear to affect the IOP. Phenylephrine hydrochloride (an α1-adrenergic agonist) differs from epinephrine in that it lacks a hydroxyl group at the 4-position of the benzene ring. This agent induces mydriasis, which is maximal within 60 min. Tropicamide/phenylephrine combination treatment has been also reported to result in elevated IOP. Kim et al. (14) reported significant IOP elevation in normal participants with open-angle glaucoma after the application of 2.5% (w/v) phenylephrine and 1% (w/v) tropicamide. Shaw et al. (9) found significant IOP elevations in 32% of patients with open-angle glaucoma after the application of 2.5% (w/v) phenylephrine and 1% (w/v) tropicamide. In a study enrolling normal eyes and eyes with primary open-angle glaucoma (POAG) and PE glaucoma, elevated IOP was observed after mydriasis in all except the normal eyes; however, these changes were not significant (15). The relationship between pharmacological mydriatics and IOP change is listed in Table 2. The drug concentration of 0.5% phenylephrine/0.5% tropicamide (both w/v) combination (a sympathomimetic agent/parasympathetic blocker) we used in this study was much lower than that reported in other studies.
Table 2
Relationship between pharmacological mydriatics and intraocular pressure
Author(s) | Year | Subjects | Main results |
Harris LS | 1968 | POAG, normal | IOP elevation was seen in 23% of open-angle glaucoma |
Valle O | 1976 | POAG | as for provocative test |
Shaw BR | 1986 | POAG | significant pressure elevation occurred in 37 eyes (32%) |
Hancox | 2002 | OAG, cataract, medical retina | change in IOP following dilatation was seen in all three groups (mean 0.4 mmHg) |
Pukrushpan P | 2006 | Non-glaucoma patients | post-dilatation IOP was equivalent to pre-dilatation IOP |
Shihadeh WA | 2011 | PE | PE were at risk of developing delayed post-dilation IOP rises |
Qian CX | 2012 | normal | 35% of patients had IOP elevation of > 2 mm Hg |
Kim JM | 2012 | normal | a significant increase in IOP after dilation |
Atalay E | 2015 | POAG, PE glaucoma, normal | glaucoma patients experienced a higher rate of IOP elevation |
Our study | 2021 | NTG | IOP increased significantly in the medically treated period |
POAG (OAG); primary open-angle glaucoma, PE; psudoexfoliation, NTG; normal tension glaucoma, IOP; intraocular pressure |
Even if IOP is well-managed in the outpatient clinic, glaucoma may progress, as reflected by large IOP fluctuations (6, 26, 27). Trabeculectomy is the most common surgical treatment for glaucoma, reducing not only IOP per se but also suppressing IOP fluctuations (21–23, 28). In one report on diurnal IOP variation after trabeculectomy/mitomycin C, such surgery significantly reduced not only the mean IOP but also IOP fluctuations during both day and night (23). Even earlier, filtration surgery was reported to reduce the mean diurnal IOP, range of diurnal variation, and day-to-day IOP variability (28).
IOP fluctuations caused by postural changes are thought to be short-term (minutes) in nature (29), as are fluctuations induced by mydriasis. Hirooka et al. (21) reported that the mean IOP difference between the sitting and supine positions was 4.1 ± 1.6 mmHg during the medication period; this difference reduced to 2.2 ± 1.5 mmHg after trabeculectomy. Both studies cited above found that IOP fluctuations were well-controlled after successful trabeculectomy. Sawada et al. (22) investigated the IOP fluctuations caused by postural changes in Japanese patients with glaucoma. The IOP difference between the sitting and lateral decubitus positions was 3.3 mmHg in the eye drop group, but only 1.0 mmHg in the trabeculectomy group; thus, surgery significantly suppressed the IOP fluctuations caused by postural changes.
We found a significant IOP increase after mydriasis during the drug-treatment period in eyes NTG for the first time, but this was suppressed after filtration surgery. Although this was not a cross-sectional study (unlike previous reports), rather a long-term preoperative/postoperative work, we consider that the reliability of our study might be relatively high. However, given the small number of patients, further study is needed to determine whether filtration surgery indeed better suppresses IOP fluctuations compared to medical treatment.
Our study had several limitations. First, the number of cases studied was relatively small. A short data collection period would be acceptable if only IOP fluctuations were evaluated. Nevertheless, at least 12 IOP measurements were performed over the 3-year follow-up period (six each in the presence and absence of mydriasis; 4 visits/year). If the follow-up period was extended to 5 years, at least 20 measurements were taken (10 each in the presence and absence of mydriasis). In addition, the IOP measurement time points were “scattered” between the morning and afternoon. Since this was a retrospective study, IOP measurement times could not be unified. In addition to diurnal variations, IOP measurements are susceptible to errors and seasonal variations; more measurements increase reliability. This is the main reason why we chose a follow-up period of ≥ 10 years; the number of available subjects was small, and a very long follow-up was essential. In addition, automatic static VF testing was performed routinely. In open-angle glaucoma patients, the IOP increases after such testing (30); thus, any IOP fluctuation may not have been clearly separated from other effects. The aqueous humor outflow resistance increases when the angle narrows on the induction of a continuous mydriatic state in the dark (31). The stress caused by VF testing affects ciliary aqueous humor production via the sympathetic nervous system (32). Ni et al. (30) reported that 109 open-angle glaucoma patients (109 eyes) exhibited a significant increase (1.2 mmHg) in the mean IOP after automatic, static VF examination. However, we believe that any effect of VF testing on IOP was minimized because we allowed all participants to rest between the VF examination and IOP measurement. Regarding the surgical method, a single procedure markedly reduced IOP (33); there was no significant difference in this context between a single procedure and combined procedures (34, 35). There is no indication that combined surgery lowers IOP better. Thus, we considered it safe to include the combined cataract surgery group in our overall population. Finally, since we included only NTG patients, who were believed to show small IOP fluctuations, data for high IOP or XFG eyes, in which IOP fluctuations would be expected to be greater (25), are required in the future.
In conclusion, we investigated the effects of mydriasis on IOP and of filtration surgery on mydriasis-induced IOP fluctuations in NTG eyes by using long-term preoperative/postoperative data including the total IOP of each patient was over 40 times. During the preoperative drug-treatment period, a significant increase in IOP was observed after mydriasis, but no significant IOP change was observed after filtration surgery. Filtration surgery has been reported to reduce IOP and limit IOP fluctuations, we suggest that this surgery can also suppress mydriasis-induced IOP fluctuations.