Abstract
Background
Micropulse transscleral cyclophotocoagulation (MP-TSCPC) lowers intraocular pressure (IOP), but the mechanisms underlying its IOP-reducing effect remain incompletely understood. Although early postoperative flare elevation has been reported in association with IOP reduction, the relationship during the mid-term postoperative period has not been well characterized. In this study, the mid-term period was defined a priori as 3–18 months after surgery.
Methods
This retrospective exploratory study included 25 eyes of 25 patients who underwent initial MP-TSCPC at Ishida Eye Clinic between March 2019 and May 2022 and had available postoperative flare measurements. Aqueous flare was assessed using a laser flare meter, and IOP was measured primarily by Goldmann applanation tonometry. Flare increase ratio (%) and IOP reduction ratio (%) were calculated relative to baseline. Associations were evaluated using Spearman’s rank correlation coefficient. To account for multiple comparisons across postoperative time points, p-values were adjusted using the Benjamini–Hochberg procedure, primarily considering a false discovery rate (FDR) threshold of 0.05; findings at FDR < 0.10 were interpreted as exploratory.
Results
The mean age was 80.4 ± 10.3 years. The mean preoperative IOP was 17.6 ± 6.9 mmHg, and the mean preoperative flare value was 13.9 ± 7.7 photon counts/ms. Postoperative IOP showed significant reductions at 1 and 12 months, and flare values were significantly elevated at multiple time points through 24 months. Significant positive correlations between flare increase ratio and IOP reduction ratio were observed at 3 months (ρ = 0.54, p = 0.026), 18 months (ρ = 0.964, p = 0.0027), and at the final visit (ρ = 0.41, p = 0.022). After adjustment for multiple comparisons, only the 18-month correlation remained significant at FDR < 0.05 (q = 0.022), whereas the correlations at 3 months (q = 0.069) and at the final visit (q = 0.088) were significant at FDR < 0.10 and were therefore considered exploratory.
Conclusions
In this small exploratory cohort, sustained postoperative aqueous flare elevation was associated with greater mid-term IOP reduction after MP-TSCPC. However, given the limited sample size and observational design, these findings should be interpreted cautiously, and causal mechanisms cannot be established.
Trial registration
Approval Number: R2025063 (University of Toyama Ethics Committee). Registration date: July 10, 2025.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12886-026-04697-w.
Keywords: Mid-term intraocular pressure, Aqueous flare value, Micropulse transscleral cyclophotocoagulation, AS-OCT, Coefficient of aqueous outflow
Background
Micropulse transscleral cyclophotocoagulation (MP-TSCPC) is a laser procedure that reduces intraocular pressure (IOP) by delivering microsecond pulses of a diode laser to the ciliary body through the sclera, interspersed with rest periods. This technique can be applied even in refractory glaucoma, including surgically challenging or previously operated eyes, and has been recognized as an effective therapeutic option for lowering IOP [1]. Proposed mechanisms include suppression of aqueous humor production and enhancement of uveoscleral outflow [2, 3], although the precise pathways remain incompletely understood.
Laser-induced tissue damage generally elicits inflammation, which may influence IOP dynamics [4]. Kimura et al. reported a positive correlation between flare elevation at one month and IOP reduction at three months after MP-TSCPC [5]. However, this observation was limited to the early postoperative period, and the relationship between flare and IOP during the mid-term postoperative phase (defined in this study as 3–18 months) has not been sufficiently examined.
Clinical evidence suggests that ocular inflammation, such as uveitis, may be associated with IOP reduction [6–8], and more pronounced inflammation has been linked to hypotony [9, 10]. The non-pigmented ciliary epithelium, the principal site of aqueous humor production, is known to be vulnerable to inflammatory injury [11]. Persistent flare elevation after MP-TSCPC has also been reported [12], raising the possibility that postoperative inflammatory changes may be associated with sustained IOP reduction.
The aim of this study was to evaluate the association between mid-term flare levels and IOP reduction after MP-TSCPC in an exploratory retrospective cohort. We sought to clarify whether sustained postoperative flare elevation is correlated with IOP reduction during the mid-term follow-up period.
Methods
Study design and participants
This retrospective exploratory observational study adhered to the tenets of the Declaration of Helsinki and was approved by the Research Ethics Office for Human Subjects of the University of Toyama (approval number: R2025063).
We included 25 consecutive patients who underwent their first micropulse transscleral cyclophotocoagulation (MP-TSCPC) at Ishida Eye Clinic between March 2019 and May 2022 and had measurable aqueous flare values both preoperatively and postoperatively. A total of 33 eyes underwent first MP-TSCPC during the study period. Five eyes were excluded due to unavailable pre- or postoperative flare measurements, and three eyes were excluded to avoid inter-eye correlation. Ultimately, 25 eyes of 25 patients were included in the analysis. When both eyes were treated, only the later-operated eye was included to avoid inter-eye correlation. MP-TSCPC was performed not only in cases of markedly elevated IOP but also in patients demonstrating glaucoma progression in whom further incisional surgery was considered undesirable due to advanced age, medical comorbidities associated with increased surgical risk, or prior glaucoma surgery. In this study, the mid-term postoperative period was defined a priori as 3–18 months after treatment.
MP-TSCPC
MP-TSCPC was performed using the CYCLO G6 laser system (IRIDEX, Mountain View, CA, USA) equipped with a MicroPulse P3 probe. Following sub-Tenon’s anesthesia, sweeping laser applications were delivered to the superior and inferior hemispheres at 2,000 mW power, a 31.3% duty cycle, and an exposure duration of 80 s per hemisphere. Postoperatively, topical levofloxacin and betamethasone were administered for approximately three weeks. Preoperative glaucoma medications were continued at the discretion of the treating physician.
Aqueous flare and intraocular pressure
Anterior chamber flare (photon counts/ms) was measured at baseline and at 1, 3, 6, 12, 18, 24, and 36 months after treatment using a laser flare meter (FM-700; Kowa, Nagoya, Japan). Measurements obtained after additional interventions (repeat MP-TSCPC or glaucoma surgery) were excluded from analysis. Flare increase ratio (%) was calculated as: Flare increase ratio = (Flare_post − Flare_baseline) / Flare_baseline × 100.
IOP was measured primarily using Goldmann applanation tonometry (GAT). Non-contact tonometry (NCT) was used only when GAT was unavailable and occurred only twice in the entire dataset. Given this minimal frequency (two measurements in total), the impact of NCT on correlation analyses was considered negligible.IOP reduction ratio (%) was calculated as: IOP reduction ratio = (IOP_baseline − IOP_post) / IOP_baseline × 100.
Correlations between flare increase ratio and IOP reduction ratio were examined at each postoperative time point and at the final visit. The “final visit” was defined as the last available follow-up visit prior to any additional intervention (repeat MP-TSCPC or glaucoma surgery) or the last available observation in eyes that did not require retreatment. Follow-up duration varied among eyes. Subgroup analyses according to glaucoma subtype were conducted descriptively.
Outflow facility measurement
To evaluate the effect of MP-TSCPC on the conventional trabecular outflow pathway, outflow facility (C value) was measured using Schiötz tonography at baseline, 3 months, and 6 months postoperatively.
Anterior segment optical coherence tomography (AS-OCT)
AS-OCT imaging was performed using CASIA2 (Tomey, Nagoya, Japan) to assess for ciliochoroidal detachment (CD). Images were obtained from four quadrants (superior, temporal, inferior, and nasal). CD was defined as positive if present in at least one quadrant (Fig. 1). Imaging was performed at baseline, 1 week, 1 month, 3 months, and 6 months after treatment. Eyes were categorized into CD-positive and CD-negative groups, and longitudinal changes in IOP and flare values were compared.
Fig. 1.
Anterior segment optical coherence tomography (AS-OCT) images obtained in four quadrants (A: superior, B: temporal, C: inferior, D: nasal) showing ciliochoroidal detachment (CD). White arrows indicate the locations of CD
Statistical analysis
Continuous variables are presented as mean ± standard deviation, with medians and interquartile ranges provided when appropriate. Paired comparisons were performed using the Wilcoxon signed-rank test. Unpaired comparisons were performed using the Wilcoxon rank-sum test or Kruskal–Wallis test, as appropriate. Associations between flare increase ratio and IOP reduction ratio were evaluated using Spearman’s rank correlation coefficient (ρ). Correlation coefficients, corresponding p-values, and the number of eyes contributing to each analysis are reported. To account for multiple comparisons across postoperative time points, p-values were adjusted using the Benjamini–Hochberg procedure. The false discovery rate (FDR) was primarily controlled at 0.05. Findings at FDR < 0.10 were considered exploratory. At time points with very small sample sizes, analyses were interpreted descriptively without formal hypothesis testing.All analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical interface for R (The R Foundation for Statistical Computing, Vienna, Austria) [13]. A two-sided p-value < 0.05 was considered statistically significant.
Results
Baseline patient characteristics are summarized in Table 1. The mean age was 80.4 ± 10.3 years, and 14 patients (56%) were male. The mean preoperative IOP was 17.6 ± 6.9 mmHg, and the mean baseline aqueous flare value was 13.9 ± 7.7 photon counts/ms.
Table 1.
Baseline patient characteristics
| Over all n =25 |
|
|---|---|
| Age(yrs), mean ± SD, | 80.4 ± 10.3 |
| Median(IR) | 82(71–90) |
| Sex | |
| Male(%) | 14(56) |
| Female(%) | 11(44) |
| Study eye | |
| Right(%) | 14(56) |
| Left(%) | 11(44) |
|
Baseline IOP(mmHg), mean ± SD, Median(IR) |
17.6 ± 6.9 17(14–21) |
|
Baseline LogMAR, mean ± SD, Median(IR) |
0.37 ± 0.66 0.15(0-0.3) |
|
No. of glaucoma medications, mean ± SD, Median(IR) |
4.5 ± 2.1 4(3-5.25) |
| Aqueous flare values(photon counts/ms), mean ± SD, | 13.9 ± 7.7 |
| Median(IR) | 13.5(7.8–20.3) |
| Glaucoma diagnosis | |
| POAG (%)PXG(%)CACG(%)UG(%) | 19(76)4(16)1(4)1(4) |
| Lens status | |
|
phakia(%) pseudophakia(%) |
3(12) 22(88) |
| Prior trabeculotomy(%) | 1(4) |
| Prior trabeculectomy(%) | 6(24) |
SD=standard deviation; IR=interquartile range; IOP=intraocular pressure; LogMAR = Logarithm of the Minimum Angle of Resolution; POAG = primary open-angle glaucoma; PXG =pseudoexfoliative glaucoma; CACG = chronic angle-closure; UG=uveitic glaucoma
Glaucoma diagnoses included primary open-angle glaucoma (POAG) in 19 eyes (76%), pseudoexfoliation glaucoma (PXG) in 4 eyes (16%), chronic angle-closure glaucoma (CACG) in 1 eye (4%), and uveitic glaucoma (UG) in 1 eye (4%). The UG case was associated with idiopathic intraocular inflammation related to intraocular lens dislocation.
Previous glaucoma surgery included trabeculectomy in 6 eyes (24%) and trabeculotomy in 1 eye (4%).
To assess potential baseline differences according to prior trabeculectomy status, comparisons were performed between eyes with and without previous trabeculectomy (Supplementary Table 1). No significant differences were observed in baseline IOP, while baseline flare tended to be higher in eyes with prior trabeculectomy (p = 0.056).
Longitudinal changes in flare values and IOP are shown in Table 2. Flare values were significantly elevated compared with baseline at all postoperative time points up to 24 months (Wilcoxon signed-rank test, all p < 0.01).Postoperative IOP was significantly lower than baseline at 1 month (p = 0.005) and 12 months (p = 0.027), whereas reductions at other time points did not reach statistical significance. Because the number of eyes decreased substantially after 18 months (n ≤ 7 at 24 months; n = 1 at 36 months), findings beyond 18 months are presented descriptively.
Table 2.
Time course of flare values and IOP after MP-TSCPC
| Aqueous flare values(photon counts/ms), mean ± SD, Median(IR) |
flare increase ratio (%), mean ± SD, Median(IR) |
N |
P value (vs. baseline) |
IOP(mmHg), mean ± SD, Median(IR) | IOP reduction ratio (%), mean ± SD, Median(IR) |
N |
P value (vs. baseline) |
|
|---|---|---|---|---|---|---|---|---|
| Baseline | 13.9 ± 7.713.5(7.8–20.3) | 25 | 17.6 ± 6.917(14–21) | 25 | ||||
| 1 months |
39.1 ± 14.1 40.1(34.6–44.6) |
442 ± 818 182(82–465) |
14 | 0.0004* |
13.6 ± 5.0 14(10–16) |
16.8 ± 32.2 17.6(0–38) |
25 | 0.005* |
| 3 months |
38.8 ± 20.9 29.8(24.7–51.1) |
377 ± 534 159(73–580) |
17 | 0.00002* |
15.4 ± 7.6 13(11–18) |
5.1 ± 42.3 7.7(-14.3-36.8) |
25 | 0.16* |
| 6months |
31.5 ± 13.1 26.9(21.1–38.1) |
134 ± 112 105(35–230) |
13 | 0.0002* |
14.8 ± 8.7 14(10.5–17) |
4.7 ± 47.7 11.8(-9.4-34.7) |
23 | 0.09* |
| 12months |
25.4 ± 14.9 23.1(17.4–30.4) |
200 ± 407 73(27–182) |
16 | 0.0007* |
14.2 ± 3.7 14.5(11.3–17) |
4.8 ± 43.8 18.0(-4.7-29.6) |
22 | 0.027* |
| 18months |
42.2 ± 16.5 41.8(32.2–48.5) |
202 ± 189 94(81–290) |
7 | 0.001* |
11.5 ± 3.6 11(10–15) |
15.9 ± 41.5 25(-10.4-35.3) |
11 | 0.56* |
| 24months |
40.4 ± 18.5 40.9(23.9–49.8) |
282 ± 155 274(164–336) |
5 | 0.0005* |
15.3 ± 3.9 16(12-18.5) |
-21.8 ± 38.9 -42.9.(-46.4-0) |
7 | 0.26* |
| 36months | 16.8 | 8.4 | 1 | 0.03* |
14.8 ± 5.7 14.5(10.5–17.8) |
-24.9 ± 39.5 -33.0(-44- -14) |
4 | 0.32* |
SD=standard deviation; IR=interquartile range; IOP=intraocular pressure; MP-TSCPC=micropulse transscleral cyclophotocoagulation *Wilcoxon signed-rank test
Correlations between flare increase ratio and IOP reduction ratio are summarized in Table 3. Significant positive correlations were observed at:3months (ρ = 0.54, p = 0.026, n = 17),18 months (ρ = 0.964, p = 0.0027, n = 7) and Final visit (ρ = 0.41, p = 0.022, n = 25). To account for multiple comparisons across postoperative time points, p-values were adjusted using the Benjamini–Hochberg procedure. After adjustment, the correlation at 18 months remained significant at FDR < 0.05 (q = 0.022). The correlations at 3 months (q = 0.069) and at the final visit (q = 0.088) met the FDR < 0.10 threshold and were therefore interpreted as exploratory findings. Correlations at 24 and 36 months were based on very small sample sizes (n ≤ 7) and are presented descriptively without inferential interpretation.
Table 3.
Correlation between flare increase ratio and IOP reduction ratio
| Flare increase ratio (%), mean ± SD, Median(IR) |
N | IOP reduction ratio (%), mean ± SD, Median(IR) |
N | correlation coefficient A and B (ρ) |
p-values | q値 | |
|---|---|---|---|---|---|---|---|
| Baseline | 25 | 25 | |||||
| Month 1 |
442 ± 818 182(82–465) |
14 |
16.8 ± 32.2 17.6(0–38) |
25 | 0.033 | 0.91* | 0.91 |
| Month 3 |
377 ± 534 159(73–580) |
17 |
5.1 ± 42.3 7.7(-14.3-36.8) |
25 | 0,54 | 0.026* | 0.069 |
| Month 6 |
134 ± 112 105(35–230) |
13 |
4.7 ± 47.7 11.8(-9.4-34.7) |
23 | 0.308 | 0.31* | 0.50 |
| Month 12 |
200 ± 407 73(27–182) |
16 |
4.8 ± 43.8 18.0(-4.7-29.6) |
22 | 0.243 | 0.365* | 0.49 |
| Month 18 |
202 ± 189 94(81–290) |
7 |
15.9 ± 41.5 25(-10.4-35.3) |
11 | 0.964 | 0.0027* | 0.022 |
| Month 24 |
282 ± 155 274(164–336) |
5 |
-21.8 ± 38.9 -42.9(-46.4-0) |
7 | -0.2 | 0.789* | 0.90 |
| at the final visit(average 14.5 ± 6.9 months) |
229 ± 354 92(34–274) |
25 |
3.2 ± 43.7 13.3(-28.6-25.0) |
25 | 0.41 | 0.022* | 0.088 |
|
at the final visit (excluded prior glaucoma surgery and UG, CACG) |
262 ± 404 94(61–367) |
17 |
-4.4 ± 47.6 11.8(-37.5-23.1) |
17 | 0.25 | 0.183 * | 0.366 |
Additional treatment was required in 14 eyes (56%) due to insufficient IOP reduction, all of which underwent repeat MP-TSCPC. The mean interval until retreatment was 17.8 ± 6.2 months. No severe complications were observed, except for one case of marked postoperative inflammation, which improved with topical steroids. A descriptive comparison between retreatment and non-retreatment groups is provided in Supplementary Table 2. Among 25 eyes, 14 required repeat MP-TSCPC (56%), whereas 11 maintained IOP control without retreatment. Baseline IOP was higher in the retreatment group (19.1 ± 7.0 mmHg) than in the non-retreatment group (15.8 ± 6.7 mmHg). Baseline aqueous flare values were numerically higher in the non-retreatment group.
At 3 months, flare increase ratios were elevated in both groups (410 ± 400% in retreatment vs. 348 ± 655% in non-retreatment). IOP reduction ratios at 3 months tended to be smaller in the retreatment group. At the final visit, flare increase ratios remained elevated in both groups, whereas IOP reduction ratios were more variable in the retreatment group. Given the limited sample size, these comparisons are descriptive and exploratory and were not subjected to formal statistical testing.
At the final visit, the mean follow-up duration was 14.5 ± 6.9 months (median 12 months; IQR 12–18 months). The mean IOP reduction ratio was 3.2 ± 43.7%, and the mean flare increase ratio was 229 ± 354%.A scatter plot illustrating the association at the final visit is shown in Fig. 2. A moderate positive correlation was observed (ρ = 0.41, p = 0.022; q = 0.088, exploratory at FDR < 0.10).
Fig. 2.
Scatter plot showing the relationship between the flare increase ratio and the intraocular pressure (IOP) reduction rate at the final follow-up visit (ρ = 0.41, p = 0.022)
Subgroup data by glaucoma type are shown in Table 4. Because CACG and UG included only one case each, Table 4 is descriptive and does not imply statistical subgroup comparison.
Table 4.
Rate of IOP reduction and rate of increase in flare value at last follow up by glaucoma type
| Over all n=25 |
POAG n=19 |
PXG n=4 |
CACG n=1 |
UG n=1 |
|
|---|---|---|---|---|---|
|
Last follow up IOP(mmHg), mean ± SD, Median(IR) |
15.0 ± 4.2 16(13–18) |
14.9 ± 4.6 16(12–18) |
15.6 ± 3.0 15(14.5–16.3) |
11 | 18 |
|
Last follow up IOP reduction ratio (%), mean ± SD, Median(IR) |
3.2 ± 43.7 13.3(-28.6-25.0) |
0.2 ± 47 14.3(-33-24.0) |
1.5 ± 27.6 11.8(-1.9-12.2) |
38.9 | 51.4 |
| Last follow up aqueous flare values(photon counts/ms), mean ± SD, Median(IR) |
31.1 ± 15.2 24.8(19.7–41.9) |
32.0 ± 16.6 24.4(20.6–43.3) |
25.8 ± 11.5 21.6(18.2–29.2) |
31.1 | 40.7 |
| Last follow up flare increase ratio (%), mean ± SD, Median(IR) |
229 ± 354 92(34–274) |
146 ± 164 84(48–167) |
570 ± 750 292(146–716) |
8.9 | 668 |
| Follow up time (months), mean ± SD, Median(IR) |
14.5 ± 6.9 12(12–18) |
16.1 ± 6.9 18(12–18) |
12 | 6 | 3 |
SD=standard deviation; IR=interquartile range; IOP=intraocular pressure; POAG = primary open-angle glaucoma; PXG =pseudoexfoliative glaucoma; CACG = chronic angle-closure; UG=uveitic glaucoma
Changes in outflow facility are shown in Table 5. The baseline C value was 0.14 ± 0.11 µL/min/mmHg and remained unchanged at 3 months (0.14 ± 0.07 µL/min/mmHg; p = 0.331) and 6 months (0.14 ± 0.07 µL/min/mmHg; p = 0.90), indicating no statistically detectable change in conventional trabecular outflow within the observed period.
Table 5.
Time course of C value
| C value(µL/min/mm Hg ), mean ± SD, Median(IR) |
N |
P value (vs. baseline) |
|
|---|---|---|---|
| Baseline |
0.14 ± 0.11 0.08(0.07–0.18) |
23 | |
| Month 3 |
0.14 ± 0.07 0.13(0.07–0.17) |
19 | 0.331* |
| Month 6 |
0.14 ± 0.07 0.13(0.07–0.17) |
22 | 0.90* |
SD=standard deviation; IR=interquartile range; MP-TSCPC=micropulse transscleral cyclophotocoagulation; C value = coefficient of aqueous outflow * Wilcoxon signed rank test
AS-OCT findings are summarized in Supplementary Table 3. Ciliochoroidal detachment (CD) was detected in 6 eyes (24%) at 1 week postoperatively. CD resolved in 5 eyes by 1 month and persisted in 1 eye for at least 6 months.
The CD-positive group exhibited significantly lower IOP values at 1 week and at 1, 3, and 6 months postoperatively. No significant difference was observed at 12 months.
Flare values did not differ significantly between CD-positive and CD-negative groups at any time point.
Discussion
The present study demonstrated that aqueous flare values remained elevated into the mid-term period following MP-TSCPC, and that the magnitude of flare increase ratio was positively associated with the IOP reduction ratio. While previous reports have described short-term associations between postoperative flare elevation and IOP reduction [5], the present findings extend this relationship beyond the early postoperative phase.
Importantly, after adjustment for multiple comparisons using the Benjamini–Hochberg procedure, the correlation remained statistically significant at 18 months (FDR < 0.05), whereas the associations observed at 3 months and at the final visit met the FDR < 0.10 threshold and should therefore be interpreted as exploratory. Given the limited sample size at later time points, particularly at 18 months (n = 7), these findings should be considered hypothesis-generating rather than confirmatory.
Laser-induced tissue effects are known to trigger inflammatory responses. The sustained flare elevation observed in this cohort suggests that inflammatory changes may persist beyond the immediate postoperative period. The positive association between flare increase ratio and IOP reduction ratio at selected time points raises the possibility that inflammatory mechanisms contribute to continued IOP lowering after MP-TSCPC.
However, correlation does not establish causation. Several unmeasured factors—including postoperative medication adjustments, topical steroid intensity, and baseline disease severity—may have influenced both flare values and IOP outcomes.
No significant changes in tonographic outflow facility (C-value) were detected at 3 or 6 months postoperatively. This finding suggests that a measurable alteration in conventional trabecular outflow was not observed within the tested timeframe.
Nevertheless, absence of change in C-value does not exclude involvement of outflow-related mechanisms. Tonography may not capture localized, segmental, or dynamic alterations in aqueous humor drainage. Furthermore, the study was not powered to detect small changes in outflow facility. Therefore, both conventional and unconventional outflow pathways cannot be definitively excluded as contributors to IOP reduction.
Taken together, the stable C-value and the sustained flare elevation suggest that suppression of aqueous humor production may contribute to mid-term IOP reduction, although this interpretation remains inferential because aqueous production was not directly measured.
AS-OCT findings (Supplementary Table 3) showed that ciliochoroidal detachment (CD) occurred in 24% of eyes at 1 week postoperatively. Eyes with CD exhibited significantly lower IOP at 1 week and at 1, 3, and 6 months, but this difference was no longer evident at 12 months.
This temporal pattern is consistent with prior reports indicating that CD may facilitate transient increases in uveoscleral outflow [14, 15]. Because CD typically resolves within one month, the disappearance of IOP differences thereafter supports the interpretation that CD contributes primarily to early IOP reduction rather than sustained effects.Notably, flare values did not differ significantly between CD-positive and CD-negative eyes at any time point (Supplementary Table 3). This suggests that the mid-term association between flare elevation and IOP reduction is unlikely to be solely explained by CD-related outflow changes.
Approximately 60% of eyes required repeat MP-TSCPC. The relatively high retreatment rate underscores the clinical heterogeneity of treatment response in this cohort.
Flare measurements were not systematically obtained at the exact time of IOP re-elevation or retreatment. Therefore, it remains unclear whether flare declined concurrently with loss of IOP control. Prospective studies with protocolized flare measurements around retreatment events would be necessary to clarify this temporal relationship. Because retreatment may reflect insufficient or transient IOP control, and because flare dynamics were not standardized at recurrence, the present associations should be interpreted cautiously. Although approximately 56% of eyes required retreatment, flare elevation was observed in both retreatment and non-retreatment groups. This suggests that postoperative inflammatory response was not confined to eyes with sustained IOP reduction. However, the variability in IOP reduction within the retreatment group indicates heterogeneous treatment response, and causal interpretation cannot be inferred.
Limitations
Several limitations warrant consideration. First, potential selection bias should be acknowledged. Among 33 eyes that underwent first MP-TSCPC during the study period, five eyes were excluded due to unavailable pre- or postoperative flare measurements, and three eyes were excluded to avoid inter-eye correlation. Exclusion of cases with incomplete flare data may have introduced selection bias, as patients with missing measurements could have differed systematically in postoperative inflammatory response or IOP reduction. Therefore, the findings may not be fully generalizable to all MP-TSCPC–treated eyes.
Second, the sample size was limited, particularly at later postoperative time points and within glaucoma subtypes. Although the correlation at 18 months remained significant after FDR correction, the small number of eyes at this time point necessitates cautious interpretation. Analyses at 24 months and beyond should be regarded as exploratory due to limited statistical power.
Third, follow-up duration varied among eyes, and the “final visit” did not occur at a uniform postoperative interval. This variability introduces potential time-related bias and may confound associations observed at the final visit. Because final visits occurred at different postoperative stages, the temporal relationship between flare elevation and IOP reduction cannot be uniformly interpreted.
Fourth, approximately 60% of eyes required retreatment with repeat MP-TSCPC. Flare measurements were not systematically obtained at the exact time of IOP re-elevation or retreatment, limiting our ability to evaluate whether flare declined concurrently with IOP recurrence. Therefore, the temporal dynamics between inflammation and IOP control remain incompletely characterized.
Fifth, aqueous humor production was not directly measured. Objective assessments such as fluorophotometry were not performed. Thus, the hypothesis that inflammatory processes suppress aqueous production remains speculative.
Sixth, this was an observational study based on correlation analyses. Potential confounders—including baseline IOP, postoperative medication adjustments, anti-inflammatory treatment intensity, and prior glaucoma surgery—were not adjusted for using multivariable modeling. Accordingly, causal inference cannot be established.
Finally, postoperative inflammation is not unique to MP-TSCPC and may occur after various glaucoma procedures. The sustained flare elevation observed in this study may reflect a nonspecific inflammatory response rather than a mechanism specific to MP-TSCPC. Given subgroup heterogeneity—including pseudoexfoliation, uveitic, chronic angle-closure glaucoma, and prior glaucoma surgery—the findings should be interpreted as exploratory associations rather than definitive mechanistic evidence.
Conclusions
In this exploratory cohort, sustained postoperative aqueous flare elevation was associated with greater mid-term IOP reduction following MP-TSCPC. However, given the small sample size, heterogeneous population, observational design, and high retreatment rate, these findings should not be interpreted as evidence of causality.
Larger prospective studies with standardized follow-up intervals, predefined responder stratification, multivariable adjustment, and direct assessment of aqueous humor dynamics are required to clarify the underlying mechanisms.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
Not applicable.
Author contributions
MO: data interpretation, manuscript preparation, statistical analysis YN: data acquisition, NI: conceptualization GI: revision TH: conceptualization, revision RA: revision AH: clinical supervision. All authors approved the final manuscript.
Funding
No specific funding was received.
Data availability
All data generated or analyzed during the current study are included within the article.
Declarations
Ethics approval and consent to participate
This retrospective observational study adhered to the tenets of the Declaration of Helsinki and was approved by the institutional review board of our hospital (approval number: R2025063). The study was approved by the Research Ethics Office for Human Subjects, University of Toyama. Informed consent to participate was obtained from all of the participants in the study.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
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Data Availability Statement
All data generated or analyzed during the current study are included within the article.