The Effect of Trabeculectomy on Disc Tissue Blood Flow Across Quadrants in Open Angle Glaucoma

Abstract

Précis:

Trabeculectomy increases tissue blood flow superior and temporal in the optic nerve head (ONH). Improvement of tissue blood flow superior and temporal in the optic nerve could be an indicator of the effectiveness of glaucoma treatment.

Objective:

To investigate changes in tissue blood flow at the ONH before and after trabeculectomy.

Materials and Methods:

This prospective study included 53 eyes who underwent trabeculectomy. The mean blur rate of the tissue area mean blur rate of the tissue area (MT) was determined using laser speckle flowgraphy preoperatively and 1 and 3 months postoperatively. MT, laser speckle flowgraphy waveform parameters [blowout score (BOS) and Resistivity Index (RI)], intraocular pressure (IOP), and ocular perfusion pressure (OPP) were analyzed preoperatively and at 3 months postoperatively.

Results:

Postoperatively, IOP decreased (17.9±6.0–9.2±3.4 mm Hg) and OPP increased (43.3±9.2–52.1±6.4 mm Hg). As previously described, BOS increased (73.5±8.3–76.7±6.5; P< 0.001) with an inverse correlation to IOP and in proportion with OPP; RI decreased (0.40±0.1–0.35±0.08; P< 0.001) with an inverse correlation to OPP and in proportion to IOP. However, we found that MT increased significantly after surgery (7.9±2.2–8.8±2.2 AU; P= 0.002) without significant association between MT and IOP or OPP. In the 4 quadrants of the ONH, BOS significantly increased, while RI significantly decreased after surgery in all quadrants. In contrast, MT significantly increased in the superior and temporal quadrants only.

Conclusions:

Blood flow increases in the superior and temporal ONH.

Glaucoma is a multifactorial disease, and lowering intraocular pressure (IOP) is the only evidence-based treatment known to slow its progression.^1–3 However, in some cases, visual field damage progresses even with low IOP, which suggests that other causes possibly including blood flow.^4–7

Laser speckle flowgraphy (LSFG) is an image analysis method that uses the laser speckle phenomenon to provide a two-dimensional map of blood flow indices of the fundus.⁸ The mean blur rate (MBR) of the speckle images has high reproducibility in normal and glaucoma subjects,^9,10 and is highly correlated with actual tissue blood flow in the optic nerve head (ONH) of monkeys and rabbits, measured by microsphere and hydrogen gas clearance methods, respectively.^11–13 The MBR, an important parameter of LSFG, represents the relative velocity of red blood cells in arbitrary units (AUs) and is highly correlated with tissue blood flow in the optic nerve papilla.^8,13 Tissue area MBR mean blur rate of the tissue area (MT) means the blood flow in the microcirculatory area from the ONH minus the area containing the large vessels. LSFG also provides MBR waveform parameters, which quantitatively display the hemodynamics within a single heartbeat in the measurement area (Fig. 1).¹⁴ Skew and Acceleration Time Index (ATI) differ significantly between normal and mild normal tension glaucoma eyes. Normal tension glaucoma eyes also have higher blowout time (BOT) and lower ATI than compared with normal eyes, resulting in a flatter MBR curve.¹⁴ In eyes with open angle glaucoma (OAG), LSFG has also demonstrated that decreased blood flow in the optic nerve papilla precedes a decrease in peripapillary retinal nerve fiber layer thickness.¹⁵ Further, a previous study reported that higher vascular resistance and consequently higher vascular stiffness were associated with more rapid functional loss in glaucoma suspects, as determined using LSFG.¹⁶

FIGURE 1.

Figure and equation for each waveform parameter of the LSFG. AC indicates Alternate Current; ATI, Acceleration Time Index; BOS, blowout score; BOT, blowout time; DC, Direct Current; LSFG, laser speckle flowgraphy; MBR, mean blur rate; RI, Resistivity Index.

Trabeculectomy is performed in patients with glaucoma and uncontrolled IOP. Only a few studies have examined the effects of trabeculectomy on ocular blood flow using LSFG, and none of them have observed significant differences in MBR.^17,18 However, among patients in those studies, LSFG waveform parameter blowout score (BOS) was significantly elevated, and the Resistivity Index (RI) and ATI were significantly reduced, both of which may be associated with the optic nerve papillary blood flow. The purpose of this prospective study was to evaluate changes in the optic nerve papillary blood flow using LSFG, before and after trabeculectomy.

MATERIALS AND METHODS

Study Participants and Trabeculectomy

This prospective study included 53 eyes of 53 patients (1 eye per patient) with glaucoma who underwent trabeculectomy without any combined surgery at Kagawa University Hospital, Kagawa-ken, Japan. The study protocol followed the principles of the Declaration of Helsinki, and written informed consent was obtained from each patient after approval from the Kagawa University School of Medicine Ethics Committee (2019–197). Patients diagnosed with glaucoma who were scheduled for trabeculectomy, as well as those who had undergone trabeculotomy and cataract surgery >6 months before the present trabeculectomy, were included. Patients with ocular diseases other than glaucoma and cataracts as well as those with a history of intraocular surgery other than the previous, were excluded. Eyes with a long axis of ≥28 mm and patients who required additional IOP-lowering medication and intraocular surgery, including bleb reconstruction and cataract surgery, within the postoperative observation period were also excluded.

Trabeculectomy was performed using conjunctival and semilunar scleral flaps. Mitomycin C (0.04%) was applied for 3 minutes, and the scleral flap was closed using 10-0 nylon sutures. Postoperatively, topical moxifloxacin and betamethasone were administered and tapered, as needed. To enhance filtration, the bleb was managed with an argon laser suture lysis.

Laser Speckle Flowgraphy Evaluation

The optic nerve papillary blood flow was assessed using LSFG (LSFG-NAVI version 3.1.39.2 software; Softcare Ltd.). The principles and methods of LSFG have been described in previous studies.^8,18 Briefly, when red blood cells move, the speckle pattern changes. The speckle pattern produced by the red blood cells is captured using a digital camera and analyzed using built-in software to generate flow information. MBR, the main output parameter of LSFG, represents the relative blood flow velocity, and it is expressed in AU. The edge of the optic nerve papilla is surrounded by an ellipse, and its position is stored in the system software. MBR images of the ONH were recorded at 30 frames/s for 4 seconds. The beginning and end of the heartbeats, recorded for 4 seconds, were automatically detected. Images corresponding to the same phase within a single heartbeat were combined into a single image. The average MBR of the heartbeats was calculated and displayed as a heartbeat map.

The “Vessel Extraction Function” in LSFG-NAVI automatically detected the vascular and tissue areas in the ONH and calculated the mean vascular and tissue areas. We used MT for our analysis because it has been shown to be correlated with absolute blood flow values measured using the microsphere and hydrogen gas clearance methods in primates and rabbits.^11,13,19 LSFG-NAVI displays the shape of the MBR waveform during one cardiac cycle with parameters to evaluate ocular blood flow dynamics (pulse waveform analysis). The definition and calculation of pulse waveform parameters have been described in previous studies (Fig. 1).^20–23 In this study, 5 pulse waveform parameters were analyzed. First, the BOS, which indicates the blood flow rate in one heartbeat, was calculated from the difference between the maximum and minimum MBRs and the mean waveform distribution as follows:

$$BOS=100\times (2-[MBR\mathit{max}-MBRmin]/MBRaverage)/2$$

Second, the RI was calculated by dividing the difference between the maximum and minimum MBR by the maximum MBR.

$$RI=(MBRmax-MBRmin)/MBRmax$$

Both the BOS and RI are thought to be related to vascular resistance.

Third, the ATI was defined as the ratio of the time to reach the peak pulse wave value in one heartbeat.

$$\mathit{ATI}=100\mathit{A?\; length\; to\; peak}/\mathit{length\; of\; a\; heartbeat}$$

The Smaller the Acceleration Time Index, the More Rapidly the Mean Blur Rate Increases to the Peak

Fourth, BOT was defined as the ratio of the half-width (the time when the waveform is larger than half of the average of the minimum and maximum values).

$$\mathit{BOT}=100A\mathrm{?}\mathit{half}\mathrm{\_}\mathit{width}/\mathit{width\; of\; a\; heartbeat}$$

The higher the BOT, the higher the percentage of a single heartbeat and the higher the level of MBR maintained.

Fifth, skew represented the asymmetry of the MBR waveform in the waveform distribution. If the waveform was perfectly symmetrical, the skew was zero. If the peak of the pulse wave arrived earlier than in the symmetrical waveform, the skew was higher. If the peak arrived later, the skew was lower.

Measurement of Clinical Parameters

IOP was measured using a Goldmann baroreflex tonometer (Haag-Streit, Bern, Switzerland) on the same day LSFG was performed and the data were used for analysis. Systolic blood pressure, diastolic blood pressure, and heart rate were measured before LSFG. The mean blood pressure (MBP) and ocular perfusion pressure (OPP) were calculated as follows:

$$\mathit{MBP}=\mathit{DBP}+1/3(\mathit{SBP}-\mathit{DBP})$$

$$\mathit{OPP}=2/3\mathit{MBP}-\mathit{IOP}$$

Statistical Analyses

IOP, OPP, MBP, MT, BOT, BOS, skew, ATI, and RI were evaluated before, and at 1 and 3 months post-trabeculectomy. The repeated analysis of variance was performed, and multiple comparisons were made using the Tukey method for items that showed significant differences. Significance was set at P <0.05.

RESULTS

The baseline patient characteristics are shown in Table 1. Of the 53 participants, 31 were men and 22 were women. There were 39, 13, and 1 patient(s) with OAG, secondary glaucoma (SG), and exfoliation glaucoma (EG), respectively. The causes of SG are 5 cases of unknown iridocyclitis, 3 cases of cytomegalovirus, 4 cases of sarcoidosis, and 1 case of rheumatoid arthritis. The mean age of the patients was 66.6 ± 13.2 years (mean ± SD).

TABLE 1.

Baseline Patient Characteristics Before Trabeculectomy

Variables	Total (n = 53)
Age (y)	66.6±13.2
Sex (M/F)	31/22
Diagnosis (OAG/SG/EG)	39/13/1
Axial length (mm)	24.8±1.6
Refraction (diopter)	-2.7±2.5
Mean deviation (dB)	-16.6±6.7
Central cornea thickness (µm)	518.6±34.2
IOP (mm Hg)	17.9±6.0
MBP (mm Hg)	91.8±11.8
OPP (mm Hg)	43.3±9.2
Pulse rate (bpm)	75.5±13.4
No. preoperative antiglaucoma medications	3.8±0.8
Prostaglandin analogs (cases)	40
β antagonists (cases)	46
Carbonic anhydrase inhibitors (cases)	47
α-2 agonist (cases)	39
Rho kinase inhibitor (cases)	25
Previous intraocular surgery (eyes)
Cataract surgery	29
Trabeculotomy	9
Systemic hypertension (cases)	25
Oral calcium channel blockers (cases)	19
Oral angiotensin II receptor blockers (cases)	19
Oral β blockers (cases)	2
Diabetes mellitus (cases)	6

The data are presented as means ± SDs.

EG indicates exfoliation glaucoma; IOP, intraocular pressure; MBP, mean blood pressure; OAG, open angle glaucoma; OPP, ocular perfusion pressure; SG, secondary glaucoma.

Table 2 shows the trends in IOP, OPP, and MBP at 1 and 3 months after trabeculectomy. The postoperative IOP significantly decreased from a preoperative value of 17.9±6.0–7.6±3.8 mm Hg (P < 0.001) after 1 month and 9.2±3.4 mm Hg (P < 0.001) after 3 months. Meanwhile, the postoperative OPP significantly increased from a preoperative value of 43.3±9.2–54.6±8.8 mm Hg (P <0.001) after 1 month and 52.1±6.4 mm Hg, (P < 0.001) after 3 months.

TABLE 2.

Changes in Ocular Parameters Before and After Trabeculectomy (n = 53)

	Before treatment	After 1 mo	After 3 mo
IOP (mm Hg)	17.9 ± 6.0	7.6 ± 3.8*	9.2 ± 3.4*
OPP (mm Hg)	43.3 ± 9.2	54.6 ± 8.8*	52.1 ± 6.4*
MBP (mm Hg)	91.8 ± 11.8	93.3 ± 14.2	92.0 ± 9.8

The data are presented as means ± SDs.

The repeated analysis of variance was performed before, 1, and 3 months after trabeculectomy.

^* Significant changes compared with initial values (P < 0.001).

IOP indicates intraocular pressure; MBP, mean blood pressure; OPP, ocular perfusion pressure.

Table 3 shows the MT and the trends in the 5 waveform parameters of LSFG, including BOT, BOS, skew, ATI, and RI, preoperatively and at 1 and 3 months after trabeculectomy in all cases, OAG cases and SG + EG cases. In all cases, MT increased significantly from a preoperative value of 7.9±2.2–8.8 ± 2.3 AU (P < 0.001) at 1 month and remained at 8.8±2.2 AU (P = 0.002) at 3 months. BOS also showed a significant increase from 73.5±8.3 to 6.9±5.8 (P < 0.001) at 1 month and 76.7±6.5 (P < 0.001) at 3 months. Conversely, RI decreased significantly from 0.40±0.1 to 0.35±0.07 (P < 0.001) at 1 month and remained at 0.35±0.08 (P < 0.001) at 3 months. In contrast, BOT, skew, and ATI did not show any significant changes postoperatively. The analysis was performed with receiver operating characteristic (ROC) curves, considering a cut-off value for IOP. ROC analysis showed an area under the curve of 0.709, with a cutoff value of 11.5 mm Hg, sensitivity of 57%, and specificity of 85%. In OAG cases, MT increased significantly from a preoperative value of 7.9±1.9–8.5 ± 2.0 AU (P = 0.001) at 1 month but did not increase to 8.3±2.0 AU (P = 0.064) at 3 months. BOS showed a significant increase from 74.1±8.4 to 76.7±6.1 (P = 0.003) at 1 month and 76.5±5.8 (P = 0.006) at 3 months. RI decreased significantly from 0.38±0.10 to 0.35±0.08 (P = 0.004) at 1 month and remained at 0.36±0.07 (P = 0.029) at 3 months. In SG + EG cases, MT increased significantly from a preoperative value of 8.2±2.7–9.4±2.9 AU (P = 0.002) at 1 month and remained at 9.1±2.6 AU (P = 0.023) at 3 months. BOS did not increase significantly from a preoperative value of 70.2±8.4–75.8±5.0 AU (P = 0.06) at 1 month but increased to 77.0±8.2 AU (P = 0.02) at 3 months. RI decreased significantly from 0.43±0.10 to 0.36±0.06 (P = 0.036) at 1 month and remained at 0.34±0.09 (P = 0.009) at 3 months.

TABLE 3.

Changes in Waveform Parameters of LSFG Preoperatively and After Trabeculectomy (n = 53) All Cases (n = 53)

	Before treatment	After 1 mo	After 3 mo
MT (AU)	7.9 ± 2.2	8.8 ± 2.3*	8.5 ± 2.2†
BOT	49.5 ± 5.7	49.7 ± 8.4	47.4 ± 5.0
BOS	73.5 ± 8.3	76.9 ± 5.8*	76.7 ± 6.5*
Skew	11.1 ± 3.1	11.2 ± 4.3	11.7 ± 2.8
ATI	32.5 ± 7.5	33.0 ± 7.1	33.2 ± 4.7
RI	0.40 ± 0.10	0.35 ± 0.07*	0.35 ± 0.08*
OAG (n = 39)
MT (AU)	7.9 ± 1.9	8.5 ± 2.0†	8.3 ± 2.0
BOT	49.4 ± 6.1	49.5 ± 7.2	48.2 ± 5.0
BOS	74.1 ± 8.4	76.7 ± 6.1†	76.5 ± 5.8†
Skew	11.2 ± 2.9	11.7 ± 2.8	11.5 ± 2.8
ATI	32.2 ± 6.9	32.2 ± 5.0	33.4 ± 4.3
RI	0.38 ± 0.10	0.35 ± 0.08†	0.36 ± 0.07‡
SG + EG (n = 14)
MT (AU)	8.2 ± 2.7	9.4 ± 2.9†	9.1 ± 2.6‡
BOT	49.7 ± 5.5	50.0 ± 11.2	45.0 ± 4.2
BOS	70.2 ± 8.4	75.8 ± 5.0	77.0 ± 8.2‡
Skew	10.9 ± 3.7	9.8 ± 6.9	12.4 ± 2.7
ATI	33.5 ± 8.9	35.5 ± 11.0	32.6 ± 5.5
RI	0.43 ± 0.10	0.36 ± 0.06‡	0.34 ± 0.09†

The data are presented as means ± SDs. The unit is AU for all the parameters. The repeated analysis of variance was performed before, and 1 and 3 months after trabeculectomy. Significant changes compared with initial values are indicated as:

^* P < 0.001.

^† P < 0.01.

^‡ P < 0.05.

ATI indicates Acceleration Time Index; AU, arbitrary unit; BOS, blowout score; BOT, blowout time; EG, exfoliation glaucoma; LSFG, laser speckle flowgraphy; OAG, open angle glaucoma; RI, Resistivity Index; SG, secondary glaucoma.

Factors influencing MT, BOS, and RI, which showed significant changes, were analyzed through univariate analysis of the changes in IOP and OPP from preoperative to 3 months postoperative. BOS showed a significant inverse correlation with IOP (correlation coefficient: −0.64, P < 0.001), indicating that as IOP decreases, BOS increases. RI was significantly positively correlated with IOP (0.58, P < 0.001) and significantly inversely correlated with OPP (−0.51, P < 0.001), suggesting RI increases with IOP and decreases with OPP. Conversely, MT did not exhibit significant correlations with either IOP (−0.12, P = 0.40) or OPP (0.047, P = 0.74; Table 4). Scatter plots show the relationships between MT, BOS, RI change, and IOP, OPP change (3 months postoperative​​​​​​​–preoperative; Fig. 2).

TABLE 4.

Univariate Analysis Among MT, BOS, RI and IOP, OPP Change (3 mo Postoperative vs Preoperative)

	MT	BOS	RI
IOP
Correlation coefficient	-0.12	-0.64	0.58
Significant probability	0.40	<0.001*	<0.001*
OPP
Correlation coefficient	0.047	0.48	-0.51
Significant probability	0.74	<0.001*	<0.001*

Significant changes are indicated as:

^* P < 0.001

BOS indicates blowout score; IOP, intraocular pressure; OPP, ocular perfusion pressure; RI, Resistivity Index.

FIGURE 2.

Scatter plots showing the relationships between (A) MT change, (B) BOS change, (C) RI change, and IOP change (3 mo postoperative–preoperative), and (D) MT change, (E) BOS change, (F) RI change, and OPP change (3 mo postoperative–preoperative). BOS indicates blowout score; IOP, intraocular pressure; OPP, ocular perfusion pressure; RI, Resistivity Index.

Table 5 shows the trends of MT, BOS, and RI in each of the 4 quadrants (superior, inferior, temporal, and nasal) of the ONH at 1 and 3 months postoperatively, following the quadrant division and analysis methodology as reported by Kiyota et al¹⁵ (Fig. 3). Compared with preoperative values, MT significantly increased in the superior quadrant from 8.5±2.4 to 9.3±2.7 AU (P < 0.001) at 1 month and to 9.0±2.5 AU (P = 0.023) at 3 months, in the inferior quadrant from 8.3±2.5 to 8.8±2.7 AU (P = 0.030) at 1 month, and in the temporal quadrant from 6.2±2.3 to 6.7±2.3 AU (P = 0.007) at 1 month and to 6.7±2.3 AU (P = 0.003) at 3 months postoperatively. BOS significantly increased in all quadrants from a preoperative value at 1 month and 3 months. Similarly, RI significantly decreased in all quadrants compared with preoperative values at 1 and 3 months.

TABLE 5.

The Trends of the MT, BOS, and RI in Each of the 4 Quadrants of the ONH at 1 and 3 Months Postoperatively (n = 53)

	Before treatment	After 1 mo	After 3 mo
MT (AU)
All	7.9 ± 2.2	8.8 ± 2.3*	8.5 ± 2.2†
Superior	8.5 ± 2.4	9.3 ± 2.7*	9.0 ± 2.5‡
Inferior	8.3 ± 2.5	8.8 ± 2.7‡	8.4 ± 2.5
Temporal	6.2 ± 2.3	6.7 ± 2.3†	6.7 ± 2.3†
Nasal	10.3 ± 3.0	10.7 ± 2.7	10.6 ± 3.0
BOS
All	73.1 ± 8.3	76.9 ± 5.8*	76.7 ± 6.5*
Superior	73.5 ± 8.3	76.4 ± 5.7†	76.2 ± 6.9‡
Inferior	74.6 ± 9.1	77.1 ± 6.1‡	77.0 ± 7.3‡
Temporal	72.9 ± 9.2	75.2 ± 7.5‡	75.7 ± 7.1‡
Nasal	72.9 ± 9.5	75.1 ± 6.5‡	75.6 ± 7.0†
RI
All	0.40 ± 0.10	0.35 ± 0.07*	0.35 ± 0.08*
Superior	0.39 ± 0.10	0.35 ± 0.07†	0.35 ± 0.08‡
Inferior	0.37 ± 0.11	0.35 ± 0.08‡	0.35 ± 0.09‡
Temporal	0.39 ± 0.10	0.36 ± 0.08†	0.36 ± 0.08†
Nasal	0.40 ± 0.11	0.37 ± 0.08‡	0.36 ± 0.08†

The data are presented as means ± SDs.

The repeated analysis of variance was performed before, 1 month after, and 3 months after trabeculectomy. Significant changes compared with initial values are indicated as:

^* P < 0.001.

^† P < 0.01

^‡ P < 0.05

AU indicates arbitrary unit; BOS, blowout score; ONH, optic nerve head; RI, Resistivity Index.

FIGURE 3.

LSFG image of the ONH divided into 4 quadrants (superior, inferior, temporal, and nasal). LSFG indicates laser speckle flowgraphy; ONH, optic nerve head.

DISCUSSION

This study evaluated the changes in blood flow to the ONH and its waveform parameters using LSFG in patients with glaucoma who underwent trabeculectomy. There were no significant differences from other similar studies in terms of sex ratio or age.^17,18

Table 2 shows the changes in IOP, OPP, and MBP, indicating that IOP was significantly decreased at both 1 and 3 months postoperatively, while OPP was significantly increased, as previously described.^17,18 The IOP at 3 months postoperatively was lower in our study (9.3 mm Hg) than in previous studies (10.8 or 12.4 mm Hg).^17,18

In all cases, as observed from Table 3, which shows the changes in LSFG parameters, MT and BOS increased significantly at 1 and 3 months postoperatively, while RI decreased significantly. ROC analysis showed a cutoff value of 11.5 mm Hg. This suggests that if the postoperative IOP is <11.5 mm Hg, blood flow is likely to increase. It is possible that tissue blood flow improved because IOP decreased beyond autoregulatory capacity.

In OAG cases, MT increased significantly after 1 month but not significantly after 3 months. BOS increased significantly at 1 and 3 months postoperatively, and RI decreased significantly at both 1 and 3 months. In SG + EG cases, MT increased significantly at 1 and 3 months postoperatively. BOS did not increase significantly after 1 month but increased significantly after 3 months postoperatively. RI decreased significantly at 1 and 3 months postoperatively. Corroborating with our findings, Takeshima et al¹⁸ and Masai et al¹⁷ found a significant increase and decrease, respectively, in BOS RI at 3 months postoperatively compared with preoperative values. The strong inverse correlation between BOS and RI was an expected result, given that the formulas for calculating BOS and RI are inverse calculations. Furthermore, our results were also similar to theirs in that ATI, BOT, and skew did not show significant postoperative changes. However, they reported that blood flow in the tissue of the optic nerve papillae did not show any significant changes. This finding is inconsistent with our findings. We observed a significant improvement in MT after trabeculectomy. This may be because the postoperative IOP is lower in our study than in previous studies, as stated previously.

In univariate analysis (Table 4), IOP was inversely correlated with BOS and significantly correlated with RI. The OPP was inversely correlated with RI. MT was not correlated with IOP or OPP. These results are also similar to those of the previous studies.^17,18

Previous reports have suggested that retinal blood flow has an autoregulatory function; therefore, even if choroidal blood flow changes when IOP decreases, retinal blood flow does not change significantly. The possible reason for this result is that IOP after trabeculectomy was lower in our study than in previous studies.^17,18

Table 5 shows the changes of the MT, BOS, and RI in each of the 4 quadrants of the ONH at 1 and 3 months postoperatively. To our knowledge, this is the first time that the LSFG of the 4 quadrants of the ONH have been measured before and after trabeculectomy. MT was significantly increased in the superior and temporal area at both 1 and 3 months postoperatively and significantly increased in the inferior at 1 month postoperatively. BOS was significantly increased and RI was significantly decreased in all quadrants at both 1 and 3 months postoperatively. Kiyota et al¹⁵ reported that superior and temporal sectors of the ONH are more likely to be preceded by reduced MT than nerve fiber layer defect in glaucomatous eyes. Our results showed that MT was significantly increased in these sectors 3 months postoperatively.

Trible et al²⁴ was one of the earliest who found improvements in an increase in blood flow velocity and a decrease in vascular resistance in the central retinal artery and short posterior ciliary arteries after trabeculectomy using Color Doppler. Hafez Ali et al²⁵ found that therapeutic IOP reduction significantly improved ONH rim blood flow in open angle glaucoma patients, while no such change was observed in ocular hypertension patients, indicating a potential impairment of ONH autoregulation in glaucoma. Berisha et al²⁶ used scanning laser Doppler flowmetry to evaluate blood flow changes in the ONH after trabeculectomy in patients with primary OAG. They observed a significant increase in blood flow to the ONH 10 weeks after trabeculectomy that was associated with an increase in OPP. Three other studies that evaluated the effect of trabeculectomy on pulsating ocular blood flow showed that trabeculectomy significantly reduced IOP and increased ocular blood flow.^27–29 Shoji et al³⁰ used optical coherence tomography angiography and reported that the foveal avascular zone area is decreased with IOP-lowering surgery in patients with primary OAG and that change in the foveal avascular zone area was significantly correlated with both preoperative foveal sensitivity and change in IOP. Our results, together with other methods described for measuring ONH blood flow suggest improvement after trabeculectomy.

This study has some limitations. First, the LSFG image, which reflects retinal blood flow, might include input/contributions from choroidal blood flow, as it could be challenging to distinguish these flows completely. Second, we had a small sample size to study the effect of trabeculectomy on optic nerve papillary blood flow. Third, preoperative use of IOP-lowering medications may have had some effect on the changes in MBR. Eye drops that could improve blood flow may have affected the present results. Fourth, we did not classify the degree of visual field impairment or the glaucoma type. Preoperative tissue blood flow may differ depending on the severity of visual field impairment, and the degree of improvement in tissue blood flow after surgery may also differ. Fifth, the topical tropicamide used for mydriasis might have affected tissue blood flow in the ONH. Further studies with large sample sizes may reveal the impact of the severity of visual field impairment and characteristics of different types of the disease. Furthermore, LSFG can be a useful technique for measuring improvements in blood flow.