ORIGINAL STUDY
Effect of Trabeculectomy on Ocular Hemodynamic Parameters in Pseudoexfoliative and Primary Open-angle Glaucoma Patients Ingrida Januleviciene, MD, PhD,* Lina Siaudvytyte, MS,* Vaida Diliene, MS,* Ruta Barsauskaite, MS,* Brent Siesky, PhD,w and Alon Harris, MS, PhD, FARVOw
Purpose: To evaluate the effects of trabeculectomy on ocular hemodynamic parameters in pseudoexfoliative glaucoma (PXG) and primary open-angle glaucoma (POAG) patients and to analyze serum antiphospholipid antibody levels (APLAs) in PXG. Methods: Thirty open-angle glaucoma patients were included in the prospective study. Intraocular pressure (IOP), ocular perfusion pressure (OPP), blood pressure, and pulsatile ocular blood flow (POBF) were measured. Retrobulbar blood flow (RBF) was measured using the color Doppler imaging. Venous blood samples were obtained from PXG patients; APLAs IgG levels were assessed. The level of significance was P < 0.05. Results: IOP decreased significantly in both groups after trabeculectomy [from 30.1 (7.2) to 15.0 (5.1) in PXG; from 29.1 (7.7) to 13.1 (5.5) in POAG, P < 0.05]. OPP increased from 38.9 (10.3) to 55.5 (8.6) in PXG and from 40.9 (11.0) to 56.7 (8.9) in POAG group, P < 0.05. Both groups showed significant increase in CRA PSV [from 8.75 (2.27) to 9.79 (2.31) in PXG and from 8.55 (2.59) to 10.11 (2.64) in POAG, P < 0.05]. Both groups showed an increase in POBF [from 13.09 (3.41) to 18.81 (5.70) in PXG and from 11.89 (5.79) to 19.29 (9.02) in POAG, P < 0.05). Patients with normal APLAs levels showed significant decrease in IOP [from 30.7 (8.1) to 15.2 (5.9)] and increase in POBF [from 13.24 (3.69) to 19.94 (5.03)], CRA PSV [from 8.78 (2.39) to 9.46 (2.17)], and tSPCA PSV [from 7.61 (2.15) to 8.35 (1.98)], P < 0.05. Conclusions: Trabeculectomy resulted in a significant decrease in IOP and increase in ocular blood flow. Effects of trabeculectomy in PXG patients were significantly less compared with POAG. Patients with normal APLA levels had a significant increase in ocular hemodynamic parameters compared with patients with higher APLAs levels. Key Words: trabeculectomy, retrobulbar blood flow, pulsatile ocular blood flow, antiphospholipid, pseudoexfoliative glaucoma, primary open-angle glaucoma
(J Glaucoma 2015;24:e52–e56)
Received for publication January 14, 2013; accepted March 4, 2014. From the *Eye Clinic, Lithuanian University of Health Sciences, Kaunas, Lithuania; and wGlaucoma Research and Diagnostic Center, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN. Disclosure: The authors declare no conflict of interest. Reprints: Ingrida Januleviciene, MD, PhD, Eye Clinic, Lithuanian University of Health Sciences, Eiveniu str. 2, Kaunas 50009, Lithuania (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000055
e52 | www.glaucomajournal.com
G
laucoma is an optic neuropathy leading to the retinal ganglion cell (RGC) death and typical optic nerve head (ONH) damage. Intraocular pressure (IOP) is the main and only modifiable risk factor for glaucoma.1 However, in some patients glaucoma continues to progress despite good IOP control. This indicates that other pathogenetic mechanisms beyond IOP might be involved in the pathogenesis of glaucoma. Lately, more attention has concentrated on vascular theory of glaucoma and pharmacological ocular blood flow (OBF) modulation.2–6 Vascular theory is based on the idea of abnormal perfusion due to either increased IOP or other factors leading to ONH ischemia because of breakdown of autoregulation. Autoregulation is unable to operate efficiently at very high or very low perfusion pressure levels.5 Normal perfusion pressure is uniquely individual and varies with certain cardiovascular disorders.5 Several studies have indicated that low blood pressure (BP) is a risk factor for glaucoma and compromised ocular perfusion.7 Barbados Eye Study indicated that lower BP doubles the risk for glaucoma.8 Recent studies have shown an association between nocturnal arterial hypotension and glaucomatous visual loss.5 Cherecheanu and colleagues proposed a model including a 2 insults theory, with the primary insult occurring at the ONH. Increased IOP and ischemia at the postlaminar ONH affects RGC.2 Consequently, RGCs are forced to function at reduced energy levels and are sensitive to secondary insults such as low ocular perfusion pressure (OPP), which cannot be compensated by autoregulation. That, together with oxidative stress, can ultimately lead to RGC death.2 Other modulating factors can also increase susceptibility for further damage.9 It is known that certain eye drops may have impact on OBF and its regulation. Some data support increased blood flow and the enhancement of OBF regulation with carbonic anhydrase inhibitors. Several studies have shown dorzolamide’s ability to increase various measures of OBF parameters,10–12 although other studies failed to show similar effect.13,14 Dorzolamide’s vasodilatory effects might be explained by induced acidosis in local tissues. In a mechanism different than dorzolamide, timolol may cause vasoconstriction by blocking b-2 receptors. However, some studies reported that a single instillation of timolol did not have significant effect on the retrobulbar blood flow (RBF).15,16 Pseudoexfoliation (PEX) syndrome is the most identifiable risk factor for open-angle glaucoma (OAG).17 Although pseudoexfoliative glaucoma (PXG) is associated with high pressure disease, pressure-independent risk factors, such as impaired OBF and RBF, may be present.18–20 During recent years, PEX syndrome has been shown to be a systemic process associated with cardiovascular and J Glaucoma
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Volume 24, Number 5, June/July 2015
J Glaucoma
Volume 24, Number 5, June/July 2015
cerebrovascular diseases. Antiphospholipid antibodies (APLAs) are autoantibodies directed against phospholipids and phospholipid protein complexes, which are the main constituents of all membranes. Canadian Glaucoma Study found that glaucoma patients with abnormal anticardiolipin antibody levels had a 4 times increased risk for visual field progression.21 In cases of uncontrolled IOP and progressing glaucoma, filtering surgeries are indicated. Several studies analyzed effects of trabeculectomy on ocular hemodynamics. Some researchers showed increased RBF and pulsatile ocular blood flow (POBF) after trabeculectomy, whereas other studies did not show a positive postoperative effect.22–24 The aims of our study were to evaluate the effects of trabeculectomy on ocular hemodynamics in PXG and primary open-angle glaucoma (POAG) patients, and to analyze serum immunoglobulin G (IgG) APLAs levels in patients with PXG.
METHODS Forty-six OAG patients scheduled for glaucoma surgery, because of medically uncontrolled progressive glaucoma, were included in the prospective study. No washout period for topical antiglaucoma medication was scheduled, because patients were chosen with maximum tolerable topical treatment and uncontrolled IOP. Study procedures were carried out according to the Declaration of Helsinki, study protocol was approved by the Review Board of Lithuanian University of Health Sciences. Indiana University School of Medicine, Department of Ophthalmology, provided services as the analysis reading center site for RBF images. Study objectives and methods were explained to all patients prior examination. All patients signed informed consent form. Measurements included arterial BP and pulse rate, best corrected visual acuity, Goldmann applanation tonometry, POBF (Paradigm Medical Industries Inc., San Diego, CA), and color Doppler imaging (Accuvix, Seoul, Korea) performed in both eyes, before and 1 month after surgery at the same time of the day. RBF was measured using color Doppler imaging in the ophthalmic (OA), CRA, and temporal short posterior ciliary (tSPCA) arteries, assessing peak systolic velocity (PSV) and end-diastolic velocity and calculated resistance index (RI). Venous blood samples were obtained from PXG patients; IgG APLAs levels were assessed. PXG patients were divided depending on APLAs levels: patients with normal (< 15 GPLU/mL) and higher (borderline or increased) (Z15 GPLU/mL) APLA levels. The inclusion criteria were OAG patients above 18 years of age with medically uncontrolled IOP and progressing glaucoma, scheduled for surgical treatment and willing to sign informed consent form before initiation of the study. Pregnant or nursing women, patients with uncontrolled systemic diseases, planned combined cataract, and glaucoma surgery and patients with a history of other eye diseases or trauma were excluded from the study.
Statistical Analysis The statistical data analysis was performed using the computer program SPSS 17.0 for Windows. All variables were defined by methods of descriptive statistics. The analysis of the quantitative variables included calculation of the mean and SD [x (SD)]. Means of continuous variables were compared by the Student t test for independent samples. The Mann-Whitney nonparametric test was used when the assumption of the data Copyright
r
Ocular Hemodynamic Changes After Trabeculectomy
normality was rejected. Paired Samples t test or the Wilcoxon test was used to compute the difference between the 2 variables for each case to determine if the average difference is significantly different from 0. The level of significance P < 0.05 was considered significant.
RESULTS Forty-six OAG patients were recruited, but 16 patients discontinued from the study because of difficulties to perform all study procedures. Thirty OAG patients (56.7% woman, 43.3% men) aged 65.7 (9.7) years have finished all study procedures. Thirty eyes (13 right, 17 left) were examined. Seven patients had postoperative complications: 3—cystic bleb, 4—transient hypotony, all of which resolved by the second study visit. Per protocol, these patients were not excluded from the study. Fourteen patients carried the diagnosis of PXG and 16 patients had POAG. Patient characteristics are shown in Table 1. Patients were examined 1 day before surgery and 1 (0.3) month after surgery. Best corrected visual acuity was 0.33 (0.32) in PXG group and 0.49 (0.39) in POAG group, with no statistically significant changes after surgical glaucoma treatment, P > 0.05. Number of glaucoma medications statistically significantly decreased from 3.5 (0.7) to 0.3 (0.7) (a 91.4% reduction) in PXG group and from 2.9 (1.3) to 0.3 (0.7) (an 89.7% reduction) in POAG group, P < 0.05. A statistically significant decrease in IOP was noted in both groups after trabeculectomy, from 30.1 (7.2) to 15.0 (5.1) mm Hg (by 50.2%) in PXG group and from 29.1 (7.7) to 13.1 (5.5) mm Hg (by 55.0%) in POAG group, P < 0.05. OPP increased from 38.9 (10.3) to 55.5 (8.6) (by 42.7%) in PXG group and from 40.9 (11.0) to 56.7 (8.9) (by 38.6%) in POAG group; the same effect was achieved on SPP (respectively, by 19.1% and 16.2%), DPP (by 41.8% and 30.4%), P < 0.05 (Table 2). Changes in RBF and POBF parameters are shown in Table 3. Both groups showed statistically significant increases in CRA PSV after trabeculectomy (from 8.75 (2.27) to 9.79 (2.31) (by 11.9%) in PXG group and from 8.55 (2.59) to 10.11 (2.64) (by 18.2%) in POAG group (P < 0.05), although a statistically significant decrease in TABLE 1. Patients Characteristics
PXG Group POAG Group (N = 14) (N = 16) Mean (SD) Mean (SD) Age (y) Men [N (%)] Women [N (%)] Glaucoma treatment (y) Glaucoma medications Before surgery After surgery Glaucoma eye drops per day (before surgery) Systemic medications [N (%)] b-blockers ACE inhibitors Angiotensin II inhibitors Other drugs
66.4 6 8 3.5
(11.1) (42.9) (57.1) (3.3)
3.5 (0.7) 0.3 (0.7) 4.9 (0.5) 6 5 1 5
(42.9) (35.7) (7.1) (35.6)
65.1 7 9 8.4
(8.1) (43.7) (56.3) (7.2)
2.9 (1.3) 0.3 (0.7) 3.9 (1.8) 9 3 6 8
P 0.72 0.02* 0.17 0.89 0.30
(56.3) (37.5) (37.5) (50)
*Significance level P < 0.05. ACE indicates angiotensin converting enzyme; POAG, primary openangle glaucoma; PXG, pseudoexfoliative glaucoma.
2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.glaucomajournal.com |
e53
Januleviciene et al
J Glaucoma
Volume 24, Number 5, June/July 2015
TABLE 2. Changes in IOP, OPP, SPP, DPP, and BP After Trabeculectomy
PXG Group Before Surgery Mean (SD) IOP OPP SPP DPP Systolic BP Diastolic BP
30.1 38.9 106.6 52.9 136.7 83.5
POAG Group After Surgery Mean (SD)
(7.2) (10.3) (22.1) (10.3) (19.9) (6.6)
15.0 55.5 127.0 75.0 142.9 86.4
Before Surgery Mean (SD)
(5.1)* (8.6)* (16.3)* (15.4)* (15.0) (6.8)
29.1 40.9 113.1 54.3 142.2 83.4
After Surgery Mean (SD)
(7.7) (11.0) (23.8) (13.1) (19.5) (8.8)
13.1 56.7 131.4 70.8 144.4 83.8
(5.5)* (8.9)* (17.0)* (9.1)* (16.2) (6.8)
*Paired Samples t test or the Wilcoxon test. Significance level P < 0.05. BP indicates blood pressure; DPP, diastolic ocular perfusion pressure; IOP, intraocular pressure; OPP, ocular perfusion pressure; POAG, primary openangle glaucoma; PXG, pseudoexfoliative glaucoma; SPP, systolic ocular perfusion pressure.
DISCUSSION
RI was observed only in POAG group [tSPCA from 0.55 (0.06) to 0.49 (0.09) (by 10.9%), P < 0.05]. Both groups showed statistically significant increases in POBF [from 13.09 (3.41) to 18.81 (5.70) (by 43.7%) in PXG group and from 11.89 (5.79) to 19.29 (9.02) (by 55.1%) in POAG group, P < 0.05], although only POAG group showed a statistically significant increase in pulse volume [from 4.87 (2.31) to 6.63 (3.08) (by 25.3%), P < 0.05]. Analyzing patients with PXG, we found that 10 patients had normal APLAs levels 8.7 (2.9) GPLU/mL (range, 4.2 to 13.6) and 4 patients had higher APLAs levels 22.6 (7.1) GPLU/mL (range, 17.0 to 33.0). Characteristics of these patients are shown in Table 4. Patients with higher APLAs levels had lower IOP [28.8 (4.9)] and higher OPP [41.63 (8.23)] compared with patients with normal APLAs levels, but the difference was not statistically significant, P > 0.05. Patients with normal APLAs levels showed not only a statistically significant decrease in IOP [from 30.7 (8.1) to 15.2 (5.9) (by 50.5%)], but also increases in POBF [from 13.24 (3.69) to 19.94 (5.03)] (by 50.6%), CRA PSV [from 8.78 (2.39) to 9.46 (2.17)] (by 7.7%), and tSPCA PSV [from 7.61 (2.15) to 8.35 (1.98) (by 9.7%)], P < 0.05 (Table 5).
Results of our study showed that trabeculectomy statistically significantly decreased IOP and increased RBF parameters in patients with PXG and POAG. Both groups had a significant increase in CRA PSV, but a significant decrease in tSPCA RI was only observed in POAG patients. Trible et al22 found an increase in retrobulbar vessels flow velocities after trabeculectomy in POAG patients. Recently, Yamazaki and Hayamizu carried out a study evaluating the effect of trabeculectomy on ocular hemodynamics and visual field progression. Their results showed an increase in retrobulbar vessels velocities, decrease in RI, and stable visual field defects postoperatively compared with nonoperative eyes. Contrary to previously mentioned studies, Cantor23 did not find any significant improvement in ocular hemodynamics after trabeculectomy, but only 17 patients (19 eyes) were included in the study and elimination of possible confounding effects of ocular hypotensive agents may have influenced lack of significant change in RBF parameters. Previous researches showed that PXG is associated with impaired OBF. It seems that PEX widely affects vascular structures and increases RI.25 It may also be associated with
TABLE 3. Changes in RBF and POBF Velocities After Trabeculectomy
PXG Group
OA PSV (cm/s) EDV (cm/s) RI CRA PSV (cm/s) EDV (cm/s) RI tSPCA PSV (cm/s) EDV (cm/s) RI Pulse volume POBF
POAG Group
Before Surgery Mean (SD)
After Surgery Mean (SD)
Before Surgery Mean (SD)
After Surgery Mean (SD)
32.23 (4.88) 7.61 (3.24) 0.77 (0.08)
33.31 (5.82) 7.69 (3.07) 0.77 (0.08)
32.76 (7.89) 7.85 (4.03) 0.77 (0.08)
35.92 (12.28) 10.02 (4.61) 0.74 (0.09)
8.55 (2.59) 2.91 (0.49) 0.64 (0.08)
10.11 (2.64)* 3.58 (0.08)* 0.63 (0.08)
8.75 (2.27) 3.13 (0.56) 0.63 (0.07) 7.50 3.61 0.50 5.66 13.09
(1.85) (0.61) (0.12) (1.67) (3.41)
9.79 (2.31)* 3.33 (0.73) 0.64 (0.12) 8.28 3.95 0.52 7.46 18.81
(1.77)* (0.79) (0.09) (3.21) (5.70)*
7.45 3.36 0.55 4.87 11.89
(0.72) (0.41) (0.06) (2.31) (5.79)
7.92 3.99 0.49 6.63 19.29
(0.85) (0.71)* (0.09)* (3.08)* (9.02)*
*Paired Samples t test or the Wilcoxon test (significance level P < 0.05). CRA indicates central retinal artery; EDV, end-diastolic volume; OA, ophthalmic artery; POAG, primary open-angle glaucoma; POBF, pulsatile ocular blood flow; PSV, peak systolic volume; PXG, pseudoexfoliative glaucoma; RBF, retrobulbar blood flow; RI, resistance index; tSPCA, temporal short posterior ciliary artery.
e54 | www.glaucomajournal.com
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Glaucoma
Volume 24, Number 5, June/July 2015
Ocular Hemodynamic Changes After Trabeculectomy
TABLE 4. PXG Patients Characteristics According to APLAs Levels
Age (y) Body mass index (kg/m2) Glaucoma treatment period (y) No. systemic medications No. glaucoma medications
PXG Patients With Normal APLAs Level [8.7 (2.9)] (N = 10) Mean (SD)
PXG Patients With Higher APLAs Level [22.6 (7.1)] (N = 4) Mean (SD)
P
63.5 (11.6) 27.2 (3.8)
73.5 (6.4) 27.0 (2.2)
0.12 0.78
3.3 (3.0)
3.8 (4.4)
0.89
1.7 (1.5)
1.0 (0.8)
0.42
3.6 (0.5)
3.3 (0.9)
0.52
*Significance level P < 0.05. APLAs indicates antiphospholipidic antibodies; PXG, pseudoexfoliative glaucoma.
ischemic ophthalmic and systemic disorders.26 Martinez and Sanchez25 compared retrobulbar hemodynamic parameters in PEX syndrome and PXG. The study showed that hemodynamic parameters, especially in the central retinal artery (CRA), were significantly lower in patients with PXG. They also found that RBF parameters were more altered in POAG than in PXG.27 According to Kerr et al,28 POBF and pulse volume are significantly lower in untreated POAG patients or patients with ocular hypertension with IOP above 25 mm Hg. After topical treatment there was a significant increase in POBF associated with decreased IOP. Our study showed an increase in POBF parameters after trabeculectomy with significantly greater effect in POAG than PXG group. Higher POBF and pulse volume were associated with significant IOP decrease after surgery. James29 also showed an increase in POBF after surgical treatment. Our study found significant increase in OPP, SPP, and DPP after surgical treatment. These results could be possibly explained by significant postoperative decrease in IOP. OPP is a complex variable that might be affected by one or more of its components—mainly IOP and BP, but also several other factors as body posture, blood viscosity, vascular diameter, and others.30 In 2005, Berisha et al31 found significant increase in POBF and OPP after
trabeculectomy.31 Kara et al32 found that IOP decrease following trabeculectomy caused choroidal thickening associated with reduction in IOP, decreased axial length, and increased OPP. It is suggested that the balance between IOP and BP, influenced by autoregulatory capacity of the eye might determine whether an individual will develop progressing glaucomatous optic nerve damage. However, to better define the role of OPP in glaucoma progression or to support the value of increasing OPP as therapy for glaucoma, large scale, prospective longitudinal studies are needed. Altintas and colleagues found that plasma levels of APLA IgG in patients with PEX syndrome and PXG were statistically significantly higher than in healthy subjects. In our study we found different levels of APLAs in PXG, but 71.4% of patients had normal APLAs levels. Patients with higher APLAs levels were older and had lower baseline IOP. However, patients with normal APLA levels showed not only a significant decrease in IOP but also an increase in POBF, CRA, and tSPCA PSV after trabeculectomy. Results of our study did not show any significant difference in body mass index between groups, but other studies found that obese patients have higher APLAs levels.33 Authors suggest that elevated levels of APLAs in PEX and PXG patients may be associated with increased risk of vascular diseases.34 It is likely that higher APLAs levels indicate disturbed ocular vascular autoregulation, but it will require further studies for more detailed investigation. Limitations of our study were small number of study participants and difficulties for patients to attend all study procedures. This study did not include a washout period, and hypotensive agents could have possible sustained effects on RBF. Because of our small sample size, comparisons between different levels of APLAs were not possible in the current investigation. It is currently unknown whether or not APLAs are sensitive markers in glaucoma. In the Canadian Glaucoma Study, patients with an abnormal APLA level were almost 4 times likely to have glaucoma progression than patients with normal APLA levels. Although the hazard ratio was remarkably large and highly statistically significant in that study, only a small number of patients had positive APLA values.21
CONCLUSIONS Trabeculectomy resulted in a statistically significant decrease in IOP and increase in OBF parameters. Effects of
TABLE 5. PXG Patients IOP, OPP, RBF, and POBF Parameters According to APLAs Levels
PXG Patients With Normal APLAs Level [8.7 (2.9)] (N = 10)
IOP OPP CRA PSV tSPCA PSV POBF
PXG Patients With Higher APLAs Level [22.6 (7.1)] (N = 4)
Before Surgery Mean (SD)
After Surgery Mean (SD)
Before Surgery Mean (SD)
After Surgery Mean (SD)
30.7 (8.1) 37.7 (11.2)
15.2 (5.9)* 55.2 (8.54)*
28.8 (4.9) 41.63 (8.23)
14.5 (3.0)* 56.16 (10.19)
8.78 (2.39)
9.46 (2.17)*
8.67 (2.29)
10.59 (2.81)
7.61 (2.15) 13.24 (3.69)
8.35 (1.98)* 19.94 (5.03)*
7.25 (0.92) 12.75 (3.07)
8.09 (1.08) 16.00 (7.08)
*The Wilcoxon t test (significance level P < 0.05). APLAs indicates antiphospholipidic antibodies; CRA, central retinal artery; IOP, intraocular pressure; OPP, ocular perfusion pressure; POBF, pulsatile ocular blood flow; PSV, peak systolic volume; PXG, pseudoexfoliative glaucoma; RBF, retrobulbar blood flow; tSPCA, temporal short posterior ciliary artery.
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.glaucomajournal.com |
e55
Januleviciene et al
J Glaucoma
trabeculectomy in PXG patients were significantly less than in patients with POAG. Patients with normal APLA levels had a statistically significant increase in ocular hemodynamic parameters compared with patients with higher APLA levels. Further studies are required to analyze APLA effects in different patients groups. REFERENCES 1. Leske MC, Heijl A, Hussein M, et al. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol. 2003;121:48–56. 2. Cherecheanu AP, Garhofer G, Schmidl D, et al. Ocular perfusion pressure and ocular blood flow in glaucoma. Curr Opin Pharmacol. 2012;13:1–7. 3. Hwang JC, Kondur R, Zbang X, et al. Relationship among visual field, blood flow and neural structure measurements in glaucoma. Invest Ophthalmol Vis Sci. 2012;53:3020–3026. 4. Stuart WC, Feldman R, Mychaskiw MA. Ocular blood flow in glaucoma: the need further clinical evidence and patient outcomes research. Br J Ophtalmol. 2007;91:1263–1264. 5. Hayreh SS. Blood flow in the optic nerve head and factors that may influence it. Prog Retin Eye Res. 2001;20:595–624. 6. Deokule S, Vizzeri G, Boehm AG, et al. Correlation among choroidal, parapapillary, and retrobulbar vascular parameters in glaucoma. Am J Ophthalmol. 2009;147:736–743. 7. Bonomi L, Marchini G, Marraffa M, et al. Vascular risk factors for primary open angle glaucoma: the EgnaNeumarkt study. Ophthalmology. 2000;107:1287–1293. 8. Leske MC, Wu SY, Hennis A, et al. Risk factors for incident open-angle glaucoma: the Barbados Eye Studies. Ophthalmology. 2008;115:85–93. 9. Burgoyne CF. A biomechanical paradigm for axonal insult within the optic nerve head. Exp Eye Res. 2011;93:120–132. 10. Siesky B, Harris A, Kagemann L, et al. Ocular blood flow and oxygen delivery to the retina in primary open-angle glaucoma patients: The addition of dorzolamide to timolol monotherapy. Acta Ophthalmol. 2010;88:142–149. 11. Moss AM, Harris A, Siesky B, et al. Update and critical appraisal of combined timolol and carbonic anhydrase inhibitors and the effect on ocular blood flow in glaucoma patients. Clin Ophthalmol. 2010;4:233–241. 12. Siesky B, Harris A, Brizendine E, et al. Literature review and meta-analysis of topical carbonic anhydrase inhibitors and ocular blood flow. Surv Ophthalmol. 2009;54:33–46. 13. Bernd AS, Pillunat LE, Bo¨hm AG, et al. Ocular hemodynamics and visual field in glaucoma treated with dorzolamide. Ophthalmologe. 2001;98:451–455. 14. Bergstrand IC, Heijl A, Harris A. Dorzolamide and ocular blood flow in previously untreated glaucoma patients: a controlled double-masked study. Acta Ophthalmol Scand. 2002;80:176–182. 15. Nicolela MT, Buckley AR, Walman BE, et al. A comparative study of the effects of timolol and latanoprost on blood flow velocity of the retrobulbar vessels. Am J Ophthalmol. 1996;122:784–789. 16. Galassi F, Sodi A, Renieri G, et al. Effects of timolol and dorzolamide on retrobulbar hemodynamics in patients with newly diagnosed primary open-angle glaucoma. Ophthalmologica. 2002;216:123–128.
e56 | www.glaucomajournal.com
Volume 24, Number 5, June/July 2015
17. Mitchell P, Wang JJ, Hourihan F. The relationship between glaucoma and pseudoexfoliation: the Blue Mountains Eye Study. Arch Ophthalmol. 1999;117:1319–1324. 18. Schlo¨tzer-Schrehardt U, Naumann GO. Ocular and systemic pseudoexfoliation syndrome. Am J Ophthalmol. 2006;141: 921–937. 19. Yuksel N, Karabas VL, Arslan A, et al. Ocular hemodynamics in pseudoexfoliation syndrome and pseudoexfoliation glaucoma. Ophthalmology. 2001;108:1043–1049. 20. Yuksel N, Karabas VL, Demirci A, et al. Comparison of blood flow velocities of the extraocular vessels in patients with exfoliation or primary open-angle glaucoma. Eye. 2001;215: 424–429. 21. Chauhan BC, Mikelberg FS, Balaszi AG, et al. Canadian Glaucoma Study Group. Canadian Glaucoma Study, 2: risk factors for the progression of open-angle glaucoma. Arch Ophthalmol. 2008;126:1030–1036. 22. Trible JR, Costa VP, Sergott RC, et al. The influence of primary open-angle glaucoma upon the retrobulbar circulation: baseline, postoperative and reproducibility analysis. Trans Am Ophthalmol Soc. 1993;91:245–261; discussion 261-265. 23. Cantor LB. The effect of trabeculectomy on ocular hemodynamics. Tr Am Ophth Soc. 2001;99:241–252. 24. Yamazaki Y, Hayamizu F. Effect of trabeculectomy on retrobulbar circulation and visual field progression in patients with primary open-angle glaucoma. Clin Ophthalmol. 2012;6: 1539–1545. 25. Martinez A, Sanchez M. Retrobulbar hemodynamic parameters in pseudoexfoliations syndrome and pseudoexfoliative glaucoma. Graefes Arch Clin Exp Ophthalmol. 2008;246: 1341–1349. 26. Mitchell P, Wang JJ, Smith W. Association of exfoliation syndrome with increased vascular risk. Am J Ophthalmol. 1997;124:685–687. 27. Martinez A, Sanchez M. Ocular haemodynamics in pseudoexfoliative and primary open-angle glaucoma. Eye. 2008;22: 515–520. 28. Kerr J, Nelson P, O’Brien C. Pulsatile ocular blood flow in primary open-angle glaucoma and ocular hypertension. Am J Ophthalmol. 2003;136:1106–1113. 29. James CB. Effect of trabeculectomy on pulsatile ocular blood flow. Br J Ophthalmol. 1994;78:818–822. 30. Ramdas WD, Volfs RCW, Hofman A, et al. Ocular perfusion pressure and the incidence of glaucoma: real effect or artifact?: the Rotterdam study. Invest Ophthalmol Vis Sci. 2011;52: 6875–6881. 31. Berisha F, Schmetterer K, Vass C, et al. Effect of trabeculectomy on ocular blood flow. Br J Ophthalmol. 2005;89:185–188. 32. Kara N, Baz O, Altan C, et al. Changes in choroidal thickness, axial length, and ocular perfusion pressure accompanying successful glaucoma filtration surgery. Eye (Lond). 2013; 27:940–945. 33. Marcovina SM, Koschinsky ML, Albers JJ, et al. Report of the national heart, lung, and blood institute workshop on lipoprotein(a) and cardiovascular disease: recent advances and future directions. Clin Chem. 2003;49:1785–1796. 34. Altintas O, Yuksel N, Sonmez GT, et al. Serum antiphospholipid antibody levels in pseudoexfoliation. J Glaucoma. 2012; 21:326–330.
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Effect of Trabeculectomy on Ocular Hemodynamic Parameters in Pseudoexfoliative and Primary Open-angle Glaucoma Patients Ingrida Januleviciene, MD, PhD,* Lina Siaudvytyte, MS,* Vaida Diliene, MS,* Ruta Barsauskaite, MS,* Brent Siesky, PhD,w and Alon Harris, MS, PhD, FARVOw
Purpose: To evaluate the effects of trabeculectomy on ocular hemodynamic parameters in pseudoexfoliative glaucoma (PXG) and primary open-angle glaucoma (POAG) patients and to analyze serum antiphospholipid antibody levels (APLAs) in PXG. Methods: Thirty open-angle glaucoma patients were included in the prospective study. Intraocular pressure (IOP), ocular perfusion pressure (OPP), blood pressure, and pulsatile ocular blood flow (POBF) were measured. Retrobulbar blood flow (RBF) was measured using the color Doppler imaging. Venous blood samples were obtained from PXG patients; APLAs IgG levels were assessed. The level of significance was P < 0.05. Results: IOP decreased significantly in both groups after trabeculectomy [from 30.1 (7.2) to 15.0 (5.1) in PXG; from 29.1 (7.7) to 13.1 (5.5) in POAG, P < 0.05]. OPP increased from 38.9 (10.3) to 55.5 (8.6) in PXG and from 40.9 (11.0) to 56.7 (8.9) in POAG group, P < 0.05. Both groups showed significant increase in CRA PSV [from 8.75 (2.27) to 9.79 (2.31) in PXG and from 8.55 (2.59) to 10.11 (2.64) in POAG, P < 0.05]. Both groups showed an increase in POBF [from 13.09 (3.41) to 18.81 (5.70) in PXG and from 11.89 (5.79) to 19.29 (9.02) in POAG, P < 0.05). Patients with normal APLAs levels showed significant decrease in IOP [from 30.7 (8.1) to 15.2 (5.9)] and increase in POBF [from 13.24 (3.69) to 19.94 (5.03)], CRA PSV [from 8.78 (2.39) to 9.46 (2.17)], and tSPCA PSV [from 7.61 (2.15) to 8.35 (1.98)], P < 0.05. Conclusions: Trabeculectomy resulted in a significant decrease in IOP and increase in ocular blood flow. Effects of trabeculectomy in PXG patients were significantly less compared with POAG. Patients with normal APLA levels had a significant increase in ocular hemodynamic parameters compared with patients with higher APLAs levels. Key Words: trabeculectomy, retrobulbar blood flow, pulsatile ocular blood flow, antiphospholipid, pseudoexfoliative glaucoma, primary open-angle glaucoma
(J Glaucoma 2015;24:e52–e56)
Received for publication January 14, 2013; accepted March 4, 2014. From the *Eye Clinic, Lithuanian University of Health Sciences, Kaunas, Lithuania; and wGlaucoma Research and Diagnostic Center, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN. Disclosure: The authors declare no conflict of interest. Reprints: Ingrida Januleviciene, MD, PhD, Eye Clinic, Lithuanian University of Health Sciences, Eiveniu str. 2, Kaunas 50009, Lithuania (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/IJG.0000000000000055
e52 | www.glaucomajournal.com
G
laucoma is an optic neuropathy leading to the retinal ganglion cell (RGC) death and typical optic nerve head (ONH) damage. Intraocular pressure (IOP) is the main and only modifiable risk factor for glaucoma.1 However, in some patients glaucoma continues to progress despite good IOP control. This indicates that other pathogenetic mechanisms beyond IOP might be involved in the pathogenesis of glaucoma. Lately, more attention has concentrated on vascular theory of glaucoma and pharmacological ocular blood flow (OBF) modulation.2–6 Vascular theory is based on the idea of abnormal perfusion due to either increased IOP or other factors leading to ONH ischemia because of breakdown of autoregulation. Autoregulation is unable to operate efficiently at very high or very low perfusion pressure levels.5 Normal perfusion pressure is uniquely individual and varies with certain cardiovascular disorders.5 Several studies have indicated that low blood pressure (BP) is a risk factor for glaucoma and compromised ocular perfusion.7 Barbados Eye Study indicated that lower BP doubles the risk for glaucoma.8 Recent studies have shown an association between nocturnal arterial hypotension and glaucomatous visual loss.5 Cherecheanu and colleagues proposed a model including a 2 insults theory, with the primary insult occurring at the ONH. Increased IOP and ischemia at the postlaminar ONH affects RGC.2 Consequently, RGCs are forced to function at reduced energy levels and are sensitive to secondary insults such as low ocular perfusion pressure (OPP), which cannot be compensated by autoregulation. That, together with oxidative stress, can ultimately lead to RGC death.2 Other modulating factors can also increase susceptibility for further damage.9 It is known that certain eye drops may have impact on OBF and its regulation. Some data support increased blood flow and the enhancement of OBF regulation with carbonic anhydrase inhibitors. Several studies have shown dorzolamide’s ability to increase various measures of OBF parameters,10–12 although other studies failed to show similar effect.13,14 Dorzolamide’s vasodilatory effects might be explained by induced acidosis in local tissues. In a mechanism different than dorzolamide, timolol may cause vasoconstriction by blocking b-2 receptors. However, some studies reported that a single instillation of timolol did not have significant effect on the retrobulbar blood flow (RBF).15,16 Pseudoexfoliation (PEX) syndrome is the most identifiable risk factor for open-angle glaucoma (OAG).17 Although pseudoexfoliative glaucoma (PXG) is associated with high pressure disease, pressure-independent risk factors, such as impaired OBF and RBF, may be present.18–20 During recent years, PEX syndrome has been shown to be a systemic process associated with cardiovascular and J Glaucoma
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Volume 24, Number 5, June/July 2015
J Glaucoma
Volume 24, Number 5, June/July 2015
cerebrovascular diseases. Antiphospholipid antibodies (APLAs) are autoantibodies directed against phospholipids and phospholipid protein complexes, which are the main constituents of all membranes. Canadian Glaucoma Study found that glaucoma patients with abnormal anticardiolipin antibody levels had a 4 times increased risk for visual field progression.21 In cases of uncontrolled IOP and progressing glaucoma, filtering surgeries are indicated. Several studies analyzed effects of trabeculectomy on ocular hemodynamics. Some researchers showed increased RBF and pulsatile ocular blood flow (POBF) after trabeculectomy, whereas other studies did not show a positive postoperative effect.22–24 The aims of our study were to evaluate the effects of trabeculectomy on ocular hemodynamics in PXG and primary open-angle glaucoma (POAG) patients, and to analyze serum immunoglobulin G (IgG) APLAs levels in patients with PXG.
METHODS Forty-six OAG patients scheduled for glaucoma surgery, because of medically uncontrolled progressive glaucoma, were included in the prospective study. No washout period for topical antiglaucoma medication was scheduled, because patients were chosen with maximum tolerable topical treatment and uncontrolled IOP. Study procedures were carried out according to the Declaration of Helsinki, study protocol was approved by the Review Board of Lithuanian University of Health Sciences. Indiana University School of Medicine, Department of Ophthalmology, provided services as the analysis reading center site for RBF images. Study objectives and methods were explained to all patients prior examination. All patients signed informed consent form. Measurements included arterial BP and pulse rate, best corrected visual acuity, Goldmann applanation tonometry, POBF (Paradigm Medical Industries Inc., San Diego, CA), and color Doppler imaging (Accuvix, Seoul, Korea) performed in both eyes, before and 1 month after surgery at the same time of the day. RBF was measured using color Doppler imaging in the ophthalmic (OA), CRA, and temporal short posterior ciliary (tSPCA) arteries, assessing peak systolic velocity (PSV) and end-diastolic velocity and calculated resistance index (RI). Venous blood samples were obtained from PXG patients; IgG APLAs levels were assessed. PXG patients were divided depending on APLAs levels: patients with normal (< 15 GPLU/mL) and higher (borderline or increased) (Z15 GPLU/mL) APLA levels. The inclusion criteria were OAG patients above 18 years of age with medically uncontrolled IOP and progressing glaucoma, scheduled for surgical treatment and willing to sign informed consent form before initiation of the study. Pregnant or nursing women, patients with uncontrolled systemic diseases, planned combined cataract, and glaucoma surgery and patients with a history of other eye diseases or trauma were excluded from the study.
Statistical Analysis The statistical data analysis was performed using the computer program SPSS 17.0 for Windows. All variables were defined by methods of descriptive statistics. The analysis of the quantitative variables included calculation of the mean and SD [x (SD)]. Means of continuous variables were compared by the Student t test for independent samples. The Mann-Whitney nonparametric test was used when the assumption of the data Copyright
r
Ocular Hemodynamic Changes After Trabeculectomy
normality was rejected. Paired Samples t test or the Wilcoxon test was used to compute the difference between the 2 variables for each case to determine if the average difference is significantly different from 0. The level of significance P < 0.05 was considered significant.
RESULTS Forty-six OAG patients were recruited, but 16 patients discontinued from the study because of difficulties to perform all study procedures. Thirty OAG patients (56.7% woman, 43.3% men) aged 65.7 (9.7) years have finished all study procedures. Thirty eyes (13 right, 17 left) were examined. Seven patients had postoperative complications: 3—cystic bleb, 4—transient hypotony, all of which resolved by the second study visit. Per protocol, these patients were not excluded from the study. Fourteen patients carried the diagnosis of PXG and 16 patients had POAG. Patient characteristics are shown in Table 1. Patients were examined 1 day before surgery and 1 (0.3) month after surgery. Best corrected visual acuity was 0.33 (0.32) in PXG group and 0.49 (0.39) in POAG group, with no statistically significant changes after surgical glaucoma treatment, P > 0.05. Number of glaucoma medications statistically significantly decreased from 3.5 (0.7) to 0.3 (0.7) (a 91.4% reduction) in PXG group and from 2.9 (1.3) to 0.3 (0.7) (an 89.7% reduction) in POAG group, P < 0.05. A statistically significant decrease in IOP was noted in both groups after trabeculectomy, from 30.1 (7.2) to 15.0 (5.1) mm Hg (by 50.2%) in PXG group and from 29.1 (7.7) to 13.1 (5.5) mm Hg (by 55.0%) in POAG group, P < 0.05. OPP increased from 38.9 (10.3) to 55.5 (8.6) (by 42.7%) in PXG group and from 40.9 (11.0) to 56.7 (8.9) (by 38.6%) in POAG group; the same effect was achieved on SPP (respectively, by 19.1% and 16.2%), DPP (by 41.8% and 30.4%), P < 0.05 (Table 2). Changes in RBF and POBF parameters are shown in Table 3. Both groups showed statistically significant increases in CRA PSV after trabeculectomy (from 8.75 (2.27) to 9.79 (2.31) (by 11.9%) in PXG group and from 8.55 (2.59) to 10.11 (2.64) (by 18.2%) in POAG group (P < 0.05), although a statistically significant decrease in TABLE 1. Patients Characteristics
PXG Group POAG Group (N = 14) (N = 16) Mean (SD) Mean (SD) Age (y) Men [N (%)] Women [N (%)] Glaucoma treatment (y) Glaucoma medications Before surgery After surgery Glaucoma eye drops per day (before surgery) Systemic medications [N (%)] b-blockers ACE inhibitors Angiotensin II inhibitors Other drugs
66.4 6 8 3.5
(11.1) (42.9) (57.1) (3.3)
3.5 (0.7) 0.3 (0.7) 4.9 (0.5) 6 5 1 5
(42.9) (35.7) (7.1) (35.6)
65.1 7 9 8.4
(8.1) (43.7) (56.3) (7.2)
2.9 (1.3) 0.3 (0.7) 3.9 (1.8) 9 3 6 8
P 0.72 0.02* 0.17 0.89 0.30
(56.3) (37.5) (37.5) (50)
*Significance level P < 0.05. ACE indicates angiotensin converting enzyme; POAG, primary openangle glaucoma; PXG, pseudoexfoliative glaucoma.
2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.glaucomajournal.com |
e53
Januleviciene et al
J Glaucoma
Volume 24, Number 5, June/July 2015
TABLE 2. Changes in IOP, OPP, SPP, DPP, and BP After Trabeculectomy
PXG Group Before Surgery Mean (SD) IOP OPP SPP DPP Systolic BP Diastolic BP
30.1 38.9 106.6 52.9 136.7 83.5
POAG Group After Surgery Mean (SD)
(7.2) (10.3) (22.1) (10.3) (19.9) (6.6)
15.0 55.5 127.0 75.0 142.9 86.4
Before Surgery Mean (SD)
(5.1)* (8.6)* (16.3)* (15.4)* (15.0) (6.8)
29.1 40.9 113.1 54.3 142.2 83.4
After Surgery Mean (SD)
(7.7) (11.0) (23.8) (13.1) (19.5) (8.8)
13.1 56.7 131.4 70.8 144.4 83.8
(5.5)* (8.9)* (17.0)* (9.1)* (16.2) (6.8)
*Paired Samples t test or the Wilcoxon test. Significance level P < 0.05. BP indicates blood pressure; DPP, diastolic ocular perfusion pressure; IOP, intraocular pressure; OPP, ocular perfusion pressure; POAG, primary openangle glaucoma; PXG, pseudoexfoliative glaucoma; SPP, systolic ocular perfusion pressure.
DISCUSSION
RI was observed only in POAG group [tSPCA from 0.55 (0.06) to 0.49 (0.09) (by 10.9%), P < 0.05]. Both groups showed statistically significant increases in POBF [from 13.09 (3.41) to 18.81 (5.70) (by 43.7%) in PXG group and from 11.89 (5.79) to 19.29 (9.02) (by 55.1%) in POAG group, P < 0.05], although only POAG group showed a statistically significant increase in pulse volume [from 4.87 (2.31) to 6.63 (3.08) (by 25.3%), P < 0.05]. Analyzing patients with PXG, we found that 10 patients had normal APLAs levels 8.7 (2.9) GPLU/mL (range, 4.2 to 13.6) and 4 patients had higher APLAs levels 22.6 (7.1) GPLU/mL (range, 17.0 to 33.0). Characteristics of these patients are shown in Table 4. Patients with higher APLAs levels had lower IOP [28.8 (4.9)] and higher OPP [41.63 (8.23)] compared with patients with normal APLAs levels, but the difference was not statistically significant, P > 0.05. Patients with normal APLAs levels showed not only a statistically significant decrease in IOP [from 30.7 (8.1) to 15.2 (5.9) (by 50.5%)], but also increases in POBF [from 13.24 (3.69) to 19.94 (5.03)] (by 50.6%), CRA PSV [from 8.78 (2.39) to 9.46 (2.17)] (by 7.7%), and tSPCA PSV [from 7.61 (2.15) to 8.35 (1.98) (by 9.7%)], P < 0.05 (Table 5).
Results of our study showed that trabeculectomy statistically significantly decreased IOP and increased RBF parameters in patients with PXG and POAG. Both groups had a significant increase in CRA PSV, but a significant decrease in tSPCA RI was only observed in POAG patients. Trible et al22 found an increase in retrobulbar vessels flow velocities after trabeculectomy in POAG patients. Recently, Yamazaki and Hayamizu carried out a study evaluating the effect of trabeculectomy on ocular hemodynamics and visual field progression. Their results showed an increase in retrobulbar vessels velocities, decrease in RI, and stable visual field defects postoperatively compared with nonoperative eyes. Contrary to previously mentioned studies, Cantor23 did not find any significant improvement in ocular hemodynamics after trabeculectomy, but only 17 patients (19 eyes) were included in the study and elimination of possible confounding effects of ocular hypotensive agents may have influenced lack of significant change in RBF parameters. Previous researches showed that PXG is associated with impaired OBF. It seems that PEX widely affects vascular structures and increases RI.25 It may also be associated with
TABLE 3. Changes in RBF and POBF Velocities After Trabeculectomy
PXG Group
OA PSV (cm/s) EDV (cm/s) RI CRA PSV (cm/s) EDV (cm/s) RI tSPCA PSV (cm/s) EDV (cm/s) RI Pulse volume POBF
POAG Group
Before Surgery Mean (SD)
After Surgery Mean (SD)
Before Surgery Mean (SD)
After Surgery Mean (SD)
32.23 (4.88) 7.61 (3.24) 0.77 (0.08)
33.31 (5.82) 7.69 (3.07) 0.77 (0.08)
32.76 (7.89) 7.85 (4.03) 0.77 (0.08)
35.92 (12.28) 10.02 (4.61) 0.74 (0.09)
8.55 (2.59) 2.91 (0.49) 0.64 (0.08)
10.11 (2.64)* 3.58 (0.08)* 0.63 (0.08)
8.75 (2.27) 3.13 (0.56) 0.63 (0.07) 7.50 3.61 0.50 5.66 13.09
(1.85) (0.61) (0.12) (1.67) (3.41)
9.79 (2.31)* 3.33 (0.73) 0.64 (0.12) 8.28 3.95 0.52 7.46 18.81
(1.77)* (0.79) (0.09) (3.21) (5.70)*
7.45 3.36 0.55 4.87 11.89
(0.72) (0.41) (0.06) (2.31) (5.79)
7.92 3.99 0.49 6.63 19.29
(0.85) (0.71)* (0.09)* (3.08)* (9.02)*
*Paired Samples t test or the Wilcoxon test (significance level P < 0.05). CRA indicates central retinal artery; EDV, end-diastolic volume; OA, ophthalmic artery; POAG, primary open-angle glaucoma; POBF, pulsatile ocular blood flow; PSV, peak systolic volume; PXG, pseudoexfoliative glaucoma; RBF, retrobulbar blood flow; RI, resistance index; tSPCA, temporal short posterior ciliary artery.
e54 | www.glaucomajournal.com
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Glaucoma
Volume 24, Number 5, June/July 2015
Ocular Hemodynamic Changes After Trabeculectomy
TABLE 4. PXG Patients Characteristics According to APLAs Levels
Age (y) Body mass index (kg/m2) Glaucoma treatment period (y) No. systemic medications No. glaucoma medications
PXG Patients With Normal APLAs Level [8.7 (2.9)] (N = 10) Mean (SD)
PXG Patients With Higher APLAs Level [22.6 (7.1)] (N = 4) Mean (SD)
P
63.5 (11.6) 27.2 (3.8)
73.5 (6.4) 27.0 (2.2)
0.12 0.78
3.3 (3.0)
3.8 (4.4)
0.89
1.7 (1.5)
1.0 (0.8)
0.42
3.6 (0.5)
3.3 (0.9)
0.52
*Significance level P < 0.05. APLAs indicates antiphospholipidic antibodies; PXG, pseudoexfoliative glaucoma.
ischemic ophthalmic and systemic disorders.26 Martinez and Sanchez25 compared retrobulbar hemodynamic parameters in PEX syndrome and PXG. The study showed that hemodynamic parameters, especially in the central retinal artery (CRA), were significantly lower in patients with PXG. They also found that RBF parameters were more altered in POAG than in PXG.27 According to Kerr et al,28 POBF and pulse volume are significantly lower in untreated POAG patients or patients with ocular hypertension with IOP above 25 mm Hg. After topical treatment there was a significant increase in POBF associated with decreased IOP. Our study showed an increase in POBF parameters after trabeculectomy with significantly greater effect in POAG than PXG group. Higher POBF and pulse volume were associated with significant IOP decrease after surgery. James29 also showed an increase in POBF after surgical treatment. Our study found significant increase in OPP, SPP, and DPP after surgical treatment. These results could be possibly explained by significant postoperative decrease in IOP. OPP is a complex variable that might be affected by one or more of its components—mainly IOP and BP, but also several other factors as body posture, blood viscosity, vascular diameter, and others.30 In 2005, Berisha et al31 found significant increase in POBF and OPP after
trabeculectomy.31 Kara et al32 found that IOP decrease following trabeculectomy caused choroidal thickening associated with reduction in IOP, decreased axial length, and increased OPP. It is suggested that the balance between IOP and BP, influenced by autoregulatory capacity of the eye might determine whether an individual will develop progressing glaucomatous optic nerve damage. However, to better define the role of OPP in glaucoma progression or to support the value of increasing OPP as therapy for glaucoma, large scale, prospective longitudinal studies are needed. Altintas and colleagues found that plasma levels of APLA IgG in patients with PEX syndrome and PXG were statistically significantly higher than in healthy subjects. In our study we found different levels of APLAs in PXG, but 71.4% of patients had normal APLAs levels. Patients with higher APLAs levels were older and had lower baseline IOP. However, patients with normal APLA levels showed not only a significant decrease in IOP but also an increase in POBF, CRA, and tSPCA PSV after trabeculectomy. Results of our study did not show any significant difference in body mass index between groups, but other studies found that obese patients have higher APLAs levels.33 Authors suggest that elevated levels of APLAs in PEX and PXG patients may be associated with increased risk of vascular diseases.34 It is likely that higher APLAs levels indicate disturbed ocular vascular autoregulation, but it will require further studies for more detailed investigation. Limitations of our study were small number of study participants and difficulties for patients to attend all study procedures. This study did not include a washout period, and hypotensive agents could have possible sustained effects on RBF. Because of our small sample size, comparisons between different levels of APLAs were not possible in the current investigation. It is currently unknown whether or not APLAs are sensitive markers in glaucoma. In the Canadian Glaucoma Study, patients with an abnormal APLA level were almost 4 times likely to have glaucoma progression than patients with normal APLA levels. Although the hazard ratio was remarkably large and highly statistically significant in that study, only a small number of patients had positive APLA values.21
CONCLUSIONS Trabeculectomy resulted in a statistically significant decrease in IOP and increase in OBF parameters. Effects of
TABLE 5. PXG Patients IOP, OPP, RBF, and POBF Parameters According to APLAs Levels
PXG Patients With Normal APLAs Level [8.7 (2.9)] (N = 10)
IOP OPP CRA PSV tSPCA PSV POBF
PXG Patients With Higher APLAs Level [22.6 (7.1)] (N = 4)
Before Surgery Mean (SD)
After Surgery Mean (SD)
Before Surgery Mean (SD)
After Surgery Mean (SD)
30.7 (8.1) 37.7 (11.2)
15.2 (5.9)* 55.2 (8.54)*
28.8 (4.9) 41.63 (8.23)
14.5 (3.0)* 56.16 (10.19)
8.78 (2.39)
9.46 (2.17)*
8.67 (2.29)
10.59 (2.81)
7.61 (2.15) 13.24 (3.69)
8.35 (1.98)* 19.94 (5.03)*
7.25 (0.92) 12.75 (3.07)
8.09 (1.08) 16.00 (7.08)
*The Wilcoxon t test (significance level P < 0.05). APLAs indicates antiphospholipidic antibodies; CRA, central retinal artery; IOP, intraocular pressure; OPP, ocular perfusion pressure; POBF, pulsatile ocular blood flow; PSV, peak systolic volume; PXG, pseudoexfoliative glaucoma; RBF, retrobulbar blood flow; tSPCA, temporal short posterior ciliary artery.
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.glaucomajournal.com |
e55
Januleviciene et al
J Glaucoma
trabeculectomy in PXG patients were significantly less than in patients with POAG. Patients with normal APLA levels had a statistically significant increase in ocular hemodynamic parameters compared with patients with higher APLA levels. Further studies are required to analyze APLA effects in different patients groups. REFERENCES 1. Leske MC, Heijl A, Hussein M, et al. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol. 2003;121:48–56. 2. Cherecheanu AP, Garhofer G, Schmidl D, et al. Ocular perfusion pressure and ocular blood flow in glaucoma. Curr Opin Pharmacol. 2012;13:1–7. 3. Hwang JC, Kondur R, Zbang X, et al. Relationship among visual field, blood flow and neural structure measurements in glaucoma. Invest Ophthalmol Vis Sci. 2012;53:3020–3026. 4. Stuart WC, Feldman R, Mychaskiw MA. Ocular blood flow in glaucoma: the need further clinical evidence and patient outcomes research. Br J Ophtalmol. 2007;91:1263–1264. 5. Hayreh SS. Blood flow in the optic nerve head and factors that may influence it. Prog Retin Eye Res. 2001;20:595–624. 6. Deokule S, Vizzeri G, Boehm AG, et al. Correlation among choroidal, parapapillary, and retrobulbar vascular parameters in glaucoma. Am J Ophthalmol. 2009;147:736–743. 7. Bonomi L, Marchini G, Marraffa M, et al. Vascular risk factors for primary open angle glaucoma: the EgnaNeumarkt study. Ophthalmology. 2000;107:1287–1293. 8. Leske MC, Wu SY, Hennis A, et al. Risk factors for incident open-angle glaucoma: the Barbados Eye Studies. Ophthalmology. 2008;115:85–93. 9. Burgoyne CF. A biomechanical paradigm for axonal insult within the optic nerve head. Exp Eye Res. 2011;93:120–132. 10. Siesky B, Harris A, Kagemann L, et al. Ocular blood flow and oxygen delivery to the retina in primary open-angle glaucoma patients: The addition of dorzolamide to timolol monotherapy. Acta Ophthalmol. 2010;88:142–149. 11. Moss AM, Harris A, Siesky B, et al. Update and critical appraisal of combined timolol and carbonic anhydrase inhibitors and the effect on ocular blood flow in glaucoma patients. Clin Ophthalmol. 2010;4:233–241. 12. Siesky B, Harris A, Brizendine E, et al. Literature review and meta-analysis of topical carbonic anhydrase inhibitors and ocular blood flow. Surv Ophthalmol. 2009;54:33–46. 13. Bernd AS, Pillunat LE, Bo¨hm AG, et al. Ocular hemodynamics and visual field in glaucoma treated with dorzolamide. Ophthalmologe. 2001;98:451–455. 14. Bergstrand IC, Heijl A, Harris A. Dorzolamide and ocular blood flow in previously untreated glaucoma patients: a controlled double-masked study. Acta Ophthalmol Scand. 2002;80:176–182. 15. Nicolela MT, Buckley AR, Walman BE, et al. A comparative study of the effects of timolol and latanoprost on blood flow velocity of the retrobulbar vessels. Am J Ophthalmol. 1996;122:784–789. 16. Galassi F, Sodi A, Renieri G, et al. Effects of timolol and dorzolamide on retrobulbar hemodynamics in patients with newly diagnosed primary open-angle glaucoma. Ophthalmologica. 2002;216:123–128.
e56 | www.glaucomajournal.com
Volume 24, Number 5, June/July 2015
17. Mitchell P, Wang JJ, Hourihan F. The relationship between glaucoma and pseudoexfoliation: the Blue Mountains Eye Study. Arch Ophthalmol. 1999;117:1319–1324. 18. Schlo¨tzer-Schrehardt U, Naumann GO. Ocular and systemic pseudoexfoliation syndrome. Am J Ophthalmol. 2006;141: 921–937. 19. Yuksel N, Karabas VL, Arslan A, et al. Ocular hemodynamics in pseudoexfoliation syndrome and pseudoexfoliation glaucoma. Ophthalmology. 2001;108:1043–1049. 20. Yuksel N, Karabas VL, Demirci A, et al. Comparison of blood flow velocities of the extraocular vessels in patients with exfoliation or primary open-angle glaucoma. Eye. 2001;215: 424–429. 21. Chauhan BC, Mikelberg FS, Balaszi AG, et al. Canadian Glaucoma Study Group. Canadian Glaucoma Study, 2: risk factors for the progression of open-angle glaucoma. Arch Ophthalmol. 2008;126:1030–1036. 22. Trible JR, Costa VP, Sergott RC, et al. The influence of primary open-angle glaucoma upon the retrobulbar circulation: baseline, postoperative and reproducibility analysis. Trans Am Ophthalmol Soc. 1993;91:245–261; discussion 261-265. 23. Cantor LB. The effect of trabeculectomy on ocular hemodynamics. Tr Am Ophth Soc. 2001;99:241–252. 24. Yamazaki Y, Hayamizu F. Effect of trabeculectomy on retrobulbar circulation and visual field progression in patients with primary open-angle glaucoma. Clin Ophthalmol. 2012;6: 1539–1545. 25. Martinez A, Sanchez M. Retrobulbar hemodynamic parameters in pseudoexfoliations syndrome and pseudoexfoliative glaucoma. Graefes Arch Clin Exp Ophthalmol. 2008;246: 1341–1349. 26. Mitchell P, Wang JJ, Smith W. Association of exfoliation syndrome with increased vascular risk. Am J Ophthalmol. 1997;124:685–687. 27. Martinez A, Sanchez M. Ocular haemodynamics in pseudoexfoliative and primary open-angle glaucoma. Eye. 2008;22: 515–520. 28. Kerr J, Nelson P, O’Brien C. Pulsatile ocular blood flow in primary open-angle glaucoma and ocular hypertension. Am J Ophthalmol. 2003;136:1106–1113. 29. James CB. Effect of trabeculectomy on pulsatile ocular blood flow. Br J Ophthalmol. 1994;78:818–822. 30. Ramdas WD, Volfs RCW, Hofman A, et al. Ocular perfusion pressure and the incidence of glaucoma: real effect or artifact?: the Rotterdam study. Invest Ophthalmol Vis Sci. 2011;52: 6875–6881. 31. Berisha F, Schmetterer K, Vass C, et al. Effect of trabeculectomy on ocular blood flow. Br J Ophthalmol. 2005;89:185–188. 32. Kara N, Baz O, Altan C, et al. Changes in choroidal thickness, axial length, and ocular perfusion pressure accompanying successful glaucoma filtration surgery. Eye (Lond). 2013; 27:940–945. 33. Marcovina SM, Koschinsky ML, Albers JJ, et al. Report of the national heart, lung, and blood institute workshop on lipoprotein(a) and cardiovascular disease: recent advances and future directions. Clin Chem. 2003;49:1785–1796. 34. Altintas O, Yuksel N, Sonmez GT, et al. Serum antiphospholipid antibody levels in pseudoexfoliation. J Glaucoma. 2012; 21:326–330.
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
