To explore the relationship between plasma and aqueous humor (AH) endothelin-1 (ET-1) levels and retinal microvascular parameters measured by optical coherence tomography angiography (OCT-A) in pseudoexfoliative glaucoma (XFG) and primary open-angle glaucoma (POAG) patients versus controls.
Methods
The plasma and AH ET-1 levels were assessed using enzyme-linked immunosorbent assay (ELISA) in 23 patients with XFG, 20 patients with POAG and 34 control subjects who underwent elective cataract surgery. Microvascular parameters in the optic disc and macula were measured by OCT-A four months after surgery. The relationship between plasma and AH ET-1 levels and OCT-A parameters was analysed.
Results
This study included 77 eyes of 77 participants. The XFG group had higher AH ET-1 levels compared to both control (p = 0.009) and POAG (p = 0.004) groups, whereas the POAG and control groups were similar (p = 0.999). Negative correlation was found between AH ET-1 levels and whole, parafoveal, perifoveal superficial capillary plexus vascular density (SCP VD) (p < 0.05 for all) and whole, peripapillary, superior hemisphere, inferior hemisphere, inferior temporal radial peripapillary capillary vascular density (RPC VD) (p < 0.05 for all). The plasma ET-1 levels did not differ significantly among the groups (p = 0.161), and no statistically significant correlation was observed between the plasma ET-1 levels and any OCT-A parameter.
Conclusion
While plasma ET-1 levels showed no differences between groups or correlation with OCT-A parameters, elevated AH ET-1 levels in XFG and their strong correlation with OCT-A vascular parameters suggest that the intraocular effects of ET-1 may be more significant than its systemic effects in XFG pathogenesis.
WeinrebRNAungTMedeirosFA. The pathophysiology and treatment of glaucoma: a review. Jama2014; 311: 1901–1911.
2.
LommatzschCRothausKSchopmeyerL, et al.Elevated endothelin-1 levels as risk factor for an impaired ocular blood flow measured by OCT-A in glaucoma. Sci Rep2022; 12: 11801.
3.
European glaucoma society terminology and guidelines for glaucoma, 5th edition. Br J Ophthalmol2021; 105: 1–169.
4.
FlammerJOrgülSCostaVP, et al.The impact of ocular blood flow in glaucoma. Prog Retin Eye Res2002; 21: 359–393.
5.
BayraktarSİpekATakmazT, et al.Ocular blood flow and choroidal thickness in ocular hypertension. Int Ophthalmol2022; 42: 1357–1368.
6.
CelliniMStrobbeEGizziC, et al.Endothelin-1 plasma levels and vascular endothelial dysfunction in primary open angle glaucoma. Life Sci2012; 91: 699–702.
7.
ChenCLBojikianKDGuptaD, et al.Optic nerve head perfusion in normal eyes and eyes with glaucoma using optical coherence tomography-based microangiography. Quant Imaging Med Surg2016; 6: 125–133.
8.
LommatzschCRothausKKochJM, et al.Vessel density in glaucoma of different entities as measured with optical coherence tomography angiography. Clin Ophthalmol2019; 13: 2527–2534.
9.
RaoHLPradhanZSSuhMH, et al.Optical coherence tomography angiography in glaucoma. J Glaucoma2020; 29: 312–321.
10.
ShoshaniYZHarrisAShojaMM, et al.Endothelin and its suspected role in the pathogenesis and possible treatment of glaucoma. Curr Eye Res2012; 37: 1–11.
11.
ChenHYChangYCChenWC,et al.Association between plasma endothelin-1 and severity of different types of glaucoma. J Glaucoma2013; 22: 117–122.
12.
ChoritzLMachertMThiemeH. Correlation of endothelin-1 concentration in aqueous humor with intraocular pressure in primary open angle and pseudoexfoliation glaucoma. Invest Ophthalmol Vis Sci2012; 53: 7336–7342.
13.
HollóG. Influence of large intraocular pressure reduction on peripapillary OCT vessel density in ocular hypertensive and glaucoma eyes. J Glaucoma2017; 26: e7–e10.
14.
KoukoulaSCKatsanosATentesIK, et al.Retrobulbar hemodynamics and aqueous humor levels of endothelin-1 in exfoliation syndrome and exfoliation glaucoma. Clin Ophthalmol2018; 12: 1199–1204.
15.
TezelGKassMAKolkerAE, et al.Plasma and aqueous humor endothelin levels in primary open-angle glaucoma. J Glaucoma1997; 6: 83–89.
16.
AhoorMHGhorbanihaghjoASorkhabiR,et al.Klotho and endothelin-1 in pseudoexfoliation syndrome and glaucoma. J Glaucoma2016; 25: 919–922.
17.
EmreMOrgülSHaufschildT, et al.Increased plasma endothelin-1 levels in patients with progressive open angle glaucoma. Br J Ophthalmol2005; 89: 60–63.
18.
ReschHKarlKWeigertG, et al.Effect of dual endothelin receptor blockade on ocular blood flow in patients with glaucoma and healthy subjects. Invest Ophthalmol Vis Sci2009; 50: 358–363.
19.
CioffiGAOrgülSOndaE, et al.An in vivo model of chronic optic nerve ischemia: the dose-dependent effects of endothelin-1 on the optic nerve microvasculature. Curr Eye Res1995; 14: 1147–1153.
20.
HowellGRMacalinaoDGSousaGL, et al.Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma. J Clin Invest2011; 121: 1429–1444.
21.
OrgülSCioffiGABaconDR,et al.An endothelin-1-induced model of chronic optic nerve ischemia in rhesus monkeys. J Glaucoma1996; 5: 135–138.
22.
SasaokaMTaniguchiTShimazawaM, et al.Intravitreal injection of endothelin-1 caused optic nerve damage following to ocular hypoperfusion in rabbits. Exp Eye Res2006; 83: 629–637.
23.
McGradyNRMintonAZStankowskaDL, et al.Upregulation of the endothelin A (ET(A)) receptor and its association with neurodegeneration in a rodent model of glaucoma. BMC Neurosci2017; 18: 27.
24.
HollóGKatsanosAKonstasAG. Management of exfoliative glaucoma: challenges and solutions. Clin Ophthalmol2015; 9: 907–919.
25.
SuwanYGeymanLSFardMA, et al.Peripapillary perfused capillary density in exfoliation syndrome and exfoliation glaucoma versus POAG and healthy controls: an OCTA study. Asia Pac J Ophthalmol (Phila)2018; 7: 84–89.
26.
KoliakosGGKonstasAGSchlötzer-SchrehardtU, et al.Endothelin-1 concentration is increased in the aqueous humour of patients with exfoliation syndrome. Br J Ophthalmol2004; 88: 523–527.
27.
YarmohammadiAZangwillLMDiniz-FilhoA, et al.Optical coherence tomography angiography vessel density in healthy, glaucoma suspect, and glaucoma eyes. Invest Ophthalmol Vis Sci2016; 57: 451–459.
28.
CelliniMPossatiGLProfazioV, et al.Color Doppler imaging and plasma levels of endothelin-1 in low-tension glaucoma. Acta Ophthalmol Scand Suppl1997; 224: 11–13.
29.
GeevargheseAWollsteinGIshikawaH,et al.Optical coherence tomography and glaucoma. Annu Rev Vis Sci2021; 7: 693–726.
30.
JiaYWeiEWangX, et al.Optical coherence tomography angiography of optic disc perfusion in glaucoma. Ophthalmology2014; 121: 1322–1332.
31.
MwanzaJCBudenzDL. New developments in optical coherence tomography imaging for glaucoma. Curr Opin Ophthalmol2018; 29: 121–129.
32.
HuangDJiaYGaoSS, et al.Optical coherence tomography angiography using the optovue device. Dev Ophthalmol2016; 56: 6–12.
33.
GhanemAAElewaAMArafaLF. Endothelin-1 and nitric oxide levels in patients with glaucoma. Ophthalmic Res2011; 46: 98–102.
34.
KaiserHJFlammerJWenkM,et al.Endothelin-1 plasma levels in normal-tension glaucoma: abnormal response to postural changes. Graefes Arch Clin Exp Ophthalmol1995; 233: 484–488.
35.
LiSZhangACaoW,et al.Elevated plasma endothelin-1 levels in normal tension glaucoma and primary open-angle glaucoma: a meta-analysis. J Ophthalmol2016; 2016: 2678017.
36.
SugiyamaTMoriyaSOkuH,et al.Association of endothelin-1 with normal tension glaucoma: clinical and fundamental studies. Surv Ophthalmol1995; 39: S49–S56.
37.
MammoZHeislerMBalaratnasingamC, et al.Quantitative optical coherence tomography angiography of radial peripapillary capillaries in glaucoma, glaucoma suspect, and normal eyes. Am J Ophthalmol2016; 170: 41–49.
38.
HayashiYMinaminoNIsumiY, et al.Effects of thiopental, ketamine, etomidate, propofol and midazolam on the production of adrenomedullin and endothelin-1 in vascular smooth muscle cells. Res Commun Mol Pathol Pharmacol1999; 103: 325–331.
39.
ShinJWSungKRUhmKB, et al.Peripapillary microvascular improvement and Lamina cribrosa depth reduction after trabeculectomy in primary open-angle glaucoma. Invest Ophthalmol Vis Sci2017; 58: 5993–5999.
40.
ZéboulonPLévêquePMBrasnuE, et al.Effect of surgical intraocular pressure lowering on peripapillary and macular vessel density in glaucoma patients: an optical coherence tomography angiography study. J Glaucoma2017; 26: 466–472.
41.
ZhangQJonasJBWangQ, et al.Optical coherence tomography angiography vessel density changes after acute intraocular pressure elevation. Sci Rep2018; 8: 6024.
