|Year : 2016 | Volume
| Issue : 1 | Page : 14-17
Ocular perfusion pressure and anticardiolipin antibodies in glaucomatous Egyptian patients
Maha Shahin1, Hossam T Al-Sharkawy1, Amany M El-Diasty2
1 Department of Ophthalmology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
|Date of Submission||25-Jun-2015|
|Date of Acceptance||08-Sep-2015|
|Date of Web Publication||16-Mar-2016|
Hossam T Al-Sharkawy
Department of Ophthalmology, Faculty of Medicine, Mansoura University, Mansoura 35516
Source of Support: None, Conflict of Interest: None
The aim of the present study was to investigate the association of antiphospholipid antibodies and ocular perfusion pressure (OPP) with primary open-angle glaucoma (POAG) in an Egyptian population.
Patients and methods
A total of 44 patients were enrolled in the study: 22 with POAG and 22 controls. All patients underwent blood pressure measurement, ophthalmic examination, and blood tests. OPP was defined as 2/3΄[diastolic BP+1/3΄(systolic BP-diastolic BP)]-IOP. Blood was examined for the level of immunoglobulin G and immunoglobulin M anticardiolipin (aCL) antibodies using the enzyme-linked immunosorbent assay technique.
There was no statistically significant difference between the two groups regarding age, sex, immunoglobulin G aCL antibodies, or immunoglobulin M aCL antibodies. OPP was statistically lower in patients with POAG compared with control.
The results of the present study do not confirm the hypothesis that POAG coexists with elevated blood levels of aCL antibodies. High OPP offers relative protection from glaucoma development.
Keywords: anticardiolipin antibodies, ocular perfusion pressure, primary open-angle glaucoma
|How to cite this article:|
Shahin M, Al-Sharkawy HT, El-Diasty AM. Ocular perfusion pressure and anticardiolipin antibodies in glaucomatous Egyptian patients. Delta J Ophthalmol 2016;17:14-7
|How to cite this URL:|
Shahin M, Al-Sharkawy HT, El-Diasty AM. Ocular perfusion pressure and anticardiolipin antibodies in glaucomatous Egyptian patients. Delta J Ophthalmol [serial online] 2016 [cited 2020 May 31];17:14-7. Available from: http://www.djo.eg.net/text.asp?2016/17/1/14/178762
| Introduction|| |
In 2002, glaucoma became the second leading cause of blindness globally instead of the third according to the WHO ,. Glaucoma is particularly important in an aging world population with impact on public health as blindness and visual impairment caused by glaucoma are irreversible. As a chronic eye disease, glaucoma leads to a loss of retinal ganglion cells over the years, which results in characteristic optic nerve damage and typical visual field defects. Affected patients may not be aware that they are in danger of losing their sight in the early stages of the disease. They may only complain of few symptoms of the gradual loss of vision when retinal nerve fibers are permanently lost. To avoid this feasible prevention, effective diagnostics and appropriate treatment are strongly needed. This can only be achieved if general understanding of glaucoma is improved. 'The medical understanding of the nature of glaucoma has changed profoundly in the past few years and a precise comprehensive definition and diagnostic criteria are yet to be finalized' .
The etiology of primary open-angle glaucoma (POAG) remains controversial. Phospholipase A2 has been shown to be involved in neuronal cell death . Antiphospholipid antibodies are immunoglobulins belonging to a group of a heterogenous autoantibodies directed against phospholipids and phospholipid protein complexes, which are the main constituents of all membranes. The presence of these immunoglobulins has been associated with systemic thromboembolic events, such as deep vein thrombosis, pulmonary embolism, hearing loss, myocardial infarction, and acute cerebral ischemia ,,. Altintas et al. (2011) , have found that elevated serum antiphospholipid antibodies are more common in patients with pseudoexfoliation glaucoma, and also that immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to phospholipids and their subspecies, cardiolipin, phosphatidylserine, and b2-glycoprotein, may be altered in POAG and normotensive glaucoma patients. Recently, ocular perfusion pressure (OPP) alteration was postulated to be a causative mechanism in POAG . OPP is an important determinant of ocular blood flow . It is maintained by autoregulatory mechanisms allowing adaptation to metabolic demands. Vascular dysregulation and unstable ocular blood flow has been linked to POAG and POAG progression . The aim of this study was to investigate the association of anticardiolipin antibodies (aCL) and OPP with POAG in an Egyptian population.
| Patients and methods|| |
The study was approved by the Human Ethics Committee, and all patients signed informed consent before participating in the study. All applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during this research. Patients attending the outpatient clinics of Mansoura Ophthalmology Center were examined for signs of POAG. Exclusion criteria included patients receiving antiglaucomatous treatment or systemic β-blockers; hypertriglyceridemia (>1.9 mmol/l) or hypercholesterolemia (>5.6 mmol/l); smoking and hazy media; ocular diseases that might lead to false results (e.g. corneal disorders with possible impact on visual acuity and visual field, including corneal ulceration, corneal injury, corneal dystrophy, and corneal swelling; disorders of the ocular lens, including mature cataract, brown cataract, and congenital cataract, with impact on visual acuity and visual field; retinal disorders with possible impact on visual acuity and visual field, including acquired macular disorders (e.g. age-related macular degeneration); retinal vascular disorders (e.g. diabetic retinopathy, retinal detachment; neurological disorders and optic nerve disorders, with possible impact on visual activity and visual field, including status after cerebrovascular accident, optic neuritis, and optic neuropathy); severe systemic disease with possible impact on serum antibody levels, including chronic viral hepatitis, chronic inflammatory pulmonary disorders, systemic malignancies, viral infections (AIDS, infectious mononucleosis, influenza), bacterial infections (tuberculosis, syphilis, leprosy, brucellosis, salmonellosis, subacute endocarditis), and parasitic diseases (malaria, filariasis, schistosomiasis).
All patients underwent ophthalmologic examination including visual acuity, slit-lamp examination, fundus contact lens examination, field of vision, and retinal nerve fiber layer (RNFL) measurements by optical coherence tomography (OCT).
POAG was diagnosed if glaucomatous cupping and characteristic field defects were present along with thinned RNFL on OCT and open angles on gonioscopy with raised intraocular pressure (IOP) (>21 mmHg). IOP was measured by using a Goldmann applanation tonometer (Haag-Streit, Bern, Switzerland).
Measurement of blood pressure
Blood pressure (BP) was recorded for all the participants in the right upper arm in sitting position using a mercury sphygmomanometer. Two seated brachial BP measurements were taken. A third measurement was taken if either the systolic BP or diastolic BP in the first two measurements differed by more than 10 mmHg. OPP was calculated as 2/3 × [DBP + 1/3 × (SBP-DBP)]-IOP, where DBP is diastolic blood pressure, SBP is systolic blood pressure, and IOP is intraocular pressure.
Measurement of anticardiolipin antibodies
Five milliliters of venous blood were withdrawn from each patient. The samples were centrifuged and the separated sera were stored in deep freezer at −70°C until the time of assay. Serum samples were examined for aCL antibodies. IgG and IgM were determined using enzyme-linked immunosorbent assay technique. Patients were considered positive for IgG aCL antibodies when it was greater than 10 GPL U/ml and negative when the titer was less than 10 GPL U/ml. Patients were considered positive for IgM aCL antibodies when it was greater than 7 MPL U/ml and negative when the titer was less than 7 MPL U/ml.
For descriptive statistics of the quantitative variables, the mean, range, and SD were used to describe central tendency and dispersion. Differences between the means of the independent samples were analyzed by Student's t-tests.
| Results|| |
In total, 22 glaucomatous patients (group A) were enrolled in the study. On the other hand, 22 comparable patients (group B) with normal IOP, cup/disc ratio, field of vision, and normal thickness of the RNFL on OCT were included in the control group. The groups were comparable with regard to age and sex. Overall, 70.45% of patients were men (group A included 17 men, whereas group B included 14 men). Age ranged from 42 to 79 years old with a mean of 60.1 ± 8.71 years. Mean age in group A was 57.38 ± 8.93 years ranging from 42 to 79 years. Mean age in group B was 62.81 ± 7.78 years ranging from 47 to 75 years (P = 0.06).
IgG aCL antibodies in group A ranged from 1.50 to 7.5 GPL unit (mean = 3.89 ± 1.78). In group B, IgG aCL antibodies ranged from 1.90 to 10.6 GPL unit (mean = 5.11 ± 2.13) (P = 0.083). IgG aCL antibodies were negative in all patients (100%) in group A, and positive in one case only in group B (4.55% of patients). IgM aCL antibodies in group A ranged from 0.30 to 14.80 MPL unit (mean = 4.04 ± 3.32). In group B, IgM aCL antibodies ranged from 0.80 to 12.5 MPL unit (mean = 4.47 ± 2.80) (P = 0.067). IgM aCL antibodies were positive in three patients (13.64%) in both groups.
Mean OPP in group A was 36.43 ± 12.44 mmHg and ranged from 15 to 57 mmHg. In group B it ranged from 33 to 53 mmHg with a mean of 44.50 ± 6.81 mmHg (P = 0.033).
| Discussion|| |
POAG is a chronic progressive optic neuropathy characterized by retinal ganglion cell death and associated visual field loss . The exact pathophysiological mechanism of optic nerve damage in glaucoma is not clearly understood . In addition to the mechanical effect of raised IOP , several vascular risk factors, such as systemic hypertension, atherosclerosis, vasospasm, etc., have also been suggested as potential risk factors for POAG ,,.
Many researchers reported patients who develop glaucoma progression despite optimal treatment and successful intraocular depression ,. Duke-Elder  in 1953 was the first to suggest the role of vascular elements in the pathogenesis of POAG followed by many other reports ,,,.
Latalska et al. (2004)  reported the presence of elevated levels of antiphospholipids in aqueous humor and serum in patients with glaucoma and suggested that this may be a risk factor for progression of glaucomatous neuropathy. However, in the present study, IgG and IgM concentrations of aCL antibodies were not significantly increased in POAG patients compared with controls. An association between aCL antibodies and the progression of glaucomatous optic neuropathy confirmed that the risk for the progression of glaucoma is as much as four times higher in patients with elevated serum aCL antibodies compared with individuals without increased aCL antibodies. Although the difference was statistically significant, the percentage of participants with increased aCL antibodies (5.5% of the 258 participants) did not differ from that of the general population, which is 2-7% ,,. The results in the present study are in agreement with the findings of Tsakiris et al.  who did not detect any significant differences in antiphospholipid antibody levels (aCL antibodies and lupus anticoagulants) between POAG patients and controls.
Impact of OPP on glaucoma has received greater attention in the recent years . In the present study, OPP was statistically lower in cases of POAG compared with control. In a 9-year follow-up study, participants with low mean OPP (<40 mmHg) at baseline had almost three times higher risk of POAG compared with those with higher baseline mean OPP .
The vascular hypothesis of POAG suggests that a low BP in relation to IOP can lead to low mean OPP, thus impairing perfusion of the optic head with resultant glaucomatous cupping and visual field loss ,,,. Low perfusion pressure can be due to relatively low BP or relatively high IOP, but there is no conclusive evidence to show that either variable alone is solely responsible for low ocular perfusion in POAG. One limitation to the study is that the calculation of mean OPP was done using theoretical formula that may not reflect the real physiological status of ocular perfusion. Direct measurement of ocular blood flow could result in different outcomes. In addition, there are inevitable measurement inaccuracies during assessment of BP and IOP. Despite these limitations, several large studies have shown that calculated OPP is a highly relevant parameter in glaucoma . Multiple population-based studies have identified OPP as a risk factor for glaucoma in addition to IOP. ,,.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Resnikoff S, Pascolini D, Etya′ale D, et al.
Global data on visual impairment in the year 2002. Bull World Health Organ 2004; 82:844-851.
Kingman S. Glaucoma is second leading cause of blindness globally. Bull World Health Organ 2004; 82:887-888.
Mathisen G, Thorkildsen H, Paulsen R. Secretory PLA2-IIA and ROS generation in peripheral mitochondria are critical for neuronal death. Brain Res 2007; 1153:43-51.
Levin J, Branch W, Rauch J. The antiphospholipid antibody syndrome. N Eng J Med 2002; 346:752-763.
Bick R. Antiphospholipid thrombosis syndromes. Haematol Oncol Clin North Am 2003; 17:115-147.
Bachor E, Kremmer S, Kreuzfelder E, et al.
Antiphospholipid antibodies in patients with sensorineural hearing loss. Eur Arch Otorhinolaryngol 2005; 262:622-626.
Altintas O, Yuksel N, Sonmez GT, et al.
Serum antiphospholipid antibody levels in pseudoexfoliation. J Glaucoma 2012; 21:326-330.
Leske MC. Ocular perfusion pressure and glaucoma: clinical trial and epidemiologic findings. Curr Opin Ophthalmol 2009; 20:73-78.
Liang Y, Downs JC, Fortune B, et al.
Impact of systemic blood pressure on the relationship between intraocular pressure and blood flow in the optic nerve head of nonhuman primates. Invest Ophthalmol Vis Sci 2009; 50:2154-2160.
Flammer J, Haefliger IO, Orgul S, Resink T. Vascular dysregulation: a principal risk factor for glaucomatous damage? J Glaucoma 1999; 8: 212-219.
Moore D, Harris A, Wudunn D, et al.
Dysfunctional regulation of ocular blood flow: a risk factor for glaucoma? Clin Ophthalmol 2008; 2: 849-861.
Omoti AE, Enock ME, Okeigbemen VW, et al.
Vascular risk factors for open angle glaucoma in African eyes. Middle East Afr J Ophthalmol 2009; 16:146-150.
Flammer J, Orgül S, Costa VP, et al.
The impact of ocular blood flow in glaucoma. Prog Retin Eye Res 2002; 21:359-393.
Deokule S, Weinreb RN. Relationships among systemic blood pressure, intraocular pressure, and open-angle glaucoma. Can J Ophthalmol 2008; 43:302-307.
Quaranta L, Gandolfo F, Turano R, et al.
Effects of topical hypotensive drugs on circadian IOP, blood pressure, and calculated diastolic ocular perfusion pressure in patients with glaucoma. Invest Ophthalmol Vis Sci 2006; 47:2917-2923.
Sommer A, Tielsch JM, Katz J, et al.
Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey. Arch Ophthalmol 1991; 109: 1090-1095.
Duke-Elder S. Primary glaucoma as a vascular disease; the James A. Craig prize lecture. Ulster Med J 1953; 22:3-16.
Hulsman CA, Vingerling JR, Hofman A, et al.
Blood pressure, arterial stiffness, and open-angle glaucoma: the Rotterdam study. Arch Ophthalmol 2007; 125:805-812.
Klein BE, Klein R, Knudtson MD. Intraocular pressure and systemic blood pressure: longitudinal perspective: the Beaver Dam Eye Study. Br J Ophthalmol 2005; 89:284-287.
Leske MC, Wu SY, Hennis A, et al.
BESs Study Group. Risk factors for incident open-angle glaucoma: the Barbados Eye Studies. Ophthalmology 2008; 115:85-93.
Orzalesi N, Rossetti L, Omboni SOPTIME Study Group. Osservatorio sulla Patologia glaucomatosa, Indagine Medico Epidemiologica); CONPROSO (Collegio Nazionale dei Professori Ordinari di Scienze Oftalmologiche) Vascular risk factors in glaucoma: the results of a national survey. Graefes Arch Clin Exp Ophthalmol 2007; 245:795-802.
Latalska M, Gerkowicz M, Pietras-Trapiel M. Levels of antiphospholipid antibodies in the serum and aqueous humor of glaucoma Patients. Klin Oczana 2004; 106:419-420.
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.
Hammam T, Montgomery D, Morris D, Imrie F. Prevalence of serum autoantibodies and paraproteins in patients with glaucoma. Eye (Lond) 2008; 22:349-353.
Kremmer S, Kreuzfelder E, Klein R, et al.
Antiphosphatidylserine antibodies are elevated in normal tension glaucoma. Clin Exp Immunol 2001; 125:211-215.
Tsakiris DA, Osusky R, Kaiser HJ, et al.
Lupus anticoagulants/anticardiolipin antibodies in patients with normal tension glaucoma. Blood Coagul Fibrinolysis 1992; 3:541-545.
Costa VP, Arcieri ES, Harris A. Blood pressure and glaucoma. Br J Ophthalmol 2009; 93:1276-1282.
Caprioli J, Coleman AL. Blood Flow in Glaucoma Discussion. Blood pressure, perfusion pressure, and glaucoma. Am J Ophthalmol 2010; 149:704-712.
Topouzis F, Founti P. Weighing in ocular perfusion pressure in managing glaucoma. Open Ophthalmol J 2009; 3:43-45.
Hayreh SS. Blood flow in the optic nerve head and factors that may influence it. Prog Retin Eye Res 2001; 20:595-624.
Quaranta L, Katsanos A, Russo A, Riva I. 24.hour intraocular pressure and ocular perfusion pressure in glaucoma. Surv Ophthalmol 2013; 58:26-41.
Tielsch JM, Katz J, Sommer A, et al.
Hypertension, perfusion pressure and primary open angle glaucoma. A population-based assessment. Arch Ophthalmol 1995; 113:216-221.
Bonomi L, Marchini G, Marraffa M, et al
. Vascular risk factors for primary open angle glaucoma: the Egna-Neumarkt Study. Ophthalmology 2000; 107:1287-1293.