Ocular perfusion pressure and anticardiolipin antibodies in glaucomatous Egyptian patients

Maha Shahin; Hossam T Al-Sharkawy; Amany M El-Diasty

doi:10.4103/1110-9173.178762

ORIGINAL ARTICLE

Year : 2016 | Volume : 17 | 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

Correspondence Address:
Hossam T Al-Sharkawy
Department of Ophthalmology, Faculty of Medicine, Mansoura University, Mansoura 35516
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/1110-9173.178762

Abstract

Aim
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.
Results
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.
Conclusion
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 2022 Aug 18];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 [1],[2]. 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' [3].

The etiology of primary open-angle glaucoma (POAG) remains controversial. Phospholipase A2 has been shown to be involved in neuronal cell death [4]. 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 [5],[6],[7]. Altintas et al. (2011) [8], 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 [9]. OPP is an important determinant of ocular blood flow [10]. 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 [11]. 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.

Statistical analysis

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 [12]. The exact pathophysiological mechanism of optic nerve damage in glaucoma is not clearly understood [13]. In addition to the mechanical effect of raised IOP [14], several vascular risk factors, such as systemic hypertension, atherosclerosis, vasospasm, etc., have also been suggested as potential risk factors for POAG [13],[14],[15].

Many researchers reported patients who develop glaucoma progression despite optimal treatment and successful intraocular depression [16],[17]. Duke-Elder [18] in 1953 was the first to suggest the role of vascular elements in the pathogenesis of POAG followed by many other reports [19],[20],[21],[22].

Latalska et al. (2004) [23] 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% [24],[25],[26]. The results in the present study are in agreement with the findings of Tsakiris et al. [27] 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 [28]. 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 [21].

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 [9],[29],[30],[31]. 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 [32]. Multiple population-based studies have identified OPP as a risk factor for glaucoma in addition to IOP. [21],[33],[34].

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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