Aqueous Humor and Serum Levels of Ischemia Modified Albumin (IMA): A Novel Biomarker in Primary Glaucoma

The increase of intraocular pressure (IOP) is one of the risk factors, which is also the only factor that able to be controlled by medications or surgery. Therefore, the target of glaucoma treatments is to lower the IOP to delay the disease progression. High IOP is the result of aqueous humor (AQH) build-up. Pathogenesis of glaucoma also associated with oxidative stress process. Moreover, vasoconstriction of vessels as the result of peroxynitrite (ONOO-) is also causing the reduction optic nerve blood flow, which further resulting in RGC death. Oxidative stress also leads to increase endothelin-1, responsible to vasoconstriction of vessels and reduction of the optic nerve blood flow, resulting in RGC death. Neuronal transport in the optic nerve head is also disrupted by increasing activation of endothelin. Therefore, ischemia, apoptosis of RGC and further damage in glaucoma.

Early diagnosis, prompt treatment, and progression monitoring in glaucoma have been challenging. Patient evaluation needs to be thorough with the complete clinical examination, IOP measurements, structural, and functional imaging modalities. Screening examination based only on IOP measurements is no longer considered precise, especially in early stage patients with normal IOP range.

A novel parameter for early diagnosis, monitoring treatment response, and disease progression may contribute to improve disease prognosis in glaucoma. Molecular biomarkers are now thought to be able to diagnose glaucoma in its early stages or patients with high-risk developing glaucoma, also in glaucoma treatments. Oxidation induces albumin structure modifications. The binding of the oxidative stress to one of the albumin's chains causes the formation of IMA, which is considered a novel biomarker of ischemia-related events and oxidative stress. IMA levels were higher in serum and aqueous humor in diabetic retinopathy (DR). The changes in glaucoma progression have been considered able to depict by systemic antioxidant levels, and oxidative stress biomarkers. This study by Rusmayani et al aimed to analyze IMA levels in the serum and aqueous humor as an early diagnostic parameter and their correlation to RNFL thinning in primary glaucoma.

Patients were divided into the control and glaucoma groups. The control group was patients with senile cataracts. The glaucoma group consisted of patients diagnosed for the first time as primary open-angle glaucoma (POAG) or primary angle closure glaucoma (PACG). Exclusion criteria were secondary glaucoma and patients with systemic disease. A complete cataract examination was done for all patients, and glaucoma examinations for the glaucoma group. In both groups, the IMA aqueous humor was obtained during cataract and glaucoma procedure. Serum levels of IMA, malondialdehyde (MDA), and tumor necrosis factor alpha (TNF-α) were examined during preoperative examinations.

Control group comprised 33 participants, and glaucoma group 41 patients (21 PACG and 20 POAG).. Glaucoma group had significant higher level of IMA in aqueous humor compared to control group, but opposite findings in serum IMA levels between groups. POAG patients had a higher aqueous IMA level compared to PACG group and correlated significantly with IOP. IMA AQH also negatively correlated to the RNFL thickness in both POAG and PACG group. Cut off 9.5 ng/mL was considered as a normal limit value to differentiate between control and glaucoma group.

IMA aqueous humor levels represent the state of intraocular local oxidative stress in glaucoma patients. IMA serum levels do not represent the intraocular abnormalities of glaucoma caused by local oxidative stress with an intact ocular blood barrier. Serum TNF-α and MDA levels were not found to be associated with RNFL depletion in glaucoma patients. Therefore, serum biomarkers are unable to illustrate glaucoma pathogenesis and intraocular local damage.

The state of systemic oxidative stress does not reflect the local intraocular events in glaucoma. IMA AQH levels were found to increase with RNFL thinning in glaucoma. The value for the IMA aqueous humor level reference is 9.5 ng/mL as probable early diagnosis for glaucoma. This figure can be considered as a reference value for screening testing through the anterior chamber paracentesis method, especially in individuals with risk factors. IMA AQH levels in patients with POAG describe a chronic ischemic process associated with increased IOP for a longer time accompanied by accumulation of oxidative stress. IMA AQH levels reflecting intraocular oxidative stress as a factor affecting RNFL thinning in POAG and PACG groups, but were not correlated by increased IOP in PACG.

Source: Rusmayani et al; Clinical Ophthalmology 2022:16

https://doi.org/10.2147/OPTH.S388382