Evaluation of corneal morphology among newly detected patients with primary open angle glaucoma

Author(s): Nagalakshmi Narayana-Swamy* and Alhaj Farhath Tasneem Introduction: Glaucoma is an insidious blinding disease that may present in a variety of clinical scenarios. While Intraocular pressure is a major risk factor in its pathophysiology, patients have the disease without any documented elevation in pressure. To avoid missing a diagnosis of glaucoma, a thorough and careful evaluation of all the structural and functional co ... Abstract View Full Article View DOI: 10.17352/2455-1414.000064


Introduction
Glaucoma is the leading cause of irreversible blindness worldwide. Primary open angle glaucoma is the most common form of glaucoma worldwide and accounts to an incidence of 0.5%-8.8% [1]. Although the Aravind Comphrensive Eye Survey [2], study conducted among the southern rural population and the Andhra Pradesh eye disease study conducted among urban population showed a prevalence of 1.7% and 2.6% respectively in individuals aged 40years and older.
Glaucoma is characterized by progressive death of ganglion cells with optic disc cupping and functionally noted with visual fi eld detioration. All these changes are common but not always associated with raised IOP [3]. Numerous hypothesis have been noted eluding the pathophysiology of glaucoma including the mechanical theory of elevated IOP, vascular theory implicating chronic hypoxia, excitotoxicity and neurodegeneration secondary to autoimmune mechanism and infl ammatory cytokine induced cell death [4]. However the scleral lamina of Optic Nerve Head(ONH) and inner retina are the primary sites of axonal injury [5]. The hallmark of glaucomatous optic neuropathy is the cup enlargement with progressive thinning of neuroretinal rim [6]. The cup disc ratio depends on the size of the cup but a ratio greater than 0.65 is found in less than 5% of the individuals [7]. A difference of less than or equal to 0.2 is seen in more than 96% of health subjects [8]. Therefore when signifi cant asymmetry is noted between eyes possibility of glaucoma should be considered.
The ocular risk factors include thinner Central corneal thickness, myopia, disc hemorrhage, increased Cup Disc Ratio and asymmetric cupping. Non ocular risk factor includes older age, African race, positive family history, adult onset Diabetes mellitus, female sex, peripheral vasospasm, smoking and alcoholism [9][10][11][12].
Because of the wide variation in appearance of the disc, it is diffi cult to ascertain the glaucomatous damage. Hence Visual fi elds are better predictors of a progressive disease, requiring a mandatory evaluation of the glaucoma. In general clinically recognizable disc changes precede detectable fi eld loss [13] and the presence or absence of glaucomatous fi led defects can also be predicted based on appearance of ONH [14,15]. This decrease is accelerated in glaucoma [17]. Meta-analysis and reviews have been found the normal mean Central Corneal Thickness of 544μm and 95% confi dence intervals noted to be 477-610μm [18]. Patients with ocular hypertension have been found to have higher Central Corneal Thickness by 50μm higher than glaucomatous patients. And normotensive glaucomatous patients were shown to have thinner corneas [19,20]. Few studies have published that thinner Central Corneal Thickness is associated with severity of glaucoma [21]. Also it is noted that thinner Central Corneal Thickness have higher risk of progression from ocular hypertension to Primary open angle glaucoma.
The study of endothelial cell morphology among glaucomatous patients had set in a great interest in fi eld of glaucoma. Endothelial cell density is often reduced in patients with glaucoma. The pre-existing factor includes elevated Intraocular pressure, congenital abnormalities, ocular surgery and trauma [22]. Knorr, et al., [23], reported 31% reduction in endothelial cell density in Primary open angle glaucoma group in comparison to normal group in contrast to this Korrey, et al., showed no comparison of changes with Endothelial cell density in glaucomatous patients and ocular hypertensives [24].
In our present study we evaluated the relationship between corneal morphology and Central corneal thickness among newly detected glaucomatous patients in comparison with healthy subjects.

Materials and methods
The present prospective case control study was conducted

Inclusion criteria
Newly detected primary open angle glaucomatous patients.

Investigations
The following investigations and interventions were done on newly detected primary glaucoma patients and glaucoma suspects, in case group and participants on control group: • Visual acuity test (with and without pinhole) as assessed by Snellen's chart.        Table 9.        Figure 5).
The mean ECD was signifi cantly low among the newly detected cases of primary glaucoma. The POAG patients showed a mean difference of 92.4cells (3.44%) and 312.52 cells (11.66%) compared with the normal group respectively.
A modest increase in IOP(<40mm Hg) for a prolonged period of time is essential to have even a minute effect on the corneal endothelium and corneal thickness. Patients with an healthy endothelium rarely develop changes, unless there is an acute and long lasting elevation in IOP [27].
Surprisingly, our analysis showed signifi cant difference in Coeffi cient of Variation (CV) and Hexagonality (H) among the groups( Figure 6, Table 6). This is in complete disagreement with previous fi ndings in the literature as changes in CV and Hexagonality indicate acute corneal endothelial damage [28][29][30]. Justifying our fi nding is a study which states that an elevated or abnormal rate of polymegathism is usually the fi rst sign of endothelial damage. This fi nding indicates physiological stress to the corneal endothelium and an overactive wound repair mechanism [31].
This lends support to the previous fi ndings in the study on, role of CCT in diagnosis of glaucoma which also found to have signifi cantly higher CCT in ocular hypertensive than in those of glaucoma and the normals [32].
The Ocular Hypertension Treatment Study (OHTS) has now recognized lower Central Corneal Thickness (CCT) as an independent risk factor for the development of POAG in eyes with ocular hypertension (OH) [33]. We need not sound a note of caution as both our study groups having CCTs within normal limit and we also considered CCTs of every patient by correcting their IOP using modifi ed Ehler's correction factor.
The mean score for cIOP among newly detected primary glaucoma patients (23.53mm Hg) ( Figure 4, Table 4) was   it may also cause a decrease in corneal endothelial cell density.
However, we need to evaluate the time period required for this small rise in IOP to cause reduction in corneal endothelial cell density, leading to disease progression [36]. confi rmed that endothelial cell counts in glaucoma groups were inversely proportional to the means of IOP .
Our results share similarities to the above mentioned fact by showing a decrease in endothelial cell count to 2000-2500 cells/mm2 when there was a surge in IOP more than 20mm Hg.
The signifi cant difference in the CDR between glaucomatous (0.68±0.10) and healthy eyes (0.34±0.08) was expected, and agrees with the principles of glaucomatous diagnostic criteria.
Although our results differ slightly from George Tomais (2008), which showed that CDR ( Figure 3, Table 3) was highest in POAG than the normal, but this difference wasn't signifi cant [37].
Our study provides considerable insight about the relationship between ECD, CCT and CDR which are derivatives of neural crest. We observed that with ECD and CCT are inversely proportional to CDR (Figure 7, Table 9). This phenomenon could be related with the underestimation of IOP measurement in eyes with thin corneas and probably with the high tolerance of lamina cribrosa in eyes with thick corneas.
Based on that remark, we could consider that the coexistence of thin cornea and big C/D area ratio in a glaucoma suspect, may contribute to glaucoma progression. Pakaravam and colleagues (2007) confi rmed that CDR was inversely correlated with CCT in patients with POAG [38].
Hence it is important that understanding the relationship with corneal morphology and CCT in glaucomatous patients is vital in understanding the disease pathology and to aid treatment. Further studies in glaucoma, which take ECD into account, will need to be performed by classifying glaucoma suspects into fi ve groups i.e; Type I-Normal IOP, no damage, Type II-Normal IOP, possible damage, Type III-High IOP, no damage, Type IV-High IOP, possible damage and Type V-Possible glaucomatous damage .We are confi dent that this may further improve the knowledge about the role of ECD in glaucoma suspects.