INTRODUCTION
Central corneal thickness plays a major role in the management of many types of glaucoma. Ocular hypertensive (OHT) studies (Kass et al. 2002, Gordon et al. 2002) has not only reported thin cornea as a predictor for the development of primary open angle glaucoma (POAG) but Copt et al (1999) has also reclassified more than 56% of OHT patients based on the corrected central corneal thickness (CCT). Additionally, Kim and Chen (2004) demonstrated progression of disease was more likely in POAG patients with thinner corneas, hence giving another insight in the role of CCT in managing glaucoma patients. Correlation between corneal thickness and the severity of the disease in the POAG group has been described by many authors using advanced glaucoma intervention study (AGIS) scoring (Kim & Chen 2004, Herndon et al. 2004). However, this relationship is not well described for the NTG group of patients.
Optical coherence tomography shows good topographic relationship between structural damage and functional loss (visual field loss) (Wollstein et al. 2004, Wollstein et al. 2005). The average RNFL thickness was found to have the strong- est correlation with severity of the dis- ease, followed by the inferior and supe- rior quadrant measurements. The aim of this study was to investigate a possible correlation between the severity of glau- coma (based on RNFL thickness as measured by OCT) and CCT among NTG and POAG group of patients.
MATERIALS AND METHODS
Patients
An observational study of patients who were treated for primary open angle and normotensive glaucoma was carried out at UKMMC, Kuala Lumpur from January 2006 to April 2007. This study was ap- proved by the Medical Research and Ethics Committee UKM.
Design
Medical records of the patients were re- viewed retrospectively for selection of cases. Sample size was calculated using the sample size calculation program ver- sion 2.1.30 February 2003. High tension glaucoma was diagnosed if the baseline IOP prior to treatment was more than 21mmHg with the presence of open an- gle on gonioscopy and glaucomatous optic disc changes. Those with baseline readings less than 21mmHg were classi- fied as having normal tension glaucoma (NTG). All patients had glaucomatous visual field defects as confirmed by the Humphrey Visual Field test and only pa- tients who were on medical treatment with no previous surgery were recruited for this study. Patients with significant anterior segment disease causing poor signal strength on the OCT were ex- cluded from the study. Other exclusion criteria were those with diabetic retino- pathy, contact lens user and high myopia of more than - 6 dioptre. The worse eye was chosen for the study.
Measurement of CCT was done using a specular microscope SP-3000P (Topcon Corporation, Tokyo). This method used a non contact technique to measure the corneal thickness, which was reported to have better repeatability compared to ultrasound pachymetry (Bovelle et al. 1999). Three readings with a standard deviation of less than 3µm were used, and the average was calculated for the analysis. Subsequently, measurement of RNFL was done by a single operator us- ing the Stratus 3 OCT (Carl Zeiss Medi- tech, Dublin,CA) on well-dilated eyes. Good signal strength of 7 or more was included for analysis. Diagnosis was confirmed by looking at their previous record of baseline IOP before treatment and patients who were treated elsewhere with no known pretreatment IOP were excluded from the study. Purpose and details of the study were explained to the patient and informed consent was ob- tained. Demographic data, past medical history and ocular history were obtained from all patients.
The worse eye was chosen based on the humphrey visual field. Eyes with counting finger or worse vision were ex- cluded. Visual acuity using the logMar chart was recorded and autorefraction was done to look at the level of refractive error. Anterior segment examination was performed and intraocular pressure was measured before gonioscopy was done. All patients were dilated and examination of the retina was performed to look for the presence of other ocular pathology which may affect the RNFL measure- ment. Optical coherence tomography was done for all patients with a dilated pupil and only those with a good signal strength were included in the study. Data was then collected and those with in- complete documentation were excluded. Data of the patients were then analyzed.
RESULTS
A total of 190 eyes from 190 patients were included in the study. There were 60 patients in the normal tension glau- coma (NTG) group, 61 patients for pri- mary open angle glaucoma (POAG) group and 69 patients for the normal (control) group. Age for all the groups were normally distributed (Shapiro-Wilk p > 0.05). Parametric statistical tests were used for the data analyses. All p-values were 2-sided and were considered statis- tically significant when the values were less than 0.05.
Mean age for the POAG group was 64.5±10.2 years, NTG group 65.0±7.6 years and the normal group 61.6±8.2 years old (One way ANOVA, p=0.195). Intraocular pressure was significantly different between the three groups (p<0.0001) (Table 1). Central corneal thickness of the NTG group was found to be thinnest among the three groups. Sig- nificant differences were noted between the CCT of the NTG patients compared to the control group (p < 0.05) (Table 1).
RNFL thickness was thinner in both glaucoma groups compared to the con- trol group of patients (p<0.05) (Table 2). Both glaucoma groups had similar level of severity of disease based on RNFL (p >0.05).
A significant Pearson correlation coeffi- cient was found in the POAG group be- tween the CCT and RNFL in the superior quadrant and average thickness (r=0.265, p<0.05 and r=0.417, p<0.05 respectively). No significant correlation was found between the CCT and RNFL for the NTG group (Table 3, Figures 1, 2).
DISCUSSION
Normotensive glaucoma was long consi- dered as a subset of POAG, sharing many similar characteristics except for the elevated IOP (Sowka 2005). In this study, mean CCT for NTG patients were found to be the thinnest compared to the POAG and the control groups. However, based on published calculations, (Doughty & Zaman 2000) the differences were too small to influence the IOP mea- surement in a clinically meaningful way. Therefore the measured IOP achieved using the 'gold standard' technique of Goldmann tonometry may not differ significantly from the actual IOP in NTG patients. However, POAG patients were found to have relatively comparable corneal thickness with the normal population supporting the fact that the disease is truly an effect of an ageing trabecular meshwork. The value for CCT in this study however was slightly lower compared to other studies which mainly used ultrasound pachymetry to measure the CCT (Bechmann et al. 2000).
Significant correlation between the CCT and severity of RNFL was only found for the POAG group but not for the NTG group of patients. The results obtained were also comparable with a cross sec- tional study done using AGIS scoring which did not find any significant correla- tion between the corneal thickness and severity of the disease in NTG patients (Bechmann et al. 2000). The different findings between these two groups of patients may implicate the possibility of different pathophysiology of the disease.
Cioffi and Liebman (2002) proposed possible relationship between a thin cor- nea and intracellular matrix changes at the level of lamina cribosa may predis- pose to glaucomatous changes. This idea would be an additional risk factor for this group of patients. Despite controlling the IOP, progression may seem to be inevitable in the presence of a thin cor- nea. However, this possibility may not be applicable to the NTG patients as similar correlation between the CCT and severity of the disease was not found. Therefore, consideration of NTG as a subset of POAG has to be evaluated with caution. Although clinically the appearance on gonioscopy may be similar, further eval- uation at the cellular and genetic level may help to answer these questions. Other influential factors that may contri- bute to the severity of the disease for the NTG group were proposed by Doyle (Doyle et al. 2005). Higher association of systemic disease in the NTG group may affect the ocular perfusion indirectly leading to optic nerve damage in this group of patients (Doyle et al. 2005).
To date, there has been no study done to look at the association of CCT and severity of glaucoma in the NTG group using the OCT. However, this study was a cross sectional study and the stability of the disease was not analyzed. As such, the possibility of further RNFL pro- gression was not taken into considera- tion. A prospective long term study may give a better understanding of the corre- lation between the corneal thickness and RNFL.
CONCLUSION
Significant correlation between the cor- neal thickness and severity of glaucoma is only present in POAG patients but not for NTG cases. Our results suggest that CCT is related to the severity of POAG- related visual loss thus measuring the corneal thickness in this group of patients may help to determine which patient would benefit from close monitoring. Furthermore, the old consideration of NTG as a subset of POAG may not be applicable with many studies showing dissimilar detail characteristics between those two groups.
ACKNOWLEDGEMENTS
The authors would like to express their greatest gratitude to the Department of Ophtalmology for the continous support throughout the study, Prof Dr Ropilah Abdul Rahman, Dr Fam Han Borr from Singapore National Eye Centre and Dr Nor Fariza Ngah from Hospital Selayang for their critical comments on this study.