Morphometric characteristics of optic disc in patients with myopia and primary open-angle glaucoma

Background/Aim. Primary open-angle glaucoma is a multifactorial and progressive neuropathy, characterised by the acquired loss of ganglion cells of the retina and their axons. One of the risk factors for primary open-angle glaucoma is myopia over 5 diopters (D). The aim of our work was to investigate two groups of patients with primary open-angle glaucoma and myopia by using confocal scanning laser ophthalmoscopy, and to find out if the size of refractive error influences optic disk morfometric characteristics. Methods. One hundred eyes of one hundred patients with primary open-angle glaucoma and myopia were involved in our study. All the patients were classified into two groups, the first one with myopia < 5 D, and the second one with myopia 5 D. The Heidelberg retina tomograph is a technique we used in our study. We analized morfometric parameters of patients optic discs, with the aim to find a correlation between the parameters in each group separeatly, and also to find differences between the same parameters from both groups. Results. There were significant differences in disc area, cup area, rim area and mean RNFL thickness between the two groups. The size of damage of neuroretinal rim in the group with high myopia was 27%, and in the group with lower myopia 14%. The most frequently damaged segment of neuroretinal rim in the patients with high myopia was nasal segment and in the patients with low myopia infero-temporal one. The least frequently damaged segment of neuroretinal rim in both groups was temporal one. Conclusion. Optic discs of glaucomatous patients with high myopia have bigger diameter, also bigger and more irregularly distributed damaged zone of neuroretinal rim, and also thinner retinal nerve fiber layer compared to glaucomatous patients with lower myopia.


Introduction
Glaucoma is an eye disease characterized by the increase of intraocular pressure, increase of excavation of the optic disc and paracentral scotomas in visual field.According to the etiopathogenesis, it can be primary, secundary and congenital.Primary open-angle glaucoma is multifactorial and progressive neuropathy, characterised by the acquired loss of ganglion cells of the retina and their axons.Together with the loss of nerve fibers typical changes occur on the optical disc, as well as changes in the visual field 1,2 .Clinical evaluation of optic disc is an absolutely necessary as the basis for the diagnosis and monitoring of patients with glaucoma 3 .One of the risk factors for primary open-angle glaucoma is myopia over the 5 diopters (D) 4 .Myopia is a defect of the eye that causes light to focus in front of the retina instead of directly on it, resulting in an inability to see distant objects clearly.Benign myopia is a refraction mistake that appears in the puberty period and reaches values of maximally -6 or -7 D, but with the correctional lenses normal visual acquity can be reached.Characteristics of benign myopia is that the retina has no pathological changes.Malignant myopia is a pathological condition of the eye and occurs in early childhood, progressively develops over lifetime and reaches values up to -15 D to -20 D. Malignant myopia is a degenerative eye disease, and changes in the retina are characteristic findings of malignant myopia 4 .The Heidelberg Retina Tomography II (HRT II) represents confocal scanning laser ophtalmoscopy which provides precise topographical mapping of the optic disc and peripapillar retina.It enables obtaining series of global morphometrical parametres, and parametres for each one of the six segments at which the neuroretinal rim is devided, based on three-dimensional reconstruction 5 .Various studies have shown the importance of HRT in the diagnosis and monitoring of patients with glaucoma, and detection of degenerative changes at the neuroretinal rim of eyes of patients with myopia 6,7 .
The aim of our study was to use HRT in two groups of patients diagnosed with primary open-angle glaucoma and myopia, too, to assess whether the size of refractive errors affect the morphometric characteristics of optic disc, and to determine the relationships and connections between the morphometric parameters obtained within the groups themselves and between two groups of patients.The aim of our study was also to determine if the Heidelberg Retinal Tomography instrument can distinguish between morphological characteristics of glaucomatous eyes with low myopia and glaucomatous eyes with high myopia.

Methods
The study included topographic data of 100 eyes of 100 patients from the data base in the cabinet for HRT, at the Ophtalmological Institute of the Faculty of Medicine the Belgrade University.The included patients had the diagnosis of primary open-angle glaucoma and myopia ( 1 D or 12 D).The included patients data on previous operative procedures, as well as eye trauma.The whole group was divided into eyes with a myopic refractive error less than -5 D (n = 50), and eyes with a refractive error equal to or higher than -5 D (n = 50) (Table 1).
Scanning confocal laser, Heidelberg Retina Tomograph (HRT II, Heidelberg Engineering Inc. Heidelberg, Germany) was used in this study for the collection of any necessary data (Figure 1).HRT II uses confocal scanning laser ophtalmoscopy by which we can get a series of photographies of the cross section of the optical nerve head of different deepness and after 3 D reconstruction it produces topographical photographies of the papilla and peripapillar retina.After it does that, HRT II, by the analysis aplication (Heidelberg Eye Explorer) summs up different structural parameters of the optical nerve 8 .To quantify morphometric rim and cup parameters in optic disc topography, a reference plane is defined.The reference plane is parallel to the retinal surface.It needs to be stable so that the parameters change only when true structural changes in the optic disc occur.Within the disc margin, the retinal surface located above the reference plane is defined as rim and below the reference level as cup  (Figure 2).In order to verify the quality of topographic images we used topographic images with standard deviation less than 40 μm.Twelve morphometric parametres were taken into consideration in this study: disc area (mm 2 ), cup area (mm), rim area (mm²), cup-to-disc area ratio (C/D ratio), cup volume (mm³), rim volume (mm³), mean cup depth (mm), maximum cup depth (mm), height variation contour (mm), cup shape measure (mm), mean retinal nerve fiber layer (mRNFL) thickness (mm) and RNFL cross-sectional area (mm²).Moorfields regression analysis (MRA) is a part of HRT programe, and represents method for detecting glaucomatous damage with the HRT.The MRA analyses the regression of the logarithm of the global and six sectoral rim areas (1.temporal, 2. supero-temporal, 3. infero-temporal, 4. nasal, 5. supero-nasal, 6. infero-nasal) to the matching disc areas and compares the results to a normative database.It defines these areas as damaged, borderline and normal based on the 95% and 99.9% confidence intervals (Figure 3).The method accurately discriminates between healthy controls and early glaucoma patients diagnosed using stereoscopic optic disc photography 9 .In our study we had to determine the group with larger damage of the neuroretinal rim (in percent) and which segment of the neuroretinal rim the most frequently and the least frequently often represented as the damaged for each group separately.
Statistical analysis included parameters data incorporated into the software program SPSS version 19.0 for Windows XP.We analysed the examined morphometrical parametres of the optical disc (disc area, cup area, rim area, cup volume, rim volume, cup/disc area ratio, mean cup depth, maximum cup depth, height variation contour, cup shape measure, mean RNFL thickness, RNFL cross sectional area) of the patients from both groups, with the aim to establish the existance of mutual correlation between the mean RNFL thickness and other parametres in each of the groups separately, and the existence of statistically significant dif-ference between the same parametres between the groups (statistically significant difference was when p < 0.05).First, we calculated basic statistical parametres (minimal value -MIN, maximal value -MAX, middle -, standard deviation -SD, coefficient of the variation -CV).We used the method of linear correlation (statistically significant correlation was when p < 0.05) by which we examined the correlation between the examined morphometrical parametres, then parametric and non-parametric tests for the evaluation of the significance of the difference (t-test and Mann-Whitney U-test).

Results
We calculated average values, standard deviations, minimal and maximal values of all the examined parametres for both groups of the patients (Table 2).
In the group with low myopia (< 5D), we established the existence of statistically significant correlation between mRNFL and disc area, cup area, rim area, cup volume, rim volume, cup/disc area ratio, height variation contour, cup shape measure, RNFL cross sectional area (Table 3).
In the group with high myopia ( 5 D) we established the existence of some statistically significant correlation between mRNFL and cup area, rim area, RNFL crosssectional area, cup/disc area ratio, maximum cup depth, rim volume (Table 3).
According to the distribution of parameters values by the use of statistical tests for the evaluation of significance difference (t-test or Mann-Whitney U-test) among the same examined parameters from both groups, we established the existence of statistically significant differences between: disc area, cup area, rim area and mean RNFL thickness (Table 4).
By reading Moorfields analysis of HRT findings of both groups, we found that: the damage size of neuroretinal rim was higher in the group with high miopia (27%) than in the group of the patients with low miopia (14%).We also found that in the group with low miopia (< 5 D) the segment most often classified as damaged was infero-temporal, and the least often temporal one, untill in the group with high miopia ( 5 D) the segment most often classified as damaged was nasal segment, and the least often temporal one (Table 5).

Discussion
Our study shows statistical analysis of HRT topographical parameters of the optic disc in patients with primary open-angle glaucoma and myopia, too.Myopia is one of the most common ocular abnormalities reported worldwide, and its association with glaucoma is well-recognized.The prevalence of myopia is high in patients with ocular hypertension, primary open-angle glaucoma, and normal-tension glaucoma [10][11][12][13] .The risk of developing glaucoma is two to Strana 55 Gvozdenovi R, et al.Vojnosanit Pregl 2013; 70(1): 51-56.three times higher in myopic individuals than in nonmyopic individuals, and this risk factor is independent of other risk factors for glaucoma 13 .Currently, glaucoma is diagnosed by considering the appearance of the optic disc and retinal nerve fiber layer and by standard achromatic perimetry 14 .However, myopic individuals often have enlarged optic discs with a more oval configuration and larger areas of peripapillary atrophy 15,16 .Because of these features, glaucomatous changes cannot be easily interpreted in myopic discs, possibly leading to a misdiagnosis of glaucoma.In early glaucoma, structural change is known to precede functional damage 17,18 .The RNFL is a sensitive indicator for predicting early glaucomatous changes [19][20] , and the extent of RNFL damage correlates with the severity of functional deficit in the visual field 21,22 .Thus, RNFL assessment may be more valuable than optic disc assessment in the case of myopic subjects.We compared the obtained results by the use of tests for the examination of the correlation and establishing differences between the examined parameters with the findings of other authors.The relationship between RNFL thickness and myopia has been extensively investigated [23][24][25][26][27][28][29][30] .However, whether RNFL thickness could vary with the refractive status of the eye remains unclear.It is therefore important to investigate whether there is any correlation between RNFL measurements and the axial length/refractive error in myopic patients, considering that the risk of developing glaucoma increases with the severity of myopia.Considering different approaches of various studies to the connection between myopia and glaucoma we examined the morphological characteristics of optical discs of patients diagnosed with primary open-angle glaucoma and high and low refractive errors in order that the results obtained in our study help ophthalmologists in routine examinations of the HRT findings, to help them to avoid errors in diagnosis of glaucomatous or myopic damage to the optic disk and its surroundings.We established highly statistically significant correlations between different parameters of both groups.Similar results were reported in studies of Adegbehingbe and Ouertani 31 , and in the studie of Eid et al. 32 .Between the same examined parametres from both groups we established statistically significant differences in the following parametres: disc area, cup area, rim area i mean RNFL thickness.Similar results can be found in the study of Dichtl et al. 33 .
The damage size of neuroretinal rim is higher in the group with high myopia ( 5 D) than in the group with low miopia, similar as the findings of Dichtl et al. 33 .In the group with low miopia (< 5 D) the segment most often classified as damaged was infero-temporal, and the least often temporal one, the finding reported also by Jonas et al. 34 while in the group with high miopia ( 5 D) the segment most often classified as damaged was nasal segment and the least often, temporal one.Limitation of the study was conditioned not just by its retrospective nature, but also by the lack of other clinical information on the patients included in the study, for the sake of the comparison with the findings of HRT, which is significant in the glaucoma diagnostic.

Conclusion
Glaucomatous eyes with high myopia ( 5 D) have larger diameters of optic disc, also larger cup and thinner layer of retinal nerve fibers, compared with the glaucomatous patients with low miopia (< 5 D), while the cup to disc area ratio has no significant difference between these two groups of patients.The increase of the cup and cup to disc area ratio leads to the reduction in average retinal nerve fiber layer thickness was a common morphometric characteristic of optic discs in both groups of patients.Probability of neuroretinal rim damage was 93% higher within the glaucomatous eyes with high, than within the glaucomatous eyes with low myopia.The most ofted damaged segment of the neuroretinal rim in patients with high myopia was nasal segment while in those with lower myopia was infero-temporal one.The rarest damaged segment of the neuroretinal rim in both groups of patients was temporal segment.The findings of Heidelberg Retina Tomography II make it possible to distinguish morphological characteristics of optic discs in both groups of patients.

Table 3 Correlation between the mean retinal nerve fiber layer (RNFL) thickness and other parameters in both groups of patients
* p < 0,05; ** p < 0,01

Table 4 The difference between the same parameters in both groups of patients
* p < 0,05; ** p < 0,01