An assessment of variation in macular volume and RNFL thickness in myopes using OCT and their significance for early diagnosis of primary open-angle glaucoma.

PURPOSE: An assessment of variation in Macular Volume and RNFL Thickness in myopes using OCT, and their significance for early diagnosis of Primary Open Angle Glaucoma(POAG). MATERIALS AND
METHOD: Total of 122 eyes of 61 Indian Myopic subjects of both sex and various age groups underwent retinal nerve fiber layer thickness, macular volume in 6mm analysis by Rtvue Avanti SD-OCT, Optovue Technology V6.1.1,after taking due consent from ethical committee. Subjects were divided into two groups based on their refractive error, Group A <6 D and Group B >6D. The results were evaluated to determine the above mentioned measurements and their variation with myopic refractive error.
RESULTS: The RNFL thickness in four Quadrants and an inner circle were taken. The mean thickness in inner circle in both groups were 101.48μm (SD±13.34 μm) and 92.38 μm (SD±11.99μm) respectively, which was statistically significant. The difference was also significant in superior, nasal and inferior quadrant. Statistically the difference was not significant in temporal quadrant. The macular volume was calculated in 6mm diameter. The mean value in Group A was 7.82mm3±0.54 mm 3. The mean value in Group B was 7.44mm3±0.98mm3. The statistical analysis showed the difference between the two groups is statistically significant.
CONCLUSION: RNFL thickness is an established way to diagnose open angle glaucoma in preperimetric stage. Macular Volume is also found to be co-related with the risk. Myopes are known to be at higher risk to develop POAG. Hence, measurement of RNFL thickness by OCT should be made a mandatory investigation in High Myopes.

Introduction

Myopia is that form of refractive error where parallel rays of light coming from infinity focus in front of the sentient layer of the retina at rest. The classical view is that two types of myopia exist: first, there are cases which are physiological variants of normal, referred to as simple myopia. Second, group is made up of cases where higher degrees are concerned, and the condition is of more serious nature. It is often hereditary, called as pathological myopia. Simple myopia is a condition of limited progression whereas pathological myopia may increase to such a degree that it merits consideration as a medical entity on its own [Figure 1].[1]

Figure 1

Schematic diagram of myopic eye (Source: Google images)

The prevalence of ametropia is as follows: low myopia (<2D) – 29%, moderate myopia (2–6D) – 7%, high myopia (>6D) – 2.5%, emmetropia and hypermetropia – 61%, and high hypermetropia – 0.5%.

Optical coherence tomography (OCT) is a noncontact, noninvasive technique to obtain cross-sectional image of the retina with millimeter penetration and micrometer level axial and transverse resolution of the macula, optic disc, and anterior segment. The technique was first demonstrated in 1991 with axial resolution ~30 μm. At present, with the advanced technology, we have conventional OCT with 10 μm and three-dimensional OCT with 5 μm resolution.[23]

Myopic eyes are at 2–3-time higher risk of developing glaucoma than emmetropic eyes.[45] OCT is widely used for preperimetric diagnosis of glaucoma. Although the thinning of retinal nerve fiber layer (RNFL) Thickness is a feature of glaucoma, it is uncertain whether RNFL thickness (RNFLT) varies with myopia. Several reports state variable results related to RNFLT in myopes.[456789101112131415161718] Hoh et al. stated that there is no definitive relation between myopic refractive error and RNFLT; other studies, however, stated that OCT is not reliable investigation in highly myopic eyes, based on observation of thinner RNFL by OCT.[4891011121516] They also suggest that topographic profile of RNFL in myopes is different than that in emmetropes, with more pronounced thinning in certain sectors.[611] The purpose of this study is to investigate whether there is any correlation between peripapillary RNFLT and macular volume using OCT.

Materials and Methods

The study was carried out in a tertiary care center from January 1, 2016, to October 31, 2016, after taking due consent from the ethical committee. Sixty-one myopic participants above 21 years of age were chosen who were willing, healthy and had no other ocular complaints other than refractive errors. Most of them were patients, attendants, and students. Known cases of glaucoma were excluded from the study. Participants were divided into two groups based on their refractive errors. Group A – myopic error up to 6D and Group B had participants having myopia more than 6D.

The participants were examined for refractive error both subjective and objective. The intraocular pressure (IOP) was measured, central corneal thickness was taken, and keratometry and axial length was taken. Anterior segment was examined using slit lamp and fundus was seen through 20D indirect ophthalmoscope.

OCT was done using Avanti spectral-domain (SD) OCT, RTvue Optovue Technology. Macular thickness and volume were measured using MM6 (macular mapping at 6 mm) program and RNFLT was measured by RNFL3.45 program. Macular thickness was measured at 1 mm, 3 mm, and 6 mm diameter. Macular volume was taken at 6 mm. Both eyes of each participant were examined. Imaging was performed after pharmacological pupillary dilatation. One experienced examiner, well versed with the operation of the machine, scanned all the cases. A signal strength index (SSI) >40 was accepted. An image was finalized for analysis purpose only if the full extent and depth of the retina was distinguishable clearly. No blinking or eye movement artifacts were accepted.

Macular thickness was examined using MM6 mode (macular mapping at 6 mm). It reconstructs a false color topographic image displayed with numeric average of thickness measurement for each of the 9 map regions with 6 mm × 6 mm area centered on the fovea. Macula was divided into 9 regions with three concentric rings measuring 1 mm, 3 mm, and 6 mm. The circles of radii 3 mm and 6 mm were further divided into four sectors at 45°–225° and 135°–315°. The thickness is measured by identifying the layers of the retina and measuring the distance between internal limiting membrane and inner boundary of retinal pigment epithelium (RPE) [Figure 2].

Figure 2

Macular mapping at 6 mm diameter. (Source: Image from records of Optical Coherence Tomography Avanti Optovue)

RNFLT was measured within an area of diameter 3.45 mm around optic disc. The innermost circle was divided into superior and inferior halves. Outer circle was divided into four sectors – temporal, superior, nasal, and inferior at 45°, 135°, 225°, and 315°, respectively. Outermost circle was divided into 8 sectors at 0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315° [Figure 3].

Figure 3

Retinal nerve fiber layer thickness around optic disc at 3.45 mm diameter. (Source: Image from records of Optical Coherence Tomography Avanti Optovue)

Results

Both the groups were comparable on the basis of age and sex. The occupation of each participant was also taken into account. There were 64 eyes (32 participants) in Group A and 58 eyes (29 participants) in Group B. The mean spherical refractive error of Group A was −2.27D and Group B was −10.79D. Mean keratometry (+43.5D and +43.7D, respectively), mean central corneal thickness (505 μm and 497 μm, respectively), and IOP (13.25 and 13.40 mmHg, respectively) were also comparable. Mean axial lengths were 23.83 mm and 27.82 mm, respectively, which was significantly higher in Group B.

Macular volume was taken in 6 mm diameter. The mean values were 7.82 mm3 and 7.44 mm3, respectively, for both the groups which was statistically significant [Table 1]. RNFL thickness was compared in four quadrants, temporal, superior, nasal and inferior [Tables 2–6].

Table 1

Comparison of Group A and Group B on macular volume (within 6 mm diameter) (mm3) (n=64 Group A and 58 Group B)

Table 2

Comparison of Group A and Group B on retinal nerve fiber temporal quadrant (n=64 Group A and 58 Group B)

Table 6

Comparison of Group A and Group B on retinal nerve fiber layer optical coherence tomography-inner circle (n=64 Group A and 58 Group B)

To summarise, the comparison of the mean values in the two groups, in four quadrants and inner circle, are [Table 7].

Table 7

The comparison of the mean values in the two groups, in four quadrants, and inner circle

Discussion

This study attempts to examine the relationship between the myopic refractive error and macular volume and RNFLT.

In patients of pathological myopia, it is theorized that foveal thickness is higher in high myopic errors though the peri- and para-foveal macular thickness decreases along with increasing myopic error. Since we have considered volume in 6 mm diameter, hence lower volume in Group B is consistent with this theory. In April 2014, Hung et al. did a study on 72 highly myopic eyes of which 31 were known patients of glaucoma and 41 were control.[19] Macular thickness and macular volume (in 6 mm) were investigated using Stratus OCT. They found significant lower values of macular thickness and volume in outer four quadrants. Moreover, they found outer inferior quadrant to be the most important predictor of glaucoma in high myopia.

In 2015, Malakar et al. conducted a study to examine the relation of high myopia with RNFLT.[20] Twenty-five highly myopic and 20 emmetropic patients were randomly selected after excluding glaucoma and RNFLT measured using the fourier domain (FD) OCT. The mean RNFLT in both the groups was 87.89 μm and 111.64 μm, respectively. This finding is similar to our study.

In June 2011, Mansoori et al. did a study in Hyderabad to assess the ability of SD OCT peripapillary RNFLT parameters to distinguish normal eyes and early glaucomatous eyes among Asian Indian people.[21] This study proved that spectral OCT/Scanning laser ophthalmoscope (SLO) can very well differentiate normal eyes from patients with early-stage glaucoma and therefore can be used for early diagnosis of glaucoma. In our study, we found the mean RNFLT in low myopes and high myopes to be 102.47 μm and 92.54 μm, respectively, which is quite close to the findings of Mansoori et al. done on controls and glaucoma patients.

In January 2013, Enam et al. did a study to assess the association between the function of postsynaptic activity of the visual pathway at striate cortex (mfVEP responses) and the structural integrity of the RNFL (by measuring the macular and circumpapillary RNFLT).[22] They found that the circumpapillary RNFLT is a more sensitive detector of glaucoma than the macular one; however, both are affected by glaucoma and can be used for structural evaluation of the RNFL.

High myopia and primary open-angle glaucoma

Several studies indicate that the risk of glaucoma increases with the extent of myopic refractive error. Mostly, these studies have shown that moderate-to-high degree of myopia is associated with raised risk of primary open-angle glaucoma (POAG). The Blue Mountains Eye Study is one of the more frequently cited studies when discussing the association between myopia and glaucoma. It had suggested a strong relationship between POAG and myopia, with an odds ratio of 2.3 in eyes with low myopia (between 1. 0 and 3.0D) and 3.3 in eyes with moderate-to-high myopia (>3.0D).[23]

In the Barbados Eye Study, myopia was one of the many risk factors for POAG.[24]

The Beaver Dam Eye Study showed that, after removing confounding factors, people with myopia were 60% more likely to have glaucoma than those with emmetropia.[25]

Among Asian studies, the Singapore Malay Eye Study showed the relation between moderate or high myopia (>–4D) and POAG.[26]

In Beijing Eye Study, intermediate-to-high myopia may be a risk factor associated with glaucomatous optic neuropathy.[27]

One of the largest screening surveys of myopia and glaucoma was performed in Sweden, the Early Manifest Glaucoma Trial. It covered 32,918 individuals, 57–79 years of age, and examined for glaucoma. Refractive error was measured by autorefractors and glaucoma was defined as reproducible perimetric disease. It found that the prevalence of newly detected glaucoma increased with increasing myopia (P < 0.0001) across all age groups.[28]

However, an association between myopia and POAG was not found in every study, as in the Ocular Hypertension Treatment Study.[29]

A study was conducted by Chao et al. on twenty patients of Chinese ancestry with myopic refractive error. (Myopia >6D was present in 30 out of 40 eyes). They did not find axial length to be a risk factor for visual field loss (P > 0.99, Freeman-Halton extension of the Fisher's exact test).[30]

These results show that other factors besides increased length of the eyeball play an important role in the etiology of visual field loss in this subset of patients.[30] Cross-sectional studies have limitations. Ideally, the data from a longitudinal cohort study will be most appropriate as the onset of glaucoma can be variable and delayed compared with the onset and stabilization of myopia.[31]

Several theories have been proposed to explain an association between myopia and POAG. It has been thought to be due to several mechanisms, one of which is increased susceptibility of the optic nerve head to be damaged by raised IOP and the increased effect of shearing forces on the optic nerve head. One of the potential sight-threatening conditions associated with myopia is glaucoma, which occurs due to progressive degeneration of retinal ganglion cells. An important investigation to detect early structural change in glaucoma is based on the thickness of the RNFL. Several studies have showed that RNFL measurement is sensitive indicator for early detection of glaucoma, and the extent of RNFL damage closely follows the severity of functional deficit in the visual field.

One more cross-sectional analysis of 4 926 Beaver Dam Wisconsin Caucasian population of 43–86 years of age showed that a myopic refraction was associated with raised IOP (P < 0.001).[25]

Several studies have found that, for a given IOP in eyes with POAG, optic nerve damage appears to be more pronounced in high myopic eyes with large optic discs than in eyes with nonhighly myopic error.[32] This may show a higher susceptibility for glaucomatous optic nerve fiber loss in highly myopic eyes compared with nonhighly myopic.

Optical coherence tomography and scanning of myopic eyes

Observation of myopic macular area using a contact or noncontact lens is challenging because the atrophy lowers the contrast. This hinders the detailed observation and understanding of the pathophysiology. OCT has facilitated both visualization and understanding of retinal microstructures, its pathogenesis, interaction, and progression.[33]

Examiners often have difficulties obtaining clear and high-contrast OCT images in highly myopic eyes. The characteristics findings are

Poor fixation due to large central scotoma

Deep posterior staphyloma in the presence of which the peripheral tissue often drops off from the image

RNFL thickening and plaque-like formation in parapapillary region

Intraretinal cystic changes in parapapillary area

Abnormal retinal sloping near the optic disc margin

RPE and photoreceptor loss.[34]

The definition of disc margin is based on detection of RPE-Choroid border. The presence of peripapillary atrophy induces a misalignment of the disc margin read by OCT.

Peripapillary atrophy is more commonly seen among patients of glaucoma, high myopia. It is also difficult to distinguish the changes in these pathologies with the changes due to growing age. In our study, the average age was 24.9 years and 28.25 years in Groups A and B, respectively, with minimum variations. Hence, the effect of growing age can be ignored. Other causes of thinning of nerve fiber layer can be age-related macular degeneration, optic neuropathy, brain tumor or any other long-standing compressive lesion, cataract, cystoid macular edema, epiretinal membrane, and diabetic retinopathy. Since the cases were chosen ruling out any other ocular and optical disease, hence the causes of RNFL thinning in this study can be assumed to be either pathological myopia or glaucoma.[34]

Conclusion

This study was conducted to find the relation between myopic refractive errors and RNFLT and macular volume. There was found a significant relationship between these entities. Most important among these values was the RNFLT.

The current normative database fed in the machines might be misleading for a correct diagnosis of glaucoma in varying degrees of myopia. Before making a confirmative diagnosis, the axial length-induced magnification effect should be taken into consideration by ophthalmologists. The current OCT database should be improved by taking axial length into account.

RNFLT is an established way to diagnose open-angle glaucoma in preperimetric stage. Myopes are known to be at higher risk to develop POAG than hypermetropes or emmetropes. Hence, the measurement of RNFLT by OCT should be made a mandatory investigation in high myopes. It is important to investigate factors of refractive errors associated with glaucoma in longitudinal studies. Further prospective, clinical, and epidemiological studies will improve our understanding of the pathogenesis of glaucoma. High myopic participants should be routinely followed and closely monitored to diagnose glaucoma early.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Table 3

Comparison of Group A and Group B on retinal nerve fiber layer superior quadrant (n=64 Group A and 58 Group B)

Table 4

Comparison of Group A and Group B on retinal nerve fiber layer nasal quadrant (n=64 Group A and 58 Group B)

Table 5

Comparison of Group A and Group B on retinal nerve fiber layer inferior quadrant (n=64 Group A and 58 Group B)