|
 |
| ORIGINAL ARTICLE |
|
| Year : 2022 | Volume
: 15
| Issue : 1 | Page : 36-42 |
|
|
Correlation of retinal nerve fiber layer thickness with perimetric staging in primary open-angle glaucoma – A cross-sectional study
K Subrahmanya Bhat, M Vaishnavi Reddy, Vijay Pai
Department of Ophthalmology, K. S. Hegde Medical Academy, Mangalore, Karnataka, India
| Date of Submission | 09-Sep-2020 |
| Date of Decision | 12-Aug-2021 |
| Date of Acceptance | 09-Oct-2021 |
| Date of Web Publication | 02-Mar-2022 |
Correspondence Address:
Dr. M Vaishnavi Reddy
Department of Ophthalmology, K. S. Hegde Medical Academy, Deralakatte, Mangalore - 575 018, Karnataka
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ojo.ojo_345_20
 Abstract | | |
BACKGROUND: Glaucoma is a progressive optic neuropathy, characterized by structural optic nerve damage with corresponding field defects. Primary open-angle glaucoma (POAG) is the most common. Although perimetry is the gold standard, retinal nerve fiber layer (RNFL) thickness by spectral-domain optical coherence tomography (SD-OCT) has proved reliable in the detection of pre-perimetric glaucoma. There is preferential involvement of various sectors of the peripapillary RNFL in the different stages of POAG.
PURPOSE: The purpose of this study is to assess RNFL thickness and determine preferential involvement of different sectors of peripapillary RNFL in the various stages of POAG using SD-OCT.
MATERIALS AND METHODS: Forty-nine patients with POAG underwent complete ophthalmic examination including visual field testing and RNFL thickness measurement. Perimetric findings were used to categorize them into mild, moderate, and severe stages of glaucoma. The RNFL thickness values were analyzed and compared with perimetric results.
RESULTS: The average RNFL loss in mild, moderate, and severe POAG was 25.44%, 29.67%, and 44.15%, respectively. A statistically significant correlation (P < 0.05) between RNFL loss and severity of glaucoma was found in all except the superior and temporal sectors. A statistically significant (P < 0.05) negative correlation was noted between visual field index and RNFL loss in all sectors except the nasal-superior in moderate POAG and all sectors in severe POAG. Mean deviation and RNFL loss showed a significant positive correlation in temporal-inferior (TI) sector in mild POAG and all sectors in the severe group.
CONCLUSION: RNFL thickness decreases with increase in glaucoma severity and is a reliable parameter to differentiate mild from severe POAG. The TI followed by nasal-inferior RNFL sector is the most sensitive to glaucomatous damage in all three stages.
Keywords: Optical coherence tomography, perimetry, primary open-angle glaucoma, retinal nerve fiber layer
How to cite this article:
Bhat K S, Reddy M V, Pai V. Correlation of retinal nerve fiber layer thickness with perimetric staging in primary open-angle glaucoma – A cross-sectional study. Oman J Ophthalmol 2022;15:36-42 |
How to cite this URL:
Bhat K S, Reddy M V, Pai V. Correlation of retinal nerve fiber layer thickness with perimetric staging in primary open-angle glaucoma – A cross-sectional study. Oman J Ophthalmol [serial online] 2022 [cited 2022 May 19];15:36-42. Available from: https://www.ojoonline.org/text.asp?2022/15/1/36/338886 |
| Introduction | |  |
Glaucoma is a group of diseases, characterized by optic neuropathy consistent with remodeling of connective tissue of the optic nerve head and loss of neural tissue associated with the development of visual field defects. Approximately 11.2 million people in India suffer from glaucoma, of which 6.48 million have primary open-angle glaucoma (POAG).[1] The structural changes due to retinal ganglion cell (RGC) loss lead to functional visual field loss. Perimetry is used as a base line at diagnosis as well as for monitoring of the disease. The classification of glaucoma into various stages helps in the assessment and documentation of visual field loss, allowing the detection of progression. It is sensitive and specific, but subjective and shows intertest variability.[2] Visual field defects are found after 25%–30% RGC loss,[3] which may lead to patients with early glaucomatous damage remaining undetected.
Optical coherence tomography (OCT) is more sensitive to changes in visual function than perimetry. Since it specifies the RNFL thickness in various quadrants, the area most susceptible to damage can be determined. It is especially useful in patients whose perimetric results are not reliable.[4]
| Materials and Methods | | |
Study design
Descriptive, noninterventional, and hospital-based study.
Inclusion criteria
Confirmed cases of POAG with characteristic optic disc changes and corresponding visual field defects, based on Anderson's criteria,[5] reporting to the Department of Ophthalmology, Justice K. S Hegde Charitable Hospital.
Exclusion criteria
Patients with refractive error >−6.00 D, axial length >24 mm, corneal scarring, significant media opacities, secondary glaucoma, severe nonproliferative diabetic retinopathy (NPDR), PDR, retinal diseases affecting the visual field, nonglaucomatous optic neuropathy, diseases affecting visual pathways, patients with a history of ocular trauma or intraocular surgery (except uncomplicated cataract surgery and/or trabeculectomy in confirmed POAG patients).
All the study participants underwent refraction, slit-lamp examination, intraocular pressure (IOP) measurement by Goldmann's applanation tonometry, pachymetry, fundus examination using +90 D lens, gonioscopy, visual field testing using Humphrey's Field Analyzer, Swedish Interactive Threshold Algorithm (SITA) 24-2 (Carl Zeiss Meditec, Dublin, CA, USA). Acceptable visual field tests included false positive and false negatives of <33% and fixation losses <20%. Eyes were classified as having mild, moderate, or severe glaucoma using Hodapp-Parrish-Anderson criteria.[6]
A scan circle of 3.5 mm diameter around the optic nerve was taken and peripapillary RNFL thickness in global, nasal-superior (NS), temporal-superior (TS), temporal-inferior (TI), nasal-inferior (NI), nasal and temporal sectors was measured using spectral domain OCT (SD-OCT) (Heidelberg Engineering SD-OCT system, Spectralis OCT 14603, software 6.5). Acceptable OCT scans were those with signal-to-noise ratio >25 decibels (dB).
Written informed consent was obtained from all the participants, and Institutional Ethics Committee clearance was obtained.
Statistical analysis was performed using the SPSS software version 25 (IBM Corp., Armonk, N.Y., USA). P < 0.05 was considered statistically significant.
| Results | | |
Forty-nine eyes of 27 patients, of which 22 (44.9%) were male and 27 (55.1%) were female, were included in this study. The age of the patients ranged from 41 to 83 years, with a mean age being 56.22 ± 10.1 years [Figure 1]. The difference in age, BCVA, central corneal thickness (CCT), and IOP values between the three groups was not statistically significant [Table 1]. | Table 1: Age, best-corrected visual acuity, intraocular pressure, and cup-disc ratios
Click here to view |
The average visual field index (VFI), mean deviation (MD), and pattern standard deviation (PSD) were 65.35 ± 29.95%, −11.84 ± 8.88 dB, and 7.77 ± 4.05 dB, respectively. The Chi-square test comparing VFI, MD, and PSD in eyes with mild, moderate, and severe glaucoma showed a statistically significant difference in all the three parameters between the three groups (P < 0.001) [Table 2]. Post hoc Tukey test comparing VFI and MD revealed a statistically significant difference between mild versus severe (P < 0.001) and moderate versus severe groups (P = 0.002, P < 0.001) but not between mild and moderate groups. A similar analysis done for PSD showed a statistically significant difference among all the groups [Table 3]. There was a significant positive correlation between MD and VFI with a correlation coefficient (r) of 0.9218 [Figure 2]. There was a nonlinear correlation between PSD and VFI [Figure 3]. | Figure 2: Correlation of mean deviation with visual field index (r = 0.9218, P < 0.00001)
Click here to view |
 | Figure 3: Correlation of pattern standard deviation with visual field index (r = 0.4636, P = 0.000808)
Click here to view |
 | Table 2: Comparison of visual field parameters in the glaucoma sub-groups
Click here to view |
On OCT, the mean global RNFL thickness was 62.45 ± 17.75 μm which is significantly lower than normal. The percentage RNFL loss was 36.1%, 34.2%, 35.4%, 33%, 45.1%, 51.3%, and 30% in the global, TS, NS, nasal, NI, TI, and temporal sectors, respectively. Mean RNFL thickness in the three glaucoma groups was calculated [Figure 4] and [Table 4]. In all three groups, maximum RNFL loss occurred in the TI sector followed by the NI. There was a statistically significant difference in the amount of RNFL lost with severity of POAG in all except the superior and temporal sectors [Figure 5] and [Table 5]. | Figure 4: Mean retinal nerve fiber layer thickness: Normative database, mild moderate and severe group
Click here to view |
 | Table 4: Mean retinal nerve fiber layer thickness normative database mild, moderate, and severe primary open-angle glaucoma
Click here to view |
A negative correlation was found between VFI and RNFL loss which was statistically significant (P < 0.05) in the global, NI and TI sectors in mild POAG and in all quadrants except the NS in moderate POAG. All sectors showed statistically significant negative correlation in severe POAG [Table 6]. In all the three groups, a positive correlation was found between MD and RNFL loss. It was statistically significant in all the sectors only in severe POAG [Table 7]. A poor correlation was observed between PSD and RNFL loss [Table 8]. | Table 6: Correlation of visual field index with retinal nerve fiber layer loss
Click here to view |
 | Table 7: Correlation of mean deviation with retinal nerve fiber layer loss
Click here to view |
 | Table 8: Correlation of pattern standard deviation with retinal nerve fiber layer loss
Click here to view |
| Discussion | | |
Forty-nine eyes with established glaucoma were included in this study. There was no significant difference in age or sex distribution among the three glaucomatous groups. The CCT values progressively decreased and IOP increased with the severity of glaucoma. Although this is consistent with a study done by Moghimi et al.,[8] the results in our study were not statistically significant. Since several subjects in our study had already been diagnosed with POAG and were on treatment, the IOP values included were not the baseline IOP that the patient presented with. In patients with relatively higher IOP values, the readings may be explained by inadequate treatment or poor compliance with medication. Of the 27 study participants, 22 had established glaucoma in both eyes. In four patients, the second eye had normal optic disc findings; IOP, GHT, and RNFL thickness within normal limits. These eyes were not included in our study but followed up to detect the appearance of glaucomatous changes. One patient had central retinal vein occlusion.
VFI values were significantly different in each group in our study, which was also found in another study that concluded that VFI is a reliable parameter for staging the severity of glaucoma.[9] There was statistically significant difference in VFI and MD between the mild versus severe and moderate versus severe groups, but not between the mild and moderate groups. This may be because the number of patients in moderate group (n = 9) were lower than in other groups. As multiple parameters are considered in perimetric staging, categorization may be difficult and less accurate. A strong positive correlation (r = 0.9218, P < 0.00001) occurred in this study between VFI and MD. Similar results (r = 0.956) were reported by Iutaka et al.[10] A study of 60 patients found a significant correlation between VFI and MD as well as VFI slope and MD slope.[11] Dorairaj et al.[12] found an excellent correlation between MD and VFI (r2 = 0.95) in moderate-to-severe glaucoma.[13] The comparison of VFI and PSD in our study showed a nonlinear correlation. PSD is not useful for detecting progression since it peaks at an MD of about − 12 dB. As the glaucomatous damage increases further, it reverses toward 0 dB such that patients with mild and advanced glaucoma have similar PSD values.[14]
The difference in RNFL thickness between the mild, moderate, and severe glaucoma groups in the TS, NS, nasal, NI, and TI sectors in our study was significant, implying that the susceptibility of each sector to glaucomatous damage differs with the stage of the disease. This corresponds with the study done by Kaw et al.[4] Zivkovic et al.[15] reported a significant difference in RNFL thickness in superior, inferior, nasal, and temporal quadrants in the different stages of glaucoma (χ2 = 273.36, DF = 3, P < 0.001). A statistically significant difference in RNFL thickness between normal and glaucomatous patients as well as early, developing and late stages of glaucoma was present in a study by Liu et al.[16]
The average RNFL loss in our study was 25.44%, 29.67%, and 44.15% in the mild, moderate, and severe groups, respectively. Similar values of 25% RNFL loss in early glaucoma and 48% in severe glaucoma were noted by Sihota et al.[17] El-Naby et al.[18] reported a 14.9%, 25.1%, and 37.2% RNFL loss in the three groups while another study showed a loss of 22.21%, 22.06%, and 42.72% in the three stages.[4] The TI followed by the NI sector was most susceptible to glaucomatous damage in all three groups in our study. Wu et al.[19] reported that the highest correlation between RNFL thickness and visual field defect values was in the TI sector. Zivkovic´et al.[15] found that the temporal quadrant was significantly thinner than all the other quadrants followed by the nasal quadrant while others[20],[21],[22] found that the inferior quadrant was the thinnest. Sehi et al.[21] found additional average and superior quadrant RNFL thinning in the later stages of glaucoma. The temporal sectors in our study were found to show least thinning in all three glaucoma groups similar to other studies which compared RNFL thickness in normal and glaucomatous eyes.[18] The TI and NI sectors can be monitored for progression in glaucoma patients as these sectors show a significant difference in RNFL loss, especially between the mild and severe perimetric stages. Leung et al.[23] reported that the TI quadrant was also most frequently associated with glaucoma progression.
In the present study, as the VFI decreased, RNFL thickness decreased, that is, the RNFL loss increased. This finding is in agreement with those of Liu et al.[16] and Kimura et al.[11] A nonlinear relationship was found between VFI and estimated RGC counts, with VFI underestimating the amount of RGC loss in early glaucoma by Marvasti et al.[22] Rao[24] reported that VFI showed maximum correlation with average and superior RNFL thicknesses in mild and moderate groups contrary to our study, where it correlated best with RNFL in the TI sector in mild POAG, all the sectors in moderate except NS and all except the TS and temporal sectors in severe POAG.
In our study, there was a positive correlation between MD and RNFL loss as seen in studies by Kaw et al. and Taliantzis et al.[4],[20] who found strong (r = 0.73) and moderate (r = 0.58) correlations of RNFL thickness with MD and loss variance (r = 0.51; r = 0.53), respectively. MD was found to have a significant positive correlation with RNFL thickness by other studies.[18],[25],[26] In a study by Choi et al.,[27] most of the RNFL sectors had a significant positive correlation with MD while in advanced glaucoma, the superior RNFL quadrant showed the greatest positive correlation (r = 0.452). In our study, MD in the mild group showed a good positive correlation with RNFL loss in the global (r = 0.589, P = 0.027) and TI sectors (r = 0.781, P = 0.001) while in severe glaucoma, all the sectors showed a statistically significant correlation.
An increase in PSD value in our study was associated with a corresponding increase in mean RNFL loss but was not statistically significant. In studies done by Kaw et al.[4] and Arun et al.,[25] a significant association was found between PSD and RNFL thickness. Parisi et al.[26] found a highly significant correlation (r = 0.663, P < 0.001) between average RNFL thickness and corrected PSD. The poor statistical correlation in our study may due to the relatively higher number of severe POAG patients in whom PSD trend reverses when MD worsens beyond −12 dB. Taliantzis et al.[20] reported strong correlations between average RNFL thickness and visual field indices only in those with progressive structural changes (P < 1%) on OCT, although, sectoral RNFL thickness was considered a reliable parameter. In contrast, our study showed that all three groups had a moderate to excellent correlation of global RNFL thickness with visual field indices which corresponds with the findings of El-Naby et al.[18] and Zangwill et al.[28]
| Conclusion | | |
Peripapillary RNFL thickness is a useful measure to discriminate between mild and severe stages of POAG. The TI sector followed by NI is most susceptible to glaucomatous damage. RNFL thickness in these sectors can be used to diagnose early POAG.
The limitations of our study are a small sample size (49 eyes) and the difference in number of patients in each glaucoma sub-group which may limit the extent to which the results of this study can be extrapolated to the general population. Further studies to include more data from Asian populations would enable the creation of a normative database and a reference range for normal RNFL thickness values in each sector that is applicable to the Indian population.
Another limitation of this study is that although RNFL thickness measurements by different instruments follow the anatomic distribution, the machines may generate significantly different total and sectoral thickness values.[29] This must be taken into consideration while comparing OCT scans from different instruments.
RNFL thickness values in this study along with more longitudinal studies and creation of a new algorithm and scoring system for the detection of progression can be used to categorize patients into the various stages of POAG based on RNFL thickness.
This will allow the early detection of disease progression so that further loss of visual function can be prevented.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | George R, Ve RS, Vijaya L. Glaucoma in India: Estimated burden of disease. J Glaucoma 2010;19:391-7.  |
| 2. | Turalba AV, Grosskreutz C. A review of current technology used in evaluating visual function in glaucoma. Semin Ophthalmol 2010;25:309-16. |
| 3. | Kerrigan-Baumrind LA, Quigley HA, Pease ME, Kerrigan DF, Mitchell RS. Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. Invest Ophthalmol Vis Sci 2000;41:741-8. |
| 4. | Kaw SM, Martinez JM, Tumbocon JA, Atienza N. Correlation of average RNFL thickness using the STRATUS OCT with the perimetric staging of glaucoma. Philipp Acad Ophthalmol 2012;37:19-23. |
| 5. | Kanski J, Bowling B. Glaucoma. In: Kanski's Clinical Ophthalmology. 8th ed. Edinburgh, NY: Saunders Ltd; 2015. p. 928. |
| 6. | Susanna R Jr., Vessani RM. Staging glaucoma patient: Why and how? Open Ophthalmol J 2009;3:59-64. |
| 7. | Spectralis Glaucoma Module Premium Edition. User Manual Software Version 6.5. Heidelberg, Germany: Heidelberg Engineering GmbH; 2016. p. 78. |
| 8. | Moghimi S, Torabi H, Hashemian H, Amini H, Lin S. Central corneal thickness in primary angle closure and open angle glaucoma. J Ophthalmic Vis Res 2014;9:439-43. [ PUBMED] [Full text] |
| 9. | Kuzhuppilly N, Patil S, Dev S, Deo A. Reliability of visual field index in staging glaucomatous visual field damage. J Clin Diagn Res 2018;12:NC05-8. |
| 10. | Iutaka NA, Grochowski RA, Kasahara N. Correlation between visual field index and other functional and structural measures in glaucoma patients and suspects. J Ophthalmic Vis Res 2017;12:53-7. [ PUBMED] [Full text] |
| 11. | Kimura S, Kimura T, Ono K, Murakami A. Correlation between visual field index values and mean deviation values of Humphrey field analyzer. Nippon Ganka Gakkai Zasshi 2011;115:686-92. |
| 12. | Dorairaj S, Nasser C, Barkana Y. The Visual FIeld Index (VFI) – Correlation with Mean Deviation (MD) and visual disability parameters in advanced glaucoma. Invest Ophthalmol Vis Sc 2014;55:4301. |
| 13. | Sousa MC, Biteli LG, Dorairaj S, Maslin JS, Leite MT, Prata TS. Suitability of the visual field index according to glaucoma severity. J Curr Glaucoma Pract 2015;9:65-8. |
| 14. | |
| 15. | Zivkovic M, Jaksic V, Jovanovic P, Zlatanovic M, Zlatanovic G, Djordjevic-Jocic J. Peripapillary retinal nerve fiber layer thickness in different glaucoma stages measured by optical coherence tomography. VSP 2017;74:121-6. |
| 16. | Liu X, Ling Y, Luo R, Ge J, Zheng X. Optical coherence tomography in measuring retinal nerve fiber layer thickness in normal subjects and patients with open-angle glaucoma. Chin Med J (Engl) 2001;114:524-9. |
| 17. | Sihota R, Sony P, Gupta V, Dada T, Singh R. Diagnostic capability of optical coherence tomography in evaluating the degree of glaucomatous retinal nerve fiber damage. Invest Ophthalmol Vis Sci 2006;47:2006-10. |
| 18. | El-Naby AE, Abouelkheir HY, Al-Sharkawy HT, Mokbel TH. Correlation of retinal nerve fiber layer thickness and perimetric changes in primary open-angle glaucoma. J Egypt Ophthalmol Soc 2018;111:7-14. [Full text] |
| 19. | Wu H, de Boer JF, Chen L, Chen TC. Correlation of localized glaucomatous visual field defects and spectral domain optical coherence tomography retinal nerve fiber layer thinning using a modified structure-function map for OCT. Eye (Lond) 2015;29:525-33. |
| 20. | Taliantzis S, Papaconstantinou D, Koutsandrea C, Moschos M, Apostolopoulos M, Georgopoulos G. Comparative studies of RNFL thickness measured by OCT with global index of visual fields in patients with ocular hypertension and early open angle glaucoma. Clin Ophthalmol 2009;3:373-9. |
| 21. | Sehi M, Zhang X, Greenfield DS, Chung Y, Wollstein G, Francis BA, et al. Retinal nerve fiber layer atrophy is associated with visual field loss over time in glaucoma suspect and glaucomatous eyes. Am J Ophthalmol 2013;155:73-82.e1. |
| 22. | Marvasti AH, Tatham AJ, Zangwill LM, Girkin CA, Liebmann JM, Weinreb RN, et al. The relationship between visual field index and estimated number of retinal ganglion cells in glaucoma. PLoS One 2013;8:e76590. |
| 23. | Leung CK, Yu M, Weinreb RN, Lai G, Xu G, Lam DS. Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: Patterns of retinal nerve fiber layer progression. Ophthalmology 2012;119:1858-66. |
| 24. | Rao A. Comparison of relation between visual function index and retinal nerve fiber layer structure by optical coherence tomography among primary open angle glaucoma and primary angle closure glaucoma eyes. Oman J Ophthalmol 2014;7:9-12. [ PUBMED] [Full text] |
| 25. | Arun A, Sadhana A, Shankar RD. Correlation between structural retinal nerve fibre layer thickness and functional visual field loss in Primary open angle glaucoma. Bali Med J 2015;4:28. |
| 26. | Parisi V, Manni G, Centofanti M, Gandolfi SA, Olzi D, Bucci MG. Correlation between optical coherence tomography, pattern electroretinogram, and visual evoked potentials in open-angle glaucoma patients. Ophthalmology 2001;108:905-12. |
| 27. | Choi JA, Shin HY, Park HL, Park CK. The Pattern of Retinal Nerve Fiber Layer and Macular Ganglion Cell-Inner Plexiform Layer Thickness Changes in Glaucoma. Journal of Ophthalmology, vol. 2017, Article ID 6078365, 8 pages, 2017. https://doi.org/10.1155/2017/6078365. |
| 28. | Zangwill LM, Williams J, Berry CC, Knauer S, Weinreb RN. A comparison of optical coherence tomography and retinal nerve fiber layer photography for detection of nerve fiber layer damage in glaucoma. Ophthalmology 2000;107:1309-15. |
| 29. | Pierro L, Gagliardi M, Iuliano L, Ambrosi A, Bandello F. Retinal nerve fiber layer thickness reproducibility using seven different OCT instruments. Invest Ophthalmol Vis Sci 2012;53:5912-20. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]
|
