Glaucoma diagnostic performance of macular ganglion cell complex thickness using regular and long axial length normative databases

www.nature.com/scientificreports OPEN Glaucoma diagnostic performance of macular ganglion cell complex thickness using regular and long axial length normative databases Henry Shen‑Lih Chen1,2, Xiao Chun Ling1*, Da‑Wen Lu3, Lan‑Hsing Chuang2,4, Wei‑Wen Su1,2, Yung‑Sung Lee1,2, Wei‑Chi Wu1,2 & Po‑Han Yeh1 The risks of misdiagnosing a healthy individual as glaucomatous or vice versa may be high in a population with a large majority of highly myopic individuals, due to considerable morphologic variability in high myopic fundus. This study aims to compare the diagnostic ability of the regular and long axial length databases in the RS-3000 Advance SD-OCT (Nidek) device to correctly diagnose glaucoma with high myopia. Patients with high myopia (axial length ≥ 26.0 mm) in Chang Gung Memorial Hospital, Taiwan between 2015 and 2020 were included. Glaucoma was diagnosed based on glaucomatous discs, visual field defects and corresponding retinal nerve fiber layer defects. The sensitivity, specificity, diagnostic accuracy and likelihood ratios of diagnosing glaucoma via mGCC thickness in both superior/inferior and GChart mapping using the regular and long axial length normative databases. The specificity and diagnostic accuracy of mGCC thickness for distinguishing glaucomatous eyes from nonglaucomatous eyes among highly myopic eyes were significantly improved using the long axial length database (p = 0.046). There were also significant proportion changes in S/I mapping as well as GChart mapping (37.3% and 48.0%, respectively; p < 0.01) from abnormal to normal in the myopic normal eye group when using the long axial length normative database. The study revealed that clinicians could utilize a long axial length database to effectively decrease the number of false-positive diagnoses or to correctly identify highly myopic normal eyes misdiagnosed as glaucomatous eyes. Glaucoma is regarded as a multifactorial optic neuropathy characterized by progressive loss of retinal ganglion cells, retinal nerve fiber layer (RNFL) thinning, and ultimately irreversible visual impairment. In East Asian countries, myopia affects a significant proportion of the p opulation1. Studies have shown that moderate-to-high myopia is associated with increased risks of primary open angle glaucoma, ocular hypertension and normal tension glaucoma2–4. Similarly, a myopic fundus can pose significant challenges in correctly diagnosing glaucoma because of its considerable morphologic variability, tilted disc, physiologic cupping, shallower optic cups and peripapillary atrophy5,6. Thus, the risks of misdiagnosing a healthy individual as glaucomatous or vice versa may be high in a population with a large majority of highly myopic individuals. Longer axial lengths (ALs) and vitreous chamber depths were also appreciated in myopic eyes7. The relationship of long AL and high myopia was first postulated by Von Graefe. Progression patterns in the topography of the posterior pole of highly myopic eyes, including concomitant decreased retinal thickness and macular atrophy, were associated with elongations of A L8. Consequently, regional variations in macular or RNFL thicknesses might affect the evaluation of glaucoma in highly myopic eyes9. To resolve this issue, investigators have suggested evaluating assessments of macular ganglion cell complex (mGCC) thickness via spectral-domain optical coherence tomography (SD-OCT)10,11. The thickness of mGCCs can play an important role in the early diagnosis of g laucoma12. As a complementary measurement to RNFL thickness assessment, mGCC thickness assessment can aid in the clinical evaluation of glaucoma, even in highly myopic individuals13,14. 1 Department of Ophthalmology, Chang Gung Memorial Hospital, No. 5, Fu‑Hsin Road, Linkou, Taoyuan 333, Taiwan. 2College of Medicine, Chang Gung University, Taoyuan, Taiwan. 3Department of Ophthalmology, Tri-Service General Hospital, Taipei, Taiwan. 4Department of Ophthalmology, Chang Gung Memorial Hospital, Keelung, Taiwan. *email: Scientific Reports | (2022) 12:11263 | https://doi.org/10.1038/s41598-022-15255-x 1 Vol.:(0123456789) www.nature.com/scientificreports/ However, there are two aspects to be considered in the evaluation of thicknesses and significance maps of average mGCCs in highly myopic eyes. One is that the elongation of AL can produce ocular magnification of retinal images15. In instances where magnification is not corrected, the SD-OCT scan area will become wider in eyes with longer ALs, thus leading to possible misdiagnosis16. Another aspect to consider is that population data of individuals with high myopia, hyperopia or astigmatism are not usually included in the normative database of mGCC thicknesses17,18. This results in reduced accuracy and precision of glaucoma diagnosis in highly myopic individuals due to the normative database not representing all patient populations. In addition to correcting for ocular magnification due to AL elongation via its built-in software, the RS-3000 Advance SD-OCT (Nidek, Co. Ltd. Japan) comprises two sets of normative databases embedded: the regular nonmyopic database for eyes with ALs < 26 mm and the long AL database for eyes with ALs between 26 and 29 mm17,19. The purpose of this study was to compare the diagnostic ability of these two distinct databases in the RS-3000 Advance SD-OCT device to accurately diagnose glaucoma in Taiwanese eyes with high myopia. Materials and methods Study population. The study was an observational cross-sectional study. Patients with high myopia (AL ≥ 26.0 mm) examined at the Glaucoma Service at the Department of Ophthalmology, Chang Gung Memorial Hospital, Taiwan, between January 2015 and August 2020 were included. The study was approved by the Institutional Review Board and the Ethics Committee of Chang Gung Memorial Hospital, Taiwan. All procedures adhered to the tenets of the Declaration of Helsinki. A written or signed informed consent was obtained for every participant in the study after providing adequate information and opportunity for the subject to consider all options, have all their questions answered, as well as continuing to response to the participants as the situation requires. Study protocol. Standard study protocols detailed below were compatible with methodology previously published by our group20. Comprehensive ophthalmic evaluation was performed for every patient as follows: slit-lamp examination, intraocular pressure measurements via Goldmann applanation tonometry, central corneal thickness measurements, gonioscopic examination by a Goldmann three-mirror lens, optic nerve head and fundus evaluation, digital color fundus photography (Digital Non-Mydriatic Retinal Camera, Canon, Tokyo, Japan), AL measurements by Optical Biometer AL-Scan (Nidek, Co. Ltd. Japan), central 30–2 Swedish Interactive Threshold Algorithm standard automated perimetry using a Humphrey Field Analyzer (Carl Zeiss Meditec, Dublin, CA, USA), measurements of (...truncated)