Systematic review of macular ganglion cell complex analysis using spectral domain optical coherence tomography for glaucoma assessment

Table 1 Properties of the various spectral domain optical coherence tomography instruments

	Cirrus HD-OCT (Carl Zeiss Meditec, Inc., Dublin CA, United States)	RTVue (Optovue, Inc., Fremont, CA, United States)	Spectralis (Heidelberg Engineering, Heidelberg, Germany)	3D OCT 2000 (Topcon Corporation, Tokyo, Japan)
Macular layer measured	GCIP	GCC	The entire retina (from =BM to ILM)	Macular RNFL GCIP (GCL+) GCC (GCL++)
Maps provided	Thickness map, deviation map and sectors	Thickness map, deviation map and significance map	Thickness map, asymmetry map, hemisphere asymmetry map and mean thickness map	Thickness map, significance map, average thickness asymmetry map
Grid dimensions (mm)	6 × 6	7 × 7	8 × 8	6 × 6

OCT: Optical coherence tomography; GCIP: Combined retinal ganglion cell (RGC) and inner plexiform layer (IPL); RNFL: Retinal nerve fiber layer; GCC: Ganglion cell complex = macular RNFL + GCIP; BM: Bruchs membrane; ILM: Internal limiting membrane.

Table 2 Summary of major studies investigating macular spectral domain optical coherence tomography for glaucoma assessment

Ref.	SD-OCT instrument	Patients	Type of glaucoma assessment	Main outcomes
Tan et al[39]	RTVue	310 eyes: 125 normal, 76 PPG, 109 PG	Glaucoma detection	GCC thickness had significantly higher diagnostic power than macular retinal thickness in differentiating between PPG and normal eyes
Kim et al[43]	3D OCT 2000	204 eyes: 64 normal, 68 PPG, 72 early PG	Glaucoma detection	GCC thickness steadily decreased from normal to PPG to early glaucoma. GCIP and GCC, but not mNFL were significantly different between PPG and controls and had similar discrimination ability as cpRNFL analysis
Lee et al[44]	3D OCT 2000	63 early PG eyes, 33 with and 30 without paracentral VF defects	Assessment of paracentral VF defects	Regional structural assessment of MIRL was a better indicator of paracentral scotoma than cpRNFL measurements (AROC 0.77 vs 0.644, respectively)
Akashi et al[49]	Cirrus, RTVue, 3D OCT 2000	232 eyes: 87 normal, 145 PG	Glaucoma detection ability in different SD-OCT instruments	Diagnosis of glaucoma with average GCC thicknesses was similar between the three SD-OCT instruments. RTVue exhibited better diagnostic abilities than Cirrus and 3D OCT 2000 for superior GCC thickness
Rolle et al[50]	RTVue	271 eyes: 163 with positive family history of POAG, 108 eyes without	Glaucoma detection	RNFL superior, GCC average, GCC superior and GCC inferior were significantly thinner and the GLV was higher in healthy eyes with a positive family history of POAG than in normal eyes without history
Kim et al[51]	Spectralis	106 PG eyes	Assessment of macular thickness and visual field defects	A significant relationship between VFS and MRT values was found and was strongest in the arcuate region. About 17% structural loss was necessary to detect functional loss
Inuzuka et al[52]	Cirrus	67 PG eyes	Glaucoma detection	GCC thickness of the inner or outer sector of the parafovea decreased as the corresponding hemifield defect increased. GCC thickness changes in apparently normal hemifield correlated with progression of the glaucomatous defects
Seong et al[53]	RTVue	167 eyes: 65 normal, 102 NTG	NTG assessment	MIRL thickness was strongly correlated and glaucoma discrimination ability was comparable with cpRNFL thickness in early VF defects. cpRNFL had better diagnostic ability than MIRL in eyes with advanced or peripheral VF defects
Na et al[55]	RTVue	173 eyes: 68 normal, 105 PPG	Glaucoma detection	PPG patients had significantly reduced GCC thickness in all sectors compared to healthy subjects. Superior GCC thickness average was best for detecting localized RNFL defects
Rao et al[56]	RTVue	106 eyes: 34 PPG, 72 with large physiologic optic disc cupping	Glaucoma detection	GCC parameters had moderate diagnostic ability to differentiate PPG from large physiologic cups. Inferior quadrant GCC thickness had the best AROC (0.75)
Iverson et al[57]	RTVue	97 eyes: 23 normal, 74 PPG	Glaucoma detection	GCC thickness had high specificity (91%) in normal eyes and moderate specificity (77%) in glaucoma suspects. About half of GCC measurements classified as outside normal limits were not replicable
Mwanza et al[58]	Cirrus	99 eyes: 49 normal, 50 early PG	Glaucoma detection	GCIP parameters were significantly thinner in the glaucoma compared to the control group. Diagnosis based on at least 1 abnormal GCIP parameter yielded 88% sensitivity and 81.6% specificity
Kim et al[60]	RTVue	186 PG eyes	Structural-functional relationship	All GCC parameters significantly correlated with best corrected visual acuity in severe, but not in early-to-moderate glaucoma patients
Leung et al[62]	Cirrus	222 eyes: 72 normal, 150 PG	Impact of age on glaucoma progression evaluation	Age-related change in macular measurements affected analysis of glaucoma progression. This was more substantial in macular than in cpRNFL progression
Sung et al[65]	Cirrus	98 advanced PG eyes	Glaucoma progression detection	Difference in the rate of change of average macular thickness was significant between progressors and non-progressors, but not in average cpRNFL thickness
Na et al[66]	Cirrus	279 PG eyes	Glaucoma progression detection	Differences in the rate of change of average macular and cpRNFL thickness were significant between progressors and non-progressors
Naghizadeh et al[67]	RTVue	68 eyes: 17 normal, 51 PG	Glaucoma progression detection	GLV and FLV detected structural progression even with mild functional progression. Progression rates were significantly different between progressing and stable eyes
Anraku et al[68]	RTVue	56 PG eyes	Glaucoma progression detection	Baseline GCC (average and inferior hemifield) were significantly thinner in fast progressors compared to slow progressors

SD-OCT: Spectral-domain optical coherence tomography; PPG: Pre-perimetric glaucoma; PG: Perimetric glaucoma; GCC: Ganglion cell complex; GCIP: Combined retinal ganglion cell and inner plexiform layer; mNFL: Macular nerve fiber layer; cpRNFL: Circumpapillary retinal nerve fiber layer; VF: Visual fields; MIRL: Macular inner retinal layers; AROC: Area under the receiver operating characteristics curve; POAG: Primary open-angle glaucoma; GLV: Global loss volume; VFS: Visual field sensitivity; MRT: Mean retinal thickness; NTG: Normal tension glaucoma; FLV: Focal loss volume.