Dr.Amol Thanpal Wanjari, W19188, Dr. Rakesh Shakya, Dr. Dhananjay Giri
AIM: To compare macular Ganglion Cell Complex (GCC) & peripapillary RNFL thickness in control, pre-perimetric & glaucoma patients.
Case controlled, cross sectional study. 30 controls,
37 pre-perimetric & 30 glaucoma patients who met study criteria were included. GCC & pRNFL thickness were evaluated by SD-OCT.
PRNFL & GCC thickness was 83.66±8.76µm & 76.92±9.51µm in glaucoma patients respectively. It was 101.63±7.28µm & 85.28±5.86µm inpre-perimetric, 113.51± 9.07µm & 98.17±7.91µm in controls respectively. Mean difference for pRNFL & GCC by ANOVA was statistically significant in all group [ pRNFL (p<0.001) & GCC (p<0.001) ]. Pearson correlation coefficient(r) for GCC with the pRNFL thickness is r = 0.83 (p < 0.001).
Macular GCC & pRNFL thickness are significantly thin in pre-perimetric & glaucoma patients than controls. GCC can be used as a supplementary tool in detection of early glaucoma as loss is significant in pre-perimetric glaucoma also.
Glaucoma is a progressive, irreversible optic neuropathy causing a gradual loss of ganglion cell axons. Early detection is therefore essential for the institution of pressure reducing treatment to stop or delay progressive loss of visual function. Despite recent technological advances , the diagnosis of glaucoma is still based on visual field loss and the appearance of the optic disc. For visual field defects to be evident on white on white perimetry, it requires at least 40% of neuronal cell loss to occur which is irreversible.  Newer perimetric methods were launched with great enthusiasm but they seem to have a limited role to play.
In glaucoma damage occurs in retinal ganglion cells (RGCs) and their axons, leading to characteristic changes in the structure of the optic disc and retinal nerve fiber layer (RNFL). Such structural damage influences the visual function of the glaucoma patient. [2 ] However, as the structural loss of RGCs often precedes the functional glaucomatous Visual Field defects,[3–6] various structural imaging devices have been developed to offer reliable detection of glaucoma when the condition is at the preperimetric stage. [7–9]
Use of Optical Coherence Tomography (OCT) in the diagnosis and follow up of glaucoma has gained universal acceptability in recent years. It can give very accurate parameters for optic nerve head assessment along with the retinal nerve fibre layer analysis.  Even so, early diagnosis remains a challenge and requires correlation with other factors. Recent studies on the use of OCT in glaucoma have explored the ability of this technology to detect the ganglion cell complex thickness which is defined as the combination of nerve fibre, ganglion cell, and inner plexiform layers. The ganglion cell complex is studied by the OCT which has the maximum density at the macula. Roughly, one lac ganglion cells are found in the human retina and 50% of this number is present in Macula. 
This anatomic arrangement suggests that a macula scan with Ganglion Cell Complex (GCC) analysis could be early indicator of this disease.  This study was designed to study the role of GCC in early diagnosis of glaucoma. The pupose of this study was to compare macular Ganglion Cell Complex (GCC) & peripapillary RNFL (pRNFL) thickness in control , pre-perimetric & glaucoma patients.
MATERIALS AND METHODS
This was a Case controlled , cross sectional study conducted between September 2015 and February. Institutional ethical clearance was taken. Participants were given detailed information and consent was taken.
30 normal controls ,37 pre-perimetric glaucoma patients & 30 glaucoma patients were enrolled in the study. The eligibility criteria for the groups are briefly described in the following paragraphs.
The Normal group (30 eyes) had: intraocular pressure (IOP) of <21 mm Hg; a normal Humphrey SITA 24-2 standard visual field (mean deviation [MD] and pattern standard deviation [PSD] within 95% limits of the normal reference and a glaucoma hemifield test within 97% limits); a central corneal thickness >500 μm; normal optic nerve head, defined as intact neuroretinal rim without peripapillary hemorrhages, notches, localized pallor, or RNFL defects; normal RNFL; an open anterior chamber angle; and no history of chronic ocular or systemic corticosteroid use,no family history of glaucoma.
The Preperimetry glaucoma group (37 eyes) had: optic nerve head changes, such as diffuse or localized rim thinning, disc (splinter) hemorrhage, vertical cup/disc ratio greater than the fellow eye by > 0.2, or notch in the rim detected on baseline dilated fundus examination and confirmed by masked reading of stereo disc photographs with reliable and reproducible normal Humphrey SITA 24-2 standard visual field.
The glaucoma group (30eyes) had :above optic nerve head changes or RNFL defects with glaucomatous (abnormal) VF loss [PSD (P < 0.05) or GHT (P < 1%) outside normal limits in a consistent pattern on both qualifying VF’s].
Patients with angle closure glaucoma, other secondary glaucoma, coexisting ocular pathology that affects retinal thickness measurement including DR, ARMD, epiretinal membrane ,Media opacity ( >2+ Nuclear sclerosis or PSC ), visual field with low reliability ,OCT scan results with artifacts ( signal strength <8 ), high refractive errors ( > ± 6D spherical & > ± 3D cylindrical ), were excluded.
Selected patients underwent a detailed ophthalmic examination including Best Corrected Visual Acuity (BCVA) on LogMAR chart, anterior segment examination including pupillary reaction, anterior chamber angle assessment by gonioscopy, intra ocular pressure measurement by Goldmann applanation tonometry, slit lamp biomicroscopy & pachymetry .Visual field examination was done by Humphrey Automated Perimetry (HAP) & Mean Deviation (MD), Pattern Standard deviation (PSD) parameters were noted. Single well trained examiner did OCT after papillary dilatation. Macular Ganglion Cell Complex (GCC) & peripapillary RNFL (pRNFL) thickness was measured by SD‑OCT ( Optovue Inc. Fremont,CA.). One eye of each patient was randomized to be part of analysis.
ANOVA test was used to compare mean of RNFL & GCC. Pearson correlation of coefficient (r) was used to correlate macular GCC thickness with pRNFL thickness. p value < 0.05 was considered significant.
A total 97 patients were enrolled in the study. The mean age of glaucoma patients was 49.17 ( SD 13.36 )years, pre-perimetric glaucoma was 49.08 (SD 15.61) years and controls was 46.53 (SD 12.59). In the glaucoma group, 60% were males and 40 % were females.In the preperimetric glaucoma group, 54.06% were males and 45.94% were females and in control group 50% were males and 50 % were females.
Mean pRNFL & GCC thickness was 83.66±8.76μm & 76.92±9.51μm in glaucoma patients respectively. Mean pRNFL & GCC thickness was 101.63±7.28μm & 85.28±5.86μm in pre-perimetric ,113.51±9.07μm & 98.17±7.91μm in controls respectively.
Table 2. Comparative OCT data for study group
|Mean pRNFL thickness||Mean Macular GCC thickness|
|Pre-perimetric glaucoma Group||101.63±7.28μm||85.28±5.86μm|
The difference of mean for RNFL and GCC by ANOVA was statistically significant for controls, glaucoma patients and pre-perimetric glaucoma group pRNFL (p < 0.001) and GCC (p < 0.001). Pearson correlation coefficient for ganglion cell layer had a statistically significant correlation (r = 0.83) with the pRNFL thickness (p < 0.001).
Glaucoma management involves visual field testing and morphologic assessment of ONH and the RNFL. It is known that structural damage precedes detectable visual field loss measured with the standard automatic perimetry.  The quantitative morphometric analysis of ONH and RNFL contribute to a more reliable, reproducible, and early assessment in glaucoma: in this regard, it has been proved by Li et al  that RTVue-OCT may provide objective, quantitative, and reproducible images of the ONH and RNFL thickness in glaucoma.
In glaucoma GCC is first to be affected so evaluation of GCC is early indicator of damage. It is found that 50% retinal ganglion cells are present in Macula. These cells constitute 35-40% of total retinal thickness in macula. Central macular thickness has been used by some authors for early diagnosis of glaucoma but with a limited role. SD-OCT can measure GCC thickness,and its assessment can be better than macular thickness for early diagnosis of glaucoma.
In the present study we found that values of pRNFL were lower in glaucoma (83.66±8.76μm) and pre-perimetric glaucoma patients (101.63±7.28μm) than normal control (113.51±9.07μm). Similarly values of GCC were lower in glaucoma (76.92±9.51μm) and pre-perimetric glaucoma patients (85.28±5.86μm) than normal control (98.17±7.91μm) . As values of both pRNFL and GCC were lower in pre-perimetric glaucoma patients than normal control indicating its utility in early diagnosis of glaucoma.
Ishikawa et al  developed a macular segmentation algorithm to measure sublayer thickness for glaucoma diagnosis: they showed that macular inner retinal complex (ganglion cell layer, inner plexiform layer, inner nuclear layer) was thinner in eyes with perimetric glaucoma Tan et al [l9] showed that macular GCC thickness has a glaucoma discrimination ability comparable with papillary RNFL thickness. They also found that FLV and GLV have higher diagnostic accuracy than the GCC average: this may mean that, in some cases, pattern parameters are more sensitive or more specific. Kim et al  observed that macular GCC thickness and pRNFL thickness showed similar diagnostic performance for detecting early glaucoma. Experimental animal models have shown that GCC loss correlates well with visual field defects.  Studies have mentioned utility of electroretinogram and ganglion cell axons imaging in early diagnosis of glaucoma. 
So along with the RNFL, the GCC thickness measurement also provides additional useful information in the early diagnosis and management of glaucoma patients. GCC thickness is also advantageous over pRNFL thickness as it is technically easier, variability of cell density in central retina is less compared to pRNFL and reproducibility is better than RNFL.
There are few limitations of the present study. Firstly this study did not include long term follow up of patients so further studies are required to study the role of serial GCC scans in glaucoma progression. Secondly, we also could not compare the visual field loss severity indicators like mean deviation (MD) with GCC or RNFL loss which could have been a better parameter to study in advanced cases of glaucoma because this was beyond the scope of this study, as our main aim was to study role of GCC in early diagnosis in glaucoma.
We can conclude that macular GCC & pRNFL thickness are significantly thin in pre-perimetric & glaucoma patients than controls. GCC thickness measurement on OCT could be use as a supplementary tool in detection of early glaucoma as loss is significant in pre-perimetric glaucoma also.
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