Dr. Nabanita Barua, B13505, Dr. Sonu Goel, Dr. Chitra Sitaraman, Dr. Sonai Mukherjee
ANALYSIS OF MACULAR GANGLION CELL COMPLEX AND RETINAL NERVE FIBRE LAYER IN PRIMARY OPEN ANGLE GLAUCOMA, OCULAR HYPERTENSION AND NORMAL POPULATION
INTRODUCTION :
Glaucoma, by definition, is a multi-factorial optic neuropathy characterized by a loss ofretinal ganglion cells with subsequent loss of the retinal nerve fibers ultimately resulting in visual impairment. In the macula, the Retinal ganglion cell complex (RGC) layer is >1 cell layer thick with an RGC body diameter 10 to 20 times larger compared with their axons. Optical coherence tomography provides objective, quantitative, reproducible measurements of the retina and RNFL thickness, direct measurements of the RNFL are calculated from cross sectional retinal images at pre-perimetric stage. Retinal nerve fiber layer loss and their functional correlationis well documented in literature. In pre-perimetric stage 20 micron loss of retinal nerve fiber layer is suggestive of progression. Taking retinal nerve fiber layer loss on OCT as consistent measurement, the study aimed at finding whether ganglion cell complex is the earlier indicator of development of glaucoma. The inclusion of established glaucoma patients and their functional and structural correlation provided the basis for comparison of extent of loss documented by RNFL and GCC. Study of ocular hypertensive versus normal population provided the basis of comparison of earlier predictability of GCC versus RNFL in preperimetric glaucoma.
MATERIAL AND METHOD:
The study was approved by our institutional review board and complied with tenets of the declaration of Helsinski. Patients provided written informed consent.
PRIMARY OPEN ANGLE GLAUCOMA
INCLUSION CRITERIA:
Patient of Primary Open Angle Glaucoma and fulfilling the following criteria were included.
(1) Changes in the optic disc that is suggestive of progressive glaucomatous damage(diffuse or localized rim thinning and disc hemorrhage, notch, bayonetting, baring or vertical cup-to-disc ratio greater than 0.3 or difference in cup disc ratio of more than 0.2 in the 2 eyes, in absence of significant difference in disc size)
(2) Presence of glaucomatous visual field defects that corresponded with the Retinal Nerve Fibre Layer( RNFL) defects and optic nerve head abnormalities
(3) Gonioscopically open angles
EXCLUSION CRITERIA:
(1) Any Secondary glaucomas in the form of uveitic glaucoma, neo vascular glaucoma, lenticular, pigmentary and pseudo exfoliation glaucoma, vitreo retinal disease
(2) History of accelerated hypertension, coronary artery disease, diabetes and any past cerebrovascular accident
(3) Best-corrected visual acuity worsethan 6/60
(4) Retinal pathology
(5) Presence of significant cataract
OCULAR HYPERTENSION(OHT)
INCLUSION CRITERIA
(1) Open angle
(2) IOP >21 mm Hg byApplanation Tonometry (corrected for central corneal thickness)
(3) Absence of visual field defect
EXCLUSION CRITERIA
(1) BCVA less than 6/6
(2) Macular pathology
(3) Diabetes, uncontrolled hypertension
NORMAL POPULATION
INCLUSION CRITERIA
(1) Intraocular pressure of less than 21 mmHg
(2) A normal appearing optic disc head, no RNFL defect in red free fundus photography
(3) Normal Static Automated Perimetry(SAP) result
EXCLUSION CRITERIA
(1) History of chronic ocular disease of volunteers
(2) Systemic diseases that might have affected the eyes and systemic corticosteroid use.
These volunteers should have undergone the same comprehensive ophthalmic examination and OCT.
CLINICAL ASSESSMENT:
◘ Review of medical history
◘ best corrected visual acuity (BCVA) with any add on refractive error at presentation
◘ IOP by applanation tonometry
◘ Slit lamp biomicroscopy for anterior segment examination including type of lenticular changes, gonioscopy,
◘ Direct ophthalmoscopy/ disc examination with 90D
◘ Central corneal thickness
◘ Visual field by static perimetry (Humphrey VF 24-2)
◘ OCT RNFL AND GCC : Ganglion cell complex has 5 parameters: average, superior and inferior, focal and global loss of volume. Retinal nerve fiber layer has 3 parameters: average, superior and inferior. It is a single day cross sectional study with no follow up.
FOLLOW-UP:
Single day cross sectional study.
Prototype patient
The SPSS program was used for statistical analysis (Med Calc software v 12.2.10). An ANOVA test was used to compare the measured parameter values between the patient groups. Sensitivity, specificity for OCT parameters were determined. P-values of 0.05 were considered as statistically significant. One way ANOVA and post hoc Tukey HSD test was applied to look for RNFL thickness, and macular thickness measurement differences between glaucomatous, OHT and healthy eyes. The relationships between mean RNFL/GCC thickness and Mean Deviation (MD) were evaluated with regression analyses. Pearson’s correlation coefficients were used to assess the correlations between continuous variables. Receiver operating characteristic (ROC) curves were used to describe the ability to differentiate glaucomatous and OHT from healthy eyes of each of the FD-OCT
Patients were divided into 5 groups: POAG/normal, POAG/OHT, OHT/normal, EARLY POAG/normal, early POAG/OHT. ROC was calculated for each parameter in each subgroup. The early POAG group were included to detect which parameter was more diagnostic in early cases (MD< 6dB).
- The graph below shows three ROC curves representing excellent, good, and worthless tests plotted on the same graph. The accuracy of the test depends on how well the test separates the group being tested into those with and without the disease in question. Accuracy is measured by the area under the ROC curve. An area of 1 represents a perfect test; an area of .5 represents a worthless test. A rough guide for classifying the accuracy of a diagnostic test is the traditional system:
- 90-1 = excellent (A)
- .80-.90 = good (B)
- .70-.80 = fair (C)
- .60-.70 = poor (D)
- .50-.60 = fail (F)
RESULTS: It was an age and sex matched population.
Ganglion cell complex and retinal nerve fiber layer is highly significant in POAG versus OHT and normal population (p 0.000, <.0.001). No significant difference in GCC or RNFL in OHT versus control population (p >0.05).
| PARAMETERS | POAG | OHT | CONTROL |
| GCC avg (μ) | 78.19+12.21
(53.05-100.84) |
92.17+ 8.02
(73.51-109.63) |
91.11+5.48
(80.69-112.23) |
| GCC sup (μ) | 80.16+12.01
(53.35-101.01) |
91.64+ 8.11
(76.66-109.05) |
90.67+5.41
(80.06-111.09) |
| GCC inf(μ) | 77.36+ 13.64 μ
(49.76-100.69) |
93.12+9.05
(69.28-112.79) |
92.03+5.24
(81.33-118.43) |
| Focal Loss of Volume (FLV) | 5.77+ 5.28
(.007-24.915) |
2.68+2.96
(0.014-11.16) |
0.85 +.76
(0.004-14.653) |
| Global Loss of Volume (GLV) | 17.89+ 11.76
(.098-44.384) |
8.44 + 6.02
(0.473-26.689) |
6.657+3.56
(1.004-14.653) |
| Parameters | POAG | OHT | Controls |
| Average RNFL | 83.24+17.86
(53.35 -122.5) |
99.52+12.56
(73.4-132.41) |
103.12+ 9.32
(71.77-130.5) |
| Superior RNFL | 87.32+18.32
(53.34-126.5) |
98.56+16.47
(70.66-160.92) |
101.39 + 9.84
72.78-130.630 |
| Inferior RNFL | 86.68+ 2.12
(47.76-124.640) |
100.40+13.36
(67.85-131.48)) |
103.4+11.14
(86.68-132.5) |
All parameters shows strong correlation with Mean deviation
| GCC avg | GCC sup | GCC inf | FLV | GLV | RNFL avg | RNFL
sup |
RNFL
Inf |
|
| r | -0.566 | -0.552 | -0.57 | 0.551 | 0.604 | -0.504 | -0.41 | -0.535 |
| P | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
POAG/ control: .
the study finding: Area for GCC average .820 with 95 % confidence limit is from .750 to .877 . With cut off of value of 82.66 sensitivity and specificity is maximum: 65% sensitivity and 94.8% specific
AUC for GCC superior average the area under the ROC (AROC) curve for sup average is .774. 95 % confidence limit is .700- .837. With cut off limit of 83.71, sensitivity is 64.1% specificity is 91.0%.
AUC for GCC inferior average the area under the ROC (AROC) curve for average GCC was .827. 95% confidence limit is from 0.758-0.883. With cut off value of 84.41 sensitivity is 67% and specificity is 84.41%.
Area under ROC for FLV is .791. CI of 95% is .718-0.852. With cut off value of 2.035 sensitivity is 67.9% specificity is 94.9%. AUC of GLV: Area under ROC is 0.796. CI of 95% is 0.724-0.857.With cut off value of 12.499 sensitivity is 64.9% and specificity is 98.7%.Area under ROC for average RNFL is .821. CI of 95% is .752-0.878. With cut off value of 93.49 sensitivity is 76.6% specificity is 84.6%. Area under ROC for superior RNFL is .763. CI of 95% is .688-0.828. With cut off value of 90.03 sensitivity is 64.9% specificity is 87.2%. Area under ROC for inferior RNFL is .816. CI of 95% is .746-0.874. With cut off value of 91.79 sensitivity is 67.9% specificity is 89.7%.
In POAG/OHT population also inferior GCC had highest AUC (.825)
In OHT/normal population none of the parameters were statistically significant.
In early POAG/OHT and Early POAG/normal population only Inferior GCC had statistically significant AUC value (.715). Rest all parameters didn’t have statistically significant AUC .
DISCUSSION:
Observation of Kim et al closely resembles documenting equal diagnostic capability of ganglion cell complex with retinal nerve fibre layer. In their study also Inferior GCC showed highest AUC but difference was not statistically significant.
Ishikawa et aldeveloped 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.
Leung et alused the Stratus TD-OCT (Carl Zeiss, Dublin, CA) to evaluate macular nerve fibre layer thinning in glaucoma. They reported a reduction in macular nerve fibre layer thickness in glaucomatous eyes compared with normal eyes. Schulze et alobservation was similar. Glaucoma patients showed a significant reduction in GCC and macular retinal thickness compared to patients with OHT and normal subjects. No differences in GCC were found between the patients with OHT and normal subjects.This also resembles outcomes of Teresa Roll,they concluded AUCs didn’t significantly differ in macular and peripapillary RNFL values. The study finding are similar to Schulze et al. No differences were found between patients with OHT and normal subjects with regard to ONH, RNFL and GCC parameters.
The study concluded GCC and RNFL showed equal predictive capability to differentiate POAG from normal, Inferior GCC having highest predictive value. GCC and RNFL showed equal predictive capability, Inferior GCC had highest area under curve. Inferior GCC was the best parameter to differentiate early glaucoma (MD<-6dB) from normal and glaucoma from OHT population/ pre-perimetric population.
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