Corneal endothelial density: An indicator for primary glaucoma progression

Aditya Kailas Khadamkar; Shubha Nagpal

doi:10.4103/sjopthal.sjopthal_5_20

ORIGINAL ARTICLE

Year : 2020 | Volume : 12 | Issue : 2 | Page : 46-50

Corneal endothelial density: An indicator for primary glaucoma progression

Aditya Kailas Khadamkar, Shubha Nagpal
Department of Ophthalmology, Bharati Vidyapeeth Medical College and Hospital, Pune, Maharashtra, India

Date of Submission	21-Feb-2020
Date of Decision	21-Aug-2020
Date of Acceptance	08-Sep-2020
Date of Web Publication	09-Mar-2021

Correspondence Address:
Dr. Shubha Nagpal
Department of Ophthalmology, Bharati Vidyapeeth Medical College and Hospital, Pune - 411 043, Maharashtra
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/sjopthal.sjopthal_5_20

Abstract

Purpose: Glaucoma is a progressive optic neuropathy causing death of retinal ganglion cells and their axons resulting in visual morbidity. This study was aimed to evaluate the impact of primary glaucoma on retinal nerve fiber layer (RNFL) thickness and corneal endothelial damage and to establish any correlation between these two. Materials and Methods: A total of 104 patients (179 eyes) diagnosed as primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG), and normotensive glaucoma (NTG) were included in this study. Secondary glaucoma, postviral infection, ocular trauma, ocular surgery, and diabetes mellitus were criteria for exclusion. Average retinal nerve fiber layer (AvRNFL) thickness and endothelial cell count (cell density [CD]) were measured. Statistical analysis was done using Spearman's correlation coefficient. Results: The AvRNFL thickness in POAG (n = 120) was 83.83, PACG (n = 46) was 81.45, and Normotensive (NTG) (n = 13) was 71.07 μ. The mean CD values were 2416.68 cells/mm², 2622.543 cells/mm², and 2482.69 cells/mm², respectively. A significant positive correlation between these two values was observed in POAG (P = 0.004) but not seen in PACG or NTG. Conclusion: Corneal endothelium loss may be an indicator of disease progression and RNFL thinning in patients of POAG. Routine specular microscopy evaluation of these patients can be helpful, and low endothelial counts indicate RNFL damage.

Keywords: Endothelial cell count, glaucoma, retinal nerve fiber layer thickness

How to cite this article:
Khadamkar AK, Nagpal S. Corneal endothelial density: An indicator for primary glaucoma progression. Sudanese J Ophthalmol 2020;12:46-50

How to cite this URL:
Khadamkar AK, Nagpal S. Corneal endothelial density: An indicator for primary glaucoma progression. Sudanese J Ophthalmol [serial online] 2020 [cited 2023 Jun 2];12:46-50. Available from: https://www.sjopthal.net/text.asp?2020/12/2/46/311043

Introduction

Glaucoma encompasses a diverse group of disorders. All forms of the disease have in common a potentially progressive and characteristic optic neuropathy which is associated with visual field loss and in which intraocular pressure is usually a key modifying factor.^[1] It is also unique among ophthalmic diseases as its underlying pathophysiology spans both anterior and posterior segments.

Glaucoma is a major public health problem and the second leading cause of blindness in the world. The worldwide burden is expected to increase to 79.6 million by 2020, with an estimated prevalence of 11.9 million in India.^[2],[3]

Perimetry and retinal nerve fiber layer (RNFL) analysis are used to detect functional and structural damage of the optic nerve head and progression of the disease process. In glaucoma, a drop in the endothelial cell density (CD) has been observed,^[4] which may be accompanied by polymegathism and polymorphism.^[5] Studies have been done to assess RNFL changes in various types of glaucomas and to correlate these with variables such as intraocular pressure,^[6] visual field loss,^[7] and macular ganglion cell complex.^[8] Further, studies have also analyzed the corneal endothelial cell damage in glaucoma. In this study, an attempt has been made to evaluate endothelial cell loss and RNFL changes in patients diagnosed with primary glaucoma and to establish any significant correlation between these two factors.

Materials and Methods

This cross-sectional, observational study of 179 eyes of 104 adults with primary glaucomas was conducted between September 1, 2017, and February 28, 2019. Patients attending the glaucoma clinic and diagnosed as primary glaucomas were included in the study. Based on intraocular pressure recording, characteristic optic disc findings, gonioscopic evaluation for angle width, and Humphrey field analysis, they were grouped as primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG), and normotensive glaucoma (NTG). Secondary glaucoma, postviral infection, ocular trauma, ocular surgery, and diabetes mellitus were criteria for exclusion.

All participants were assessed for best-corrected visual acuity. Anterior and posterior segment evaluation, intraocular pressure measurement by applanation tonometer, central corneal thickness, gonioscopy, and visual field charting (Humphrey field analyzer) were performed.

Central CD was measured using the specular microscope (Topcon SP-1P). Optic nerve head analysis was done using optical coherence tomography (OCT) (three-dimensional [3D] disc program of the Topcon 3D OCT-1 Maestro) to study the RNFL thickness, and the average retinal nerve fiber layer (AvRNFL) values were considered.

Statistical analysis

Data were analyzed using the software Statistical Package for the Social Sciences version 25.0 (SPSS, IBM Armonk, New York, United States). ANOVA test was used to compare CD and AvRNFL in three groups. Spearman's correlation coefficient was used to find the correlation between CD and AvRNFL. P < 0.05 was considered statistically significant.

Results

Of the 104 patients evaluated, 56 (54%) were male and 48 (46%) were female. In the POAG and NTG groups, there was a preponderance of males (41 males and 25 females in POAG and 6 males and 3 females in NTG). However, in the PACG group, the number of females was more than double that of males (9 males and 20 females).

Of the 179 eyes included in the study, 120 eyes (67%) had POAG, 46 eyes (26%) had PACG, and 13 eyes (7%) had NTG.

The age of the patients ranged from 31 years to 80 years. Patients diagnosed as NTG were younger (average of 44.92 years) than those in the POAG group (average of 60.18 years) or the PACG group (average of 56.80 years). A strong inverse correlation was observed between age and CD (P < 0.0001 with Pearson's correlation coefficient R = −0.273) across the entire study group [Graph 1].

The CD in all the study participants ranged from a minimum of 1408 cells/mm² to a maximum of 3156 cells/mm², with a mean of 2474.37 cells/mm². In the POAG group, the value ranged from 1408 cells/mm² to 3156 cells/mm², with a mean of 2416.68 ± 374.94 cells/mm². In PACG, the range was from 1899 cell/mm² to 3100 cells/mm², with a mean of 2622.54 ± 344.19 cells/mm², and in NTG, it was from 1879 cell/mm² to 2816 cells/mm², with a mean of 2482.69 ± 293.28 cells/mm². A significant reduction in CD was found in the POAG group (P = 0.019) but not in the PACG and NTG groups of patients [Table 1].

Table 1: Corneal endothelial cell density

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The AvRNFL thickness varied from a minimum of 35 μ to a maximum of 122 μ, with a mean of 82.30 μ across all the eyes evaluated. In the POAG group, the value was a minimum of 44 μ and a maximum of 122 μ (mean: 83.83 ± 16.41 μ). In PACG, the range was from 47 μ to 113 μ (mean: 81.46 ± 17.55 μ), and in NTG, it was from 35 μ to 91 μ (mean: 71.08 ± 18.35 μ) [Table 2].

Table 2: Demographic and ophthalmic data of primary open-angle, primary angle-closure, and normotensive glaucoma patients

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Correlating the AvRNFL with CD in all the three groups of patients (using the Spearman's correlation coefficient) revealed a statistically significant P value in POAG (0.004) but no significance in PACG (P = 0.963) or NTG (P = 0.865). Further, a positive correlation between these two values was seen in the POAG group (R = 0.263) but not in the PACG (R = −0.007) and NTG groups (R = −0.052) [Table 3].

Table 3: Correlation coefficient (R) and P value between mean cell density and average retinal nerve fiber layer in primary open-angle glaucoma, primary angle-closure glaucoma and normotensive glaucoma

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Discussion

The regional burden of glaucoma in India has been assessed to be 23.5% of the global blindness, with an estimated 5.8 million people affected by the disease.^[3] POAG has been reported as the most common form of glaucoma in various studies in India^[9] and the world.^[2] Of the 104 patients studied by us, the greater number was also those with POAG (63%), followed by PACG (28%) and then NTG (9%). Female preponderance was noted in the PACG group (female: male ratio of 2.22:1), as has been observed worldwide.^[9],[10] Most of the patients of POAG and PACG were in the fifth or sixth decade of life, with an average age of 60.18 and 56.80 years. However, patients with NTG had an average age of 44.92 years.

The average CD was within normal limits (2474.37 cells/mm²) but showed a wide variance ranging from 1408 cells/mm² to 3156 cells/mm². Normal corneal endothelial CD at birth ranges between 4000 and 5000 cells/mm² that declines with aging at a rate of 0.3%–0.6% per year, with an approximate value of 2000–3000 cells/mm² in a normal adult eye.^{[11],[12],[13]} A study conducted by Rao et al.^[14] at Sankara Nethralaya, Chennai, on both eyes of 537 normal Indians aged 20–87 years revealed CD ranging from 1195 to 3590 cells/mm², with a mean of 2525 ± 337 cells/mm², which is lower than that reported in Caucasian eyes by Duman et al.^[15] Endothelial CD reduction in all types of glaucomas has been reported.^[4] Our study showed an average CD within the normal range of 2000–3000 cells/mm². However, a significant reduction (P = 0.0019) was demonstrated when compared with the available Indian normative mean of 2525 ± 337 cells/mm² in POAG. However, no similar significance was present in either the PACG (P = 0.060) or NTG group (P = 0.654).

Various factors may be responsible for decreasing the CD, namely increasing age, acute attacks of prolonged angle closure, duration of the disease, and also side effects of topical antiglaucoma drugs.^[16] In our study also, we observed a significant (P < 0.0001) reduction in endothelial CD with increasing age across all the three groups of patients. All eyes except one in the normotensive glaucoma group had an endothelial count above 2000. In a study conducted by Cho et al., comparing NTG, POAG, and normal controls, there was no significant difference in endothelial counts between NTG and age-matched controls.^[17] The lower intraocular pressure values and low intraocular pressure fluctuation may be responsible for preventing endothelial damage. In addition, a smaller number of patients in the NTG group as well as a lower mean age (44.92 years) may explain these normal endothelial count values.

The AvRNFL values for the normal Indian population have been reported as 104.8 ± 38.81 μ.^[18] Significant RNFL loss was seen in all the groups of patients in this study, with average values being 83.83 ± 16.42 μ in POAG, 81.46 ± 17.55 μ in PACG, and 71.08 ± 18.35 μ in NTG. These findings are consistent with most studies on glaucoma where RNFL values are consistently lower than age-matched controls.^{[19],[20],[21]} The lowest AvRNFL was seen in NTG (71.08 ± 18.35 μ) which may be explained by a delay in diagnosis and treatment in this group of patients. However, NTG, especially low-tension glaucoma, could be a disorder of the optic nerve itself, where increased fragility may result in more cupping and thinning of the optic disc neural rim.^[22]

On analysis of the data in all the three groups of patients [Table 3], we found a statistically significant (P = 0.004) positive correlation (correlation coefficient 0.263) between AvRNFL thickness and endothelial cell count in patients with POAG [Graph 2]. However, no statistically significant correlation was observed in either the PACG group (P = 0.963 and R = −0.007) or the NTG group (P = 0.865 and R = − 0.052) [Graph 3] and [Graph 4].

Thinning of the RNFL correlated well with the reduction of endothelial cell count in patients with POAG. In both the PACG and NTG groups, the endothelial damage was not as significant as that seen in the POAG patients. The lower age of the NTG patients as well as the smaller number of patients in both the NTG (13 eyes) and PACG groups (46 eyes) as compared to the PAOG group (120 eyes) may also be contributing factors. These observations suggest that in POAG especially, detection of corneal endothelium loss may be an indicator of disease progression and RNFL thinning. Inclusion of specular microscopy in the routine outpatient evaluation of these patients may be helpful, and low endothelial counts indicate RNFL damage requiring further analysis by OCT studies.

Limitations

The total number of study participants was not large. Further, the number of participants in the PACG and NTG groups was less as compared to the POAG group. In addition, the duration and severity of the disease process, number and frequency of topical antiglaucoma medications being used, and the intraocular pressure control were not considered, as it was a one-time cross-sectional analysis.

Further studies on POAG patients, to assess the CD and AvRNFL values, after incorporating these variables need to be carried out.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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