Corneal endothelium in primary angle closure glaucoma with a history of acute attack in Northeast India

INTRODUCTION

Glaucoma is a chronic progressive optic neuropathy characterized by structural changes in the optic nerve head and in the retinal nerve fiber layer, resulting in a distinct pattern of visual impairment and blindness.^[1] Glaucoma ranks as the primary cause of irreversible blindness globally, following cataracts.^[2] Glaucoma encompasses a diverse set of optic nerve conditions characterized by the gradual decline of ganglion cells and their axons. This degeneration results in the thinning of the retinal fiber layer and the excavation of the optic nerve head, eventually leading to blindness in both eyes.^[3] In primary angle-closure glaucoma (PACG), the underlying mechanism involves the obstruction of aqueous outflow due to the peripheral iris covering the trabecular meshwork, thereby impeding the drainage of aqueous humor.^[4,5] This obstruction, whether through appositional or synechial closure, leads to a rise in intraocular pressure (IOP). Subsequently, optic nerve damage occurs, resulting in structural changes and eventually leading to functional loss of the visual field.^[4,6]

Primary acute angle closure glaucoma (AACG), a subset of PACG, is characterized by a sudden elevation in IOP. According to the World Health Organization, the IOP in AACG can surpass 60 mmHg and is linked with a significant decrease in central visual acuity. Diagnostic features typically include conjunctival hyperemia, corneal cloudiness, and an irregular, often vertically oval, mid-dilated pupil that remains fixed.^[7] Following episodes of AACG, there is a documented depletion in corneal endothelial cell density.^[7,8] Preservation of these cells is crucial due to their limited regenerative capacity.^[9,10] Specular microscopy is a non-invasive imaging technique used to estimate endothelial cell count, enabling detailed in vivo analysis of the corneal endothelium in both healthy and diseased eyes.^[11-13] The study aims to evaluate corneal endothelial cell density using specular microscopy in patients reporting with AACG.

MATERIAL AND METHODS

A prospective consecutive observational study was conducted in a tertiary hospital of Northeast India from May 2022 to April 2024, enrolling 16 patients (5 males and 11 females) with an average age of 60 years. All participants had a documented history of symptomatic acute attacks of PACG in one eye, which was compared to their fellow eye without a history of acute attack. Patients with conditions potentially affecting corneal endothelial status, such as uveitis, trauma, ocular surgery, keratitis, pseudoexfoliative glaucoma, or open-angle glaucoma, were excluded from the study.

A comprehensive evaluation was performed, including assessments of visual acuity, IOP using a Goldmann applanation tonometer, gonioscopy with a Goldmann single-mirror lens, and disc evaluation wherever feasible. Specular microscopy (TOPCON -3000P), a non-contact method, was used to determine corneal endothelial cell density. Detailed specular microscopy analysis of corneal endothelial cell counts was conducted, and the results were documented and entered in the master sheet using Microsoft Excel 2013.

RESULTS

Out of the total 16 patients participating in the study, there were 5 males and 11 females, with an average age of 60.5 years. The study revealed that eyes with an acute attack of PACG (cases), experienced a significantly higher average increase in IOP of 49.69 mmHg compared to 16.13 mmHg in fellow eyes without such a history (controls) [Figure 1]. The mean endothelial cell count was 1964 cells/mm² in cases, compared to 2359 cells/mm² in controls, indicating a 17% reduction in endothelial cell density in the affected eyes [Table 1 and Figure 2]. This significant decrease highlights the impact of acute attacks on corneal endothelial health.

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Figure 1:

Mean intraocular pressure (IOP) in cases and control. mmHg: Millimeters of mercury.

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Figure 2:

Mean endothelial cell density (ECD) in cases and control.

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The study found that the average duration of acute attacks was 44.25 hours (h), with a mean decrease in corneal endothelial cell density of 395 cells/mm² [Table 2]. The average IOP was 50.75 mmHg for attacks lasting <72 h and 46.50 mmHg for those exceeding 72 h. For attacks lasting <72 h, the average endothelial cell count was 2059.33 cells/mm², with a reduction of 296 cells/mm² [Table 3 and Figure 3]. In cases of attacks exceeding 72 h, the average endothelial cell count was 1678.25 cells/mm², with a decrease of 691.50 cells/mm² [Table 3 and Figure 3]. Despite these observations, no significant correlation was found between the duration of the attack and the reduction in corneal endothelial cell density.

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Figure 3:

Duration of attack and endothelial cell density (ECD).

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DISCUSSION

PACG, a prevalent form of glaucoma in Asia, can result in acute angle closure, causing direct harm to corneal endothelial cells due to contact between the iris and cornea and the sudden rise in IOP.^[14,15]

Our study demonstrates that a prior acute angle-closure attack significantly increases the risk of corneal endothelial cell loss in PACG eyes, showing a 17% reduction in endothelial cell density compared to fellow eyes without a history of such attacks.

Supporting findings from other studies highlight the consistent association between acute attacks and endothelial cell loss. For instance, Sultana et al., (2016) observed a significant decrease in endothelial cell density in eyes with acute attacks (2104 cells/mm²) compared to fellow eyes (2615 cells/mm²).^[7] Sihota et al.,^[16] Tham et al.,^[17] Bigar and Witmer^[8] and Han and Jeon also reported similar results.^[18]

Contrasting findings were noted in a study by Chen et al. (2012), which reported no significant difference in endothelial cell density between acute and chronic PACG cases.^[19] Despite some variability, the collective evidence points to a robust correlation between acute angle-closure attacks and reduced corneal endothelial cell density.

We also evaluated the relationship between corneal endothelial cell density and the duration of acute angle-closure attacks in 16 cases. Among these, 12 patients experienced attacks lasting <72 h, with an average endothelial cell count of 2059.33 cells/mm² and a decrease of 296 cells/mm². For the 4 patients with attacks exceeding 72 h, the average endothelial cell count was 1678.25 cells/mm², with a decrease of 691.50 cells/mm². Despite these differences, we did not find a significant correlation between attack duration and endothelial cell loss, potentially due to the small sample size for longer attacks.

In contrast, Sultana et al., (2016) reported a significant decrease in endothelial cell density for attacks lasting more than 72 h (759 ± 94 cells/mm²) compared to shorter attacks (2016 ± 306 cells/mm²). Similarly, Sihota et al., observed substantial endothelial loss in prolonged attacks.^[16] The disparity in findings may highlight the influence of sample size and study design. A comparison of the present study with previously published data is shown in Table 4.

This study focuses on the impact of acute angle closure attacks on corneal endothelial cell count and validates findings from previous research. The study’s limitations include potential selection bias due to its hospital-based setting at a tertiary eye care center, susceptibility to observer and confirmation bias as a single-observer study without randomization or blinding, and the need for further validation through larger prospective studies despite an appropriately calculated sample size.

CONCLUSION

In summary, a decrease in corneal endothelial cell density was observed after an acute attack of angle closure glaucoma. Therefore, it is crucial to implement optimal pre-operative and intraoperative strategies to safeguard the corneal endothelium in eyes affected by an acute attack of angle closure glaucoma, as well as during any subsequent intraocular surgeries.