Reversal of the Optic Nerve Head Tissues after Intraocular Pressure Lowering Treatment in Open Angle Glaucoma

Abstract

Introduction: Glaucoma is a progressive optic neuropathy which affects as many as 3.5% of Korean population aged 40 years or more. Lowering of intraocular pressure (IOP) has been the mainstay of glaucoma treatment, and is the only possible intervention that could be actually done to glaucoma patients. However, many glaucoma patients are still suffering from visual loss despite of IOP lowering. This suggests that IOP lowering may not be equally effective in all glaucoma patients, and that factors other than IOP are involved in glaucoma pathogenesis. However, it remained to be determined how IOP lowering has influences on the glaucomatous optic nerve. Recently, in vivo visualization of the optic nerve head tissues became possible with the emergence of spectral domain optical coherence tomography (SD-OCT), which enabled the evaluation of changes of the optic nerve head tissues including the lamina cribrosa (LC) after IOP lowering in glaucoma. The reversal of the optic nerve tissues according to IOP lowering treatment might be a sign of released strain and stress at the level of the LC which may give relief to the compressed nerve fibers or laminar capillaries. On the other hand, if the LC reversal is not observed, other pathogenic factor other than IOP could be suspected for the mechanism of glaucomatous damage.

Purpose: The purpose of the study was to investigate the change of the optic nerve tissues including the LC after IOP lowering treatment in open angle glaucoma (OAG) patients, using enhanced depth imaging SD-OCT. and to evaluate the factors associated with the optic nerve changes. By accomplishing this purpose, the study further aimed to contemplate the effect and meaning of IOP lowering treatment in each eye, and to understand primary mechanism of glaucomatous optic neuropathy in individual glaucoma patients. This study was performed under three specific aims

First, investigation of short-term change in the optic nerve head tissues in high-tension OAG after surgical IOP lowering. Second, comparison of the short-term change in the optic nerve head tissues in high- and low-tension OAG after IOP lowering treatment. Third, investigation of long-term change in the optic nerve head tissues in high-tension OAG after surgical IOP lowering.

Methods: Optic nerves of OAG patients who underwent surgical or medical IOP-lowering treatment were scanned using enhanced depth imaging SD-OCT before treatment and after treatment during the serial follow-up. The pre- and post- treatment SD-OCT images were compared. The LC depth (the distance from the Bruchs membrane opening plane to the level of the anterior LC surface), and the thickness of the LC and prelaminar tissue were measured in each scan. The change in the optic nerve tissues after IOP lowering was observed, and the factors associated with the amount of change were investigated.

Results 1. Reversal of lamina cribrosa displacement and thickness after trabeculectomy in glaucoma - Until 6 months after trabeculectomy, decrease in the LC depth (reversal of the LC), and increase in the thickness of the LC and prelaminar tissue was observed in 35 OAG patients with IOP lowering. The magnitude of the reduction in the LC displacement was significantly associated with younger age, greater percent IOP reduction, and greater preoperative LC displacement. 2. Reversal of the lamina cribrosa displacement after intraocular pressure reduction in open angle glaucoma - The LC reversal was observed in 100 open angle glaucoma patients until 6 months after surgical or medical IOP lowering. Although the reversal was of larger amount in high-tension OAG, the LC reversal was also observed in a focal plane in low-tension OAG patients. The magnitude of LC reversal was associated with younger age, higher untreated IOP, higher baseline IOP, and greater percent of IOP reduction. 3. Variation of lamina cribrosa depth following trabeculectomy - The change of the LC was observed at 6 months and ≥2 years postoperatively in 28 OAG patients who underwent trabeculectomy. The postoperative reversal of the LC that was observed 6 months after surgery was not maintained in 9 eyes after postoperative 2 years. The degree of LC depth increase after 6 months was significantly associated with younger age, higher IOP at final follow-up, greater IOP fluctuation, and higher mean follow-up IOP from 6 months to final follow-up.

Conclusions: Reversal of the LC after IOP lowering treatment was observed in open angle glaucoma patients using enhanced depth imaging SD-OCT. The short-term LC reversal was associated with younger age and larger amount of IOP reduction. Although the reversal was more prominent in eyes with high-tension OAG, the LC reversal was also observed in a focal plane in low-tension OAG patients. In the long-term, the reversed LC was not maintained and returned to pre-treatment level in some OAG eyes. The return was likely to occur in patients who were younger and who had higher IOP and IOP fluctuation during the postoperative follow-up.