Structural Comparison of the Optic Nerve Head Based on Visual Prognosis after Acute Primary Angle Closure

Abstract

To compare optic nerve head (ONH) and peripapillary structural OCT parameters between eyes with and without visual field (VF) defects one year after an episode of acute primary angle closure (APAC) in a cohort treated uniformly treated with early clear-lens extraction. Forty-seven eyes of 47 patients with a history of APAC episode who underwent early clear-lens extraction at Chonnam National University Hospital were retrospectively reviewed. Spectral-domain optical coherence tomography (SD-OCT) performed one year after the episode was used to assess Bruch’s membrane opening-minimum rim width (BMO-MRW), retinal nerve fiber layer (RNFL) thickness, lamina cribrosa (LC) thickness and depth, and parapapillary atrophy (PPA) subdivided into PPA+BM and PPA−BM. Patients were classified according to the presence or absence of VF defects. At one year, 23 eyes (48.9%) had variable degrees of visual field (VF) defects. Compared with eyes with normal VF, the VF-defect group showed significantly thinner global BMO-MRW (p<0.001) and peripapillary RNFL (p<0.001), reduced LC thickness (p<0.001), shallower LC depth (p=0.028), and a wider PPA+BM (p<0.001). APAC patients who underwent early lens extraction may develop residual VF defect despite normalization of IOP. These defects were associated with structural damage in the rim, RNFL, LC, and PPA+BM as detected by SD-OCT. Comprehensive OCT analysis may help identify patients at risk of long-term functional sequelae after APAC.

INTRODUCTION

Acute primary angle closure (APAC) is a vision-threatening condition characterized by a sudden and marked elevation in intraocular pressure (IOP) due to abrupt closure of the anterior chamber angle. It often presents with severe ocular pain, headache, blurred vision, and nausea, and requires immediate intervention to prevent irreversible ocular damage.1,2 While rapid control of IOP often brings relief of symptoms and clinical improvement, but subtle structural damage to the optic nerve may remain even without glaucomatous changes.3,4,5,6,7,8,9

Although many APAC patients recover quickly after successful IOP reduction, a single untreated or delayed episode can cause permanent visual field (VF) damage. Even in patients with good clinical recovery, subclinical structural damage may persist. After resolution of acute episodes, optic nerve head (ONH) pallor and diffuse retinal nerve fiber layer (RNFL) thinning are often observed, even without cupping progression.3,4,7,10,11

Spectral-domain optical coherence tomography (SD-OCT) provides detailed cross-sectional images enhancing ability to evaluate the ONH and peripapillary region. SD-OCT allows detailed visualization of the peripapillary retinal nerve fiber layer (RNFL), Bruch’s membrane opening-minimum rim width (BMO-MRW), lamina cribrosa (LC), and parapapillary atrophy (PPA), all of which can be affected during episodes of acute IOP elevation. In particular, LC morphological changes and PPA widening may indicate accumulated mechanical stress on the optic nerve and can offer clues to long-term prognosis. Despite this, few studies have examined post-episode OCT findings in patients who have undergone early clear-lens extraction, particularly those evaluating LC metrics and BM-referenced PPA (PPA+BM) as long-term functional indicators.12,13

In this study, we hypothesized that residual VF loss may persist despite normalization of IOP after early lens extraction for APAC, and that this functional sequela may be related to structural damage on OCT. Therefore, to minimize media-related bias and clarify the structure-function relationship at one year after APAC, we compared BMO-MRW and RNFL, together with LC thickness/depth and PPA+BM only in pseudophakic eyes.

MATERIALS AND METHODS

This retrospective study included patients diagnosed with APAC at Chonnam National University Hospital between August 2019 and December 2020. The study protocol was approved by the Institutional Review Board of Chonnam National University Hospital. All research procedures adhered to the Declaration of Helsinki (approved No. 2022-441).

A diagnosis of APAC was established based on the following criteria: (1) at least two symptoms of acute IOP elevation (e.g., ocular pain, blurred vision, nausea, headache); (2) An IOP exceeding 21 mmHg on presentation, measured by Goldmann applanation tonometry; (3) three or more clinical signs, including conjunctival hyperemia, corneal epithelial edema, a mid-dilated pupil, and a shallow anterior chamber; and (4) gonioscopic verification of angle closure.

Initial management included medical therapy to reduce IOP and corneal edema, followed by laser peripheral iridotomy. Subsequently, all patients underwent phacoemulsification and intraocular lens implantation within two weeks of the acute episode once corneal clarity permitted; thus, all eyes were pseudophakic during follow-up. Only patients with a single APAC episode and had a follow-up period of one year after surgery were included.

Exclusion criteria were: peripheral anterior synechiae (PAS) extending more than 90°, presence of chronic angle-closure glaucoma, evidence of glaucomatous damage prior to or shortly after surgery, previous intraocular procedures or trauma, secondary angle-closure etiologies such as neovascular or uveitic glaucoma, and retinal diseases affecting visual fields. Patients with more than one APAC episode were also excluded.

Before surgery, all patients underwent a complete ophthalmic workup, including best-corrected visual acuity (BCVA), IOP measured by Goldmann applanation, slit-lamp examination, fundus photography, and ocular biometry (Lenstar; Haag-Streit AG, Koeniz, Switzerland). One year after the acute episode, all participants underwent VF test (Humphrey Field Analyzer III 840; 30-2 Swedish interactive threshold algorithm; Carl-Zeiss Meditec) and SD-OCT imaging (Heidelberg Spectralis SD-OCT; Spectralis software version 6.9.4; Heidelberg Engineering GmbH, Heidelberg, Germany).

All VF examinations were performed under standard perimetric conditions using a Goldmann size III stimulus and a background luminance of 31.5 apostilbs. Near refractive correction was applied when required. Results were accepted only if reliability indices met the following thresholds: fixation losses <20%, false positives <15%, and false negatives <25%. Participants with unreliable VF results underwent repeat testing. A VF was labeled abnormal if the Glaucoma Hemifield Test result was outside normal limits and ≥3 adjacent points on the pattern deviation plot had p-values <0.05. Diffuse field depression confirmed by abnormal mean deviation (p<0.05) on repeat testing was also categorized as a VF defect.

All participants underwent OCT imaging using SD-OCT (Heidelberg Spectralis SD-OCT; Spectralis software version 6.9.4; Heidelberg Engineering GmbH, Heidelberg, Germany) at 1-3-month intervals. The scans performed one year after the episode of acute PAC were used in this analysis. OCT images of insufficient quality (typically truncated B-scans, >10% missing data, or quality score of <30) were excluded. We measured Bruch’s membrane opening (BMO) area, global BMO-minimum rim width (MRW), and global peripapillary RNFL thickness using the Glaucoma Module Premium Edition (GMPE) software. All B-scans were checked manually, and BMO correction was performed as required. Details of the BMO correction protocol are described in our previous reports.14,15

The enhanced depth imaging (EDI) mode was used for the other ONH measurements, the methods for which have been described in detail previously.14,15 Lamina cribrosa (LC) depth, LC thickness, width of β-zone parapapillary atrophy (β-PPA) width were measured. Based on the location of the Bruch’s membrane (BM) termination, β-PPA was further divided into PPA_+BM and PPA_−BM.16,17 A built-in caliper tool in the intrinsic OCT viewer was used for the measurement, and the average data of three horizontal B-scan images (center, mid-superior and mid-inferior) were calculated and used for the analysis. The mean values obtained by two examiners (J.H.L and M.S.S) were used in the final analysis.

To measure peripapillary choroidal thickness, we manually delineated the upper and lower segmentation lines of the 360° circular RNFL scan (3.5 mm). The lines were adjusted to align with the inner scleral wall and posterior border of the RPE to define the outer and inner boundaries of the choroid, respectively. The peripapillary choroidal thickness was automatically computed using RNFL thickness measurement algorithms.

Statistical analyses were performed using SPSS version 27.0 (SPSS, Chicago, IL, USA). Data distribution was tested for normality using the Shapiro-Wilk normality test. Continuous variables were compared using the independent t-test or Mann–Whitney U test, while categorical comparisons employed chi-square analysis. Significance was defined as a p-value less than 0.05.

RESULTS

59 patients were diagnosed with APAC during the study period. After excluding eight patients for loss to follow-up and four for unreliable VF results, 47 eyes from 47 patients (39 female, 8 male) were included in the final analysis. The mean age of participants was 64.21±7.05 years. All subjects underwent successful phacoemulsification with intraocular lens implantation, and none required IOP-lowering medication during follow-up. Mean IOP at the last visit was 14.13±1.65 mmHg, with no significant difference between patients with normal and abnormal VF results (p=0.25).

Of the 47 eyes, 24 showed no VF defects, while the remaining 23 showed reproducible VF abnormalities one year after the episode. Most VF defects (17 eyes) were mild (MD≥−6 dB), although four eyes demonstrated severe loss (MD<−12 dB).

One year after the APAC episode, structural and functional outcomes were evaluated and compared between the two groups (Table 1). The eyes with VF defects showed significantly thinner global BMO-MRW (p<0.001) and peripapillary RNFL thickness (p<0.001) compared to eyes with normal VF. Sectoral analysis showed significant RNFL thinning in all six sectors in the VF-defect group, consistent with diffuse axonal loss. The VF-defect group also showed thinner LC (p<0.001), smaller LC depth (p=0.028), and larger PPA+BM (p<0.001) compared to those in the normal VF group. Fig. 1 illustrates the sectoral distribution of RNFL thickness, highlighting significant thinning across all six sectors in eyes with VF defects compared to those with normal VF. This finding supports the presence of diffuse axonal loss in the affected group. Fig. 2 shows representative cases of patients who underwent clear-lens extraction after APAC. In Fig. 2A, a patient with normal VF demonstrates preserved RNFL and BMO-MRW, whereas in Fig. 2B, a patient with VF defects shows marked thinning of RNFL, reduced LC thickness and depth, and notably enlarged PPA+BM. Visible RPE folding within the PPA+BM zone suggests prior mechanical stress due to IOP elevation. No statistically significant differences were observed for BMO area, PPA−BM, or choroidal thickness.

TABLE 1. Comparisons of OCT measurements and VF findings after one year of the episode of acute PAC.

Data are presented as mean±standard deviation, unless otherwise indicated. ^†Independent t test or Mann-Whitney U test (PPA_+BM width, PPA_−BM width, global peripapillary CT, VFI). OCT: optical coherence tomography, VF: visual field, PAC: primary angle closure, BMO: Bruch’s membrane opening, LC: lamina cribrosa, PPA_+BM: β-parapapillary atrophy with Bruch’s membrane, PPA−BM: β-parapapillary atrophy without Bruch’s membrane, CT: choroidal thickness, BMO-MRW: Bruch’s membrane opening-minimum rim width, RNFL: retinal nerve fiber layer, MD: mean deviation, PSD: pattern standard deviation, VFI: visual field index.

FIG. 1. Comparison of (A) peripapillary RNFL thickness and (B) BMO-MRW profiles based on the presence of VF defect after one year of remission of the acute episode. RNFL: retinal nerve fiber layer, BMO-MRW: Bruch’s membrane opening-minimum rim width, VF: visual field, T: temporal sector, TS: temporal-superior sector, NS: nasal-temporal sector, N: nasal sector, NI: nasal-inferior sector, TI: temporal-inferior sector. ^*Indicates p<0.05 and ^**indicates p<0.001 while comparing the sectoral thickness between the groups.

FIG. 2. Two representative patients who experienced the episode of acute primary angle closure. (A) One patient who showed visual field defects after one year of the remission of the acute episode. AS-OCT obtained at baseline examination shows relatively flat iris curvature (IC=0.09). Fundus photography and visual field examination obtained after one year of the episode shows pallor of the optic disc with diffuse thinning of the axons and generalized visual field defect (MD=−6.02 dB). B-scan images from Spectralis OCT obtained after one year of the acute episode demonstrate a folding of the end of the RPE on the lesion of PPA_+BM (red arrowhead) and thinning of the LC. (B) One patient who exhibited normal visual field after one year of the acute episode (MD=−0.23 dB). AS-OCT obtained at baseline examination shows greater iris curvature (IC=0.45). B-scan images from Spectralis OCT obtained after one year of the acute episode demonstrate relatively thick and deep LC compared with those of case A. AS-OCT: anterior segment-optical coherence tomography, IC: iris curvature, MD: mean deviation, RPE: retinal pigment epithelium, PPA_+BM: β-parapapillary atrophy with Bruch’s membrane, LC: lamina cribrosa.

DISCUSSION

This study shows that residual VF defects persist one year after APAC despite normalization of IOP following early clear-lens extraction, and that these functional sequelae are closely associated with structural damage as measured by OCT. Compared with eyes without VF defects, affected eyes had overall thinning of BMO-MRW and RNFL, decreased LC thickness with shallower LC depth, and greater PPA+BM width. Because all eyes were pseudophakic, the influence of media opacity were reduced and the structural measurements were more reliable.12,13

These results are consistent with previous studies of RNFL loss and ONH remodeling after APAC, even under controlled IOP.3,4,5,6,7,8 While previous studies have included phakic eyes or patients treated only with laser peripheral iridotomy, this study focused on a cohort treated with early lens extraction, which is known to improve angle anatomy and long-term IOP control.12,13 By limiting analyses to pseudophakic eyes, we minimized the influence of cataract or media opacity on VF and OCT metrics, strengthening the associations between structural damage and residual functional loss.

While it remains unclear whether these structural differences were present before or developed after the acute episode; however, our findings highlight the utility of SD-OCT in post-acute monitoring. Baseline SD-OCT scans were not analyzed because initial ONH and peripapillary RNFL edema made results variable and unreliable. Furthermore, during acute episodes, corneal edema, anterior chamber inflammation, and lens opacity make SD-OCT scans difficult to obtain.

Structural changes were assessed one year after the acute episode, and significant differences were found between the two groups. Thinning of the peripapillary RNFL and BMO-MRW was evident in all 6 sectors in eyes with VF defects.5,6,7,8,9,18,19,20,21,22,23 A reduction in nasal and temporal peripapillary RNFL thickness and BMO-MRW were also observed, and our results correspond with the results that VF defects found after APAC episodes are principally of the general type with more diffuse damage.4,10,24

In this study, LC was significantly thinner and LC depth was significantly smaller in eyes with VF defects after 1 year of an acute episode. Laminar thinning in glaucoma is well defined and appears to vary according to glaucoma severity.25 The acute IOP elevation causes posterior displacement of the LC, and this movement may contribute to axonal damage of retinal ganglion cells.26 After subsequent IOP reduction, anterior movement of the LC can occur, but the response is reported to be different between primary open-angle glaucoma (POAG) and APAC eyes.27 The change in the LC is significantly greater in the APAC eyes than in the POAG eyes, showing more significant anterior movement.27 Lee et al.6 also observed a decrease in LC depth during the early follow-up period after an acute episode, and further demonstrated that a larger reduction in LC depth is significantly associated with long-term peripapillary RNFL loss. They speculated that a reduction in LC depth reflects significant displacement of the LC during the acute episode, and this displacement may disrupt the structural and functional integrity between the laminar beams and axons, leading to long-term RNFL loss.6 In this study, we did not analyze the OCT scans at the early follow-up period; thus, it is unclear whether the smaller LC depth observed in eyes with VF defects was a result of greater anterior displacement of the LC. There is a possibility that the original LC depth was shallow or the initial posterior displacement of the LC during the acute episode was minimal in this group compared to the normal VF group. Based on this assumption, we speculate that eyes with inherently stiffer LC might undergo more mechanical strain with minimal LC displacement and consequently result in more functional damage.28

A comparison of the structural characteristics revealed that the presence of VF defects group showed significantly larger PPA+BM compared to the normal VF group. Wang et al.29 showed that an acute IOP elevation of >15 mmHg causes detectable changes in the morphology of the peripapillary RPE and in the position of the end of the RPE on the peripapillary BM. The changes in their study included folding of the RPE and centrifugal sliding of the RPE end on the BM away from the optic disc and were mostly observed in the temporal peripapillary region rather than in the nasal region. They reported that eyes with such changes showed enlargement of the β-PPA on en-face infrared photographs. Therefore, we hypothesize that eyes undergoing greater IOP-related strain during the acute episode may reveal larger PPA+BM and consequently result in worse functional sequelae. In our representative case shown in Fig. 2A, we could find the folding of the end of the RPE on the lesion of PPA+BM (red arrow head). However, we do not know if these structural characteristics differed at baseline or became so during the follow-up period. Cros-sectional data cannot distinguish whether such differences in several structural parameters in the poor VF sequelae group were present at baseline and is causative or occurred as a result of remodeling during the injury process. Further studies are needed to clarify whether structural changes after APAC are pre-existing or result from remodeling, and how these changes influence long-term functional outcomes.

This study applied a uniform treatment with early lens extraction and limited the analysis to pseudophakic eyes, including LC and BM-referenced PPA parameters in addition to conventional rim and axonal measures. Limitations of this study include its retrospective design, small sample size, and potential selection bias. Additionally, the absence of preoperative OCT scans precludes definitive causal inference. Nevertheless, the consistency of our findings suggests that functional sequelae are closely related to structural damage incurred during APAC.

In conclusion, a considerable proportion of patients continued to show residual VF defects one year after APAC, even with IOP normalization and early clear-lens extraction. The persistence of functional loss suggests that damage spans multiple OCT layers, from the rim and RNFL to the LC and PPA+BM, suggesting structural damage after APAC. Comprehensive OCT assessment in pseudophakic eyes helped identify patients with long-term VF defect after APAC, showing that OCT may be a practical tool for routine follow-up care.