DOI: https://doi.org/10.21203/rs.3.rs-2090827/v1
Background/Objectives: To evaluate changes in anterior segment parameters in Caucasian eyes with different angle-closure mechanisms before and after laser peripheral iridotomy (LPI)
Subjects/Methods: Sixty-six subjects underwent swept-source optical coherence tomography (SSOCT, CASIA, Tomey Corporation, Nagoya, Japan) angle imaging in the dark before and 7 days after LPI. Based on the baseline SSOCT images, the eyes were categorized into 4 angle-closure mechanisms namely pupillary block (PB), plateau iris configuration (PIC), thick peripheral iris (TPI) and large lens vault (LLV). Sixteen out of 128 cross-sectional images (11.25 degrees apart) per volume scan were selected for analysis. We used generalized estimating equation to compare quantitative parameters among angle-closure mechanisms and between before and after LPI after adjusting the inter-eye correlation.
Results: The mean age of subjects was 67.7±9.2 years, with the majority being female (82.2%). 129 eyes (67 primary angle-closure suspects, 34 primary angle-closure and 28 primary angle-closure glaucoma) were categorized into PB (n=71, 55%), PIC (n=40, 31%), TPI (n=14, 10.9%) and LLV (n=4, 3.1%). Anterior chamber depth was the shallowest in the LLV, followed by TPI, PB and PIC group at baseline. Widening of the angle and reduction of the iris curvature (IC) due to LPI were observed in all groups (all P<0.01). When compared to the PB group, the LPI-induced angle widening in the TPI group was significantly less even though the IC reduction in the TPI group was greater (all P<0.05).
Conclusions: In patients with angle closure, anterior segment morphology and LPI-induced angle widening were different amongst the various angle-closure mechanisms.
Glaucoma is the leading cause of irreversible blindness and the number of people with glaucoma worldwide is estimated to be 111.8 million in 2040.(1) Although primary open-angle glaucoma (POAG) is a more common type of glaucoma, primary angle-closure glaucoma (PACG) is more visually destructive and more likely to result in blindness.(1) The prevalence of PACG is estimated to be 0.4% in Caucasians(2) and 1.5% in Asians(3). Although pupillary block (PB) is known to be the primary anatomical mechanism underlying angle-closure, other anatomical factors such as the iris, the lens and ciliary body play significant roles in PACG pathogenesis.(4, 5) Laser peripheral iridotomy (LPI) is the primary option in angle-closure management by eliminating PB and widening the angle; however, LPI does not open or widen all eyes with primary angle-closure diseases (PACD).(6, 7)
Anterior segment optical coherence tomography (ASOCT) is a non-contact method for visualization of the anterior chamber angle and evaluation of other factors such as the thickness of iris periphery, iris cross sectional area and the lens vault (the anterior part of the lens that is not easy to assess by slit-lamp examination or gonioscopy).(8) Swept-source optical coherence tomography (SSOCT) is a new form of ASOCT that allows circumferential assessment of anterior segment structures with simultaneous 360-degree angle imaging in 128 cross sections. Recently, studies used an ASOCT image to categorize angle-closure eyes into different subgroups based on angle-closure mechanisms.(5, 9, 10) Four subgroups namely PB, plateau iris configuration (PIC), thick peripheral iris (TPI) and large lens vault (LLV) were introduced, and the anterior segment parameters were compared among these 4 groups.(5, 9, 10)
Recently, Kwon and associates found that the LPI widened the anterior chamber angle in the PB and TPI groups but not in the PIC and LLV groups. However, the study was limited by using only one B-scan (horizontal slice representing nasal and temporal quadrant) of ASOCT for the classification of angle-closure and comparison of anterior segment parameters.(9) The aim of the study was to address these limitations by using 16 cross-sectional B-scans of SSOCT images per eye to evaluate and compare quantitative parameters of the anterior segment after LPI in eyes with different mechanisms of PACD.
This was a prospective observational study conducted in accordance with the tenets of the Declaration of Helsinki and approved by the Bioethics Committee of Medical University of Lublin, Poland. Patients with bilateral angle closure aged ≥ 40 years were consecutively recruited from the glaucoma clinics of one hospital in Poland. All subjects provided written informed consent before enrollment into the study. All cases were newly diagnosed and had no previous history of glaucoma and intraocular surgery. We excluded the cases with history of LPI or laser iridoplasty.
Primary angle-closure suspect (PACS) was defined as an eye with an occludable angle (defined as appositional contact between the iris and the pigmented posterior trabecular meshwork on non-indentation gonioscopy for at least 180 degrees in the primary gaze position), normal intraocular pressure (IOP) (less than 21 mmHg), in the absence of peripheral anterior synechiae (PAS) and glaucomatous optic neuropathy (GON). Primary angle-closure (PAC) was defined as an eye with occludable angles, elevated IOP (≥ 21mmHg) and/or PAS, but in the absence of GON. Primary angle-closure glaucoma (PACG) was defined as an eye with occludable angles and GON (defined as the presence of vertical cup-disc ratio > 0.8 and/or neuro-retinal rim thinning with an associated visual field loss on standard automated perimetry).
After taking the medical and surgical history, all subjects underwent the following assessments: 1) measurement of visual acuity, 2) refraction using an autokeratometer, 3) slit lamp biomicroscopy, 4) IOP measurement with Goldmann applanation tonometry, 5) gonioscopy and 6) SSOCT imaging.(11)
All subjects underwent SSOCT imaging using the 3D-angle analysis scan protocol under standardized dark room conditions before any contact procedures. Seated subjects were examined in the primary gaze position whilst directed towards an internal fixation light. The operator retracted both eyelids, avoiding inadvertent pressure on the globe during scanning. Each volume consisted of 128 radial B-scans, each 16 mm in length and 6 mm in depth and provided cross sections of the entire anterior segment. Acquisition of SSOCT images was performed before LPI, and 7 days after LPI on all the subjects.(11)
All images were analyzed using the 360º SSOCT viewer (version 9.0, Tomey, Nagoya, Japan) and the only user input was marking the location of the scleral spur. The scleral spur was defined as the inward protrusion of the sclera where a change in curvature of the corneo-scleral interface was noted. Sixteen out of 128 frames (32 anterior chamber angles, 11.25º increments) in each SS-OCT volume scan were selected to analyze. 1) Anterior segment parameters such as anterior chamber depth (ACD), anterior chamber area (ACA), anterior chamber volume (ACV), anterior chamber width (ACW), lens vault (LV), and pupil diameter (PD), 2) anterior chamber angle parameters such as angle opening distance at 750 µm from the scleral spur (AOD750), and trabecular-iris space area (TISA750), and 3) iris parameters such as iris curvature (IC), iris thickness at 750 µm (IT750) and at 2000 µm (IT2000) from the scleral spur, iris area (IA) and iris volume (IV) were measured by the algorithm automatically.(12)
Based on the baseline SSOCT images, the eyes were then categorized into one of the 4 angle-closure mechanisms: PB, PIC, TPI, and LLV. The classification was done by independent investigators (AS and AWK) using a panel of reference images that were chosen the best ones representing the angle-closure mechanisms in the study (Fig. 1). Since the 8 cross sectional images were categorized qualitatively, there may have more than one mechanism of PACD. If it was thought that there was more than one angle-closure mechanism, a consensus on the dominant mechanism was established.
LPI was performed in the superior region (at 12 o’clock) by neodymium-doped yttrium aluminum garnet after instilling 2% pilocarpine into the eye 1 hour before the LPI. All participants were evaluated at 1 week after the LPI.
Statistical analyses were performed using SPSS statistics for Windows (IBM Corp, Version 18.0., Armonk, NY: IBM Corp). Continuous variables were described as the mean and standard deviation. We used the generalized estimating equations (GEE) to compare morphology changes in anterior segment among angle-closure mechanisms and between before and after LPI, after adjusting for inter-eye correlation, age, and gender. We used the PB group and baseline values of anterior segment as the control and compared the selected ocular variables among the groups. A post-hoc test with Bonferroni correction was applied to compare the differences in mean values of continuous variables. Statistical significance was set at P < 0.05.
129 eyes (67 PACS, 34 PAC and 28 PACG eyes) from the 66 subjects were included in the final analysis. The mean age of subjects was 67.72 ± 9.15 years with the majority being female (n = 54, 81.8%). Of 129 eyes, 71(55%) eyes were classified into the PB, 40 (31%) into the PIC, 14 (10.9%) into the TPI and 4 (3.1%) into the LLV group. Table 1 compares the demographic and ocular parameters at the baseline visit among 4 groups. The greatest axial length (Axl) was found in the PIC group and the shortest ACD was seen in the LLV group. The LV was significantly different among the groups except between the PIC and TPI groups. The PIC group had the largest angle width (AOD750 and TISA750) that was significantly different from those of the PB and TPI groups. (Table 1)
| Variables | PB (n = 71) | PIC (n = 40) | TPI (n = 14) | LLV (n = 4) | PB vs PIC | PB vs TPI | PB vs LLV | PIC vs TPI | PIC vs LLV | TPI vs LLV |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean ± SD or n (%) | P Value | |||||||||
| Age, years | 68.79 ± 8.26 | 66.95 ± 10.86 | 64.86 ± 8.78 | 66.5 ± 6.35 | 1 | 0.869 | 1 | 1 | 1 | 1 |
| Gender, female | 58 (81.7%) | 33 (82.5%) | 11 (78.6%) | 4 (100%) | ||||||
| Sph, dioptre | 1.52 ± 2.06 | 1.71 ± 2.41 | 3.27 ± 2.09 | 3.5 ± 1.68 | 1 | 0.041 | 0.471 | 0.133 | 0.706 | 1 |
| IOP, mmHg | 17.55 ± 5.11 | 20.5 ± 6.37 | 20.43 ± 9.12 | 12.75 ± 2.87 | 0.086 | 0.623 | 0.736 | 1 | 0.092 | 0.155 |
| Axial length, mm | 22.15 ± 0.79 | 22.59 ± 0.94 | 21.57 ± 0.65 | 21.13 ± 0.67 | 0.045 | 0.104 | 0.107 | 0.001 | 0.006 | 1 |
| ACD, mm | 2.05 ± 0.24 | 2.27 ± 0.18 | 1.97 ± 0.25 | 1.65 ± 0.21 | < 0.001 | 1 | 0.005 | < 0.001 | < 0.001 | 0.075 |
| ACW, mm | 11.52 ± 0.39 | 11.83 ± 0.41 | 11.15 ± 0.55 | 11.58 ± 0.19 | 0.001 | 0.015 | 1 | < 0.001 | 1 | 0.389 |
| ACA, mm2 | 13.96 ± 2.39 | 16 ± 2.08 | 13.08 ± 2.16 | 10.48 ± 1.91 | < 0.001 | 1 | 0.02 | < 0.001 | < 0.001 | 0.269 |
| ACV, mm3 | 86.95 ± 18.9 | 105.75 ± 17.08 | 79.2 ± 18.56 | 65.91 ± 17.33 | < 0.001 | 0.977 | 0.161 | < 0.001 | < 0.001 | 1 |
| Lens vault, mm | 0.86 ± 0.17 | 0.72 ± 0.21 | 0.68 ± 0.16 | 1.29 ± 0.03 | 0.002 | 0.008 | < 0.001 | 1 | < 0.001 | < 0.001 |
| Pupil diameter, mm | 3.72 ± 0.64 | 3.33 ± 0.58 | 4.09 ± 0.94 | 3.03 ± 0.93 | 0.018 | 0.372 | 0.264 | 0.002 | 1 | 0.034 |
| Iris Area, mm2 | 1.42 ± 0.21 | 1.47 ± 0.23 | 1.44 ± 0.32 | 1.57 ± 0.15 | 1 | 1 | 1 | 1 | 1 | 1 |
| Iris Volume, mm3 | 31.88 ± 4.16 | 33.35 ± 4.46 | 32.42 ± 5.59 | 31.49 ± 5.46 | 0.6 | 1 | 1 | 1 | 1 | 1 |
| AOD750, mm | 0.19 ± 0.07 | 0.23 ± 0.08 | 0.15 ± 0.05 | 0.17 ± 0.15 | 0.026 | 0.632 | 1 | 0.006 | 0.94 | 1 |
| TISA750, mm2 | 0.1 ± 0.05 | 0.13 ± 0.05 | 0.07 ± 0.03 | 0.12 ± 0.09 | 0.018 | 0.399 | 1 | 0.002 | 1 | 0.579 |
| IT750, mm | 0.34 ± 0.04 | 0.35 ± 0.05 | 0.4 ± 0.04 | 0.29 ± 0.04 | 1 | < 0.001 | 0.083 | < 0.001 | 0.064 | < 0.001 |
| IT2000, mm | 0.36 ± 0.05 | 0.34 ± 0.05 | 0.46 ± 0.07 | 0.34 ± 0.07 | 0.352 | < 0.001 | 1 | < 0.001 | 1 | 0.002 |
| Iris curvature, mm | 0.33 ± 0.07 | 0.32 ± 0.05 | 0.26 ± 0.05 | 0.4 ± 0.1 | 1 | 0.006 | 0.121 | 0.044 | 0.066 | 0.001 |
| PB is pupillary block; PIC is plateau iris configuration; TPI is thick peripheral iris; LLV is large lens vault; Sph is spherical equivalent; IOP is intraocular pressure; ACD is anterior chamber depth; ACW is anterior chamber width; ACA is anterior chamber area; ACV is anterior chamber volume; AOD750 is angle opening distance 750 µm from the scleral spur; TISA750 is trabecular iris space area 750 µm from the scleral spur; IT750 is iris thickness 750 µm from the scleral spur; IT2000 is iris thickness 2000 µm from the scleral spur. | ||||||||||
After LPI, ACV, AOD750, and TISA750 were significantly increased, and IC was significantly decreased in all groups when compared to their baseline values (all P < 0.05). (Table 2) As expected, there were no significant changes in ACD, LV, IV, IT750 and IT2000 due to LPI. (Table 2)
| Variables | Visit | PB (n = 71) | P Value | PIC (n = 40) | P Value | TPI (n = 14) | P Value |
|---|---|---|---|---|---|---|---|
| ACD, mm | Baseline | 2.05 ± 0.24 | 2.27 ± 0.18 | 1.97 ± 0.25 | |||
| Day 7 | 2.08 ± 0.24 | 0.456 | 2.27 ± 0.16 | 0.981 | 2.01 ± 0.26 | 0.661 | |
| LV, mm | Baseline | 0.86 ± 0.17 | 0.72 ± 0.21 | 0.68 ± 0.16 | |||
| Day 7 | 0.89 ± 0.17 | 0.378 | 0.73 ± 0.19 | 0.911 | 0.74 ± 0.18 | 0.311 | |
| ACV, mm3 | Baseline | 86.95 ± 18.9 | 105.75 ± 17.08 | 79.2 ± 18.56 | |||
| Day 7 | 102.36 ± 19.13 | < 0.001 | 115.43 ± 18.22 | 0.026 | 91.08 ± 21.33 | 0.156 | |
| IV, mm3 | Baseline | 31.88 ± 4.16 | 33.35 ± 4.46 | 32.42 ± 5.59 | |||
| Day 7 | 32.67 ± 3.47 | 0.237 | 33.25 ± 4.52 | 0.926 | 33.98 ± 4.23 | 0.392 | |
| AOD750, mm | Baseline | 0.19 ± 0.07 | 0.23 ± 0.08 | 0.15 ± 0.05 | |||
| Day 7 | 0.3 ± 0.09 | < 0.001 | 0.32 ± 0.09 | < 0.001 | 0.23 ± 0.07 | 0.004 | |
| TISA750, mm2 | Baseline | 0.1 ± 0.05 | 0.13 ± 0.05 | 0.07 ± 0.03 | |||
| Day 7 | 0.15 ± 0.05 | < 0.001 | 0.16 ± 0.05 | 0.006 | 0.11 ± 0.04 | 0.006 | |
| IT750, mm | Baseline | 0.34 ± 0.04 | 0.35 ± 0.05 | 0.4 ± 0.04 | |||
| Day 7 | 0.35 ± 0.05 | 0.308 | 0.35 ± 0.04 | 0.9 | 0.4 ± 0.06 | 0.889 | |
| IT2000, mm | Baseline | 0.36 ± 0.05 | 0.34 ± 0.05 | 0.46 ± 0.07 | |||
| Day 7 | 0.37 ± 0.05 | 0.637 | 0.35 ± 0.06 | 0.524 | 0.45 ± 0.07 | 0.662 | |
| IC, mm | Baseline | 0.33 ± 0.07 | 0.32 ± 0.05 | 0.26 ± 0.05 | |||
| Day 7 | 0.16 ± 0.07 | < 0.001 | 0.16 ± 0.06 | < 0.001 | 0.16 ± 0.07 | < 0.001 | |
| PB is pupillary block; PIC is plateau iris configuration; TPI is thick peripheral iris; ACD is anterior chamber depth; LV is lens vault; ACV is anterior chamber volume; IV is iris volume; AOD750 is angle opening distance 750 µm from the scleral spur; TISA750 is trabecular iris space area 750 µm from the scleral spur; IT750 is iris thickness 750 µm from the scleral spur; IT2000 is iris thickness 2000 µm from the scleral spur; IC is iris curvature; Day7 is 7 days after the laser peripheral iridotomy. | |||||||
Since the LLV group had 4 cases only, the changes in selected anterior segment parameters were compared among the remaining 3 groups using GEE after adjusting for inter-eye correlation, age, and gender. The PB group had significantly shorter ACD than the PIC group and the ACD was increased from its baseline after LPI. The PIC and TPI groups showed smaller LV than that of the PB group (all P < 0.05). (Table 3) After the LPI, the LV was greater in the TPI than the PB group, but it was smaller in the PIC group at the Day 7 visit (all P < 0.05). (Table 3)
| Variables | Anterior Chamber Depth, mm | Lens Vault, mm | ||||
|---|---|---|---|---|---|---|
| Coefficient | 95% CI | P value | Coefficient | 95% CI | P value | |
| Age | 0 | -0.01, 0 | 0.203 | 0.01 | 0, 0.01 | 0.075 |
| Gender (male as control) | -0.02 | -0.18, 0.14 | 0.801 | 0.05 | 0.06, 0.16 | 0.371 |
| Group (PB as control) | ||||||
| PIC | 0.17 | 0.04, 0.3 | 0.01 | -0.1 | -0.18, -0.02 | 0.011 |
| TPI | -0.08 | -0.27, 0.12 | 0.433 | -0.16 | -0.29, -0.03 | 0.019 |
| Time (Baseline as control) | ||||||
| Day7 | 0.02 | 0.01, 0.02 | < 0.001 | 0.03 | 0.01, 0.05 | 0.004 |
| Time x Group (PB and Baseline as control) | ||||||
| PIC x Day7 | 0.01 | 0, 0.02 | 0.195 | -0.04 | -0.06, -0.01 | 0.012 |
| TPI x Day7 | 0.01 | -0.01, 0.02 | 0.569 | 0.04 | 0, 0.08 | 0.036 |
| PB is pupillary block; PIC is plateau iris configuration; TPI is thick peripheral iris; Day7 is 7 days after the laser peripheral iridotomy. | ||||||
Table 4 shows widening of the angle width and flattening of the iris due to LPI among 3 subgroups. The LPI widened the angle width (assessed by AOD750) and flattened the IC (all P < 0.001). The LPI-induced angle widening was lesser in the TPI group when compared to that of the PB group (all P < 0.05). The TPI group had more LPI-induced iris flattening than the PB group but there was no difference between the PIC and the PB group. (Table 4)
| Variables | AOD750, mm | Iris curvature, mm | ||||
|---|---|---|---|---|---|---|
| Coefficient | 95% CI | P value | Coefficient | 95% CI | P value | |
| Age | 0 | 0, 0 | 0.822 | 0 | 0, 0 | 0.681 |
| Gender (male as control) | -0.03 | -0.09, 0.02 | 0.248 | -0.01 | -0.04, 0.01 | 0.371 |
| Group (PB as control) | ||||||
| PIC | 0.04 | 0.01, 0.07 | 0.005 | -0.01 | -0.04, 0.02 | 0.486 |
| TPI | -0.03 | -0.07, 0.07 | 0.103 | -0.05 | -0.09, -0.02 | 0.007 |
| Time (Baseline as control) | ||||||
| Day7 | 0.11 | 0.1, 0.12 | < 0.001 | -0.17 | -0.19, -0.15 | < 0.001 |
| Time x Group (PB and Baseline as control) | ||||||
| PIC x Day7 | -0.01 | -0.04, 0.01 | 0.208 | 0.01 | -0.02, 0.04 | 0.501 |
| TPI x Day7 | -0.04 | -0.07, -0.01 | 0.004 | 0.06 | 0.01, 0.11 | 0.03 |
| PB is pupillary block; PIC is plateau iris configuration; TPI is thick peripheral iris; Day7 is 7 days after the laser peripheral iridotomy. | ||||||
In this study, we evaluated the LPI-induced morphological changes in the anterior segment amongst subgroups of patients with different angle-closure mechanisms in Caucasian eyes. The most common angle-closure mechanism was PB (55%), followed by PIC (31%), TPI (10.9%) and LLV (3.1%) in this cohort. The shortest ACD and greatest LV were seen in the LLV group, and the largest angle width was found in the PIC group. The TPI group showed lesser angle widening and greater iris flattening after LPI when compared to those of the PB group. Since the SSOCT provides the cross-sectional and circumferential assessment of anterior segment, using this information to classify the angle-closure eyes into different mechanisms may provide insights into individualized management for the PACD. Imaging may also help predict which eyes could have the best benefit for a specific treatment such as LPI.
Like in previous studies, we found that the ACD at baseline was the shortest in the LLV group and the longest in the PIC group.(5, 9) The pre-LPI angle width (AOD750) was the smallest in the TPI group and was the largest in the PIC group.(5, 9) However, studies reported that the PB was accounted for 35%, the PIC was 16–22%, the TPI was 14–26% and the LLV was 17–35% in an Asian population.(5, 9, 10) In this cohort of Caucasians, the percentage of the PB was much higher but that of LLV was lower when compared to the published data. The different ethnicity may drive to this difference in angle-closure mechanisms.
It was hypothesized that the angle-closure mechanisms are based on the forces acting at four different anatomic levels: the iris, the ciliary body, the lens and posterior to the lens.(4) Since the pathophysiology of the PACD is mechanistic predominantly, the management of PACD depends highly on correctly identifying the underlying anatomical mechanism.(13) In this study, the angle was widened after the LPI in all groups(14) because the pressure gradient between anterior and posterior chamber is equalized. It leads to a reduction of the iris curvature which is a surrogate for defining pupillary block. Thus, it may have some degree of pupillary block in all the eyes of this cohort. In contrast, Kwon et al also showed that the angle was widened in the PB and TPI groups but not in the PIC groups.(9)
When compared amongst the subgroups, there were significant differences in LPI-induced angle widening and iris flattening between the PB and TPI group. Interestingly, after the LPI, the TPI group had lesser angle widening than the PB group even though their irides flattened more. The peripheral iris thickness was also not significantly different from its baseline in both groups. Therefore, the TPI group, as expected, showed less effect of LPI on angle widening because peripheral iris was thicker and was not changed due to LPI. However, the narrowing of angle or shortening of the anterior chamber depth over time(15) could not be assessed in this study and future study with long-term follow-up is needed.
Several limitations in this study warrant further discussion. First, the sample size of each group in the current study was small especially the LLV group. However, that could be the incidence rate of angle-closure mechanisms in the Polish population and future studies with a large sample size are needed to confirm it. Grading and classification of the SSOCT images were subjective and may lead to a systematic bias. The follow-up period in the current study was short (only 7 days after LPI) so the long-term changes in anterior segment in different angle-closure mechanisms should be assessed in future studies.
In summary, the LPI-induced anterior segment morphology changes were different among the angle-closure mechanisms in a Caucasian population. Subgrouping of angle-closure mechanisms based on the SSOCT images may help to predict the effect of LPI. It provides early evaluation of high-risk groups and adjusts the relevant treatment to the predominant mechanism.
Conflict of interest
The authors declare no conflict of interest.
Funding Support
Nil
Author Contribution Statement
Design of study (TA, TZ); Conduct of the study (AS, AW, TZ); Collection and management of data (TAT,AS, AW); Analysis and Interpretation of data (TAT,AS,AW); Preparation of manuscript (TAT,AS,AW,TA); Review and approval of the manuscript (TA,TZ).