Short-term changes detected by corneal topography and optical coherence tomography after prophylactic laser iridotomy in primary angle closure suspect

To evaluate early changes in anterior segment parameters by Scheimpflug–Placido disc topography system and changes in retinal layers by optical coherence tomography in primary angle-closure suspects after laser peripheral iridotomy. One eye of 26 patients with primary angle closure suspect and of 20 healthy subjects were included in this retrospective cross-sectional study. Anterior chamber depth/volume, iridocorneal angle and central corneal thickness were obtained by Scheimpflug–Placido disc topography system. Retinal thickness, retinal nerve fiber layer thickness and ganglion cell-inner plexiform layer thickness were acquired by optical coherence tomography. All the tests were repeated 1 week and 1 month after laser peripheral iridotomy. The mean ages of the patients and healthy controls were 64.8 ± 10.7 years and 64.5 ± 3.9 years, respectively (p = 0.990). Anterior chamber depth/volume and iridocorneal angle value were lower in the PACS group (p < 0.001, for all). Anterior chamber volume and iridocorneal angle increased significantly after laser peripheral iridotomy (p = 0.004, for both). While foveal thickness decreased significantly after laser peripheral iridotomy (p = 0.027), retinal nerve fiber layer thickness increased in superior and temporal quadrants (p = 0.038 and p = 0.016, respectively). Our results suggest that LPI in patients with PACS provides improved retinal thickness and RNFL thickness, as well as anterior chamber parameters.


Introduction
Primary angle-closure glaucoma (PACG) accounts for 25% of all diagnosis of glaucoma globally and is a significant cause of blindness [1].It is more common in females and in certain ethnic groups, such as particular Asian populations [2].Primary angle-closure suspects (PACS) are individuals with 180° or more contact between the iris and trabecular meshwork,

Abstract
Purpose To evaluate early changes in anterior segment parameters by Scheimpflug-Placido disc topography system and changes in retinal layers by optical coherence tomography in primary angle-closure suspects after laser peripheral iridotomy.Methods One eye of 26 patients with primary angle closure suspect and of 20 healthy subjects were included in this retrospective cross-sectional study.Anterior chamber depth/volume, iridocorneal angle and central corneal thickness were obtained by Scheimpflug-Placido disc topography system.Retinal thickness, retinal nerve fiber layer thickness and ganglion cell-inner plexiform layer thickness were acquired by optical coherence tomography.All the tests were repeated 1 week and 1 month after laser peripheral iridotomy.normal intraocular pressure, no evidence of peripheral anterior synechiae, and a healthy optic nerve [3].The contact between the iris and the trabecular meshwork might result with peripheral anterior synechiae and increased intraocular pressure (IOP) that damages the optic nerve, a condition known as primary angleclosure glaucoma.Laser peripheral iridotomy (LPI) is expected to decrease the risk of acute angle closure attacks and delay the development of PACG [3].This procedure eliminates the pressure gradient between the anterior chamber and posterior chamber thereby flattening iris convexity and widening the peripheral iridocorneal angle [4].A study on PACS reported that one in five patients progressed to angle closure glaucoma after a mean of 2.7 years follow-up [5].
The main objective of this study was to quantify early changes in anterior segment parameters [anterior chamber depth (ACD), anterior chamber volume (ACV), iridocorneal angle, central corneal thickness (CCT)] using Scheimpflug-Placido disc topography system and to investigate if there were any early changes in macular retinal thickness, peripapillary retinal nerve fiber layer (RNFL) thickness and ganglion cell-inner plexiform layer (GC-IPL) thickness by optical coherence tomography (OCT) in PACS after LPI.

Methods
For this retrospective observational study, 26 eyes of 26 subjects diagnosed with suspected primary angle-closure and 20 eyes of 20 age and sex matched healthy people were enrolled.We retrospectively included patients and healthy controls who had admitted to ophthalmology clinic between January 2021 and June 2021.An informed consent form was signed by all of the participants after the explanation of the nature and possible consequences of the study at the time of enrollment.This study was conducted in line with the Declaration of Helsinki.
All PACS subjects were enrolled from our hospital's eye clinic.The subjects were between 45 and 70 years of age.PACS was defined as an eye with angle with ≥ 180° iridotrabecular contact (equivalent to modified Shaffer grade 1 or less) without visible pigmented trabecular meshwork on gonioscopy in primary gaze, IOP of 21 mmHg or less, no peripheral anterior synechiae or glaucomatous optic neuropathy.
The subjects were excluded from the study if they had any history of ocular disease, previous intraocular surgery or penetrating eye injury, use of topical or systemic medications that could affect the anterior chamber angle.Only one eye of the patients whose both eyes met the inclusion criteria was randomly selected and included in the study.All subjects underwent a complete ocular examination including uncorrected and best-corrected visual acuity testing, slit-lamp biomicroscopy, intraocular pressure measurement with Goldmann applanation tonometry, gonioscopy, undilated examination of optic disc using + 90D lens.The gonioscopy was performed in a low-light environment using a Goldmann three-mirror contact lens.

Measurements and study procedure
The eyes of the healthy subjects and the patients prior to LPI were evaluated with the Sirius Scheimpflug-Placido disc topographer system (Schwind eye-techsolutions, Kleinostheim, Germany) which recorded ACD, ACV, iridocorneal angle and CCT.The Sirius Scheimpflug-Placido disc topographer combines a monochromatic 360º rotating Scheimpflug camera and a topography device with a 22-ring Placido disc.The combination of a 3D Scheimpflug camera and Placido topography provides highly precise anatomical information about the entire anterior segment of the eye.Figure 1 shows an image obtained by the Scheimpflug-Placido disc topographer before (1), one week (2) and one month (3) after LPI of a patient.The evaluation of macular retinal thickness, GC-IPL and peripapillary RNFL thicknesses of the subjects was done by Cirrus HD-OCT 5000 (Zeiss Meditec, Germany).All tests were performed by the same masked technician in the same rooms and conditions, without dilating the pupil.The measurements were repeated similarly at 1 week and 1 month after LPI.

Laser peripheral iridotomy
The healthy subjects in the study were applied no intervention.After obtaining an informed consent for the procedure, all the patients with PACS were administered topical pilocarpine 2% (Pilosed, Bilim Ilac, Turkey) to constrict the pupil.Brimonidine 0.15% (Alphagan P, Allergan, Ireland) was instilled before the procedure.Laser peripheral iridotomy was performed using Neodymium-doped Yttrium Aluminium Garnet laser by a glaucoma specialist with Abraham peripheral iridotomy contact lens (Ocular Instruments, Bellevue, WA, USA), in the superior region (from 10 to 2 o'clock), aiming for iris crypts and for a minimum iridotomy size of 150-200 µm.Argon settings of 500-1000 mW power with a spot size of 50 µm for a duration of 0.05 s and a yttrium-aluminum-garnet setting of 2-5 mJ were used.One hour after iridotomy, patency of iridotomy was confirmed by retroillumination and direct visualization on slit-lamp biomicroscopy.Postoperative topical brimonidine 0.15% (Alphagan-P, Allergan, Ireland) and loteprednol (Lotemax, Bausch & Lomb, Inc.) were prescribed.

Statistical analysis
Analyses were performed using the SPSS statistical software for Windows, version 21, (IBM, Armonk, NY, USA).The descriptive statistics are expressed as mean ± standard deviations for normally distributed variables, median (range) for variables without normal distribution, and the number of cases and percentages (%) for nominal variables.The normality of the data was tested by Kolmogorov-Smirnov distribution test.Pearson Chi-square test and Fisher's Exact test were used for comparison of descriptive statistics, as well as qualitative data.When the relationship between parameters were investigated, Pearson's correlation test was used for normally distributed data, and Spearman's correlation test was used for non-normally distributed data.The results were evaluated at 95% confidence interval and the level of significance was set to 0.05 in all statistical tests.

Results
The mean age of patients was 64.8 ± 10.7 years and 14 of the subjects were male.The mean age of the control group was 64.5 ± 3.9 years, and 11 of the participants were male.There was no significant difference between two groups in terms of age and gender (p = 0.990 and p = 0.919, respectively).While BCVA, IOP and CCT were similar between healthy controls and the patients with PACS; ACD, ACV and iridocorneal angle values were significantly lower in the PACS group (Table 1).All retinal thickness values in the 9 Early Treatment Diabetic Retinopathy Study (ETDRS) sectors were similar in two groups (p > 0.05).The peripapillary RNFL thickness values in superior, inferior, nasal and temporal quadrants were also similar in between these groups (p > 0.05).There was no significant difference between two groups in terms of the macular GC-IPL thicknesses in six 60° sectors segmented by the ganglion cell analysis algorithm (p > 0.05).
Intraocular pressure and anterior segment findings at baseline and at the first week and first month of the patients with PACS are represented in Table 2.The mean ACV and iridocorneal angle increased significantly one week after LPI (p = 0.004, for both), but there was no significant change between measurements at one week and one month after LPI.The other anterior segment parameters did not show significant change after LPI.When the changes in macular thickness were examined, there was a significant decrease in only foveal thickness (central ETDRS sector) (p = 0.027) and no significant change was observed in retinal thickness in other ETDRS sectors (Table 3).The mean RNFL thicknesses of the superior and temporal region increased significantly after LPI (p = 0.038 and p = 0.016, respectively) (Table 4).When GC-IPL thicknesses were evaluated, there was no significant change in the average, minimum and 6 sectoral regions (Table 5).Delta values (value of % change) were calculated for the change in between second and first examination and in between third and first examination.There was no significant correlation between these delta values of all corneal topography and OCT parameters (p > 0.05, for all).

Discussion
Our results showed that IOP and CCT were similar in healthy controls and patients with PACS.As expected, ACD, ACV and iridocorneal angle values  [6].Unlike our study, they also included patients with primary angle closure (PAC), PAC glaucoma, acute angle closure glaucoma and iris plateau configuration.However, other two studies involving a similar patient group as our study found no significant change in ACD after LPI [7,8].We thought that the discrepancy in results may be related to the different methodology of these studies.Further, it is a very rational datum that ACD did not show significant change because the position of the lens is not modified with the LPI but that of the iris.In line with the literature [6][7][8], ACV and iridocorneal angle were increased after LPI in our study.The mechanism of optic neuropathy in PACG has not been fully elucidated.However, mechanical compression in general is considered to be the main mechanism of PACG, especially in acute form.Excessively high IOP is claimed to cause apoptosis in ganglion cells and associated axons [9].The branches of the central retinal artery provide nutrients and oxygen to the inner retinal layers.The superficial retinal capillary plexus by these branches supply the RNFL, ganglion cell layer and inner plexiform layer [10].While RNFL consists of the axons of ganglion cells, GC-IPL consists of the dendrites of ganglion cells.Thus, the retinal ganglion cells receive most of their oxygen supply from the superficial retinal capillary plexus [11].A previous OCT angiography (OCTA) study showed that there was a positive correlation between parapapillary perfusion and the thicknesses of RNFL and GC-IPL in healthy population [12].However, Rao et al. [13] reported similar vessel densities in eyes with PAC compared to those of control eyes, but thinner RNFL thickness in superotemporal region in eyes with PAC.On top of that, they hypothesized that high IOP might affect RNFL measurements earlier than retinal vessel densities.Zha et al. [14] reported that RNFL was thicker in eyes with PACS than in healthy eyes.They stated that previous studies had different results in RNFL and RNFL could remain same or increased first then decrease late during an acute IOP spike episode.Due to the variable results in previous studies we assessed the change in RNFL thickness after LPI and found an improvement after LPI in patients with PACS.These results suggest that RNFL can be damaged before PAC develops, but this can be prevented by LPI.
In a longitudinal study (72 months) in eyes with PACS, the authors reported a 47% reduction in the risk of primary angle-closure or acute attack after LPI, and no long-term side effects of LPI [15].Thus, they stated that prophylactic LPI provides a modest benefit given the very low event rate observed and the reduced harm for most of the endpoints achieved over the period of performing an iridotomy.In three studies (153 eyes, 11-46 months follow-up) investigating the change in IOP after LPI in eyes with PACS, no increase in IOP was reported in any of the eyes [16][17][18].However, in one study including 239 eyes with a 56-months follow-up it was reported that 18% of eyes had increased IOP and 7% required further treatment [19].Studies evaluating the angle with gonioscopy have reported persistent angle closure ranging from 11 to 25% in eyes with PACS after LPI [20].However, side effects like increased IOP and permanent angle closure were not observed in our group, at least in the short-term follow-up period.
Limitations of the present study include its relatively small sample size, not measuring lens thickness and lens vault, short-term follow-up of the patients and the use of the Scheimpflug camera.In summary, ACV and iridocorneal angle increased in one week after LPI and remained stable at first month.One month after LPI foveal retinal thickness showed significant reduction, RNFL thicknesses of superior and temporal quadrants were increased.Our results suggest that LPI in patients with PACS provides improved retinal thickness and RNFL thickness, as well as anterior chamber parameters.Further studies conducted with spectral domain anterior segment-OCT, larger sample size and longer duration of follow-up will be more appropriate for validating of our findings.

Fig. 1
Fig. 1 Scheimpflug-Placido disc topographer images of a sample patient.The first image 1 shows a shallow peripheral anterior chamber and a narrow angle before laser peripheral

Table 1
Comparison

Table 2
Changes of intraocular pressure and topography findings of the patients with PACS after laser peripheral iridotomy PACS Primary angle-closure suspect, LPI laser peripheral iridotomy * and †: There was significant difference only in between pre-LPI and post-LPI at first week

Table 4
The mean retinal nerve fiber layer thickness values (µm) of the patients at baseline and two follow-up visits *: There was significant difference only in between pre-LPI and post-LPI at first month