Treatment effect of LPI combined with LPIp
In PAC, the iris blocks the channel draining aqueous humour, thereby causing acute or chronic IOP increases. Previous PAC treatment mainly comprised LPI, which uses a laser to establish a new drainage channel in the iris to relieve the blockage. However, a previous study found that iridotomy alone does not improve aqueous humour drainage in more than one-third of all patients. They need additionally LPIp, and LPI combined with LPIp can more effectively relieve peripheral anterior adhesions than LPI alone [4]. Therefore, in this study, we used LPI combined with LPIp to treat PACS and PAC in patients with plateau iris or hypertrophic peripheral iris.
LPIp was first proposed in the 1970s [9], but the type of laser used at that time had strong thermal effects causing damage. After continuous improvement, researchers tried to treat PACG with various light sources including argon, krypton, and diode lasers. At present, argon lasers are mainly used for treatment [10–12]. During LPIp, it is necessary to guide 1–2 light spots at the root of the iris using contact lenses [13]. The size of the laser light spot is 150 to 500 µm, the energy varies from 100 to 300 mW, and the exposure time ranges from 0.4 to 0.5 s [14]. LPIp causes contraction of the peripheral iris matrix thereby physically pulling the trabecular meshwork to open the chamber angle. Such traction is effective for adhesive closures and fresh peripheral anterior adhesions [15,16]. Histopathological studies found that laser light energy, which is absorbed by iris melanocytes and collagen around blood vessels, dissipates heat to cause thermal damage. Then, fibroblasts proliferate at the site of the thermal damage, resulting in further contraction of the cell membrane [12]. As the matrix in the laser-irradiated iris area shrinks, the iris becomes thinner, which increases the distance between the iris and trabecular meshwork, thereby reducing the probability of angle closure caused by peripheral iris accumulation [17]. This suggests that LPI mainly relieves pupil block, but LPIp is helpful to resolve chronic angle closure caused by other mechanisms including plateau iris [15,18].
After LPI combined with LPIp treatment, the IOP of all enrolled patients was significantly decreased compared to that before surgery. The results regarding the IOP-lowering effects of LPIp differ among published studies. Lee et al. found that the IOP values of patients treated with either LPI alone or LPI combined with LPIp were not significantly decreased at 1 h, 1 day, 1 week, 1 month, and 3 months after surgery [19], but this was related to low preoperative IOP values of the enrolled patients. A study with high IOP values at baseline confirmed that both LPI alone and LPI combined with LPIp significantly reduced IOP at 12 months after surgery [20]. The current study also compared the IOP within each group before and after surgery and found that the IOP in the high-energy group was significantly decreased after surgery, whereas the IOP in the low-energy group was not. This may be due to the thermal contraction of the iris generated by laser energy, which broadens the narrow or occluded angle and can at the same time pull the scleral spur backwards. The Schlemm channel is widened from a fissure to a circular shape, generating negative pressure in the Schlemm channel and redistributing aqueous humour from the anterior chamber to the Schlemm channel. The iris contraction can also affect the trabecular meshwork, widening its gap, enlarging the mesh, and facilitating the outflow of aqueous humour. Higher energy can generate greater traction force on the trabecular meshwork, make the mesh larger, and reduce the resistance for aqueous humour outflow similar to the mechanism by which cataract surgery and parasympathetic drugs reduce the IOP [21,22]. However, this difference is not obvious when comparing IOP reductions in each group. Some studies believe that although an IOP reduction during daytime may not be obvious after LPIp treatment, it can significantly reduce the positive rates in dark-room and prone tests, indicating its significance to maintain a stable IOP at night [10]. Therefore, in the future, we should also observe 24-h IOP fluctuations before and after surgery to evaluate the effectiveness of LPIp with different locations and energy levels more comprehensively.
Our study results showed that after LPI combined with LPIp, the central anterior chamber depth was not significantly increased, whereas the peripheral AOD, TIA, and anterior chamber volume were. Numerous studies have shown that LPI alone or combined with LPIp can deepen the central anterior chamber [19]. Consistent with our current results, the study by Bourne et al. also confirmed that after LPIp, the AOD 500/750 and TIA 500/750 values were increased [23]. It is generally believed that aqueous humour can directly flow from the posterior chamber to the anterior chamber after LPI for PAC or PACS in patients with pupil block as the main pathogenic factor. Thus, reducing the pressure difference between the anterior and posterior chambers can flatten the bulging iris and increase the depth of the central anterior chamber [24]. Our analysis demonstrated that the reason for this difference is that all study groups comprise patients with plateau iris or hypertrophic peripheral iris which is different from the inclusion criteria of previous studies. This can explain why among our study groups, the depth of the central anterior chamber is not significantly increased after laser treatment, whereas the peripheral anterior chamber is deepened, the chamber angle is increased, and the volume of the anterior chamber is significantly increased.
However, when comparing every two groups, the anterior chamber volume of HENP was larger than that of HEFP. This indicates that the higher energy is and the closer the laser point is to the periphery, the stronger the effect is on the increase in anterior chamber volume. When the laser energy is low, the selection of the spot position does not affect the anterior chamber volume. At present, clinical research has not reported on this phenomenon, but an animal experiment came to the same conclusion as the current study [25]. This might be due to the laser-induced thermal contraction of the iris widening the narrow or occluded angle. The higher the laser energy, the more significant the effect of the spot position on the efficacy, i.e., the closer the laser spot is to the periphery, the stronger the force of the facula contraction on the opening of the chamber angle (but not the force of the pupil opening).
Safety of LPIp combined with LPI
The reported complications of LPI combined with LPIp include hyphema in the anterior chamber, transiently increased IOP, decreased corneal endothelial cell count, decreased vision, transient atelectasis pupil, corneal endothelial cell burn, persistent uveitis, and malignant glaucoma. The incidence of various complications differs among studies. Lee et al. [19] reported that 4% of patients had anterior chamber haemorrhage, whereas Sun et al. [20] reported that iris haemorrhage was observed in 12.3% and 11.7% of patients with LPI alone and LPI combined with LPIp, respectively. Another common complication is transient ocular hypertension. Sun et al. found that in the LPI group, IOP was transiently increased in 16.9% of patients, and this percentage was even higher in the LPI plus LPIp group with 17.3%. The study by Lee et al. showed that transiently increased IOP was as high as 33%[19]. However, the definitions of transiently increased IOP were different between the two studies. The former defined that the IOP exceeded 30 mmHg, whereas the latter defined transiently elevated IOP as an increase by more than 5 mmHg compared to the preoperative value. In our study, none of these serious complications occurred. We found that the pupil diameter in each group was not significantly changed after surgery compared with the value before surgery. Only HEFP had a stronger effect on pupil diameter increase than group LENP. This suggests that if LPIp is carried out with high laser energy, the laser spot should be close to the periphery to avoid an increase in pupil diameter and the accompanying photophobia or other discomforts.
Comparison of the anterior chamber angle morphology
We can directly observe the structure of the anterior chamber angle through gonioscopy, which is regarded as the gold standard for the evaluation of this angle. However, this examination is subjective, requires from the examiner some experience, and cannot accurately quantify the angle. Furthermore, the lens must have contact with the cornea, which is difficult to achieve for patients who are at risk of infection or unable to cooperate. UBM can provide more accurate images of both anterior and posterior chamber morphology, but patients need to be examined in a supine position. The eye cup needs to be placed in the conjunctival sac, which increases the infection risk and decreases comfort during the examination [26,27]. The Pentacam is a good tool for anterior segment imaging and quantitative measurements. It can quickly calculate anterior chamber depth, pupil diameter, anterior chamber volume, and other parameters, but the accuracy of anterior chamber angle calculation is not good in patients with plateau iris [28]. AS-OCT is a fast and noncontact method for imaging structures of the anterior chamber angle. The sensitivity of AS-OCT for detecting angle closure is higher than that of gonioscopy, leading to a higher detection rate than gonioscopy [29].
Our research has some limitations. First, we did not conduct dynamic follow-ups of the enrolled patients. Only the last follow-up of more than 6 months was used for statistical analyses. In future research, we should conduct dynamic follow-ups. Second, at the initial stage of enrolment, the patients were randomly enrolled, and the baseline conditions of the patients were not matched, so the baseline levels slightly differed among groups. However, as we also compared pre- and postoperative changes within each group, the research results still have credibility. In the future, we will match the baseline conditions of patients to obtain more accurate results.
In summary, LPI combined with LPIp can effectively reduce IOP, increase anterior chamber volume, increase AOD, and widen TIA. Intraoperatively, high-energy laser spots can obtain the best effect and safety when located one spot diameter from the scleral process. Swept AS-OCT can safely and effectively quantify the structure of the anterior chamber angle.