MP-CPC has gained popularity as an effective and safe IOP-lowering glaucoma treatment. However, the precise mechanism of IOP reduction and the impact of MP-CPC on the anterior eye tissue have remained unclear. In this study, we used PS-OCT to analyze changes in scleral birefringence following MP-CPC. Our findings revealed a significant increase in birefringence in the laser-irradiated scleral area after MP-CPC (Fig. 2). Moreover, a statistically significant positive correlation between the rate of IOP reduction and the rate of birefringence increase was observed at 3 and 6 months after the procedure (Fig. 3a–d).
Birefringence is a phenomenon characterized by phase retardation when light waves penetrate birefringent materials.[17] Materials with dense structures and high orientation exhibit elevated birefringence. Collagen, known for its highly oriented structure, is a representative birefringent material in living organisms.[20] PS-OCT has been used to visualize various types of fibrosis-related scarring, such as dermal fibrosis, joint or tendon fibrosis, and gastrointestinal and lung fibrosis.[20–24] In ocular tissues, PS-OCT has been used to analyze birefringence in fibrous tissues that contain collagens with specific polarization properties, especially the cornea, sclera, and angle structures.[19, 25, 26] Liu et al.[20] recently demonstrated that the posterior scleral birefringence value was higher in myopic eyes and showed a positive correlation with longer axial length, especially in pathologic myopia. In eyes affected by high myopia, the myopic posterior sclera exhibits alterations in the arrangement of scleral collagen and reductions in interwoven fibers.[27, 28] These reports collectively suggest that higher birefringence can be associated with changes in collagen fiber microstructure as well as collagen fiber reorganization, which is consistent with the results of the present study.
Our prior research demonstrated fibrotic responses in subconjunctival and scleral tissues of rabbits following MP-CPC, even at relatively low laser power.[13] Other studies have also revealed a fibrotic response of the subconjunctival tissue following MP-CPC.[9] Indeed, an impact of MP-CPC on the conjunctiva and sclera is reasonable considering the reports of scleral thinning and persistent conjunctival hyperemia in real-world clinical practice following MP-CPC.[14, 15] Given the predominance of collagen in the sclera, the observed increase in birefringence following MP-CPC may have resulted from fibrotic reactions induced by MP-CPC or thermal energy generated by laser energy absorption, leading to collagen degeneration or reconstruction in the sclera.
Notably, the peak increase in scleral birefringence occurred 3 months after MP-CPC, aligning with the gradual progression of fibrotic responses (Fig. 2c). Although an increase in scleral birefringence was observed immediately after MP-CPC, and at 1 week and 1 month, this increase was not significantly correlated with IOP reduction. The observed trends in IOP reduction and medication scores after MP-CPC in our study were similar to those in a previous report from our institution and are consistent with previous reports from other institutions.[7, 18, 29, 30] This suggests that the MP-CPC procedures in the present study were conducted appropriately and highlights the possible importance of a sustained increase in scleral birefringence for effective IOP reduction.
Regarding the observed positive correlation between the rate of birefringence increase at 3 and 6 months after MP-CPC and the rate of IOP reduction (Fig. 3c, d), individual-patient variations may exist in the absorption of laser energy within the sclera, its conversion to thermal energy, and the subsequent scleral reactions. In clinical practice, MP-CPC does not uniformly yield identical IOP-lowering effects in all patients; instead, there are individual differences in both the efficacy and extent of IOP reduction.[7, 18, 29, 30] Consequently, significant changes in the polarization characteristics of the sclera may be more likely to occur when MP-CPC achieves a substantial IOP reduction. Moreover, MP-CPC might not be optimally executed in patients with limited IOP reduction. Factors such as improper laser positioning, variations in probe angles among patients, or complications (e.g., application of insufficient force during probe placement or the occurrence of sub-tenon anesthesia-induced conjunctival hemorrhage that absorbs the laser power) may lead to both milder collagen degeneration in the sclera and limited IOP reduction. In our study, multiple surgeons performed MP-CPC. Additionally, patients with glaucoma often exhibit ptosis and eyelid hardening due to topical prostaglandin analog treatment. These factors can further contribute to the variability in MP-CPC techniques across patients.[31, 32] The increase in scleral birefringence observed in this study may serve as a valuable tool for assessing the effectiveness of MP-CPC as well as a highly plausible explanation for the mechanisms of IOP reduction by this treatment.
This study had three main limitations. First, all patients were Japanese. Research has revealed variations in melanin content in the uvea among different racial groups. Caucasian eyes allow slightly more effective laser penetration of the sclera than Asian eyes, perhaps because there is less scattering and absorption caused by lower levels of pigmentation.[20, 33, 34] It is conceivable that the Japanese population has higher melanin content, potentially resulting in greater laser absorption during MP-CPC. Further investigations involving diverse racial groups are warranted. Second, PS-OCT measurements are fundamentally limited by the signal intensity. The sclera is a dense and highly scattering structure, and we could not explore the response of the tissue underneath the sclera because of the limited scan depth of PS-OCT. In addition, the alignment of collagen fibers determined by birefringence should be further investigated, possibly using animal models to explain the increased values. Third, we excluded patients requiring additional surgery or repeat MP-CPC during the 6-month observation period because we aimed to evaluate the effect of only one MP-CPC procedure. These exclusions may have introduced bias because such refractive cases are likely indicative of poor IOP reduction efficacy. Further studies are needed to explore the response in these cases.
In conclusion, our findings indicate an increase in scleral birefringence following MP-CPC, with a positive correlation between the rate of birefringence increase and the rate of IOP reduction. PS-OCT is emerging as a promising technique not only for evaluating MP-CPC efficacy but also for assessing post-procedural scleral remodeling.