Comparison of ultrasound cycloplasty and transscleral cyclophotocoagulation for refractory glaucoma in Chinese population

Glaucoma is an irreversible neurological blindness disease with a rising incidence annually [1]. Its major pathogenic factor is high intraocular pressure (IOP), thus lowering IOP is the only recognized method to delay its progression [2]. According to the surgeons’ experience and the patients’ conditions, which may include IOP, visual field defect, and optic nerve damage, medical therapy, lasers therapy or surgery can be selected to reduce IOP [3]. Glaucoma with poor prognosis after conventional surgery is collectively referred to as refractory glaucoma, such as glaucoma that fails after multiple filtering operations, neovascular glaucoma, glaucoma following vitrectomy and glaucoma secondary to uveitis, etc. For such glaucoma patients, especially those with poor eye conditions, poor visual function or even without visual function, cyclodestructive procedure is often adopted to reduce IOP, as well as to relieve ocular and periocular pain. In recent years, laser diode transscleral cyclophotocoagulation (TSCP) has proved to be an effective method for the treatment of refractory glaucoma and gradually become a standard treatment for refractory glaucoma [4‐6]. However, it still has serious complications, including loss of eyesight and even eyeball atrophy. Since the 1980s, ultrasound has been introduced in the treatment of glaucoma. In recent years, the development of high-intensity focused ultrasound technology has improved the accuracy of ultrasound cycloplasty (UCP) with a simplified therapeutic process [7]. The present study intends to compare the efficacy and complications between UCP and TSCP in treating refractory glaucoma, thereby providing references for clinical practice.

Refractory glaucoma represents a type of complex glaucoma that cannot be treated effectively using conventional filtering surgery and auxiliary anti-glaucoma agents. In the past, the standard therapeutic method was cyclocryotherapy. However, this approach exhibits considerable damage to the eye tissue and many complications and incurs significant pain to patients, which limits its application in clinical practice [8, 9]. Cyclodestructive surgery with LASER energy such as TSCP is a well-established alternative to cyclocryotherapy. UCP is a method that uses high intensity focused ultrasound (HIFU) to transmit power to the target organ, in which the ultrasound energy is converted into a thermal effect to coagulate the target organ without affecting the adjacent tissues [10, 11]. With the continuous improvement of the technology, UCP has come into the routine armamentarium of glaucoma surgeon. As in this study, we have shown that UCP had durable efficacy as laser coagulation in terms of IOP control in adult refractory glaucoma with less postoperative pain.

The entire UCP process takes only a few minutes. The operation is straightforward and incision-free, which results in low surgical risk and simple postoperative care [12, 13]. Preoperative evaluations include measuring the patient’s ocular axis, the white-to-white corneal diameter and the ciliary body size. These data may help the surgeons to select a proper probe. The number of treatment sectors should be determined based on the patient’s baseline IOP as mentioned. Relevant animal experiments have shown that it has a dual mechanism of reducing aqueous humour production and increasing aqueous humour outflow [14]. Besides, during UCP, the blood-aqueous water barrier is retained, which avoids the occurrence of severe inflammatory reactions. Histology has revealed that the thermal effects of ultrasound beams are sustainable and are safe for the retina [7, 15]. Earlier clinical studies on UCP have also shown its effectiveness and safety in treating glaucoma [16‐18]. A recent study comparing UCP with cyclocryotherapy in eyes with neovascular glaucoma confirmed safety advantage of UCP and equivalent efficacy [19].

TSCP has also been widely used in clinical practice as an alternative to cyclocryotherapy, and it is no longer limited to the treatment of end-stage glaucoma. It causes heat damage to the ciliary body through the thermal effect, resulting in coagulative necrosis of the pigment epithelium, matrix and reduced blood supply to the ciliary body, thus reduces the secretion of aqueous humour by the ciliary process. In addition, the contraction of the ciliary body after photocoagulation also increases the drainage of aqueous humour to a certain extent. Furthermore, photocoagulation of the ciliary body crown can pull the iris root back to reduce the trabecular meshwork obstruction [20, 21]. The TSCP process is simple and is also incision-free, with low surgical risk and easy postoperative care [22]. Intraoperatively, the number and range of photocoagulation should be determined according to the baseline IOP of the patients and the surgeon’s experience. However, the suitable laser energy, the best number and range of photocoagulation points remain inconclusive around the world [23‐25].

Results of the present study showed that both UCP and TSCP were effective in the treatment of refractory glaucoma. There were no significant differences in reducing IOP and the use of postoperative anti-glaucoma agents between the two groups. In terms of postoperative complications, UCP showed a lower pain score and a statistically insignificant but substantial trend of less mild complications. Both groups had no severe complications in our study, which echoed the safety of both modalities. Furthermore, two eyes were suffering declined visual acuity after TSCP compared with zero with UCP in our follow-up. These findings corroborate the idea of more accurate location and less nearby tissue injury with UCP procedure [26, 27].

Treatment range is a particularly important factor meriting considerations. M. Graber and colleagues reported their retrospective comparison of UCP with TSCP in refractory glaucoma in a French cohort, showing an inferior efficacy but fewer complications with UCP than with TSCP, which is slightly different from current results [28]. However, their treatment strategy was different from ours. For UCP, their treatment range was fixed to 6 sections, and for TSCP, they used higher pulse energy. In our practice, the strategy for both procedures should be personalized according to baseline IOP. In addition, a slight reduction of pulse energy in TSCP would prevent the eyes from severe complications. With the improvements in technology and techniques, UCP would achieve an efficacy equivalent to the traditional modalities.

The limitations of the present study include: (1) The sample size is relatively small with considerable heterogeneity, deriving from both glaucoma types and baseline IOP levels. However, we have balanced them between groups; (2) the follow-up time was short. All patients are still under follow-up. The long-term efficacy of the two procedures needs to be explored; and (3) as a retrospective study in nature, our results might be biased from the patient selection. Extrapolation should be cautious, and prospective studies should be done to confirm our findings.

In summary, UCP and TSCP are both safe, effective and repeatable treatment methods for refractory glaucoma in China. The UCP is more straightforward in operation, easier to perform, and causing fewer complications than TSCP. However, its long-term efficacy in refractory glaucoma patients remains to be determined. Thus, it could be selected with considering patients’ preference and surgeons’ experience.