Acute primary angle closure is a potentially blinding ocular condition, occurring with high incidence in East Asians.[5,6] It has been reported that the number of PACG patients is expected to increase to 34 million people by 2040. The primary goals of APAC treatment include relieving pupil block, opening the anterior chamber angle, and reducing the IOP. Laser peripheral iridotomy is the first-line therapy in eyes with primary angle-closure disease, but eyes with APAC are unsuitable for immediate laser peripheral iridotomy because of corneal edema, iris hyperemia, and a shallow anterior chamber.[9,10] Topical and systemic IOP-lowering medications, which are used as a first-line drug usually, involve a topical ß-blocker, topical miotic agent, carbonic anhydrase inhibitor, oral hyperosmotic agent, and intravenous hyperosmotic agent.
Brinzolamide eye drops are a classic drug for treating open-angle glaucoma and are also a commonly used drug in the treatment of PACG. However, this study found no statistically significant difference between the brinzolamide group and placebo group in any stage of the sequential APAC treatment. There are several possible reasons for this finding: (1) In terms of pathogenesis, in the case of acute angle closure, brinzolamide can only reduce the generation of aqueous humor and has no effect on the aqueous humor outflow. In other words, brinzolamide only creates conditions for the action of pilocarpine, leading to its limited effect on the therapeutic effectiveness of APAC. (2) In terms of drug effect, brinzolamide has been known to reduce IOP by less than 10 mmHg in the treatment of open-angle glaucoma. Corneal edema may affect brinzolamide absorption to some extent, and the frequent use of pilocarpine may elute brinzolamide and reduce its concentration. However, in this study, the initial IOP of APAC was greater than 40 mmHg, which made the IOP-lowering effect of brinzolamide seem smaller. (3) In terms of sequential treatment, the time to achieve successful treatment is an important index for evaluating the efficiency of emergency rescue. Both ACP and ALPI significantly reduced the IOP more rapidly than brinzolamide did. Six hours after beginning treatment, brinzolamide had just reached the peak of drug action, and ACP stepped in. However, subsequent remission depended more on pupil constriction than reduction of IOP. In other words, the application of ACP and ALPI reduced the need for brinzolamide.
The target IOP varies during the different stages of different types of glaucoma. In this study, the target IOP for successful treatment was set at <30 mmHg instead of 21 mmHg because this criterion was used to determine whether the treatment plan needed to be adjusted. When the corneal edema subsided and the pupil diameter narrowed to less than 4 mm, the IOP generally continued to decline. Even if the IOP had not dropped below 21 mmHg, there was no need for ACP or ALPI. In addition, we used pupil diameter and the degree of corneal edema as the criteria for successful treatment. The degree of corneal edema is often a reflection of the IOP levels, whereas a reduction in the pupil diameter represents the elimination of pupil block and atrial angle closure.
Emergency surgery is not the primary choice for APAC treatment because of its associated complications. The evidence is more abundant for antiglaucoma agents, ACP, and ALPI; the latter two are invasive treatments. Taking effectiveness and safety into consideration, the treatment scheme applied in this study was the sequential application of antiglaucoma agents, ACP, and ALPI. Pilocarpine eye drops were used throughout the entire treatment process. We demonstrated in this study that the vast majority of eyes emerged from the crisis within 12 hours.
The mechanisms of action of ACP and ALPI are also distinctly different: ACP alone reduces the IOP only temporarily, and APAC may recur if the pupil block is not resolved promptly. Meanwhile, ALPI mechanically pulls open the closed drainage angle, thereby reestablishing aqueous outﬂow through the normal drainage channels. It may be associated with potential risks, such as corneal burn and corneal endothelial cell damage. Furthermore, laser access to the peripheral iris may be obscured in some patients by media opacities, such as corneal edema, arcus senilis, or pterygium. There is no report on APAC treated with ALPI alone or ACP alone. In our study, ACP was able to rapidly reduce corneal edema and provide transparent optical pathways for ALPI.
In this research, the patients generally, but not always, had improved VA after treatment. Some patients were in remission, but their VA did not improve because of unrecovered corneal opacity. However, while other patients had high IOP levels, their corneas were transparent, and their VA was good. More research is needed on the specific mechanisms that affect VA.
The study still had some limitations. First, although brinzolamide is commonly used to treat PACG, open-angle glaucoma is a main indication for it, which may have affected the results. Second, there is no accurate, accepted test for visual field, but a patient's visual field is a direct indicator of disease progression. Therefore, we evaluated the therapeutic effect of the drug by the change of IOP. Finally, even without considering the cost burden, the application of brinzolamide is also associated with the following problems: APAC mainly occurs in the middle/elderly population, for whom the adverse reactions of electrolyte disorder have always been a clinical risk that cannot be ignored. During the follow-up observation after achieving control of APAC, the false appearance of low IOP caused by brinzolamide often affected the evaluation of the disease.
Based on this study’s results, we believe that in hospitals where ACP and ALPI can be performed, adding brinzolamide may be appropriate for patients with a first episode of APAC. However, brinzolamide should not be used as a first-line drug.