Correlation between intraocular pressure reduction and anterior chamber aqueous flare after micropulse transscleral cyclophotocoagulation

Glaucoma is the leading cause of blindness worldwide. The damage to the optic nerve and visual field caused by glaucoma is progressive and irreversible [1]. The only reliable evidence-based treatment for glaucoma is the lowering of intraocular pressure (IOP). Treatment options include medical, laser, and surgical therapies [2, 3]. Traditionally used continuous-wave transscleral cyclophotocoagulation (CW-CPC) is an effective method to lower IOP, but patients can develop serious complications, such as phthisis bulbi [4, 5]. Micropulse transscleral cyclophotocoagulation (MP-CPC) was approved by the US Food and Drug Administration in 2015 as a glaucoma treatment technique. MP-CPC is presumed to be a safe procedure as a result of minimizing thermal coagulation of adjacent tissues and repeating the on/off laser irradiation cycle in microseconds. However, the mechanism of lowering IOP has not been fully explained [4, 5]. MP-CPC causes anterior chamber inflammation; however, a relationship with reduced IOP has not been reported [4‐6].

The numbers of cells and the intensity of the flare, reflecting protein concentrations, increase when inflammation occurs in the anterior chamber [7, 8]. A laser flare meter has been developed in Japan to quantitate aqueous flare and cells in the anterior chamber, and the measured values are highly correlated with the numbers of anterior chamber cells and the aqueous flare observed by slit-lamp [7, 8]. Aqueous flare indicates an increase in aqueous humor protein concentrations. When the blood-ocular barriers are disrupted due to inflammation, serum protein leaks into the aqueous humor, and aqueous flare increases [8]. A laser flare meter projects a laser beam into the anterior chamber, and aqueous flare is measured using a photomultiplier to detect scattering of the laser beam by protein in the aqueous humor [7, 8]. These findings motivated us to analyze the correlation between reduced IOP and elevated aqueous flare measured by a laser flare meter after MP-CPC. To the best of our knowledge, this is the first report investigating the relationship between IOP and aqueous flare after MP-CPC. If there were a correlation between inflammation and IOP reduction, it would help elucidate the mechanism of lowering IOP by MP-CPC for the prediction of postoperative IOP.

All investigations adhered to the tenets of the Declaration of Helsinki. This study was approved by the Ethics Committee of Kumamoto University. Research information was disclosed to the patients on our website, and the freedom to refuse research use was guaranteed. This retrospective study included consecutive patients with refractory glaucoma who underwent MP-CPC between November 2018 and October 2020 at Kumamoto University Hospital. We excluded the cases in which aqueous flare could not be measured due to poor corneal transparency or poor fixation. We also excluded the case in which additional surgery was performed within 4 weeks. The aqueous flare values of all eyes were measured before and after surgery. MP-CPC was performed using a CYCLO G6™ micropulse P3 probe (IRIDEX, Mountain View, CA, USA) according to the manufacturer’s instructions. Briefly, the machine was preset to a power of 2,000 mW and a duty cycle of 31.3 %. After sub-Tenon’s anesthesia, the MP-CPC probe was applied by continuous sliding for 10–20 s per one-way, 80 s in total per hemisphere, avoiding the filtering bleb and the glaucoma drainage device (all cases were Baerveldt glaucoma implant). After the surgery, 1.5 % levofloxacin eye drops and 0.1 % fluorometholone eye drops were used for 1 week. However, in patients with excess postoperative inflammation, the fluorometholone eye drops were continued for more than 1 week or switched to betamethasone until the inflammation subsided. Patients who underwent additional surgery for reasons such as poor IOP reduction were excluded from the analysis after that time point. The IOP and aqueous flare values were measured preoperatively and at 1, 4, and 12 weeks after surgery. Most IOP readings were measured via Goldman applanation tonometry (GAT). The IOP in two eyes were measured using iCare rebound tonometry (Icare Finland Oy, Helsinki, Finland), because the IOP in these eyes could not be measured by GAT. The aqueous flare values were measured using an FM-700 laser flare meter (KOWA Co., Nagoya, Japan). Visual acuity was measured in the form of decimal visual acuity with the Landolt chart and converted into the logarithm of the minimum angle of resolution (LogMAR) scale, where counting fingers (CF), hand motion (HM), light perception (LP), and no light perception (NLP) were assigned values of 2.1, 2.4, 2.7, and 3.0, respectively [9]. The visual field of patients with good fixation were examined using a Humphrey Field Analyzer (Carl Zeiss Meditec, Dublin, CA, USA). The anterior segment was evaluated using slit-lamp biomicroscopy, and the posterior segment was evaluated using indirect ophthalmoscopy and spectral-domain optical coherence tomography (SD-OCT). History of smoking was queried on the questionnaire. Surgical success was defined as an attained IOP reading between 5 and 21 mmHg and > 20 % IOP reduction at 12 weeks after MP-CPC, compared with the baseline without the addition of other IOP reduction therapies. Correlations between the percentage IOP reduction [(preoperative IOP − postoperative IOP) / preoperative IOP] and elevated aqueous flare (postoperative flare − preoperative flare) were estimated by calculating Spearman’s rank correlation coefficient. A P-value < 0.05 was considered significant.