Primary Outcomes of combined cataract extraction technique with ab-interno trabeculectomy Dual-Blade and Endoscopic cyclophotocoagulation in patients with primary open angle glaucoma

Purpose: To provide an update of primary outcomes of combined phacoemulsification technique with ab-interno trabeculectomy Dual Blade and Endoscopic cyclophotocoagulation (ECP) in patients with primary open angle glaucoma. Methods: Retrospective case series comprised 27 consecutive eyes, with open-angle glaucoma (POAG) and cataract with combined phacoemulsification, ab-interno trabeculectomy-Kahook Dual Blade and Endocyclophotocoagulation at Instituto de ojos Oftalmosalud, Lima, Perú, between April 2017 and May 2017. Inclusion criteria were Glaucoma patients with POAG from mild to severe, according to Glaucoma Grading Scale (HODAPP), cataract condition, treatment with two or more glaucoma medications and visual field defects continued worsen. Intraocular pressure (IOP), Best corrected visual acuity (BCVA) logMAR, and number of glaucoma medications were recorded before, and 1 day, 1 week, and 1, 3, 6 and 9 months after surgery. Defining succes as IOP <14 mmHg with or without medications. Results: A total of 27 cases of glaucoma eyes were included. The mean IOP was 17.0±3.7 mmHg preoperatively, 11.6±1.9mmHg at 6 months, and 11.4±1.8 mmHg at 9 months(P<0.001). There was a corresponding drop in glaucoma medications from 1.9±1.41 at mean to 0.56±1.05 at 9 months (P<0.001). Preoperative best corrected visual acuity (BCVA) showed and improvement preoperative value from 0.4± 0.4 LogMAR (p= 0.001) to 0.2 ± 0.4 logMAR at 9 months. The main complication was blood reflux intraoperatively(66.7%), resolved within a few days. The mean IOP was reduce 32.9% from baseline and the qualifed succes was 92.6% at 9 months. Conclusions: Cataract extraction with phacoemulsification combined with ab-interno


Background
In the elderly it is common to find in the same patient cataract and glaucoma, both of which can be treated at the same time with a combined surgical treatment that consists of phacoemulsification and glaucoma surgery to improve vision and avoid progression while improving cost-effectiveness 1 .
In the pathophysiology of open angle glaucoma is described a resistance of the outflow of aqueous humour, which is mainly in the juxtacanalicular portion of the trabecular meshwork; by performing an ab-interno trabeculectomy that disease portion is removed and the conventional outflow pathway is enhanced with posterior reduction of intraocular pressure (IOP) 2-5. Endoscopic cyclophotocoagulation is one of the safest armamentarium therapies for glaucoma; the ciliary processes are visualized directly and using diode laser energy treated precisely until shrinkage and whitening, this cause a reduction of aqueous humour production which decreases IOP effectively without the complications described for cycloablative procedures such as persistent hypotony, phthisis, inflammation or visual loss [6][7] .
Gold standard filtering surgery is associated with high rate of immediate and late complications as reported in the TVT study, for this reason, there is a trend to treat glaucoma patients with minimally invasive procedures when maximal tolerated medical therapy fails to control visual field loss in initial or moderate glaucoma.
In this study a combined treatment of Phacoemulfisication, ab-interno trabeculectomy and ECP was performed to treat uncontrolled POAG, with this combined glaucoma procedures double mechanism for reducing IOP is expected, the former increases aqueous outflow and the second reduces aqueous production; an update of the technique, reduction of IOP, Declaration of Helsinsky approved this retrospective study. We also obtained an informed consent from all patients after an explanation of the procedures to be used.
Inclusion Criteria: Glaucoma patients with uncontrolled POAG from mild to advanced, according to Glaucoma Grading Scale (HODAPP), cataract condition, treatment with two or more glaucoma medications; uncontrolled was defined as progression in at least 2 visual fields and/ or retinal nerve fibre layer thinning in spectral domain optical coherence tomography (sdOCT) Exclusion Criteria: history of glaucoma surgery, any subsequent glaucoma surgery in the follow-up period, narrow angles or closed angle glaucoma, neovascular, uveitic or other secondary glaucoma, retinal or neurophthalmic diseases.
The intraocular pressure (IOP), best corrected visual acuity (BCVA) LogMAR, and number of glaucoma medications were recorded before and at 1 day, 1 week, and 1, 3, 6 and 9 months after surgery. At each visit, the IOP was measured with a Goldmann applanation tonometer. The intra and postoperative complications were recorded. Qualified Success was defined as IOP <14 mmHg with or without glaucoma medication.

Surgical modified Technique
All procedures were performed by the same surgeon (JCI). First, Phacoemulsification and IOL implantation was performed using 2,2mm keratome and 1.20 mm side-port blade, the anterior chamber was filled with preservative-free lidocaine 1%, and an ophthalmic

Statistical Analysis
To compare the changes in IOP, according to the observation period, we used the nonparametric Friedman test, followed by a post-hoc multiple comparison test. For change in the number of glaucoma medications, the signed test for paired samples was used. The statistical tests we considered significant if p value was less than 0.05. The analysis was done with statistical software R, versión 3.4.3 (https://www.r-project.org/).
All eyes with POAG were classified into 3 groups according to Glaucoma Grading Scale (HODAPP): 10 (37%) eyes were mild, 10 (37%) eyes moderate, and 7 (25.9%) eyes advanced. All 3 categories had a reduction in IOP at 9 months follow-up, but multiple comparisons with Nemenyi test after Friedman test showed a statistically significant improvement from the third month (p=0,010) in the mild glaucoma group, from the nine month for the moderate glaucoma group (p=0.031) and without statistically significant improvement in the advanced glaucoma group in any follow-up time, this can be attributed for the smaller sample size of this group. The IOP in the mild glaucoma group reduced 7.1 mmHg, in the moderate glaucoma group the reduction was 4.2 mmHg, and in the advanced glaucoma group the reduction was 6.6 mmHg at 9 months (Figure 3).

Intraocular pressure
The mean preoperative IOP was 17 week, 1, 3, 6, and 9 month respectively, (p<0.001). The mean IOP was reduced by 32.9% from baseline and the qualified success was 77.8% in the first month and 92.6% at 9 months follow-up ( Figure 4).

Visual acuity outcomes
Preoperative best corrected visual acuity (BCVA) showed and improvement from 0.4± 0.4 LogMAR to 0.2 ± 0.4 LogMAR at 9 months with no statistically significant differences.

Discussion
This retrospective study of patients with uncontrolled POAG at different stages of the disease, showed a reduction of IOP, glaucoma medication with stable best corrected visual acuity at 9 months follow-up when a combined minimally invasive procedure consisting in phaco, ab-interno trabeculectomy and ECP is performed. In our combined study, the mean IOP was reduced 32.9% from baseline and the qualified success was 92.6% at 9 months. Morales et al., with Phaco/ECP reported the results obtained for IOP lowering to 15 mmHg and report an absolute success of 11.9% and a qualified success of 72.3% 14 . A retrospective Brazilian study on 247 patients, defined success based on IOP 21mm Hg, with 3 years of follow-up reported the corresponding rates were 55.7% for absolute success and 90.7% for qualified success 15 .
By the other side, The Kahook dual-blade shows promise as a refined and economical device for the treatment of glaucoma 3 . Salinas et al. studied 53 eyes and the mean IOP decreased from 18.4±6.1 mm Hg at baseline to 13.9±3.5 mm Hg at 6 months follow-up (23.9% reduction, p<0.001); At 6 months, 63.5% achieved an IOP ≤14 mmHg and the mean number of glaucoma medications was reduced 1.2±1.3 compared to baseline (P<0.001), a reduction of 36.6% was found 16 . In our study with the combined procedures the mean IOP decreased from 17.0±3.7 mmHg at baseline to 11.6±1.9mmHg at 6 months (31.7% reduction, P<0.001), and an IOP of 11.4±1.8 mmHg at 9 months (32.9% reduction, P<0.001). The IOP was significantly reduced (P<0.001). The mean number of glaucoma medications was reduced 0.56±1.05 (29.5% reduction) from baseline to 9 months statistically significant (P<0.001). groups depending on glaucoma severity. The group with the higher glaucoma severity index (GI) has an IOP reduction of 2.34±0.19 mmHg more than the group with lower glaucoma severity index 18 . In our study, all subcategories showed a significant reduction in IOP 9 months after combined surgery. The mild group drop the IOP from 18.9 to 11.8mmHg, the moderate group from 15.3 to 11.1 mmHg, and advanced group from 17.4 to 10.8 mmHg.
The review and meta-analysis of Phaco/ECP from Kaplowitz et al., shows the most common complication is hyphema similar to the present study, the second most common complication was peripheral anterior synechiae in 24% of the patients. The most serious complication was hypotony 0.09% of all reposted cases 12 . SooHoo et al., with the use of Trabectome, all patients had transitory hyphema that resolved after 6.4 days. 3 In our study, the most common complications include hyphema 18 (66.7%), intraoperative blending was observed in all cases, corneal edema (7.4%), transient hypotony (3,7%) and temporary IOP spike (6%) with no vision sequelae and no need for reoperations.
The main weakness of the study was the retrospective nature, low sample included and no control group.

Conclusions
Cataract extraction with phacoemulsification combined with ab interno trabeculectomy and endoscopic cyclophotocoagulation effectively reduced IOP and dependence on glaucoma medication with a very safety profile and stable best corrected visual acuity in patients with uncontrolled open angle glaucoma. Further study is needed comparing this combination treatment with the gold standard filtration surgery.

Ethics approval and consent to participate
The study was approved by the Institutional Review Board Statement, the patient consented the publication of the case in writing. This report does not contain any personal information that could lead to the identification of the patient.

Consent for publication
We obtained a consent for data publication from all patients.

Avalability of data and materials
The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare to have no competing interests: JCI; LCR; JMS; NA; BRL.

Funding
No funding or grant support.