Abstract
Introduction: Glaucoma is a chronic, progressive disease of the optic nerve that can cause vision loss and blindness. High-frequency deep sclerotomy (HFDS) is a novel ab interno procedure used to lower intraocular pressure (IOP). This study aims at examining hypotensive effects of HFDS in patients with medically uncontrolled primary open-angle glaucoma (POAG). Methods: 23 patients (23 eyes) participated in this study. They were all affected by POAG and used maximum prescribed medical therapy. It is important to note that the target IOP was not detected in any study participant. The target IOP is the highest IOP value at which no new damages of the optic nerve occur. The procedure was performed with a custom-made, high-frequency dissection probe by applying bipolar current of 500 kHz. Six pockets (1 mm deep, 0.3 mm high, and 6 mm wide) were made ab interno in nasal sclera (through trabecular meshwork and Schlemm’s canal). Tobramycin/dexamethasone and pilocarpine eye drops were administered postoperatively for a month. Results: The mean value of the base IOP had been 25.6 mm Hg before the procedure. Significant complications were not recorded either during the surgery or in a postoperative follow-up period. The average IOP for our patients reduced by 8.6 mm Hg (33.6%) after a year. The mean value of the instilled anti-glaucoma eye drops had been 2.78 (SD = 0.45) before the HFDS and 0.61 (SD = 1.04) at the end of the research. The target IOP was not achieved in five cases (21.7% of our sample). Discussion/Conclusion: This study presents the data on our first surgical experience with HFDS that was conducted on 23 patients who had medically uncontrolled POAG. The results indicate that HFDS is safe and efficient in reducing IOP.
Introduction
Glaucoma is a chronic, progressive disease of the optic nerve that can result in vision loss and blindness if untreated [1]. The progression of the disease can be retarded by reducing intraocular pressure (IOP) [2]. IOP can be reduced via medical, surgical, and laser treatments.
Trabeculectomy has been a “gold standard” in surgical treatments of glaucoma for more than 40 years. In this surgical procedure, an ostium is created into the anterior chamber that allows aqueous flow to subconjunctival space, which finally results in IOP reduction [3‒7]. This procedure is associated with numerous complications that can compromise postoperative results. The complications include, inter alia, corneal epithelial defect, hyphema, bleb leakage, shallow anterior chamber, choroidal detachment, and endophthalmitis [3]. Therefore, according to glaucoma treatment guidelines, a surgical treatment should be the third stage in the treatment paradigm; it can be used as the first step but only in some late-stage glaucoma cases [4]. Since the early eighties, antimetabolites mitomycin C and 5-fluorouracil have been used to facilitate post-trabeculectomy recovery, i.e., a wound healing process, and to reduce the risks of postoperative scaring and bleb failure [8‒11]. They have provided similar results in augmenting trabeculectomy effectiveness [12, 13]. Other surgical methods, such as deep sclerectomy, have been also used in treating glaucoma. In comparison to trabeculectomy, deep sclerotomy results in lower IOP reductions but leads to fewer complications [14, 15].
During the recent years, glaucoma surgery has been evolving toward minimally invasive surgical techniques that are supposed to be more safe, efficient, and predictable than their predecessors. These minimally invasive glaucoma surgeries (MIGSs), which include limited manipulation of conjunctival and scleral tissue, have had favorable outcomes in lowering IOP. MIGS seems to be a more suitable solution than trabeculectomy when it comes to surgery durations and their safety. However, trabeculectomy is still more successful in terms of IOP decrease. The brevity and safety of MIGS procedures with respect to traditional surgical procedures makes them a more suitable solution, especially when glaucoma is treated surgically concurrently with cataract. The advantages of MIGS could move surgery as one of the first stages in the glaucoma treatment paradigm [15]. One of these relatively novel MIGS techniques for decreasing IOP is high-frequency deep sclerotomy (HFDS).
This study aims at examining the hypotensive effects of HFDS in patients with medically uncontrolled primary open-angle glaucoma (POAG) during the annual follow-up period. There have been only a few studies about the effectiveness of this surgical procedure so far. In addition, these have been our first patients who were treated by HFDS.
Materials and Methods
Twenty-three patients (23 eyes) treated with HFDS were followed for a year after the surgical procedure and regularly examined. All patients signed informed consents for participating in this study. The study was granted the approval by the Institutional Review Board and the Ethics Committee. The study was conducted from January 2016 until January 2017 at the Clinic of Ophthalmology, Medical Military Academy, Belgrade, Serbia.
All participants had been diagnosed with POAG prior to the procedure. The disease was not under control although the patients had been using the maximal tolerated anti-glaucoma therapy. Maximal tolerated medical therapy can be defined as the maximum quantity of anti-glaucoma medication that can be administered to a given patient. It is variable because some patients do not take maximal medical therapy due to the occurrence of irritations, allergies to one or more components of a medication, or because it is believed that additional eye drops would not help in lowering IOP.
All baseline characteristics about the patients were recorded: age, gender, diagnosis, and the number and type of used medications. Patients’ IOP was measured at least twice before the procedure in order to obtain the mean value that would be further used as a baseline IOP. IOP was measured with Goldmann applanation tonometer. The preoperative assessment also included ophthalmic examination, Snellen visual acuity (VA) testing, slit-lamp examination, gonioscopy of anterior chamber width, pigmentation assessment, fundoscopy (including the assessment of a cup-to-disc and pallor-to-disc ratio), and visual field testing.
The inclusion criteria for this study were that the patients with open-angle glaucoma had not reached the target IOP despite the maximal tolerated medical therapy. In addition, the age limit for the participation in this study was set at above 18. The exclusions criteria were congenital glaucoma, angle closure glaucoma of any type, secondary glaucoma, advanced-stage glaucoma, and previous glaucoma surgery. The patients who had not been followed for 12 months before the surgery were also not included in the study.
Surgical Technique
This ab interno procedure requires only two 1.2 mm incisions. The custom-made, high-frequency probe was used with the bipolar current of 500 kHz. 19-Gauge probe used here has a 0.3 × 1 mm tip. Six pockets were made ab interno in nasal sclera, moving through trabecular meshwork and a Schlemm’s canal. The dimensions of the pockets were as follows: 1 mm in depth, 0.3 mm in height, and 0.6 mm in width. The modulated current generates temperatures of approximately 130°C at the probe tip. The setup provides high-frequency power dissipation in the close vicinity of the tip. The collateral or local heating is applied as a rotational ellipsoid, so the heating of the tissue is very limited. The diathermic tip creates deep sclerotomy which enables aqueous flow to a scleral layer and creates an additional route for the drainage of aqueous humor [16].
Two clear corneal incisions were made in temporal and nasal upper quadrants. Similarly to a cataract surgery, they were 120° apart. High-density, cohesive ophthalmic viscoelastic device was then injected to fill anterior chambers. The high-frequency diathermic probe was inserted through the temporal corneal incision. 4-Mirror gonioscopic lens was used for the visual inspection of the target zone (the opposite iridocorneal angle). Via trabecular meshwork and Schlemm’s canal, the high-frequency tip penetrated nasally up to 1 mm into sclera, forming a deep sclerotomy (0.3 mm high and 0.6 wide) [16]. The same procedure was repeated for all six pockets. Bimanual irrigation/aspiration was used to evacuate ophthalmic viscoelastic device from the anterior chamber. Tobramycin/dexamethasone eye drops (Tobradex®, Alcon-couvreur, Belgium) were administered four times a day and pilocarpine (Pilocarpin®, Pharmacy Zajecar, Serbia) eye drops three times a day for 1 month after the surgery.
Follow-Up
The postoperative follow-up procedure included regular check-up visits: 1 day, 1 week, 1 month, and then 3, 6, and 12 months after the surgery. During these six visits, IOP and VA were measured and recorded, and the anterior segment was examined with a slit lamp. All major and minor complications and complaints were recorded and treated appropriately. The number and type of anti-glaucoma medications used by each patient was also recorded.
The data were analyzed with SPSS statistical software (version 22). A p value of < 0.05 was considered as statistically significant.
Results
This paper presents the results of the prospective, nonrandomized, interventional cohort study conducted at our institution in order to assess the response to HFDS according to age, gender, and baseline IOP. The baseline characteristics of the patients are presented in Table 1. The average age was 72.78 (standard deviation [SD] = 5.72) and the baseline IOP amounted to 25.61 (SD = 4.87).
During the first check-ups (1 day after the HFDS), the mean IOP value dropped to 16.52 (SD = 6.01). It equaled 21.78 (SD = 6.93) a month after the surgery and then slightly decreased to 21.35 (SD = 5.09) a month after the procedure.
The mean IOP was 17.64 mm Hg (SD = 4.19) during the check-up visits that took place 3 months after the HFDS had been performed. At this point, 1 patient was excluded from the study due to the uncontrolled IOP. In this particular case, oral anti-glaucoma medications were administered to the patient who later underwent trabeculectomy. As compared to the preoperative values, no reduction in VA was detected in the remaining patients.
The mean IOP was 17.37 (SD = 3.70) during the next regular visits (6 months after the surgery). One more patient was excluded from the study and trabeculectomy had to be performed. Between this visit and the one that took place 12 months after the procedure, 3 more patients were excluded from the study due to unregulated IOP. They underwent filtration surgery. However, the IOP values kept decreasing in the remaining patients. The average IOP was 17.00 (SD = 2.25) a year after the surgery. All results are presented in Table 2.
As Table 3 demonstrates, the IOP values predominantly decreased during the first 3 months after the HFDS was performed. The measures obtained 6 and 12 months after the procedure indicate slower pace of IOP reductions than those recorded up to 3 months after the surgery. The mean IOP values are presented in Figure 1.
The paired-samples T test was used to compare the mean values of the baseline IOP and the IOP measured 12 months after the surgery. The difference is highly statistically significant (p < 0.001).
Satisfying results were detected in 18 eyes (78.26%) a year after the surgery. Five patients had to undergo conventional surgical treatments. The data on these patients are excluded here because they could not participate in the study until its end.
We defined the complete success rate as IOP ≤21 mm Hg without IOP-lowering medications and the qualified success as IOP ≤21 mm Hg with IOP-lowering medications. The first requirement was fulfilled in 12 cases (52.17%) and the latter in 6 cases (26.09%). The number of the needed medications decreased from the average preoperative value (2.78) to 0.61 in 12 months.
We encountered quite a few complications during the follow-up period. The transient rise of IOP above the recorded preoperative values was detected in 7 eyes (30.43%). Peripheral anterior synechiae (PAS) was detected at the scleral openings of the patients who needed trabeculectomy. PAS was not observed in other patients with the postoperative IOP increase who responded well to topical medications. Only minor complications occurred during and after the surgery. There were no cases with significant postoperative hypotony and shallow or flat anterior chamber. Hyphema was detected in only one case. It resolved before the visit which took place 7 days after the surgery.
Discussion
This paper presents the results on HFDS efficiency in treating glaucoma. The patients who participated in this study were the first glaucoma cases in which we used this relatively new surgical technique. In our opinion, the learning curve is quite steep because doing surgery with goniolens requires time and practice. At least some complications that resulted in PAS formation occurred due to our relative inexperience. That is, iris was accidentally touched by the diatermic probe. In most cases, the sclerotomies created during the HFDS surgery were visible with goniolens.
Although the success rate we achieved (78%) was slightly worse than that reported by other authors [16], it is still comparable with other MIGS techniques. Having IOP reduced by 33% in 12 months is a satisfying result. Insufficient experience with this novel method is probably one of the main reasons for not obtaining better success rates.
A few complications were detected in the postoperative period. All patients who underwent trabeculectomy eventually had favorable IOP levels, so it seems that HFDS that had been performed prior had no negative effects on the success of trabeculectomy. Since conjunctiva is not damaged during HFDS, HFDS is generally not expected to hinder the outcomes of trabeculectomy.
In an earlier study, Pajic et al. [16] present their results on 53 POAG patients who underwent HFDS and were followed for the next 72 months. Their results reveal a significant decrease in IOP during the given time period – from 25.6 to 14.7 mm Hg. The satisfying results are observed in 79.2% of the cases and the authors did not report any significant complications.
Our results are similar to the findings obtained for other novel surgical methods for treating glaucoma. Maeda et al. [17] examined the surgical outcomes of Trabectome in 80 eyes. The mean preoperative IOP decreased from 26.6 ± 8.1 mm Hg to 17.4 ± 3.4 mm Hg in 6 months after the surgery. Meanwhile, the average number of medications reduced from 4.0 ± 1.4 to 2.3 ± 1.2. The study reported no serious complications. In 13 cases (18.85%), additional surgeries were necessary [17]. The authors also suggest that MIGS can be safely combined with cataract surgery [18]. Jordan et al. [19] do not record severe intraoperative and postoperative complications with Trabectome. Four years after the surgery, IOP decreased by 25% in 261 eyes affected by POAG and it lowered by 30% in 173 eyes with pseudoexfoliation glaucoma. Simultaneously, the number of anti-glaucoma medications was reduced by 43% and 44%, respectively.
The reported success rates of filtering procedures range from 57 to 90%. The complication rates of about 25% are reported by all authors. The value is relatively high, but the complications predominantly include hyphema, shallow anterior chamber, and hypotony [20‒23]. Based on the previous findings, it safe to conclude that HFDS can easily find its place in the glaucoma surgical treatment as a very quick and simple method. The additional benefit of HFDS is that it can be combined with cataract surgery. If it does not result in a favorable IOP reduction, other glaucoma surgeries can be performed further on. Even though trabeculectomy demonstrates the best results in IOP lowering, the reported complication rates and uncertain outcomes leave this method as the last line of defense.
In our opinion, HFDS provides an opportunity to use a surgical procedure earlier in a glaucoma treatment. This is beneficial for glaucoma patients due to the reduced quantity of anti-glaucoma eye drops that have to be used and lower the risks for developing the diseases of ocular surface. In addition, it can be safely combined with cataract surgery.
With our first patients, the number of local medications decreased significantly. Thus, it seems that HFDS can be introduced earlier in glaucoma treatment algorithm. Early introduction of HFDS is favorable because it can improve disease control and life quality. This is especially important for the patients whose disease requires a complicated regimen for eye drops usage and who are not compliant, obedient, and disciplined in maintaining this time-consuming routine. Finally, earlier surgery that is also safe and predictable will lower IOP in most patients. This improves the prognosis by retarding a disease progression.
Our study has certain limitations. They mainly stem from a small group of participants and the follow-up period that can be prolonged. Hopefully, in our future examinations we will be able to overcome these obstacles and provide a more comprehensive review of the results achieved with HFDS procedure.
Conclusion
The examined cases were our first experience with HFDS in glaucoma management. It is a safe and efficient method for lowering IOP in open-angle glaucoma. However, a higher number of patients is needed for more conclusive results.
Acknowledgment
We would like to thank PhD Jelena Josijević for language revision of the manuscript.
Statement of Ethics
This study was approved by the Ethics Committee of the Medical Military Academy, Belgrade, Serbia (approval reference number 2014-087). All procedures followed the tenets of the Declaration of Helsinki, and written consent was obtained from all patients and healthy controls.
Conflict of Interest Statement
There are no conflicts of interest.
Funding Sources
The authors did not receive any funding.
Author Contributions
Designed the study and did all the HFDS: Kontic Marko. Data collection: Sarenac Vulovic Tatjana, Todorovic Dusan, and Zecevic Rada. Wrote the study: Sarenac Vulovic Tatjana and Todorovic Dusan. Data analysis and interpretation and critical revision of the article: Todorovic Dusan and Zecevic Rada. Drafting of the article: Sarenac Vulovic Tatjana. Final approval of the version to be published: Kontic Marko and Sarenac Vulovic Tatjana.
Data Availability Statement
All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.