Femtosecond Laser-Assisted Cataract Surgery in Glaucoma Patients, Case Series.

Background We aim to describe the short-term effect of femtosecond laser-assisted cataract surgery (FLACS) in intraocular pressure (IOP), visual acuity (VA), number of hypotensive medications, and visual elds (VF) in glaucomatous eyes. Single-center consecutive case series study included patients with a previous glaucoma diagnosis that needed cataract surgery alone or combined with incisional glaucoma procedure. IOP was measured during surgery immediately before and after pretreatment docking with an indentation tonometer. Changes in visual acuity (VA), IOP, number of and VF were evaluated with a 90 day follow up.


Abstract Background
We aim to describe the short-term effect of femtosecond laser-assisted cataract surgery (FLACS) in intraocular pressure (IOP), visual acuity (VA), number of hypotensive medications, and visual elds (VF) in glaucomatous eyes.

Methods
Single-center consecutive case series study included patients with a previous glaucoma diagnosis that needed cataract surgery alone or combined with incisional glaucoma procedure. IOP was measured during surgery immediately before and after pretreatment docking with an indentation tonometer.
Changes in visual acuity (VA), IOP, number of medications, and VF were evaluated with a 90 day follow up.

Results
Twenty-seven eyes of 27 patients were included. Mean patient age was 70 years, 70% (n = 19) were female. Glaucoma diagnoses were: twelve patients with primary open-angle glaucoma, 13 with angleclosure glaucoma, and 2 with pseudoexfoliation glaucoma. Twenty-one patients underwent cataract surgery alone and 6 combined with an incisional glaucoma procedure (trabeculectomy or glaucoma drainage device implantation). We found no signi cant differences between pre-docking IOP Conclusion FLACS appears to perform well in the short-term in eyes with glaucoma undergoing cataract surgery alone or with an incisional glaucoma procedure. Comparable outcomes to manual phacoemulsi cation were obtained regarding IOP, VA, and postoperative period evolution.

Clinical Signi cance
Safety and e cacy of FLACS have not been properly studied in the glaucoma population, we present a case series with different glaucoma diagnoses who underwent FLACS alone or with an incisional glaucoma procedure.

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Glaucoma is the leading cause of irreversible blindness in the world. With the advent of new technologies, many different medical, laser, and surgical treatments are available. However, traditional glaucoma surgery remains the rst choice of treatment for patients with refractory glaucoma and severe damage with the risk of blindness. 1 The coexistence of glaucoma and cataracts is frequent because of the age of this population group and because glaucoma medications, lasers, and surgical procedures are known to be cataractogenic. A signi cant number of glaucoma patients will require cataract extraction alone or a combined with a glaucoma procedure over time. 2 In 2008, the rst Femtosecond Laser-Assisted Cataract Surgery (FLACS) was performed 3 and since then its use has become widespread as a safe tool. A decrease in endothelial cell loss, a well-centered and predictable capsulorhexis, better intraocular lens (IOL) position, and less phacoemulsi cation energy and time requirements have been reported in FLACS in comparison to regular manual cataract surgery. 4,5,6 The use of FLACS in glaucoma is an encouraging prospect, but very few studies on the safety of this technology in these patients are available. Many patients with glaucoma have characteristics that make cataract surgery more challenging: ocular surface disease, presence of ltering blebs or drainage devices, narrow anterior chambers, vulnerable zonules, challenging pupils, and unpredictable behavior of the anterior capsule.
During FLACS, the eye is stabilized by a suction docking system. The application of vacuum for a docking system was studied for laser in situ keratomileusis (LASIK) and it has been suggested, that it transiently raises IOP to more than 90 mmHg in non-glaucomatous eyes. 7,8 A latter ex vivo study suggested that femtosecond liquid docking systems create a minimal IOP rise, and this was also reported in other studies of FLACS, where only a transient mild IOP increase was shown in healthy eyes. 9,10 Recent FLACS studies comparing healthy and glaucomatous eyes show that both presented an initial IOP spike on the rst day after surgery, followed by a sustained IOP reduction, that was greater and persisted longer in eyes with glaucoma. 11,12 The superiority of FLACS compared to manual phacoemulsi cation cannot be determined with the evidence available today. 13 Considering the characteristics of glaucoma patients, and the added risk of IOP rising during the docking procedure in eyes with an additional vulnerability to IOP changes, we nd it is important to assess the outcomes of FLACS in this population.
In the present study, we report the short-term changes of IOP during and after FLACS either alone or combined with a glaucoma incisional procedure in eyes with glaucoma.

Methods
A single-center, interventional, prospective case series study was conducted at the Glaucoma Department of a tertiary care ophthalmology center. The study was approved by the Institutional Review Board of the hospital and followed the guidelines of the 1964 Helsinki Declaration and its later amendments.
Patients that required cataract surgery alone or in combination with a glaucoma surgery (trabeculectomy or glaucoma drainage device (GDD)) were consecutively recruited. Inclusion criteria for FLACS alone included a diagnosis of open-angle or angle-closure glaucoma, and a vision-impairing cataract (VA < 20/40). Recruited patients with progression of glaucoma despite maximal medical therapy and intolerance to topical glaucoma medications were assigned to the FLACS + glaucoma surgery group. Patients with a history of previous ophthalmological surgery of any kind, corneal or conjunctival alterations (severe ocular surface disease, allergic conjunctivitis, chronic scarring conjunctivitis, keratoconus), with VA of Hand Motion or No Light Perception, patients that could not comply with follow up appointments were excluded.
Patients who ful lled the inclusion criteria underwent a complete ophthalmological examination. IOP was taken preoperatively and postoperatively in every visit with a Goldmann Applanation Tonometer.
Preoperative glaucoma medications used were registered and classi ed by class. All patients performed Humphrey 24 − 2 white-on-white VF, with the SITA-Standard algorithm and size III stimulus; Mean Deviation (MD) was recorded preoperatively and on days 30 and 90 after surgery. Changes from baseline in VF were con rmed in at least two consecutive reliable tests. VA was assessed using the Snellen chart preoperatively and in every follow-up days 1, 7, 30, and 90.
Femtosecond laser (LenSx Laser System, Alcon Laboratories, Inc.) anterior capsulotomy and lens fragmentation were completed in all patients, a contact docking interface was used. All procedures were performed by a single experienced surgeon (R.C.D.). Laser Pretreatment was performed before any other surgical step in patients with combined procedures.
Patients who underwent FLACS with a GDD implantation had an S2 Ahmed Glaucoma Valve (AGV) (New World Medical, Rancho Cucamonga CA, USA) implanted in the superotemporal quadrant, with a long scleral tunnel (4 mm) technique and no patch graft; the AGV was implanted after the FLACS was completed.
Patients who underwent FLACS with trabeculectomy had a fornix based conjunctival ap and limbal based scleral ap. The conjunctival dissection and scleral ap were performed without entering the anterior chamber, afterward, the cataract extraction and IOL implantation were carried out, and nally the trabeculectomy was completed by entering the anterior chamber and performing a 0.7 mm punch "trabeculectomy". The scleral ap was closed using cardinal simple sutures; both scleral ap and conjunctiva were closed using 10 − 0 nylon.
During the procedure, IOP was recorded using a Schiötz indentation tonometer immediately before and after suction docking, prior administration of a topical anesthetic (tetracaine 0.5 g) with the patient in a supine position.
Data regarding VA, IOP, and VF MD were collected preoperatively and during the follow up using a computerized database (Microsoft Excel).

Results
Twenty-seven eyes of 27 patients were included, 19 women and 8 men. Mean patient age was 70 (± 9.7) years. The diagnoses included 12 patients (44.4%) with primary open-angle glaucoma, 13 with angleclosure glaucoma, and 2 with pseudoexfoliation glaucoma. Demographic data and baseline characteristics of study participants are presented in Table 1. Twenty-one patients underwent FLACS alone and 6 combined with glaucoma surgery: 2 (7.4%) with GDD, and 4 (14.8%) with trabeculectomy. No complications were recorded during the surgeries.

Discussion
Cataract surgery is frequently performed in patients with glaucoma. To this day, the debate continues whether FLACS is equivalent or superior to manual cataract surgery. When we think about performing FLACS in patients with Glaucoma we must take into account that this procedure has the added step of suction docking during pretreatment, which has been reported in several studies to raise IOP. 10,11,12 In our study, we assess short-term IOP changes and surgical outcomes when using the femtosecond laser pretreatment in patients with different types of glaucoma undergoing cataract surgery alone or in combination with glaucoma surgery.
In our patients we found similar surgical outcomes to those published with traditional manual cataract surgery regarding IOP, VA, and VF, with the added advantage of femtosecond laser precision. 13 Suction was well tolerated in glaucomatous eyes during surgery, showing no signi cant mean IOP raise immediately after suction docking or up to our 90-day nal follow-up. This contrasts with previous studies of FLACS performed in glaucomatous eyes. 10,11,12,14 In a prospective study by Darrian-Smith, 143 eyes (30% with glaucoma) were studied by measuring IOP with a rebound tonometer before and after suction docking during FLACS with Catalys Precision Laser System with Liquid Optics Interface (Abbott Medical Optics, Inc.). Their results showed a transient IOP increase from baseline that was signi cantly higher in glaucomatous eyes; after removal of suction the IOP levels decreased in both groups, but remained above preoperative values and were higher in eyes with glaucoma. 11 A retrospective case series study conducted by Shah evaluated the long term IOP changes in 504 eyes, of which 278 had glaucoma, after FLACS. They reported that both control and glaucomatous eyes had an initial IOP spike, followed by a sustained reduction from baseline up to 3 years follow up, this decrease was greater and lasted longer in eyes with glaucoma than in healthy control eyes. 12 In our study, patients who underwent FLACS with IOL implantation alone did not present an IOP elevation during surgery or in the rst 30 days of follow up, instead, they showed a lower mean IOP at day 90 after surgery in comparison to baseline.
Regarding eyes who underwent FLACS with IOL implantation and glaucoma surgery, there was an IOP reduction from day 1 after surgery, that lasted up to 90 days with a 6 mmHg decrease from baseline. This group also showed a signi cant reduction in topical glaucoma medication requirement, which is expected in combined glaucoma surgery.
When comparing FLACS outcomes, we must consider that different femtosecond systems will have different characteristics, therefore, they are not totally comparable to one another; even in the same femtosecond system, different types of suction docking interfaces can have different outcomes in IOP changes. 14 No complications that have been previously reported in FLACS, like incomplete capsulotomy, tears in anterior capsule or posterior capsule ruptures were recorded during any of the surgeries in our study. 15,16,17 BCVA was signi cantly improved in both groups. No changes in VF were recorded, but longer follow up is necessary to evaluate the real impact of this procedure in glaucoma progression.
A small sample with a short follow-up are the main limitations of our study, which allows for a descriptive case series instead of a more thorough statistical analysis. A larger sample, with a longer follow up, along with a control group would allow an analysis that could give us more conclusive results regarding the safety and outcomes of Femtosecond Laser alone or in combination with glaucoma surgery in patients with glaucoma. To our knowledge outcomes of FLACS used in combination with glaucoma surgery had not been previously reported. The use of FLACS in eyes with previous glaucoma surgery or along with Microinvasive Glaucoma Surgery (MIGS) has not been reported and could be an interesting prospect to explore.

Conclusion
Looking at our case series results, we can conclude that FLACS alone or in combination with an incisional glaucoma procedure appears to be well tolerated in eyes with glaucoma. It could be a safe alternative to traditional manual phacoemulsi cation in glaucoma patients, although further research and a larger sample with a longer follow up is warranted to evaluate the long term effects of FLACS on these patients. Consent for publication -Not applicable.
Ethics Approval and Consent to Participate -Written informed consent was obtained from all participants for the surgical procedure and participation in the study.
Availability of data and materials -The datasets obtaines during and/or analyzed during the current study available from the corresponding author on reasonable request.
Competing interests -"The authors declare that they have no competing interests" Funding Support for the study: None Authors' contributions: "RCD and CP designed this study. DA and CP collected, analyzed and interpreted all the data. RCD was the surgeon in all the reported cases. DA and CP wrote the manuscript. JJR, RCD and CP helped edit and review the manuscript and data. All authors read and approved the nal manuscript."