Molecular alterations that precede the establishment of the hallmarks of cancer: An approach on the prevention of hepatocarcinogenesis.

Chronic liver injury promotes the molecular alterations that precede the establishment of cancer. Usually, several decades of chronic insults are needed to develop the most common primary liver tumor known as hepatocellular carcinoma. As other cancer types, liver cancer cells are governed by a common set of rules collectively called the hallmarks of cancer. Although those rules have provided a conceptual framework for understanding the complex pathophysiology of established tumors, therapeutic options are still ineffective in advanced stages. Thus, the molecular alterations that precede the establishment of cancer remain an attractive target for therapeutic interventions. Here, we first summarize the chemopreventive interventions targeting the early liver carcinogenesis stages. After an integrative analysis on the plethora of molecular alterations regulated by anticancer agents, we then underline and discuss that two critical processes namely oxidative stress and genetic alterations, play the role of 'dirty work laborer' in the initial cell damage and drive the transformation of preneoplastic into neoplastic cells, respectively; besides, the activation of cellular senescence works as a key mechanism in attempting to prevent the onset and establishment of liver cancer. Whereas the detrimental effects of the binomial made up of oxidative stress and genetic alterations are either eliminated or reduced, senescence activation is promoted by anticancer agents. We argue that collectively, oxidative stress, genetic alterations, and senescence are key events that influence the fate of initiated cells and the establishment of the hallmarks of cancer.

Ab-Externo MicroShunt versus Trabeculectomy in Primary Open-Angle Glaucoma: One-Year Results from a 2-Year Randomized, Multicenter Study.

PURPOSE: To compare the effectiveness and safety of the MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG). DESIGN: One-year results from a 2-year, prospective, randomized, multicenter, noninferiority study (NCT01881425) conducted in the United States and Europe. PARTICIPANTS: Eligible patients were aged 40-85 years with intraocular pressure (IOP) ≥15 and ≤40 mmHg and mild-to-severe POAG inadequately controlled on maximum tolerated medical therapy. METHODS: Patients were randomized 3:1 to undergo stand-alone MicroShunt implantation or trabeculectomy, both performed with adjunctive mitomycin C (0.2 mg/ml for 2 minutes). MAIN OUTCOME MEASURES: The primary effectiveness end point was surgical success, defined as ≥20% reduction in mean diurnal IOP from baseline (no medication washout) at year 1 without increasing the number of glaucoma medications. Secondary effectiveness end points at year 1 were the mean IOP change from baseline and requirement for postoperative intervention. Additional end points included glaucoma medication use and adverse events. RESULTS: Overall, 395 (MicroShunt) and 132 (trabeculectomy) patients were randomized (mean Humphrey visual field mean deviation, -12.34 decibels [dB]). At year 1, probability of success was lower in the MicroShunt group compared with the trabeculectomy group (53.9% vs. 72.7%, respectively; P < 0.01). In the MicroShunt group, mean IOP ± standard deviation decreased from 21.1 ± 4.9 mmHg at baseline to 14.3 ± 4.3 mmHg (-29.1%; P < 0.01) at year 1, with a mean of 0.6 ± 1.1 glaucoma medications (baseline 3.1 ± 1.0; P < 0.01). In the trabeculectomy group, mean IOP decreased from 21.1 ± 5.0 mmHg to 11.1 ± 4.3 mmHg (-45.4%; P < 0.01), with a mean of 0.3 ± 0.9 glaucoma medications (baseline 3.0 ± 0.9; P < 0.01). Postoperative interventions, including laser suture lysis, were reported in 40.8% (MicroShunt) versus 67.4% (trabeculectomy) of patients (P < 0.01). Reported incidence of transient hypotony was higher in the trabeculectomy group versus the MicroShunt group (49.6% vs. 28.9%; P < 0.01). Vision-threatening complications were uncommon and reported in 1.0% of MicroShunt versus 0.8% of trabeculectomy patients. CONCLUSIONS: Probability of success was lower with MicroShunt compared with trabeculectomy. Although reductions in IOP and glaucoma medications over 1 year were observed in both groups, the trabeculectomy group had a lower mean IOP on fewer medications.

Effect of Laser-assisted Subepithelial Keratectomy with Mitomycin C on Corneal Optical Density Measured with Confocal Microscopy.

SIGNIFICANCE: The development of confocal microscopy allows one to obtain high-resolution corneal images like its optical density. Some studies have evaluated the optical density with Scheimpflug cameras in the early post-operative period after photorefractive keratectomy, but no studies have evaluated the long-term evolution of optical density after surface ablation when mitomycin C is used. PURPOSE: This work aimed to study the changes in corneal optical density measured with confocal microscopy in eyes treated with laser-assisted subepithelial keratectomy (LASEK) and intraoperative mitomycin C (MMC) to correct myopia. METHODS: A study of 24 consecutive myopic eyes that underwent LASEK with 0.02% MMC and a control group of 24 healthy nontreated eyes was performed. Optical density was measured using the images by the confocal microscopy of the Heidelberg Retina Tomograph II with the Rostock Cornea Module. An analysis of confocal microscopy images was performed using the ImageJ software to obtain the optical density, in gray-scale units (GSU). The optical density of the stromal bed was evaluated 3 months, 15 months, and 3 years after surgery and was compared with the optical density at the equivalent depth of the stroma in controls. RESULTS: The mean values of optical density for the LASEK group were 81.7 ± 9.7, 78.6 ± 11.7, and 73.6 ± 18.7 GSU at 3 months, 15 months, and 3 years, respectively, and it was 61.8 ± 8.2 GSU for the control group. A statistically higher optical density 3 and 15 months after LASEK with MMC was found compared with controls (P < .001). No significant difference was found in optical density at 3 years post-operatively. CONCLUSIONS: Our study suggests that, after LASEK with MMC, the anterior corneal stroma has a higher optical density at 3 and 15 months post-operatively, which gradually returns to normal values 3 years after surgery.

Outcomes of Glaucoma Drainage Device Implantation and Trabeculectomy With Mitomycin C in Glaucoma Secondary to Aniridia.

PURPOSE: To compare the outcomes of Aurolab aqueous drainage implant (AADI; Aurolab) placement and trabeculectomy with mitomycin C (MMC) in patients with glaucoma secondary to aniridia. DESIGN: Retrospective comparative interventional case series. METHODS: This study included patients with congenital aniridia who underwent AADI implantation or trabeculectomy with MMC. Surgical failure was defined as IOP > 21 mm Hg or reduced <20% from baseline, IOP ≤ 5 mm Hg, reoperation for glaucoma or a complication, or loss of light perception vision. RESULTS: A total of 30 eyes of 30 patients underwent surgical treatment, including 18 eyes that received an AADI and 12 eyes that had a trabeculectomy with MMC. The cumulative probability of failure at 2 years was 11.1% (95% CI = 2.9%-37.6%) in the AADI group and 58.3% (95% CI = 33.5%-84.8%) in the trabeculectomy group (P = .05, log-rank). At 2 years, IOP (mean ± SD) was 14.1 ± 2.8 mm Hg in the AADI group and 19.6 ± 6.6 mm Hg in the trabeculectomy group (P = .02), and the number of glaucoma medications was 1.7 ± 0.9 in the AADI group and 2.2 ± 0.8 in the trabeculectomy group (P = .25). Surgical complications developed in 1 patient in each treatment group (P = .65). Cataract surgery was performed in 5 (42%) patients in the trabeculectomy group and no patients in the AADI group (P = .01). CONCLUSIONS: Placement of an AADI resulted in lower IOP and a higher rate of surgical success compared to trabeculectomy with MMC in eyes with glaucoma associated with aniridia. Cataract extraction was more frequently required after trabeculectomy with MMC than AADI implantation.

A safety review of drug treatments for patients with systemic immunoglobulin light chain (AL) amyloidosis.

INTRODUCTION: In AL amyloidosis, a usually small plasma cell clone secretes unstable, amyloid-forming light chains, causing cytotoxicity and progressive (multi)organ function deterioration. Treatment aims at reducing/eradicating the underlying clone, to reduce/zero the supply of the amyloidogenic protein and halt the amyloidogenic cascade. AREAS COVERED: Safety data of alkylating agents, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies from clinical trials are reviewed. EXPERT OPINION: Drugs used to treat AL amyloidosis are derived from experience with multiple myeloma or other B cell malignancies. However, treating AL amyloidosis is particularly challenging, as it implies delivering anti-neoplastic therapy to a hematologic malignancy directly causing (multi)organ function deterioration, often in elderly subjects with other comorbidities and polypharmacotherapy. This unique combination translates in increased patients' frailty and higher sensitivity toward treatment-related toxicities. Therefore, dose/schedule adjustments and special precautions are needed when translating treatment experience from multiple myeloma or other B cell malignancies to AL amyloidosis. Treatment of patients with AL amyloidosis should be risk adapted, tailored to individual patients' risk profile, considering the type and extent of organ involvement, and eventual comorbidity. As several classes of effective anti-plasma cell or B cell drugs are available, therapeutic choices are also influenced by individual drug's safety profile.

Scheimpflug Corneal Densitometry Changes After Trabeculectomy.

PURPOSE: To study the possible changes in Scheimpflug corneal densitometry 6 months after mitomycin C-augmented trabeculectomy and to compare these measurements with healthy controls. METHODS: Corneal densitometry was monitored with the Pentacam HR3 before and 6 months after first-time uncomplicated mitomycin C-augmented trabeculectomy in 42 eyes of 42 white patients with open-angle glaucoma and in 22 healthy age-matched controls. Preoperative intraocular pressure (IOP), central corneal thickness, known duration of the disease, gender, the type and number of substances, applications and amount of benzalkonium chloride per day, and postoperative topical cortisone use were tested for possible correlations in the trabeculectomy group. RESULTS: There was a statistically significant reduction of mean diurnal IOP from 19.0 ± 7.7 to 11.1 ± 7.7 mm Hg (P = 0.003) and the amount of pressure-lowering substances from 3.7 ± 1.0 to 0.1 ± 0.5 (P < 0.001). Densitometry measurements decreased in the entire cornea from 25.5 ± 5.7 to 23.1 ± 5.8 grayscale units (P = 0.001) with emphasis in the anterior layer. They returned close to normal 6 months after trabeculectomy and were not statistically significantly different compared with a healthy control group (22.8 ± 3.4 grayscale unit; P = 0.824). No correlations could be found with these observations and possible causing factors studied. CONCLUSIONS: Corneal densitometry, an objective and sensitive measure of corneal transparency, returned close to normal 6 months after trabeculectomy. Although the observations cannot be associated with any causing factor in this study, the significant IOP reduction and the nearly complete cessation of topical antiglaucomatous substances including benzalkonium chloride seem to be the most plausible reasons for this finding.

Outcomes of Ipsilateral Simple Limbal Epithelial Transplantation, Tenonectomy, Mitomycin and Amniotic Membrane Transplantation for Treatment of Recurrent Pterygium.

PURPOSE: To report on the outcomes of recurrent pterygium treated by ipsilateral simple limbal epithelial transplantation (SLET), mitomycin, tenonectomy, and amniotic membrane transplantation. METHODS: A retrospective, interventional study was conducted including all patients with recurrent pterygium who underwent SLET surgery under a single surgeon using ipsilateral donor tissue with a minimum 6-month follow-up at Toronto Western Hospital, Canada. Outcome measures included the following: recurrence rates, best spectacle-corrected visual acuity, and postoperative complications. RESULTS: Ten eyes of 10 patients, aged 60.7 ± 18.5 years (range 23-79) with a mean follow-up time of 15.2 ± 10.0 months of which 50% (n = 5) were men, were included. Eight eyes (80%) had a history of 2 or less pterygium operations. Two patients had 3 and 5 previous pterygium operations, respectively. Concurrent limbal stem cell disease was noted in 6 eyes (60%). Average number of pterygium recurrences per eye was 1.9 ± 1.3 (range 1-5). Mean pre-op best-corrected visual acuity was 0.5 LogMAR (Snellen equivalent 20/60, range 20/20 to counting fingers). Best-corrected visual acuity remained the same or improved in 6 eyes (60%). Recurrence was noted in 1 eye (10%) with a history of 5 previous pterygium excisions and remained stable at the last follow-up. No patients required a second operation. CONCLUSIONS: Ipsilateral SLET with mitomycin, tenonectomy, and amniotic membrane transplantation is a novel technique to address recurrent pterygium. Concurrent limbal stem cell diseases are often present. Initial results demonstrate low recurrence. Visual improvement is modest. Stabilization of the ocular surface to improve vision is possible.

A standardized protocol of laser suture lysis in postoperative management in trabeculectomy with mitomycin C: One-year study.

AIM: To analyse the efficacy and safety of a standardized laser suture lysis protocol following trabeculectomy. MATERIALS AND METHODS: Prospective interventional study conducted at a tertiary centre, between June 2016 and July 2017. Consecutive patients undergoing primary trabeculectomy with mitomycin C (0.4 mg/mL) for open angle glaucoma were enrolled. According to study protocol, a first laser suture lysis was performed routinely when intraocular pressure was greater than 10 mmHg, starting at postoperative day 8, and a second laser suture lysis was done whenever the intraocular pressure was newly greater than 10 mmHg, with a minimum interval of 1 week after the first laser suture lysis. Primary outcome was intraocular pressure (mean value, and mean difference from baseline in percentage). Safety parameters were also analysed. RESULTS: Thirty-three eyes of 28 patients (13 males) were enrolled with a mean age of 69.6 ± 15.1 years. Pre-operative intraocular pressure was 24.9 ± 8.6 mmHg. All eyes underwent a laser suture lysis before the 12th postoperative week, with a mean intraocular pressure-lowering efficacy of 42.4% (p < 0.01). A second laser suture lysis procedure, when performed (n = 14), had an additional intraocular pressure-lowering efficacy of 26.7% (p = 0.02). Mean intraocular pressure at 1-month follow-up was 12.9 ± 8.2 mmHg, and during this period, two cases of self-limited choroidal detachments were noticed. Ten patients needed additional bleb needling. Mean intraocular pressure at 1-year follow-up was 13.8 ± 8.0 mmHg under an average of 0.4 topical intraocular pressure-lowering drugs (p < 0.01). CONCLUSION: In our study, laser suture lysis was an effective tool to lower intraocular pressure during the early postoperative period, with an acceptable safety profile.

History, presence, and future of mitomycin C in glaucoma filtration surgery.

PURPOSE OF REVIEW: Mitomycin C (MMC) is an alkylating agent with extraordinary ability to crosslink DNA, preventing DNA synthesis. By this virtue, MMC is an important antitumor drug. In addition, MMC has become the gold standard medication for glaucoma filtration surgery (GFS). This eye surgery creates a passage for drainage of aqueous humor (AqH) out of the eye into the sub-Tenon's space with the aim of lowering the intraocular pressure. A major cause of failure of this operation is fibrosis and scarring in the sub-Tenon's space, which will restrict AqH outflow. Intraoperative application of MMC during GFS has increased GFS success rate, presumably mainly by reducing fibrosis after GFS. However, still 10% of glaucoma surgeries fail within the first year. RECENT FINDINGS: In this review, we evaluate risks and benefits of MMC as an adjuvant for GFS. In addition, we discuss possible improvements of its use by adjusting dose and method of administration. SUMMARY: One way of improving GFS outcome is to prolong MMC delivery by using a drug delivery system.

Comparison of Two Analytical Methods for Busulfan Therapeutic Drug Monitoring.

BACKGROUND AND OBJECTIVES: Busulfan (Bu) is an old drug, but is still well recommended as an alkylating agent during conditioning therapy, before hematopoietic stem cell transplantation. Although its dose administration is standardized and based on patient weight, therapeutic drug monitoring is required in order to maintain its exposure [as area under the concentration-time curve (AUC) from 0 to infinity AUC0-∞] within a narrow therapeutic range and, if necessary, to adjust the dose with as short a lead time as possible. The aim of the study is to evaluate the agreement (as calculated AUC) between a gold standard analytical method and a new one that is faster and easier. METHODS: We analyzed 221 plasma samples from 37 children (0.25-16 years; 4-62.5 kg) and 11 adults (21-59 years; 45-80 kg), corresponding to 52 AUC values (ng h/mL). The drug exposure was calculated, simultaneously, by two validated analytical methods. The reference method was a high-performance liquid chromatography (HPLC) assay combined with an ultraviolet detector (UV). The test method had a triple quadrupole mass spectrometer (MS) as detector; the clean-up procedures of the samples were different and faster. RESULTS: The agreement between the two methods (reference and test) was evaluated in terms of Bu exposure differences based on Lin's concordance correlation coefficient (CCC) and represented by the Bland-Altman plot. The CCC between the AUC of the two methods was excellent (0.868; 95% CI: 0.802-0.935). The precision of the measures (expressed by Pearson's italic "r") was 0.872, and the accuracy (accounted by the bias correction factor) was 0.996. CONCLUSIONS: We can conclude that the HPLC-MS/MS assay represents a very good alternative to the reference.

Endoscopic dacryocystorhinostomy with circumostial mitomycin C injection, simultaneous limited septoplasty and the use of tissue glue.

Epiphora due to nasolacrimal duct obstruction is a common condition worsening one's quality of life. It requires surgical treatment. We present a combined technique of transnasal endoscopic dacryocystorhinostomy with simultaneous limited septoplasty, circumostial mitomycin C injection and the use of tissue glue in a case of a 72-year-old patient with nasolacrimal duct obstruction complicated by septal deviation. The multiprocedure surgery was performed successfully. Follow-up time was 2 years. The patient remained asymptomatic within the observation time. Functional and anatomical success was achieved. We believe that the transnasal endoscopic dacryocystorhinostomy extended by limited endoscopic septoplasty, circumostial mitomycin C injection and the use of fibrin glue may be a solution for selected cases of nasolacrimal obstruction accompanied by significant local septal deviation.

Glaucoma Drainage Device Technique in a Cohort of Experienced Glaucoma Surgeons in Australia and New Zealand.

PRéCIS:: Glaucoma drainage devices (GDD) by Australian and New Zealand glaucomatologists are implanted superotemporally under a peribulbar anesthesia without the use of mitomycin C. Intraluminal stents and tube fenestration are utilized and covered with a scleral graft. PURPOSE: To evaluate current practice patterns of surgical techniques for GDD among Australia and New Zealand Glaucoma Society members routinely performing GDD surgery. METHODS: Survey of surgeons who performed more than 20 GDD in past 5 years. RESULTS: Surgeon participation rate was 31/32 (96.8%). The most common surgical techniques were Baerveldt GDD (24/32, 77.4%), superotemporal placement (31/31, 100%), and peribulbar anesthesia (21/31, 67.7%). Mitomycin C antimetabolite was used routinely by 9/31 surgeons (29.0%). Most surgeons employed intraluminal stents (23/31, 74.2%) with tube fenestrations (19/31, 61.3%). GDD was placed behind the recti muscles (27/31, 87.1%) and secured with nylon (8/0, 9/0 or 10/0) by 29/31 (93.6%). Most common sclerostomy techniques for tube insertion was a 23-G needle passed ab externo (18/31, 58.1%). Tube placement was in the sulcus (11/31, 35.5%) for pseudophakic patients. The external portion of the tube was most commonly covered with a full-thickness scleral patch graft (21/31, 67.7%). Majority of surgeons (21/31, 67.7%) reviewed patients 3 to 4 times in the first month. CONCLUSIONS: Although a wide range of practice patterns for GDD implantation exists among Australia and New Zealand Glaucoma Society surgeons, there are consistent techniques currently in use to optimize patient outcomes. This report can help surgeons seeking to improve outcomes and minimize complications when trialing the different surgical options.

Cutaneous Langerhans Cell Histiocytosis Responsive to Topical Nitrogen Mustard.

Langerhans cell histiocytosis (LCH) limited to the skin is rare in adult patients. Given the challenges of prospective clinical trials for this rare disease, there is paucity in data to guide the management of cutaneous LCH. Topical nitrogen mustard is a possible treatment for cutaneous LCH with positive responses in five known adult cases in the literature. In this report, we present two adult patients with recalcitrant cutaneous LCH and no evidence of systemic involvement who had rapid and complete response on topical nitrogen mustard therapy. We provide support for topical nitrogen mustard as a treatment option for primary cutaneous LCH which may spare patients from requiring systemic immunosuppressive treatments. J Drugs Dermatol. 2020;19(8):803-805. doi:10.36849/JDD.2020.4943.

Laser irradiation activates spinal adenosine A1 receptor to alleviate osteoarthritis pain in monosodium iodoacetate injected rats.

The analgesic role of the adenosine A1 receptor is thought to involve the modulation of the spinal N-methyl D-aspartate receptor-mediated nociceptive pathway, which is suggested to be an underlying mechanism in chronic pain. Knee osteoarthritis is a degenerative condition accompanied by chronic pain. We have demonstrated that 10.6-µm laser irradiation has an antinociceptive effect in the monosodium iodoacetate -induced knee osteoarthritis in rats. However, its mechanism of action has yet to be explored. In the present work, we investigate the mechanism of 10.6-µm laser irradiation mediated antinociception in the monosodium iodoacetate -induced knee osteoarthritis. Results showed that the 10.6-µm laser significantly reversed the monosodium iodoacetate -induced nociceptive behaviors for up to 28 days. Moreover, the up-regulation of the A1 receptor and the down-regulated phosphorylation of the N-methyl D-aspartate receptor 1 subunit of the N-methyl D-aspartate receptor were observed in the spinal cord dorsal horn in the monosodium iodoacetate injected rats treated by laser irradiation. Intrathecal injection of 8-cyclopentyl-1,3-dipropylxanthine markedly reversed the effects of laser irradiation, as evidenced both by behavioral pain tests and by levels of spinal phosphorylation of N-methyl D-aspartate receptor 1. These results suggest that the spinal A1 receptor contributes to the antinociceptive effects of 10.6-µm laser, at least in part by inhibiting phosphorylation of N-methyl D-aspartate receptor 1 in the monosodium iodoacetate -induced knee osteoarthritis pain.

Duration of topical steroid application after photorefractive keratectomy with mitomycin C.

Contradictory results of postoperative steroid application in photorefractive keratectomy (PRK) led to a meta-analysis of the existing data to achieve a definite conclusion on the optimum dosage and duration of corticosteroid therapy after PRK. The overall pooled unstandardized mean difference (PUMD) of the corneal haze score was -0.20 (95% CI, -0.29 to -0.12). In subgroup analysis, the PUMD of the corneal haze score was statistically significant in 2 subgroups, -0.57 (-0.85 to -0.30) for 3 to 6 months postoperatively and -0.13 (-0.23 to -0.04) for ≤ 3 months postoperatively. Analysis of the PUMD of postoperative spherical equivalent in participants with low to moderate myopia (≥-6.00 D) and high myopia (<-6.00 D) showed positive effects of steroids on prevention of myopia regression. In conclusion, long-term topical steroid application after PRK seems unnecessary in low and moderate myopia. New randomized clinical trials using current technologies are recommended for postoperative treatments.

A Comparison of Trabeculectomy Surgery Outcomes With Mitomycin-C Applied by Intra-Tenon Injection Versus Sponge.

PURPOSE: To compare the outcomes of mitomycin-C (MMC) delivered by intra-Tenon injection vs sponge application during trabeculectomy surgery. METHODS: We retrospectively reviewed 566 patients with primary and secondary glaucoma diagnoses who received trabeculectomy surgery with MMC in an academic medical center. Exclusion criteria were age less than 18 years, no light perception vision, combined surgery, previous glaucoma incisional surgery, intraoperative 5-fluorouracil, or follow-up <1 month. Subjects were divided into 2 cohorts: MMC delivered by sponge application or by intra-Tenon injection. Main outcome measures were postoperative intraocular pressure (IOP) level and secondary measures were survival rate for IOP control, glaucoma medication use, complication rate, and vision. RESULTS: After inclusion/exclusion criteria, 316 eyes were available for analysis; 131 eyes had MMC delivered via sponge and 185 eyes via injection. Mean postoperative IOP was not significantly different between treatment groups but change in IOP from baseline was lower in the sponge vs the injection group 24 months after surgery (P = .038). The MMC sponge group had significantly more tense, vascularized, or encapsulated blebs as a late complication (P = .046). Time to failure for postoperative IOP control was not significantly different between MMC treatment groups, but older patient age and limbus-based conjunctival incision were associated with significantly longer time to fail. CONCLUSIONS: The application of MMC by injection was similar to application by sponge in lowering IOP in patients with glaucoma and the safety of both techniques appears to be comparable. Limbus-based conjunctival incision had longer time to failure for postoperative IOP control vs fornix-based incision. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Intermediate Outcomes of a Novel Standalone Ab Externo SIBS Microshunt With Mitomycin C.

PURPOSE: To determine the efficacy, risk factors for failure, and adverse events of a standalone novel ab externo SIBS microshunt with mitomycin C (MMC) during 1-year follow-up. DESIGN: Retrospective, interventional case series. SUBJECTS: Glaucomatous eyes with an intraocular pressure (IOP) above target and/or progressing on maximally tolerated medical therapy. METHODS: Consecutive patients with open-angle glaucoma (OAG) and no previous filtering surgery received an ab externo SIBS microshunt with MMC from July 2015 to November 2017. Main outcome measures were proportion of eyes at 1-year with (1) no 2 consecutive IOP readings >17 mm Hg or clinical hypotony without (complete) or with glaucoma medications (qualified); and (2) at least a 20% reduction from decision IOP. Secondary outcomes included upper IOP thresholds of 14 mm Hg and 21 mm Hg with and without a 20% IOP reduction from baseline, median IOP, medications, risk factors for failure, interventions, complications, and reoperations. RESULTS: A total of 164 eyes in 132 patients were included. Complete success was achieved in 76.9% of eyes, qualified success in 92.5%. Complete success was 75.6% for an upper IOP cut-off of 14 mm Hg and 76.9% for 21 mm Hg, and qualified success was 91.9% and 92.5%. MMC dose of 0.2 vs 0.4-0.5 mg/mL (hazard ratio [HR] 2.51; 95% CI 1.12-5.65) and primary open-angle glaucoma vs secondary open-angle glaucoma (SOAG) (HR 2.51; 95% CI 1.01-6.23) represented the only risk factors for failure in multivariable analysis. Needling was performed in 8.5% of eyes. Two eyes received surgical revision, and 1 a reoperation. CONCLUSIONS: One-year results of the ab externo SIBS microshunt demonstrated promising rates of qualified and complete success, decreased drop use, few complications, and infrequent postoperative interventions.

Reoperations for Complications Within 90 Days After Glaucoma Surgery.

OBJECTIVE: To describe reoperations in the operating room for complications encountered within 90 days after glaucoma surgery at a single institution over a 2-year period. DESIGN: Retrospective case series. SUBJECTS: Adult patients who have undergone glaucoma surgery including a tube shunt, trabeculectomy with mitomycin C, trabectome, or transcleral cyclophotocoagulation from June 1, 2015 to August 30, 2017 at a single institution. METHODS: These patients were then examined for postoperative complications that required reoperations within the first 90 days including revision of the tube shunt, revision of the trabeculectomy, drainage of the choroidal, or placement of a tube shunt. MAIN OUTCOME MEASURES: Percentage of reoperations for complications within the first 90 days after glaucoma surgery and surgical indications for these reoperations. RESULTS: A total of 622 glaucoma procedures were performed on 600 eyes in 525 patients over a 2-year period from June 1, 2015 to June 30, 2017 by 4 glaucoma surgeons at a single institution. Of these, 275 (44%) were trabeculectomy with mitomycin C, 253 (41%) were the placement of a tube shunt, 33 (5%) were cyclophotocoagulation, and 61 (10%) were trabectome procedures. Postoperative complications requiring reoperations within 90 days developed in 15 patients (2.4%) overall including 7 patients (2.5%) in the trabeculectomy with mitomycin C group and 8 patients (3.1%) in the tube shunt group. Five patients developed bleb leaks, 3 patients developed serous choroidal effusions, 3 patients had tube exposure, 1 patient had tube retraction, 1 patient had persistent iritis from iris touching the tube, and 1 had encapsulation around the tube. The rate of reoperation for complications was similar between the tube group and the trabeculectomy group (P=0.67, χ test). There were no complications requiring reoperations in 90 days for transcleral cyclophotocoagulation or trabectome. CONCLUSIONS: Early postoperative complications requiring reoperations within the first 90 days after glaucoma surgery were low and comparable with previous studies. Common indications for reoperation within 90 days include wound leak and tube shunt-related issues.

Impact of Phacoemulsification Combined with XEN Gel Stent Implantation on Corneal Endothelial Cell Density: 2-Year Results.

INTRODUCTION: Corneal integrity has long been a preoccupation of glaucoma surgeons considering glaucoma drainage device surgery or antimetabolite-enhanced trabeculectomy. Despite having demonstrated a good safety profile and significant intraocular pressure-lowering capacities, the impact of XEN gel stents on endothelial density was never specifically investigated. The purpose of this study is to assess the effect of XEN gel stents on central endothelial cell density (ECD) over 24 months. To achieve this, we compared the effect on ECD of combined XEN surgery with that of a standard phacoemulsification procedure. METHODS: This was an investigator-initiated, retrospective study, conducted at a single tertiary glaucoma center. Patients with primary or secondary open-angle glaucoma who underwent XEN implantation combined with phacoemulsification between January 2015 and June 2016 were retrospectively enrolled. Patients who had undergone standalone phacoemulsification over the same period of time were enrolled to form the control group of this comparative study. The primary outcome measure was the ECD. Patients who had undergone standalone XEN implantation and patients for whom both a baseline and 24-month ECD could not be obtained were excluded from the analysis. Percentages of ECD reductions were calculated for each studied eye, and the mean of ECD reductions was calculated for each group as well as for subgroups. RESULTS: Thirty-two eyes of 23 patients (mean age=76.0±7.9 y, 60% female) underwent standalone phacoemulsification (n=15) or combined XEN surgery (n=17) and had an ECD both at baseline and 24-month postoperatively. Mean baseline ECDs were 2568±491 versus 2379±335 cells/mm, respectively (P=0.21). In the combined XEN surgery group, 58.8% of eyes (n=10) required at least 1 mitomycin C (MMC)-enhanced needling revision to maintain their target intraocular pressure. In the standalone phacoemulsification group, ECD decreased by a mean 14.5%, from 2567.7±491.2 to 2196.1±591.9 cell/mm (P=0.072). In the combined XEN surgery group, ECD decreased by a mean 14.3%, from 2378.8±334.7 to 2039.6±451.1 cell/mm (P=0.018). The difference in percentage reduction of ECD between the 2 groups was not statistically significant (P=0.226). Within the combined XEN surgery group, the ECD decreased by a mean of 15.4% in patients who did not undergo needling revisions and by 13.1% in patients who underwent the MMC-augmented procedure (P=0.485). In the 3 patients who underwent >1 needling revision, a 21.3% reduction in ECD was observed, but the difference was not statistically significant (P=0.653). Neither the time of the first needling (P=0.452), the patients' age (P=0.285), or sex (P=0.308) was statistically associated with ECD loss. DISCUSSION: The present study demonstrated that the XEN gel implant combined with phacoemulsification produces 24-month ECD loss of a similar magnitude to that observed following standalone phacoemulsification. MMC-augmented needling revisions do not appear to have an impact on ECD.