Efficacy and safety of intraoperative injection of mitomycin C during trabeculectomy: a systematic review and meta-analysis.

PURPOSE: Trabeculectomy, a primary surgical treatment for glaucoma, often employs mitomycin C (MMC) to reduce scar formation and improve surgical outcomes. However, the optimal application method of MMC, whether by injection or sponge, remains a subject of debate. This meta-analysis aims to compare injectable and sponge-based MMC application in terms of efficacy and safety, focusing on various clinical outcomes in glaucoma patients. METHODS: A comprehensive literature search of Scopus, MEDLINE, EMBASE, Ovid, Chinese biomedical literature database, China National Knowledge Infrastructure, and Cochrane Library was done for eligible studies that report data of glaucoma patients who were administered MMC by injection or sponge application during trabeculectomy. Outcomes of interest included intraocular pressure (IOP) reduction, bleb appearance grading (height, extent, vascularity), use of anti-glaucoma medications, and rates of complete success, qualified success, and failure. Data were reported as weighted mean differences (WMD) or odds ratios (OR) with confidence intervals (CI). The random-effects inverse-variance model with DerSimonian-Laird estimate of tau2 was employed, with continuity correction applied where necessary. RESULTS: A total of 15 studies with 1276 participants were included. The meta-analysis revealed no significant difference in IOP reduction between patients treated by MMC injection and sponge application (WMD = - 0.434). Significant differences were observed in bleb appearance grading scores for height (WMD = - 0.170) and extent (WMD = 0.174), with substantial heterogeneity. The use of anti-glaucoma medications was significantly lower in the injection group (WMD = - 0.274). However, there were no significant differences in the rates of complete success, qualified success, and failure. The study demonstrated moderate to high heterogeneity across various outcomes. CONCLUSION: This meta-analysis indicated that while both injection and sponge methods of MMC application during trabeculectomy were equally effective for IOP reduction, they differ in their impact on bleb morphology and postoperative medication requirement. The findings highlight the need for individualized treatment approaches in glaucoma surgery, taking into account the specific needs and characteristics of each patient.

Evaluation of Macular Thickness in Glaucoma Patients Using Prostaglandin Analog Eye Drops Undergoing Trabeculectomy with Mitomycin C: Prospective, Comparative, Randomized, Masked Examiner Study.

INTRODUCTION: The aim of the study was to evaluate the macular thickness of glaucomatous patients undergoing trabeculectomy (TREC) with mitomycin C (MMC) with or without the use of prostaglandin analog (PA) eye drops. METHODS: In this prospective, comparative clinical trial, patients with glaucoma and indications for TREC with MMC using PA and without previous macular changes were randomized into 2 groups: the study group (SG) and the control group (CG). In the CG, PA was suspended between 30 and 60 days after the preoperative exams. The subjects were evaluated, including optical coherence tomography (OCT) with the Cirrus 4000 macular protocol preoperatively and in the postoperative period on 3 occasions: 1-3 days ("PO1"), 6-9 days ("PO7"), and 27-30 days ("PO30") after surgery. The results were compared between groups. RESULTS: Thirty-five eyes of 35 patients were included (17 in the CG and 18 in the SG). There was no statistically significant difference in age (p = 0.2), the preoperative visual field mean deviation (p = 0.08), or the preoperative intraocular pressure (SG: 24.8 ± 7.8 mm Hg vs. CG: 22.8 ± 6.0 mm Hg, p = 0.4). The preoperative macular OCT parameters were equivalent between the groups (p > 0.05). When comparing the variation of parameters between the groups between preop and PO30 there was equivalence in all of the comparisons evaluated. The presence (or absence) of the lens did not affect the results. CONCLUSION: PA eye drops did not affect macular thickness after TREC with MMC in glaucomatous patients.

Alkylating agents-induced gonadotoxicity in prepubertal males: Insights on the clinical and preclinical front.

Rising cure rates in pediatric cancer patients warrants an increased attention toward the long-term consequences of the diagnosis and treatment in survivors. Chemotherapeutic agents can be gonadotoxic, rendering them at risk for infertility post-survival. While semen cryopreservation is an option that can be provided for most (post)pubertal boys before treatment, this is unfortunately not an option prepubertal in age, simply due to the lack of spermatogenesis. Over the last couple of years, studies have thus focused on better understanding the testis niche in response to various chemotherapeutic agents that are commonly administered and their direct and indirect impact on the germ cell populations. These are generally compounds that have a high risk of infertility and have been classified into risk categories in curated fertility guidelines. However, with it comes the lack of evidence and the challenge of using informative models and conditions most reflective of the physiological scenario, in short, the appropriate study designs for clinically relevant outcomes. Besides, the exact mechanism(s) of action for many of these "risk" compounds as well as other agents is unclear. Understanding their behavior and effect on the testis niche will pave the way for incorporating new strategies to ultimately combat infertility. Of the various drug classes, alkylating agents pose the highest risk of gonadotoxicity as per previously established studies as well as risk stratification guidelines. Therefore, this review will summarize the findings in the field of male fertility concerning gonadotoxicity of akylating agents as a result of chemotherapy exposure.

Effect of ripasudil after trabeculectomy with mitomycin C: a multicentre, randomised, prospective clinical study.

BACKGROUND: To investigate if there are improvements in trabeculectomy outcomes supporting filtration bleb formation caused by Rho-associated protein kinase (ROCK) inhibitors. METHODS: This prospective, multicentre, randomised, open-label clinical study examined open-angle glaucoma patients who underwent trabeculectomy or trabeculectomy combined with cataract surgery followed by 3-month postoperative ripasudil treatments. After randomly allocating patients to ripasudil-ROCK inhibitor (ripasudil) or without ripasudil (non-ripasudil) groups. Mean intraocular pressure (IOP) changes, success rate, and number of eyedrops were compared for both groups. RESULTS: A total of 17 and 15 subjects dropped out in the ripasudil group and non-ripasudil group, respectively. At baseline, the mean IOP was 16.8±5.0 mm Hg in the ripasudil group (38 patients) and 16.2±4.4 in the non-ripasudil group (52 patients). The IOP decreased to 11.4±3.2 mm Hg, 10.9±3.9 mm Hg and 10.6±3.5 mm Hg at 12, 24 and 36 months in the ripasudil group, while it decreased to 11.2±4.1 mm Hg, 10.5±3.1 mm Hg and 10.9±3.2 mm Hg at 12, 24 and 36 months in the non-ripasudil group, respectively. There was a significant decrease in the number of IOP-lowering medications after trabeculectomy in the ripasudil group versus the non-ripasudil group at 24 (p=0.010) and 36 months (p=0.016). There was no statistically significant difference between the groups for the 3-year cumulative probability of success. CONCLUSION: Although ripasudil application did not increase the primary trabeculectomy success rate, it did reduce IOP-lowering medications after trabeculectomy with mitomycin C.

Mitomycin C 0.2 mg/ml versus Mitomycin C 0.4 mg/ml during the Implantation of an Ab Externo Polystyrene-isobutylene-styrene Microshunt: A Mega-analysis.

PURPOSE: To compare the effectiveness and adverse event profile of standalone polystyrene-isobutylene-styrene (SIBS) microshunt implantation with adjunct mitomycin C (MMC) 0.2 mg/ml and MMC 0.4 mg/ml. DESIGN: Mega-analysis using individual patient data from international prospective and retrospective clinical studies. PARTICIPANTS: Patients with glaucoma who underwent implantation of a SIBS microshunt with MMC as a standalone procedure. METHODS: A comparison of eyes that received MMC 0.2 mg/ml or 0.4 mg/ml. MAIN OUTCOMES MEASURES: Primary outcome was complete success defined as the proportion of eyes at 1 year with all of the following: (1) no 2 consecutive intraocular pressures (IOPs) > 17 mmHg; (2) no clinical hypotony; (3) ≥ 20% IOP reduction from baseline; and (4) no use of glaucoma medications. Secondary outcomes included IOP thresholds of 12 mmHg, 14 mm Hg, and 21 mmHg, median IOP, number of medications, risk factors for failure, interventions, adverse events, and reoperations. RESULTS: At 1 year, the complete success rate was significantly higher (71.3% vs. 50.46%; P < 0.001) and the median IOP was significantly lower (13.0 vs 14.2 mmHg; P < 0.05) in the MMC 0.4 mg/ml group. Mitomycin C 0.2 mg/ml was found to be a significant risk factor for failure (hazard ratio 1.75; 95% confidence interval 1.14-2.67). Needling and surgical revision occurred at a lower rate in the MMC 0.4 mg/ml group (7% vs 18.8%; P = 0.002 and 4.3% vs 13.7% P = 0.0087, respectively). Adverse events occurred at a similar frequency in both groups (26.6% MMC 0.2 mg/ml vs 29.6% MMC 0.4 mg/ml; P = 0.46), most of which were early and transient. CONCLUSION: Polystyrene-isobutylene-styrene microshunt implantation with MMC 0.4 mg/ml resulted in a higher success rate with greater IOP reduction compared with MMC 0.2 mg/ml. Higher MMC concentration was not associated with increased serious adverse events. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Outcomes of a Second Ahmed Glaucoma Implant With Mitomycin-C in Pediatric Glaucoma After Initial Valve Failure.

PRCIS: After the failure of a glaucoma drainage device in children, implantation of a second Ahmed glaucoma valve with mitomycin-C allows a significant reduction of intraocular pressure and number of medications with good medium-term and long-term survival. INTRODUCTION: The effectiveness of glaucoma drainage devices (GDD) is limited in time. There is little literature regarding the optimal management strategy after failure of a GDD in pediatric glaucoma. PURPOSE: To report the outcomes of Ahmed glaucoma valve implantation (AGV) with mitomycin-C (MMC) after failure of a GDD in children. METHODS: Retrospective chart review of patients with a history of at least 1 GDD receiving an AGV implantation with MMC between 2000 and 2019. We defined complete success as an IOP of 5-21 mm Hg without glaucoma medication and qualified success as a final IOP of 5-21 mm Hg with one or more glaucoma medication, without loss of vision. RESULTS: Twenty-one patients (22 eyes) met the inclusion criteria. The intraocular pressure and number of medications were significantly reduced. The probability of complete success was 47% [95% CI: 29%-75%] at 2 years and 34% [95% CI: 18%-65%] at 4 years. The probability of qualified success was 74% [95% CI: 56%-97%] at 2 years, and 54% [95% CI: 34%-84%] at 5 years. Failure happened in 10 eyes after a mean time of 4.3 years ±3.6 (6 mo to 15 y), 5 of which (23%) for severe complications or loss of vision. DISCUSSION: This study of implantation of a second valve with MMC reports a significant decrease in IOP and medications with medium-term and long-term success rates close to those reported for first valve implantation, although with a high risk of complications.

Pigtail with self-retaining bicanalicular intubation combined with Mitomycin C for the treatment of acquired lower punctal stenosis.

BACKGROUND: The pigtail was used to create an opening at the lower punctal site in grade 0 stenosis with insertion of self-retaining tube and Mitomycin C (MMC). METHODS: The patients with acquired lower punctal stenosis (grade 0) were divided randomly into equal groups, Group A: were treated with pigtail and MMC 0.02% and Group B: were treated with pigtail alone. The pigtail was inserted through the upper punctum until its tip reached the occluded punctum, this site was incised with a scalpel (No. 11). A self-retaining bicanalicular tube was then placed. RESULTS: Results of 36 eyes from 26 patients were included. No differences were observed between both groups regarding epiphora score, FDD test and punctal size preoperatively. The postoperative epiphora score, there were significant differences at 1 month (P = 0.035), 3 months (P = 0.005), and 6 months after removal (P < 0.001). The FDD test, there were significant differences at 6 months (P = 0.045), 1 month (P = 0.021), 3 months (P = 0.012), and 6 months post tube removal (P = 0.005). The punctal size, both groups differed at 1 month (P = 0.045), 3 months (P = 0.03), and 6 months post tube removal (P = 0.005). Only one case (5.5%) at each group showed extrusion of the tube. CONCLUSION: The pigtail probe, bicanalicular stent and MMC can be an effective method in treatment of severe punctal stenosis.

The effect of adjuvant Mitomycin C during vitrectomy on functional and anatomical outcomes in patients with severe diabetic tractional retinal detachment.

PURPOSE: To evaluate the effect of adjuvant Mitomycin C (MMC) use on the anatomical and functional success of vitreoretinal surgery (VRS) in severe diabetic tractional retinal detachment (dTRD) patients. METHODS: A retrospective analysis of consecutive patients undergoing VRS due to severe dTRD was conducted. Patients were categorized into those who received 20 µg/0.1 mL MMC via MMC sandwich method (Group 1) and those who did not (Group 2). Demographics, surgical characteristics, visual outcomes, and complications that may related to MMC were analyzed. RESULTS: A total of 25 eyes were included, 13 in Group 1 and 12 in Group 2. No statistical difference was observed in baseline characteristics between the groups. The mean best-corrected visual acuity was 1.90 ± 0.43 logMAR and 1.93 ± 0.41 logMAR preoperatively and 1.60 ± 0.78 logMAR and 1.56 ± 0.78 logMAR postoperatively in Groups 1 and 2, respectively (p = 0.154). The postoperative mean intraocular pressure was 16.23 ± 2.55 mmHg and 13.08 ± 4.94 mmHg in Groups 1 and 2, respectively (p = 0.225). The rate of re-surgery was significantly lower in Group 1 (0% vs. 41.7% in Group 2, p = 0.015). Retina was attached in all patients at the last visit. No MMC-related complication was recorded. CONCLUSION: Intraoperative adjuvant MMC application for severe dTRD significantly reduces re-surgery rates with good anatomical and functional outcomes safely.

Efficacy of Ab Interno Revision for Trabeculectomy Bleb Failure Using a Minimally Invasive Approach: A Prospective Study.

PRCIS: Ab interno bleb revision using the Grover and Fellman spatula offers potential benefits in improved intraocular pressure control and spares the conjunctiva for enhanced bleb management. PURPOSE: This study aimed to evaluate the safety and effectiveness of Ab-Interno Bleb Revision (AIBR) for treating failed trabeculectomy blebs. METHODS: This noncomparative case series enrolled glaucoma patients with failed trabeculectomy blebs who underwent AIBR and were followed up for 1 year. Eligible patients received subconjunctival Mitomycin C 0.1 mL of 0.2 mg/mL (20 µg) 5 days before the AIBR, performed using the Grover and Fellman spatula. The primary outcome measures were intraocular pressure (IOP) and the usage of IOP-lowering medications 1 year after the procedure. Secondary outcomes included the procedure's failure rate and complications. Complete success was defined as achieving an IOP between 5 and 21 mm Hg without medication, while qualified success required additional medical treatment. RESULTS: The study comprised 23 eyes from 23 patients, having a mean age of 59.66±14.93 years. Preoperatively, the mean IOP was 23.54±10.7 mm Hg, and the mean antiglaucoma medication requirement was 3.99±0.65, both significantly reduced to 15.7±6.9 mm Hg ( P =0.009) and 1.26±1.2 ( P <0.001) at 1 year, respectively. Overall, 19 eyes (82.6%) achieved success (complete success: 39.2%, qualified success: 43.4%), while in 4 (17.4%) patients, the procedure failed (IOP >21 mm Hg). 5 patients had transient hyphema, but there were no sight-threatening complications such as hypotony or choroidal detachment. CONCLUSIONS: Ab-Interno Bleb Revision (AIBR) is a safe, effective, and minimally invasive intervention for managing failed trabeculectomy blebs. By eliminating the need to reopen the conjunctiva, this technique offers a promising alternative for the treatment of this challenging condition.

Visual Field Outcomes in the Primary Tube Versus Trabeculectomy Study.

PURPOSE: To describe visual field outcomes in the Primary Tube Versus Trabeculectomy (PTVT) Study. DESIGN: Cohort analysis. PARTICIPANTS: A total of 155 eyes (155 subjects) randomly assigned to treatment with tube shunt surgery (n = 84) or trabeculectomy with mitomycin C (n = 71). METHODS: The PTVT Study was a multicenter randomized clinical trial comparing the safety and efficacy of trabeculectomy and tube shunt surgery in eyes without previous intraocular surgery. Subjects underwent standard automated perimetry (SAP) at baseline and annually for 5 years. Standard automated perimetry tests were deemed reliable if the false-positive rate was ≤ 15%. Tests were excluded if visual acuity was ≤ 20/400 or loss of ≥ 2 Snellen lines from baseline because of a nonglaucomatous etiology. Linear mixed-effects models were used to compare rates of change in SAP mean deviation (MD) between the 2 groups. Intraocular pressure (IOP) control was assessed by percentage of visits with IOP < 18 mmHg and mean IOP. MAIN OUTCOME MEASURES: Rate of change in SAP MD during follow-up. RESULTS: A total of 730 SAP tests were evaluated (average of 4.7 tests per eye). The average SAP MD at baseline was -12.8 ± 8.3 decibels (dB) in the tube group and -12.0 ± 8.4 dB in the trabeculectomy group (P = 0.57). The mean rate of change in SAP MD was -0.32 ± 0.39 dB/year in the trabeculectomy group and -0.47 ± 0.43 dB/year in the tube group (P = 0.23). Eyes with mean IOP 14 to 17.5 mmHg had significantly faster rates of SAP MD loss compared with eyes with mean IOP < 14 mmHg (-0.59 ± 0.13 vs. -0.27 ± 0.08 dB/year; P = 0.012), and eyes with only 50% to 75% of visits with IOP < 18 mmHg had faster rates than those with 100% of visits with IOP < 18 mmHg (-0.90 ± 0.16 vs. -0.29 ± 0.08 dB/year; P < 0.001). Multivariable analysis identified older age and worse IOP control as risk factors for faster progression in both treatment groups. CONCLUSIONS: No statistically significant difference in mean rates of visual field change was observed between trabeculectomy and tube shunt surgery in the PTVT Study. Worse IOP control was significantly associated with faster rates of SAP MD loss during follow-up. Older patients were also at risk for faster progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluating Primary Treatment for People with Advanced Glaucoma: Five-Year Results of the Treatment of Advanced Glaucoma Study.

PURPOSE: To determine whether primary trabeculectomy or medical treatment produces better outcomes in terms of quality of life (QoL), clinical effectiveness, and safety in patients with advanced glaucoma. DESIGN: Multicenter randomized controlled trial. PARTICIPANTS: Between June 3, 2014, and May 31, 2017, 453 adults with newly diagnosed advanced open-angle glaucoma in at least 1 eye (Hodapp classification) were recruited from 27 secondary care glaucoma departments in the United Kingdom. Two hundred twenty-seven were allocated to trabeculectomy, and 226 were allocated medical management. METHODS: Participants were randomized on a 1:1 basis to have either mitomycin C-augmented trabeculectomy or escalating medical management with intraocular pressure (IOP)-reducing drops as the primary intervention and were followed up for 5 years. MAIN OUTCOME MEASURES: The primary outcome was vision-specific QoL measured with the 25-item Visual Function Questionnaire (VFQ-25) at 5 years. Secondary outcomes were general health status, glaucoma-related QoL, clinical effectiveness (IOP, visual field, and visual acuity), and safety. RESULTS: At 5 years, the mean ± standard deviation VFQ-25 scores in the trabeculectomy and medication arms were 83.3 ± 15.5 and 81.3 ± 17.5, respectively, and the mean difference was 1.01 (95% confidence interval [CI], -1.99 to 4.00; P = 0.51). The mean IOPs were 12.07 ± 5.18 mmHg and 14.76 ± 4.14 mmHg, respectively, and the mean difference was -2.56 (95% CI, -3.80 to -1.32; P < 0.001). Glaucoma severity measured with visual field mean deviation were -14.30 ± 7.14 dB and -16.74 ± 6.78 dB, respectively, with a mean difference of 1.87 (95% CI, 0.87-2.87 dB; P < 0.001). Safety events occurred in 115 (52.2%) of patients in the trabeculectomy arm and 124 (57.9%) of patients in the medication arm (relative risk, 0.92; 95% CI, 0.72-1.19; P = 0.54). Serious adverse events were rare. CONCLUSIONS: At 5 years, the Treatment of Advanced Glaucoma Study demonstrated that primary trabeculectomy surgery is more effective in lowering IOP and preventing disease progression than primary medical treatment in patients with advanced disease and has a similar safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

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.

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.

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.