Construction of a screening system for lipid-derived radical inhibitors and validation of hit compounds to target retinal and cerebrovascular diseases.

Recent studies have highlighted the indispensable role of oxidized lipids in inflammatory responses, cell death, and disease pathogenesis. Consequently, inhibitors targeting oxidized lipids, particularly lipid-derived radicals critical in lipid peroxidation, which are known as radical-trapping antioxidants (RTAs), have been actively pursued. We focused our investigation on nitroxide compounds that have rapid second-order reaction rate constants for reaction with lipid-derived radicals. A novel screening system was developed by employing competitive reactions between library compounds and a newly developed profluorescence nitroxide probe with lipid-derived radicals to identify RTA compounds. A PubMed search of the top hit compounds revealed their wide application as repositioned drugs. Notably, the inhibitory efficacy of methyldopa, selected from these compounds, against retinal damage and bilateral common carotid artery stenosis was confirmed in animal models. These findings underscore the efficacy of our screening system and suggest that it is an effective approach for the discovery of RTA compounds.

A Case of Corneal Thinning During S-1 Oral Administration.

We experienced a case of bilateral corneal thinning during the oral taking of S-1, a combination anti-cancer drug of tegafur, gimeracil, and oteracil-potassium. A 69-year-old man was prescribed oral S-1 for the treatment of duodenal papilla adenocarcinoma and intraductal papillary mucinous neoplasm. However, he developed a decrease in visual acuity in both eyes after three cycles of S-1 oral taking, and ophthalmic examination revealed corneal thinning exceeding 100 µm and an increase in high-order irregularity of cornea in both eyes. After one month after discontinuation of S-1, his visual acuity and corneal thickness returned to its previous levels. Besides corneal ulcers and perforations, corneal thinning can be recognized as a potential corneal side effect necessitating monitoring during S-1 treatment.

Efficacy and safety of first-line or second-line selective laser trabeculoplasty for normal-tension glaucoma: a multicentre cohort study.

BACKGROUND/AIMS: This study aimed to investigate and compare the efficacy and safety of first-line and second-line selective laser trabeculoplasty (SLT) in Japanese patients with normal-tension glaucoma (NTG). METHODS: 100 patients with NTG were enrolled in this study. Patients were treated with SLT as a first-line or second-line treatment for NTG. Main outcome measures were intraocular pressure (IOP) reduction rate, outflow pressure improvement rate (ΔOP), success rate at 1 year and complications. Success was defined as ΔOP≥20% (criterion A) or an IOP reduction ≥20% (criterion B) without additional IOP-lowering eye-drops, repeat SLT or additional glaucoma surgeries. The incidence of transient IOP spike (>5 mm Hg from the pretreatment IOP), conjunctival hyperaemia, inflammation in the anterior chamber and visual impairment due to SLT were assessed. RESULTS: A total of 99 patients (99 eyes) were initially enrolled in this study, including 74 eyes assigned to the first-line SLT group and 25 eyes to the second-line SLT group. The mean IOP of 16.3±2.1 mm Hg before SLT decreased by 17.1%±9.5% to 13.4±1.9 mm Hg at 12 months after SLT in the first-line group (p<0.001), and the mean IOP of 15.4±1.5 mm Hg before SLT decreased by 12.7%±9.7% to 13.2±2.0 mm Hg at 12 months after SLT (p=0.005) in the second-line group. Both groups showed significant reductions in IOP. Higher pre-SLT IOP and thinner central corneal thickness were associated with greater IOP reduction. The success rate at 1 year was higher in the first-line compared with the second-line group, with lower pretreatment IOP and the use of IOP-lowering medication before SLT being associated with treatment failure. Most post-treatment complications were minor and transient. CONCLUSIONS: SLT may be an effective and safe treatment option for NTG, as either a first-line or second-line treatment. TRIAL REGISTRATION NUMBER: The study was registered in the UMIN-CTR (UMIN Test ID: UMIN R000044059).

Two different types of giant bleb formation following Ahmed Glaucoma valve implantation.

Purpose: This study aims to present two different types of giant bleb formation following Ahmed Glaucoma Valve (AGV) implantation: an anterior enlarged giant bleb and a posterior enlarged giant bleb. Observations: In Case 1, a 70-year-old Japanese male underwent AGV implantation for neovascular glaucoma in his right eye (OD). Preoperatively, the patient's intraocular pressure (IOP) and best corrected visual acuity (BCVA) were 23 mmHg and 0.6, respectively, OD, while using 3 antiglaucoma topical medications. Two months post-surgery, the patient began experiencing double vision. Slit lamp evaluation revealed no abnormalities, IOP and BCVA were 24.0 mmHg and 0.8, respectively, OD. A posteriorly enlarged bleb in the superotemporal quadrant OD was found to be causing displacement on T2-weighted orbital MRI. The patient underwent surgical excision of the anterior bleb wall. By three weeks post-surgery, the double vision resolved; IOP and BCVA were 17 mmHg and 0.7, respectively, and a normal bleb in the slit lamp evaluation was identified OD. In Case 2, a 10-year-old Japanese female underwent AGV implantation for childhood glaucoma associated with congenital cataract OD. Preoperatively, IOP and BCVA were 30 mmHg and 0.5, respectively, OD, while using 3 antiglaucoma topical medications. She underwent pars plana vitrectomy (PPV) in addition to AGV implantation. Seven months post-surgery, slip lamp evaluation revealed an anteriorly enlarged giant bleb that only cause her a cosmetic concern. Conclusions and Importance: There are two types of giant bleb formation following AGV implantation based on the direction of the enlargement: an anterior enlarged giant bleb and a posterior enlarged giant bleb. The introduction of this classification contribute to better understanding and management of this unusual surgical complication.

Potentially compromised systemic and local lactate metabolic balance in glaucoma, which could increase retinal glucose and glutamate concentrations.

To investigate the association between lactate metabolism and glaucoma, we conducted a multi-institutional cross-sectional clinical study and a retinal metabolomic analysis of mice with elevated intraocular pressure (IOP) induced by intracameral microbead injection. We compared lactate concentrations in serum and aqueous humor in age-matched 64 patients each with primary open-angle glaucoma (POAG) and cataract. Neither serum nor aqueous humor lactate concentrations differed between the two groups. Multiple regression analysis revealed that only body mass index showed a significant positive correlation with serum and aqueous humor lactate concentration in POAG patients (rs = 0.376, P = 0.002, and rs = 0.333, P = 0.007, respectively), but not in cataract patients. L-Lactic acid was one of the most abundantly detected metabolites in mouse retinas with gas chromatography and mass spectrometry, but there were no significant differences among control, 2-week, and 4-week IOP elevation groups. After 4 weeks of elevated IOP, D-glucose and L-glutamic acid ranked as the top two for a change in raised concentration, roughly sevenfold and threefold, respectively (ANOVA, P = 0.004; Tukey-Kramer, P < 0.05). Glaucoma may disrupt the systemic and intraocular lactate metabolic homeostasis, with a compensatory rise in glucose and glutamate in the retina.

Comparison of Schlemm's Canal Morphology Parameters Between Propensity Score-Matched Primary Open-Angle Glaucoma and Exfoliation Glaucoma.

Purpose: This study aimed to histologically compare the status of Schlemm's canal (SC) and Schlemm's canal endothelial (SCE) cells between trabeculectomy specimens from patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (EXG). Methods: A total of 182 eyes from 152 patients with POAG and 138 eyes from 116 patients with EXG underwent immunohistochemical staining for thrombomodulin. Equal numbers of cases were selected from both groups using propensity score matching. The following parameters were evaluated: total SC length, staining positive and negative SC length (PSC and NSC, respectively), opened and closed SC length, staining positive and opened SC length, staining positive and closed SC length, staining negative and opened SC length (NOSC), and staining negative and closed SC length. Results: After matching for age and gender, 87 cases were selected in each group. The EXG group had significantly higher preoperative IOP and medication scores. PSC was significantly longer in the POAG group, while NSC and NOSC were longer in the EXG group. Multiple regression analysis of these 174 cases revealed that PSC was significantly shorter in the EXG group. After matching for age, gender, preoperative IOP, and medication score, 64 cases were selected in each group, and NOSC was significantly longer in the EXG group. Conclusions: These findings suggest that in EXG, SCE loss occurs independently of background factors such as aging and medication use. The loss of SCE may have a more critical impact on IOP elevation in EXG compared to POAG.

Comparison of Phaco-Tanito Microhook Trabeculotomy between Propensity-Score-Matched 120-Degree and 240-Degree Incision Groups.

This study compared the effectiveness and safety of 120-degree (nasal) and 240-degree (bilateral) incisions in Tanito Microhook Trabeculotomy (TMH) combined with cataract surgery in patients with open-angle glaucoma. From a pool of 185 eyes, 67 eyes from 67 subjects were selected for each incision group using propensity score matching to align age, sex, glaucoma type, and preoperative intraocular pressure (IOP). The study found that preoperative IOP, initially 18.6 mmHg in both groups, decreased to 13.2 mmHg in the nasal group and 12.8 mmHg in the bilateral group 12 months postoperatively, representing reductions of 29% and 31%, respectively. Similarly, medication scores decreased from 3.4 to 2.7 in the nasal group and from 3.1 to 2.5 in the bilateral group. Notably, the bilateral incision group exhibited a significantly higher hyphema red blood cell score compared to the nasal group (p < 0.0001). Across the study period, other parameters such as IOP, medication score, visual acuity, anterior chamber flare, corneal endothelial cell density, visual field mean deviation, and the frequency of surgical complications other than hyphema were similar between the groups. The study concluded that TMH combined with cataract surgery is equally effective and safe regardless of incision width, although narrower incisions resulted in reduced early postoperative hyphema.

Exploring the Pressure Characteristics of the PRESERFLO MicroShunt in In Vitro Studies and Effects of Sclera on Device Performance.

This study aims to investigate the pressure characteristics of the PRESERFLO MicroShunt, a microinvasive glaucoma device, using an in vitro setup. Additionally, the study explores the impact of the scleral tissue surrounding the device on its pressure and lumen area. Ten PRESERFLO MicroShunts were subjected to an in vitro experimental setup. A constant flow of physiological saline was maintained at 2 µL/min using an infusion syringe pump. The PRESERFLO was connected to a pressure transducer via a 23 G needle. Pressure characteristics were measured under three different conditions: without sclera [sclera (-)], passing through sclera at a 90° angle (sclera 90°), and passing through sclera at a 30° angle (sclera 30°). The lumen area of the device was measured using microscopic observation. We observed peak and trough pressures in this experimental setting; the peak pressure (6.76 mmHg) was significantly higher than the trough pressure of 4.74 mmHg (p = 0.0020) in the sclera (-) condition. Compared to sclera (-), the peak pressures were significantly higher in the sclera 90° (7.81 mmHg, p = 0.0020) and the sclera 30° (7.96 mmHg, p = 0.0039) conditions. Additionally, compared to sclera (-), the trough pressure was significantly higher in the sclera 90° (6.25 mmHg, p = 0.0039) and the sclera 30° (5.76 mmHg, p = 0.037) conditions. The lumen area was significantly smaller in the sclera 90° condition (3515 µm2) than the sclera (-) condition (3927 µm2, p = 0.0078). The study found that when the distal end of PRESERFLO MicroShunt was free and in air, it exhibited both peak and trough pressures. The presence of scleral tissue surrounding the PRESERFLO MicroShunt affects its lumen area and pressure characteristics. Understanding these effects can provide valuable insights into the device's performance.

Dislocation of the PreserFlo MicroShunt During a Postsurgical Needling Procedure.

We report a case of PreserFlo MicroShunt (PFM) dislocation following a postsurgical needling procedure. A 58-year-old woman underwent PFM implantation for exfoliation glaucoma in her left eye (OS). There were no intraoperative complications. Preoperatively, her best-corrected visual acuity (BCVA) was 0.6, and her intraocular pressure (IOP) was 25 mmHg with three antiglaucoma medications in the OS. On postoperative day 21, the IOP was 21 mmHg OS, and the filtration bleb had shrunk. A needling procedure was performed using a sharp 26-gauge needle to lower the IOP. On postoperative day 29, the BCVA was 0.02, and the IOP was 60 mmHg OS. Gonioscopy revealed no device tip in the anterior chamber, and peripheral anterior synechia was observed at the site of PFM insertion. Anterior segment optical coherence tomography showed a dislocated device in the subconjunctival space. On postoperative day 35, the dislocated PFM was removed, and a new device was inserted. Following the reoperation, no further complications were observed, and bleb formation was obtained. In conclusion, like other glaucoma filtering surgeries, PFM may require postsurgical needling procedures. Needling procedures may cause PFM dislocation and IOP rise, resulting in the requirement for further IOP-reducing procedures.

Fellow-Eye Comparison between Phaco-Tanito Microhook Trabeculotomy and Phaco-iStent Inject W.

This study aims to compare the surgical efficacy and safety of the Tanito microhook trabeculotomy (TMH-CE) and iStent inject W (Inject-CE) when performed in combination with cataract surgery on the eyes of glaucoma patients. A total of 78 glaucomatous eyes from 39 participants were retrospectively analyzed. Intraocular pressure (IOP), the number of antiglaucoma medications, best-corrected visual acuity (BCVA), anterior chamber flare (ACF), and corneal endothelial cell density (CECD) were all evaluated preoperatively and at multiple postoperative time points. The preoperative IOP was significantly higher in the TMH-CE (19.6 ± 6.7 mmHg) than in the Inject-CE (15.7 ± 3.8 mmHg) (p < 0.0001). At the 12-month follow-up, reductions in IOP and the number of medications were more pronounced in the TMH-CE (6.6 mmHg, 27.6% and -1.1, respectively) group than Inject-CE (2.7 mmHg, 12.4% and -0.7, respectively) (p < 0.0001 and p = 0.0034), while the IOP and medication-number levels were identical between TMH-CE (13.0 ± 3.3 mmHg and 1.3 ± 0.9, respectively) and Inject-CE (12.9 ± 2.6 mmHg and 1.9 ± 0.9, respectively) (p = 0.88 and p > 0.99, respectively). The TMH-CE group exhibited a higher ACF, a higher frequency of layered hyphema, and a greater anterior chamber floating red blood cells score in the early postoperative periods. Despite these differences, the changes in BCVA, ACF, and CECD were equivalent between the two groups in later follow-up periods. TMH-CE provides a more significant IOP reduction and medication-number reduction compared to Inject-CE, while Inject-CE shows quicker BCVA recovery. This study provides valuable insights for ophthalmologists choosing the most suitable surgical approach for glaucoma and cataract patients.

Roles of Cognitive Function on Visual Field Reliability Indices among Glaucoma Patients.

This study reports the prevalence of cognitive impairment (CI) in patients attending a glaucoma outpatient clinic at a tertiary hospital. It also comprehensively assesses possible associations between CI and visual field (VF) reliability indices among glaucoma patients. The retrospective analysis included 1464 eyes from 746 subjects (mean age, 70.6 ± 11.9; 401 males and 345 females). CI was evaluated using the Mini-Cog test, revealing a suspected prevalence of 8.0% (60 out of 746) among the patients. After adjusting for various background parameters using a mixed effects regression model, an abnormal Mini-Cog score was linked to higher false negative (FN) (p = 0.0034) and false positive (FP) (p = 0.0051) but not fixation loss (FL) (p = 0.82). Among the Mini-Cog components, a lower word recall test score was associated with higher FN (p < 0.0001), with a borderline difference in FP (p = 0.054) and no significant effect on FL (p = 0.09). Conversely, a lower clock drawing test score was associated with higher FP (p = 0.038), while FL (p = 0.49) and FN (p = 0.12) remained unaffected. These findings suggest that CI can impact the reliability of VF testing among glaucoma patients, highlighting the importance of assessing cognitive function in glaucoma care.

PHACE(S) Syndrome with Ocular Involvements and No Periocular Hemangioma.

PHACE(S) syndrome is a neurocutaneous disorder with a hallmark finding of an infantile facial hemangioma (IFH) >5 cm. Eye examination of patients with PHACE(S) syndrome with no IFH at periorbital region is reported to be of low yield. We report a unique case of the syndrome with ocular manifestations without periorbital IFH or systemic findings. A 3-week-old female infant with right periauricular IFH >5 cm, extending to the neck and cheek and lower lip IFH was presented. Examination revealed pseudoptosis due to microphthalmia with esotropia and hypertropia. Both corneas were clear with diameters of 5 mm and 10 mm, right eye (RE) and left eye (LE), respectively. There was a posterior polar cataract with a poor view of the fundus RE. Ocular B-scan and magnetic resonance imaging (MRI) findings were suggestive of a dysmorphic globe, vitreous hemorrhage, spherophakia and persistent fetal vasculature RE and normal findings LE. Clinical evaluation, MRI, and MR angiography revealed no other systemic abnormalities. Subsequent follow-up visits revealed progressive clouding of the cornea with neovascularization and the development of phthisis bulbi RE at which point an ocular prosthesis was placed. The IFH was managed with dye laser and with oral propranolol. At 1 year, the patient has remained stable with no development of new local or systemic anomalies, regression of the periauricular and lip IFH, and normal development of the orbital structure RE with an ocular prosthesis in situ. Ocular involvement in patients with PHACE(S) syndrome may be present without periorbital IFH. Regardless of the location of the IFH and the presence or absence of a periocular component, it is recommended that they receive a full initial ophthalmological assessment.

Factors Associated with Topical Medication Instillation Failure in Glaucoma: VRAMS-QPiG Study.

INTRODUCTION: To report eyedrop instillation techniques and factors associated with instillation failure among glaucoma subjects in the Video-Recorded Assessment of Medication Skill and Questionnaire-based evaluation of Perception in Glaucoma Study. METHODS: In this cross-sectional observational study, subjects were 60 patients with glaucoma (mean ± standard deviation age, 68.4 ± 11.3 years; 30 men) who required ocular hypotensive medication(s). Subjects completed ophthalmologic examinations and the Mini-Cog cognitive function test; their typical eyedrop instillation technique was video-recorded. Subjects rated their technique as successes/failures by questionnaire and two examiners rated the successes/failures based on video assessment. Discrepancy between self-reported and video-assessed success/failure rates of instillation was the main outcome measures. Multivariate logistic regression identified factors in instillation failure. RESULTS: Of 48/56 (86%) self-reported successes, 27/48 (56%) failed based on video assessment; as a result, 32/56 (57%) were inconsistent between subjective and objective assessments. Overall, 30/56 (54%) failed based on video assessment. In the subject-based data model, older age [odds ratio (OR) 0.93/year, P = 0.025] and lower cognitive function score (OR 2.7/score, P = 0.025) were factors in failed instillations. In the eye-based data model, less myopic objective refractive error (OR 0.77/diopter, P = 0.016) and lower visual field foveal threshold (OR 1.1/decibel, P = 0.041) were factors in failures. CONCLUSION: In addition to older age, decreased cognitive function, hyperopia, and decreased foveal sensitivity are risks for failed eyedrop instillation. Treating physicians can screen patients who require guidance by checking the risk factors of instillation failure rather than by relying on patient reports.

Influence of Goniotomy Size on Treatment Safety and Efficacy for Primary Open-Angle Glaucoma: A Multicenter Study.

PURPOSE: To compare the efficacy and safety of 120-, 240-, and 360-degree goniotomy (GT) with or without phacoemulsification with intraocular lens implantation (PEI) for patients with primary open-angle glaucoma (POAG). DESIGN: Multicenter, retrospective, comparative, nonrandomized interventional study. METHODS: Patients diagnosed with POAG who underwent GT with or without PEI were included, and divided into 6 groups: 1) standalone 120-degree GT (120GT); 2) standalone 240-degree GT (240GT); 3) standalone 360-degree GT (360GT); 4) PEI + 120GT; 5) PEI + 240GT; and 6) PEI + 360GT. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. Success was defined as a postoperative IOP within the range of 6 to 18 mm Hg and a 20% reduction from baseline without further glaucoma surgery. Complete success and qualified success were defined as the above without and with ocular hypotensive medications, respectively. RESULTS: Three hundred eight eyes of 231 patients were included with a mean follow-up of 14.4 ± 8.6 months (6.0-48.0 months). There were no significant differences in the reductions in IOP and number of medications and cumulative survival probability for complete and qualified success rates among the 3 groups of standalone GT and PEI + GT. The 360GT group had the highest proportion of hyphema with or without PEI. CONCLUSIONS: 120GT, 240GT, and 360GT with or without PEI showed similar efficacy in reducing IOP and medications used in POAG. 360GT with or without PEI was more likely to cause hyphema compared with 120GT or 240GT. 120GT with or without PEI was sufficient for treating POAG with or without cataract..

Which is More Effective and Safer? Comparison of Propensity Score-Matched Microhook Ab Interno Trabeculotomy and iStent Inject.

INTRODUCTION: The purpose of this study was to compare the surgical outcomes between ab interno trabeculotomy (LOT) and iStent inject W implantation (iStent) both combined with cataract surgery, matching the background factors including age, intraocular pressure (IOP), medication score, central corneal thickness (CCT), and axial length. METHODS: A total of 100 eyes from 75/79 patients with primary open-angle glaucoma were included in the LOT/iStent groups. The background factors were matched between the two groups using the propensity score. RESULTS: There were no significant differences in age, IOP, medication score, CCT, and axial length, preoperatively. The postoperative medication scores were 1.3 ± 1.2 and 1.2 ± 1.2 in the LOT and iStent groups. The postoperative IOPs were 12.8 ± 2.8 and 13.1 ± 2.4 mmHg in the LOT and iStent groups, respectively. The changes in the medication score were - 0.64 ± 1.4 and - 0.44 ± 1.6 in the LOT and iStent groups, respectively. The changes in the IOP were - 2.1 ± 3.3 and - 1.5 ± 3.0 mmHg in the LOT and iStent groups, respectively. These values were not significantly different between the two groups. The postoperative IOP and changes in the IOP were significantly associated with preoperative IOP and CCT. There was no significant difference in the occurrence of postoperative complications (hyphema, 11.0% and 6.0%, and transient ocular hypertension, 8.0% and 5.0%, in the LOT and iStent groups, respectively). CONCLUSION: LOT and iStent have similar surgical outcomes with sufficient safety. Postoperative IOP was significantly associated with preoperative IOP and CCT in both groups.

Nationwide Analysis of Glaucoma Surgeries in Fiscal Years of 2014 and 2020 in Japan.

Nationwide trends in glaucoma surgical procedures were assessed by using the NDB Open Data 2014 and 2020. In Japan, 33,340 non-laser, 54,569 laser, and 88,019 total glaucoma surgeries were performed in 2014. In 2020, 60,108 non-laser, 60,547 laser, and 120,655 total glaucoma surgeries were performed. The rates from 2014 to 2020 were 180%, 111%, and 137%, respectively. In each procedure, angle surgery (326%), tube shunt surgery (383%), ciliary coagulation (489%), and gonio-laser (225%) were remarkably increased, while iridectomy (75%) and iris laser (77%) decreased during the same period. An increase in laser surgery was seen in young age groups, namely, 55-59 years old and younger, while non-laser surgery was increased in old age groups, namely, 45-49 years old and older. In 2020, 47.6 non-laser, 48.0 laser, and 95.6 total glaucoma surgeries were performed per 100,000 persons. None of the vital statistics, including prefectural population, mean age, and rate of ≥65-year-old people, were significantly associated with the number of glaucoma surgeries. Glaucoma practice patterns changed each time a new device or procedure was introduced. The results of the current study reflected the use of new procedures, such as minimally invasive glaucoma surgery, tube shunt, selective laser trabeculoplasty, and micropulse cyclophotocoagulation.

Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.

INTRODUCTION: This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. METHODS: A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. RESULTS: BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. CONCLUSION: As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. TRIAL REGISTRATION NUMBER: jRCTs051190125.

Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC­prostaglandin analogue combination therapy.

A case of two connected stents deployed during iStent inject W surgery.

BACKGROUND: We report a case with two connected stents ejected simultaneously during an iStent inject W surgery, a modified second-generation iStent Trabecular Micro-Bypass System. CASE PRESENTATION: A 57-year-old woman with primary open-angle glaucoma underwent a combined cataract and iStent inject W surgery in her left eye. After the trabecular meshwork/Schlemm's canal was pierced by the trocar of injector, the delivery button was pressed a first time, but the stent was not ejected. After the button was pressed a second time, connected two stents were ejected. After removing the dislocated stents from the anterior chamber, two stents were implanted into the desired places using another injector. Except for mild hyphema, no postoperative complication occurred. Stereomicroscopic observation showed that the two stents were connected by a broken trocar shaft. An X-ray showed that the trocar shaft was broken at the part referred to as the "sprayed trocar". Scanning electron microscopy showed that the surface features of the broken trocar and trocar tip represented tensile failure. CONCLUSIONS: Although rare, considering that the damage was seen at the structurally weak part (i.e., sprayed trocar), the same phenomenon can happen. For patient safety, surgeons are recommended to inspect the device when the deployment of either the first or second stent is unsuccessful during the iStent inject surgery.

Flow Pressure Characteristics of the Ahmed Glaucoma Valve and Possible Effect of Entrapped Air in the Tube.

Purpose: The purpose of this study was to assess the pressure characteristics of the Ahmed Glaucoma Valve (AGV) and possible effects of air trapped in the tube. Method: Physiologic saline was pumped through 17 AGVs using a syringe infusion pump, and the flow pressure was measured by a set of pressure transducers. During the infusion at a rate of 2 µL/minute, the pressure measurement was repeated twice in each AGV to determine the repriming pressures with/without air (1 µL) in the tube. Results: After a pressure surge occurred during the initial priming, the pressure decreased suddenly and then became constant. The repriming pressure, determined as the peak pressure before valve opening, was significantly (P < 0.0001, paired t-test) higher with air (26.5 ± 6.8 mm Hg) than without air (12.1 ± 3.8 mm Hg), whereas the constant pressures after repriming was equivalent between with (10.6 ± 3.7 mm Hg) and without (10.4 ± 2.9 mm Hg) air conditions (P = 0.68). Conclusions: Air in the AGV tube causes increased repriming pressure of about two-fold compared to repriming without air. This pressure increment caused by air in the capillary-sized tube might occur because of the effects of viscosity pressure and capillary pressure. Translational Relevance: To ensure stable surgical results, surgeons are advised to not allow air to remain in the tube. Pars plana tube insertion of the AGV combined with gas tamponade surgery may result in higher-than-expected intraocular pressure. Conversely, injection of air/gas can avoid postoperative hypotony when the AGV is implanted in eyes with a high risk of hypotony.

Intra-operative challenges encountered using the zepto nano-pulse precision capsulotomy device.

Purpose: The Zepto nano-pulse precision capsulotomy is a novel device for capsulorhexis formation during cataract surgery. Few complications or challenges have been reported while using this device. The purpose of this paper is to highlight two intra-operative challenges that were encountered while using the Zepto device. Observations: CASE 1 - A 65-year-old with advanced primary open angle glaucoma (POAG) and an in situ Ahmed Glaucoma Valve located in the anterior chamber. During a planned phacoemulsification procedure, the tube became trapped between the suction cup of the Zepto device and the lens, resulting in a sudden complete collapse of the anterior chamber. The procedure was completed after appropriate interventions. On post-operative day 1 Descemet folds were visible, and corneal endothelial cell density was reduced from 2101 cells/cm2 preoperatively to 1355 cells/cm2 at 19 months postoperatively. CASE 2 - A 66-year-old female with secondary cataract from chronic inflammation post trabeculectomy for advanced POAG. During a planned phacoemulsification procedure, despite synechialysis for the 360° posterior synechiae, the iris tissue was sucked into the suction cup of the Zepto device and became incarcerated over the lens. The procedure was completed after a successful intervention. Conclusions and importance: Although not previously reported and possibly rare, intra-operative complications may be encountered while using the Zepto device, particularly in complex cataract cases. For the patient's safety and satisfactory post-operative and refractive outcomes, caution must be applied.