Silencing of Dicer enhances dacarbazine resistance in melanoma cells by inhibiting ADSL expression.

Dacarbazine (DTIC) is the primary first-line treatment for advanced-stage metastatic melanoma; thus, DTIC resistance is poses a major challenge. Therefore, investigating the mechanism underlying DTIC resistance must be investigated. Dicer, a type III cytoplasmic endoribonuclease, plays a pivotal role in the maturation of miRNAs. Aberrant Dicer expression may contribute to tumor progression, clinical aggressiveness, and poor prognosis in various tumors. Dicer inhibition led to a reduction in DTIC sensitivity and an augmentation in stemness in melanoma cells. Clinical analyses indicated a low Dicer expression level as a predictor of poor prognosis factor. Metabolic alterations in tumor cells may interfere with drug response. Adenylosuccinate lyase (ADSL) is a crucial enzyme in the purine metabolism pathway. An imbalance in ADSL may interfere with the therapeutic efficacy of drugs. We discovered that DTIC treatment enhanced ADSL expression and that Dicer silencing significantly reduced ADSL expression in melanoma cells. Furthermore, ADSL overexpression reversed Dicer silencing induced DTIC resistance and cancer stemness. These findings indicate that Dicer-mediated ADSL regulation influences DTIC sensitivity and stemness in melanoma cells.

Same-Day Bilateral Intravitreal Dexamethasone Implants for the Treatment of Diabetic Macular Edema.

INTRODUCTION: The aim of this study was to evaluate the outcomes and complications associated with the use of same-day bilateral intravitreal dexamethasone (DEX) implants for the treatment of diabetic macular edema (DME). METHODS: This retrospective analysis of an open-label, multicenter, consecutive case series included 130 eyes of 65 patients with bilateral DME who were treated with intravitreal DEX implants. The patients were divided into two groups: a control group (comprising 40 eyes treated with an alternating unilateral regimen) and a study group (comprising 90 eyes treated with concomitant bilateral DEX implants). All patients were followed up monthly after implantation. The changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to sixth month after implantation, and ocular adverse effects such as intraocular pressure, cataract, and tolerability of bilateral implantation were reviewed. The primary endpoint was to assess the safety of the same-day bilateral treatment protocol. The secondary endpoints focused on evaluating the functional and anatomical changes associated with bilateral simultaneous or alternating implantations. RESULTS: At 6 months after implantation, mean BCVA increased and CRT decreased in both groups. Moreover, no serious ocular adverse effects were observed. In addition, no differences were observed between the two groups in the number of patients who required extra follow-up visits or the number of extra visits made in addition to the treatment schedule. CONCLUSIONS: Same-day bilateral intravitreal DEX implants are associated with a low complication rate and are well tolerated by patients. This safe practice may optimize efficiency and reduce the burden on both the health-care system and patients, when used to treat bilateral DME.

Therapeutic effect of cataract surgery with simultaneous intravitreal injection of aflibercept on diabetic macular edema: An observational study.

This study aimed to investigate the therapeutic effect of cataract surgery along with simultaneous intravitreal injection (IVI) of aflibercept on diabetic macular edema (DME). This cohort study enrolled 106 patients aged >40 years with type 2 diabetes mellitus and DME who received cataract surgery from January 1, 2016, to October 31, 2020. The baseline and mean data of the following parameters were collected: age, sex, glycated hemoglobin level, diabetic retinopathy (DR) grading, previous DR treatments including IVI of anti-vascular endothelial growth factor and pan-retinal photocoagulation, intraocular pressure, use of intraocular pressure-lowering medication, central subfield thickness (CST), and log MAR visual acuity (VA). Patients were categorized into 2 groups based on whether they received aflibercept IVI or not during cataract surgery and were compared using the t test and Fisher exact test for continuous and discrete variables, respectively. Beta coefficient and standard error were calculated using multiple linear regression analysis to identify the explanatory variables predictive of the net change of CST and log MAR VA. There was no difference in the net change in CST (15.24 ± 45.07 µm vs 18.62 ± 33.84 µm, P = .772) and log MAR VA (-0.27 ± 0.29 vs -0.37 ± 0.31, P = .215). Gender, glycated hemoglobin level, aflibercept IVI during cataract surgery, and baseline CST did not interfere with the morphological and functional outcomes of DME in cataract surgery. Older age was significantly and independently associated with a greater net change in log MAR VA. Proliferative DR was significantly and independently associated with a greater net change in CST and log MAR VA. A greater baseline log MAR VA was significantly and independently associated with lower net change in log MAR VA. Simultaneous aflibercept IVI for treating DME may not interfere with the functional and tomographic parameters of cataract surgery relative to cataract surgery alone. Factors influencing the outcomes of patients with DME undergoing cataract surgery are as follows: age, baseline DR staging, and baseline VA. Identifying these factors of DME preoperatively may be an important consideration in preventing it from progressing and for improving the overall visual prognosis.

Role of pilocarpine use following laser peripheral iridotomy in eyes with refractory acute angle closure glaucoma: A case report and literature review.

RATIONALE: Angle closure glaucoma (ACG) is one of the most emergent types of glaucoma in clinical practice. Laser peripheral iridotomy (LPI) could minimize pupillary block and prevent ACG from an acute attack. However, recurrent increase in intraocular pressure (IOP) may still occur despite successful LPI. The aim of this study is to highlight the importance of postLPI pilocarpine use and larger LPI size as well as to share some experiences of cataract surgery in patients with ACG. PATIENT CONCERNS: A 63-year-old female was referred to our hospital for headache, and poor control of IOP in the right eye for 3 hours. DIAGNOSES: The patient was diagnosed ACG in the right eye. Recurrence of ACG in the right eye and new-onset and recurrent ACG in the left eye were noted during follow-up, despite successful LPI. The diagnosis was confirmed through slit lamp and gonioscope examination. INTERVENTIONS: The LPI size was enlarged and pilocarpine use was maintained at 2% (1 drop 4 times a day) in both the eyes. Finally, cataract surgery was performed in both the eyes. OUTCOMES: No recurrence of ACG was noted during postLPI pilocarpine use in both the eyes. The postoperative IOP was stable for >6 months after cataract surgery without any surgical intervention or antiglaucoma medication use. No discomfort or major complication was observed. CONCLUSION: This report highlights the importance of postLPI pilocarpine use and larger LPI size in patients with refractory ACG.

Androgen Deprivation Therapy for Prostate Cancer Did Not Increase the Risk of Retinal Vascular Occlusion: A Population-Based Cohort Study.

This study aimed to evaluate the effect of androgen deprivation therapy (ADT) on retinal vascular occlusion (RVO) development in patients with prostate cancer, using data from Taiwan's National Health Insurance Research Database. A total of 1791, 1791, and 3582 patients were enrolled in the prostate cancer with ADT group, prostate cancer without ADT group, and the control group, respectively. The primary outcome was RVO occurrence, according to diagnostic codes. Cox proportional hazard regression was used to determine the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of ADT and other covariates for RVO incidence. After a follow-up interval of up to 18 years, the patients with prostate cancer who received ADT showed significantly lower RVO incidence than the control group (aHR: 0.191, 95% CI: 0.059-0.621, p = 0.0059), after adjusting for multiple confounders. Hypertension was related to higher RVO incidence (aHR: 2.130, 95% CI: 1.127-4.027, p = 0.0199). Our overall results showed that using ADT for prostate cancer did not lead to a greater risk of RVO development. In fact, the patients with prostate cancer who received ADT had lower RVO incidence than those who did not receive ADT.

Therapeutic effect of simultaneous intravitreal dexamethasone and aflibercept on diabetic macular edema.

AIMS: To report the effect of simultaneous intravitreal dexamethasone (DEX) and aflibercept for the treatment of diabetic macular edema (DME). METHODS: This retrospective analysis of an open-label, multicenter, consecutive case series included 102 eyes of 81 patients with DME. Patients were selected into two groups. The control group consisted of 50 eyes treated with aflibercept alone, and the combination group consisted of 52 eyes treated with simultaneous DEX implant and aflibercept injection. The primary endpoints were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 6. The secondary endpoint was the interval of retreatment. RESULTS: Baseline BCVA increased and CRT decreased at 6 months in both groups. Pseudophakic eyes in the combination group exhibited significantly greater BCVA improvement compared with phakic eyes (p = 0.031). Fewer intravitreal treatments were required for eyes treated with combination therapy than for those treated with aflibercept alone (1.56 ± 0.54 vs. 4.04 ± 1.26, p < .0001), with a mean retreatment interval of 3.66 ± 0.69 months. CONCLUSIONS: Simultaneous intravitreal DEX and aflibercept achieved non-inferior improvement of visual and anatomic outcomes compared with aflibercept alone for DME, but exhibited a significantly longer treatment interval and superior visual outcome in pseudophakic eyes. This therapeutic approach is considered a valid strategy for treating DME in the era of COVID-19.

Current screening practice in patients under long-term hydroxychloroquine medication in Taiwan: A nationwide population-based cohort study.

Hydroxychloroquine (HCQ), an analog of chloroquine, is widely used in various rheumatologic and dermatologic disorders. However, it may cause severe retinopathy with long-term use. The guidelines proposed by the American Academy of Ophthalmology suggested a baseline fundus examination and an annual screening after 5 years by using automated visual fields (VF) plus spectral-domain optical coherence tomography (SD-OCT). Both multifocal electroretinogram (mfERG) and fundus autofluorescence (FAF) can also be used to improve the accuracy of diagnosis. The purpose of this study was to examine if the current HCQ screening practice in Taiwan was sufficient according to the guidelines to prevent severe macular complications.This study could remind every doctor to explain visual side effects thoroughly to every patient using HCQ, and refer patients for the ophthalmologic survey to eliminate potential visual impairment caused by this medicine.This nationwide population-based cohort study included all patients who started taking HCQ (n = 5826) from January 1, 1997, to December 31, 2007, in the Longitudinal Health Insurance Database 2000. The ICD codes used for HCQ retinopathy were 362.10, 362.55, 362.89, and 362.9. Patients previously diagnosed these retinal disorders were excluded. Demographic data including sex, age, diagnostic tools used, and the date of the initial diagnosis of the subsequent HCQ-related retinal disorder were collected. Patients were divided into 2 groups. The patients taking HCQ <5 years were defined as group 1, and >5 years as group 2. The risk of developing retinal diseases between these 2 groups was compared with a 2-sample t-test for continuous variables, and Fisher's exact test for discrete variables. Multiple logistic regressions were used for odds ratio calculation.The baseline examination ratio of the automated VF, SD-OCT scans, and multifocal electroretinograms (mfERGs) in the first 3 months were only 0.2% in both groups. The screening ratio of the 3 examination tools after 5 years were 1.1% in group 1 and 1.2% in group 2. 2.5% and 3.9% of patients developed a retinal disorder after HCQ use in group 1 and 2, respectively. The risk of developing retinal disorder was significantly higher in group 2 (relative risk = 1.53, P = .006). The odds ratio (OR) was also significantly higher in group 2 (1.67 with 95% cumulative incidence 1.20-2.30)The examination ratio according to the guidelines was very low in Taiwan. Thus, it is very important for doctors who prescribe HCQ to schedule both baseline and annual ophthalmology screening tests and inform patients of possible severe ocular complications, even in the patient taking HCQ <5 years. It is also important for ophthalmologists to review medical history carefully to find out the causes of retinotoxicity. Medications should be stopped, if possible when toxicity is recognized or strongly suspected.

Simple Molecular-Engineering Approach for Enhancing Orientation and Outcoupling Efficiency of Thermally Activated Delayed Fluorescent Emitters without Red-Shifting Emission.

The inclusion of a tetraphenylbenzene (4Ph) unit in thermally activated delayed fluorescence emitters is demonstrated as a novel strategy for greatly enhancing the horizontally oriented alignment of the emitters without shifting the emission spectrum to longer wavelengths. Doping of blue-emitting 4PhOXDDMAC or greenish-blue-emitting 4PhOXDPXZ into o-DiCbzBz host layers yielded much higher degrees of horizontally oriented alignment for the emitter (up to 92%) compared to those when the 4Ph unit was excluded (69 and 75%, respectively). The enhanced alignment results in high outcoupling efficiencies of 24 and 35% in organic light-emitting diodes based on 4PhOXDDMAC and 4PhOXDPXZ, respectively, and boosts the external quantum efficiencies to values (8.8 and 29.2%, respectively) that are higher than what would be expected for randomly oriented emitters (outcoupling efficiency of 20%). These enhancements are achieved while avoiding the redshift that often occurs using the common strategy of increasing molecular length and, thereby, conjugation, to increase orientation.

Exciplex-Sensitized Triplet-Triplet Annihilation in Heterojunction Organic Thin-Film.

A new concept for organic light-emitting diodes (OLEDs) is presented, which is called exciplex-sensitized triplet-triplet annihilation (ESTTA). The exciplex formed at the organic heterojunction interface of 4,4',4″-tris(N-3-methyphenyl-N-phenyl-amino) triphenylamine and 9,10-bis(2'-naphthyl) anthracene (ADN) is used to sensitize the triplet-triplet annihilation (TTA) process on the ADN molecules. This results in a turn-on voltage (2.2 V) of the blue emission from the OLED below the bandgap (2.9 eV). From the transient electroluminescence measurement, blue emission totally came from the TTA process without direct recombination on the ADN molecules. The blue singlet exciton from the TTA process can be quenched by energy transfer to the exciplex, as revealed by transient photoluminescence measurements. This can be prevented by blocking the energy transfer path and improving the radiative recombination rate of blue emission. With the insertion of the "triplet diffusion and singlet blocking (TDSB)" layer and the incorporation of the dopant material, an ESTTA-OLED with external quantum efficiency of 5.1% was achieved, which consists of yellow and blue emission coming from the exciplex and ESTTA process, respectively.

Thermosensitive chitosan-based hydrogels for sustained release of ferulic acid on corneal wound healing.

Oxidative damage to cornea can be induced by alkaline chemical burn which may cause vision loss or blindness. Recent studies showed that exogenous application of natural antioxidants may be a potential treatment for corneal wound healing. However, low ocular bioavailability and short residence time are the limiting factors of topically administered antioxidants. Ferulic acid (FA) is a natural phenolic compound and an excellent antioxidant. The study was aimed to investigate the effects of FA in corneal epithelial cells (CECs) under oxidative stress and evaluate the feasibility of use the thermosensitive chitosan-based hydrogel containing FA for corneal wound healing. The results demonstrated that post-treatment of FA on CECs could decrease the inflammation-level and apoptosis. In the rabbit corneal alkali burn model, post-treatment FA-loaded hydrogel may promote the corneal wound healing. The results of study suggest that FA-loaded hydrogel may have the potential applications in treating corneal alkali burn.

Ocular decompression retinopathy after laser iridotomy in a patient with acute angle closure.

A 65-year-old female developed elevated intraocular pressure (IOP) with angle closure in the right eye. The fundus examination revealed vitreo-retinal hemorrhage that had occurred after neodymium-doped yttrium aluminum garnet (Nd:YAG) laser iridotomy. The retinal hemorrhage resolved spontaneously. This is a rare complication that occurs when the IOP is lowered rapidly. Ocular decompression retinopathy (ODR) was identified. We reviewed several cases of ODR that were treated by various interventions. We also discuss the possible pathogenesis, prognosis, and treatment strategy.

MicroRNAs and cataracts: correlation among let-7 expression, age and the severity of lens opacity.

BACKGROUND: Let-7 microRNA is an important regulator of cellular ageing and tissue senescence. The objective of this study is to evaluate the expression of let-7a/let-7b/let-7c microRNAs in human age-related cataracts. AIM: To evaluate the correlation among the severity of lens opacity, the level of let-7a/let-7b/let-7c microRNA expression and patient age in the context of age-related cataracts. METHODS: The authors evaluated the mRNA level of let-7a/let-7b/let-7c microRNA in lens epithelia obtained from 174 eyes with age-related cataracts. The authors also recorded the patient age and the severity of lens opacity as classified according to the modified version of the Lens Opacities Classification System version III. RESULTS: Let-7b microRNA expression was demonstrated to be positively associated with patient age (R=0.472; p<0.001). A positive correlation was also observed between higher N, C and P cataract scores and higher expression of let-7b microRNA in patients with age-related cataracts (p<0.001). However, no significant correlation was observed between the let-7a and let-7c microRNA expression levels and either the severity of lens opacity or the patient age. CONCLUSION: These findings suggest that microRNAs play a role in age-related cataracts. A local let-7b microRNA increase may represent a risk factor in the formation of age-related cataracts.

Iritis and pupillary distortion after periorbital cosmetic alexandrite laser.

BACKGROUND: To describe a case of ocular complications associated with laser-assisted periorbital cosmetic treatment and to recommend consideration of the ocular damage caused by dermatological laser therapy, including pupillary distortion and anterior uveitis. METHODS: Case report. RESULTS: A 29-year-old Caucasian woman underwent cosmetic alexandrite laser therapy in the left upper eyelid area without protective eye shields. She complained of an irregular oval pupil, photophobia, and blurred vision in her left eye. Initially, her best-corrected visual acuity (BCVA) was 30/25 (OD) and 30/25 (OS). Slit-lamp biomicroscopy revealed a distorted left pupil with 3+ cell activity in the anterior chamber, but normal intraocular pressure. She was treated with topical corticosteroids. However, marked anterior chamber activity, pigment dispersion over the iris surface, and deteriorating BCVA of 10/25 (OS) had developed at the two-week follow-up. The ocular inflammation subsided gradually and her BCVA returned to normal after intensive steroid treatment. At the six-month follow-up, an ocular examination showed poor pupillary motility and persistent pigment over the iris surface. The patient still suffered from glare in dim light and experienced problems with dark adaptation. CONCLUSIONS: Alexandrite laser treatment of the upper eyelid region may penetrate the eyelid, causing anterior uveitis and irreversible damage to the iris. We recommended appropriate eye protection during this therapeutic procedure.