Ocular, Visual, and Anatomical Outcomes in Eyes Requiring Incisional Intraocular Pressure-Lowering Surgery Following the 0.19-mg Fluocinolone Acetonide Intravitreal Implant.

BACKGROUND AND OBJECTIVE: To assess ocular, visual, and anatomical outcomes following the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) and incisional intraocular pressure (IOP)-lowering surgery in diabetic macular edema. PATIENTS AND METHODS: From a 36-month, phase 4, open-label, observational study (N = 202 eyes, 159 patients), 8 eyes (7 patients) required IOP-lowering surgery post-FAc; eyes were segregated by FAc-induced (n = 5, 2.47%) versus neovascular glaucoma (NVG)-related (n = 3, 1.49%) IOP elevations and assessed for IOP, best corrected visual acuity (BCVA), central subfield thickness (CST), and cup-to-disc ratio (c/d). RESULTS: Changes at 36 months were +5.4 letters BCVA (P > 0.05) and +0.09 c/d (P = 0.0217); IOP and CST were unchanged. FAc-induced-group eyes required fewer IOP-lowering medications than NVG-group eyes (2.0 versus 4.0; P < 0.01) but for longer duration (15.2 versus 2.6 months; P < 0.001). CONCLUSIONS: Post-FAc IOP-lowering surgery, regardless of cause, largely did not affect the outcomes measured; these procedures, then, may not meaningfully threaten positive outcomes. [Ophthalmic Surg Lasers Imaging Retina 2024;55:22-29.].

BETTER BASELINE VISION LEADS TO BETTER OUTCOMES AFTER THE 0.19-mg FLUOCINOLONE ACETONIDE INTRAVITREAL IMPLANT IN DIABETIC MACULAR EDEMA.

PURPOSE: Analysis of a 3-year, Phase 4, open-label, observational study evaluating the association of baseline best-corrected visual acuity (BCVA) with visual, treatment burden, and retinal thickness variability (RTV) outcomes and intraocular pressure (IOP)-related events after the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant. METHODS: Data from patients with diabetic macular edema (DME) who did not have a clinically significant rise in IOP after previous corticosteroid treatment (N = 202 eyes from 159 patients) were segregated by baseline BCVA of ≥20/40 or <20/40 and analyzed for BCVA, number of yearly supplemental DME treatments, RTV, and incidence of IOP-related events. RESULTS: At 36 months post-FAc, eyes with better baseline BCVA (≥20/40) maintained baseline BCVA, whereas vision in eyes with worse baseline BCVA (<20/40) increased by approximately 7 letters to 61.34 letters (Snellen equivalent approximately 20/60; P < 0.05). Treatment burden and RTV decreased post-FAc regardless of baseline BCVA. Eyes with better baseline BCVA (≥20/40) had numerically fewer IOP-related events post-FAc versus eyes with worse baseline BCVA (<20/40), including a lower incidence of incisional IOP-lowering surgery. CONCLUSION: The 0.19-mg FAc implant improved RTV and treatment burden regardless of baseline BCVA. Better baseline BCVA (≥20/40) was associated with long-term BCVA maintenance. Although eyes with worse baseline BCVA (<20/40) experienced significantly improved BCVA, it never rose to the level of those with better baseline BCVA. These data indicate that early, effective intervention in DME, before significant vision loss occurs, is key to maintaining visual outcomes.

Three-Year Safety and Efficacy of the 0.19-mg Fluocinolone Acetonide Intravitreal Implant for Diabetic Macular Edema: The PALADIN Study.

PURPOSE: To assess the long-term safety and efficacy of the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien; Alimera Sciences, Inc) in patients with diabetic macular edema (DME). DESIGN: Three-year, phase 4, nonrandomized, open-label observational study. PARTICIPANTS: Patients with DME who previously received corticosteroid treatment without a clinically significant rise in intraocular pressure (IOP; all eyes, n = 202 eyes of 159 patients; 36-month completion, n = 94 eyes). METHODS: A prospective, observational study in which patients received a 0.19-mg FAc intravitreal implant at baseline and then were observed for safety-, visual-, anatomic-, and treatment burden-related outcomes for up to 36 months. MAIN OUTCOME MEASURES: Primary safety outcomes included changes in IOP and interventions to manage IOP elevations. Secondary outcomes included changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and adjunctive DME treatment frequency RESULTS: At 36 months after FAc implantation, study eyes showed a mean CST change of -60.69 µm (P < 0.0001) and a mean BCVA change of +3.61 letters (P = 0.0222) compared with baseline. Overall median treatment frequency decreased from 3.4 treatments/year in the 36 months before FAc implantation to 1 treatment/year in the 36 months after FAc implant, a treatment burden reduction of 70.5%. Furthermore, among the group that completed 36 months of treatment (n = 94 eyes), 25.53% of eyes remained rescue free through 36 months. Mean IOP remained stable throughout the study, and IOP increases to more than 30 mmHg occurred in 10.89% of eyes. Intraocular pressure-related procedures were infrequent, with a surgical rate of 2.97%, with 1.49% attributable to steroid use (vs. surgeries attributable primarily to neovascular glaucoma). In addition, an IOP response of < 25 mmHg after the steroid challenge predicted that 96.92% of eyes would have a similar outcome to 0.19-mg FAc implant at the last visit. Intraocular pressure increases that did occur were manageable with standard treatments (n = 202 eyes). CONCLUSIONS: In patients with DME, the 0.19-mg FAc implant provided improved visual outcomes and reduced treatment burden compared with previous treatments while maintaining a favorable safety profile.

Electrically driven microfluidic platforms for exosome manipulation and characterization.

Exosomes are small extracellular vesicles that can be obtained from several body fluids such as blood and urine. Since these vesicles can carry biomarkers and other cargo, they have application in healthcare diagnostics and therapeutics, such as liquid biopsies and drug delivery. Yet, their identification and separation from a sample remain challenging due to their high degree of heterogeneity and their co-existence with other bioparticles. In this contribution, we review the state-of-the-art on electrical techniques and methods to displace, selectively trap/isolate, and detect/characterize exosomes in microfluidic devices. Although there are many reviews focused on exosome separation using benchtop equipment, such as ultracentrifugation, there are limited reviews focusing on the use of electrical phenomena in microfluidic devices for exosome manipulation and detection. Here, we highlight contributions published during the past decade and present perspectives for this research field for the near future, outlining challenges to address in years to come.

Safety and Tolerability of Intravitreal Carotuximab (DE-122) in Patients With Persistent Exudative Age-Related Macular Degeneration: A Phase I Study.

Purpose: Carotuximab (DE-122) is a novel endoglin antibody that exhibits potent anti-angiogenic activity. The aim of this study was to evaluate the safety and tolerability of a single intravitreal injection of four ascending doses of carotuximab in patients with persistent exudative age-related macular degeneration (AMD). Methods: In an open-label, dose-escalating, sequential cohort study, patients with persistent exudative AMD were assigned to an intravitreal injection of carotuximab 0.5 mg, 1.0 mg, 2.0 mg, or 4.0 mg (n = 3 per group). Safety and change in central subfield thickness (CST), as measured by spectral domain-optical coherence tomography, were assessed from baseline until day 90. Rescue therapy with an anti-vascular endothelial growth factor medication was allowed on days 8, 30, and 60. Results: Seven patients (58%) experienced at least one adverse event (AE), including five patients (41.7%) who experienced one or more AEs in the study eye and two patients (16.7%) who experienced one or more non-ocular AEs. Posterior eye deposits were reported in one patient 2 days after receiving 1.0 mg, but they resolved spontaneously by day 43. A >50-µm reduction in CST on two consecutive visits was observed in four patients (33%), including one patient in each dose cohort. Conclusions: In this study, carotuximab was generally well tolerated, with no serious AEs reported, when administered as a single intravitreal injection to patients with persistent exudative AMD. Translational Relevance: Further characterization of the safety and efficacy of carotuximab will be needed to determine what role it may have in the treatment of exudative AMD.

Rapid Lipid Content Screening in Neochloris oleoabundans Utilizing Carbon-Based Dielectrophoresis.

In this study, we carried out a heterogeneous cytoplasmic lipid content screening of Neochloris oleoabundans microalgae by dielectrophoresis (DEP), using castellated glassy carbon microelectrodes in a PDMS microchannel. For this purpose, microalgae were cultured in nitrogen-replete (N+) and nitrogen-deplete (N-) suspensions to promote low and high cytoplasmic lipid production in cells, respectively. Experiments were carried out over a wide frequency window (100 kHz-30 MHz) at a fixed amplitude of 7 VPP. The results showed a statistically significant difference between the dielectrophoretic behavior of N+ and N- cells at low frequencies (100-800 kHz), whereas a weak response was observed for mid- and high frequencies (1-30 MHz). Additionally, a finite element analysis using a 3D model was conducted to determine the dielectrophoretic trapping zones across the electrode gaps. These results suggest that low-cost glassy carbon is a reliable material for microalgae classification-between low and high cytoplasmic lipid content-through DEP, providing a fast and straightforward mechanism.

Safety and Efficacy of Intravitreal Risuteganib for Non-Exudative AMD: A Multicenter, Phase 2a, Randomized, Clinical Trial.

BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of 1.0 mg risuteganib in subjects with nonexudative age-related macular degeneration (AMD). PATIENTS AND METHODS: This was a phase 2a, prospective, double-masked, sham-controlled study. Eyes with nonexudative (dry) AMD and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 20/40 and 20/200 were included. Subjects were randomized to intravitreal 1.0 mg risuteganib or sham injection. At Week 16, subjects in the risuteganib group received a second 1.0-mg dose and the sham group crossed over to receive a dose of 1.0 mg risuteganib and were evaluated at Week 28. The primary endpoint was proportion of subjects with 8 letters ETDRS or more BCVA gain from baseline to Week 28 in the risuteganib group versus baseline to Week 12 for the sham group. BCVA was tested and subjects were observed for adverse events (AEs) every 4 weeks until completion of the study at 32 weeks. RESULTS: Forty-five subjects (risuteganib, n = 29; sham, n = 16) were enrolled in the study, of whom 39 (risuteganib, n = 25; sham, n = 14) completed the study and were included in the per protocol efficacy analysis. At baseline, mean age was 78.8 and 75.9 years and mean BCVA was 67.1 and 64.4 letters in the sham and risuteganib groups, respectively. The primary endpoint was met by 48% of the risuteganib group at Week 28 and 7% of the sham group at Week 12 (P = .013). Of the risuteganib subjects, 20% gained 15 letters or more at Week 28, whereas no patients in the sham group at Week 12 achieved this visual acuity gain. The only ocular treatment-related treatment-emergent AE was vitreous floaters, which spontaneously recovered without sequelae. No drug-related serious AE was reported. CONCLUSIONS: Risuteganib demonstrated significant BCVA improvement in patients with non-exudative AMD. No drug-related AEs were seen during a 32-week observation period. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:327-335.].

Panretinal Photocoagulation for Diabetic Retinopathy in the RIDE and RISE Trials: Not "1 and Done".

PURPOSE: To evaluate panretinal photocoagulation (PRP) treatment and re-treatment patterns in patients with diabetic retinopathy (DR) and diabetic macular edema (DME). DESIGN: Post hoc analysis of the phase 3 RIDE (clinicaltrials.gov identifier, NCT00473382) and RISE (clinicaltrials.gov identifier, NCT00473330) clinical trials of ranibizumab for the treatment of DME. PARTICIPANTS: Seven hundred fifty-nine patients were randomized for treatment. METHODS: Panretinal photocoagulation treatment patterns and clinical experiences were assessed by baseline PRP treatment status. MAIN OUTCOME MEASURES: Number and timing of on-study PRP treatment sessions undergone through month 24. Time to new proliferative event (composite end point) was also assessed. RESULTS: At baseline, approximately 25% of patients in RIDE and RISE had undergone PRP treatment before enrollment (22.2%, 24.4%, and 25.4% of patients in the sham, ranibizumab 0.3 mg, and ranibizumab 0.5 mg arms, respectively). In patients without prior PRP at baseline (n = 577), 9.5% of sham-treated patients underwent 1 or more PRP treatments through month 24, compared with 1.1% and 1.6% of patients receiving ranibizumab 0.3 mg and ranibizumab 0.5 mg, respectively (P < 0.001 for both ranibizumab arms vs. sham). In patients with prior PRP at baseline (n = 182), 19.3% of sham-treated patients underwent 1 or more PRP treatments through month 24. No ranibizumab-treated patients with prior PRP at baseline required additional on-study PRP through month 24 (P < 0.001 for both ranibizumab arms vs. sham). Ranibizumab treatment also significantly reduced clinical DR progression among patients who underwent prior PRP. By month 24 in patients with prior PRP at baseline, the probability of experiencing a new proliferative event was 10.3% and 9.9% in patients receiving ranibizumab 0.3 mg and ranibizumab 0.5 mg treatment, respectively, compared with 39.4% in sham-treated patients (P < 0.0001). Overall, sham-treated patients, including those patients who were PRP naïve at baseline who went on to require PRP, experienced more clinical events than ranibizumab-treated patients. CONCLUSIONS: In RIDE and RISE, PRP treatment was not a "1 and done" procedure, with on-study PRP re-treatment occurring in patients both with and without prior PRP treatment at baseline. Ranibizumab treatment reduced on-study PRP treatment and DR progression regardless of prior PRP treatment status at baseline.

A survey of electrokinetically-driven microfluidics for cancer cells manipulation.

Cancer is one of the leading causes of annual deaths worldwide, accounting for nearly 10 million deaths each year. Metastasis, the process by which cancer spreads across the patient's body, is the main cause of death in cancer patients. Because the rising trend observed in statistics of new cancer cases and cancer-related deaths does not allow for an optimistic viewpoint on the future-in relation to this terrible disease-the scientific community has sought methods to enable early detection of cancer and prevent the apparition of metastatic tumors. One such method is known as liquid biopsy, wherein a sample is taken from a bodily fluid and analyzed for the presence of CTCs or other cancer biomarkers (e.g., growth factors). With this objective, interest is growing by year in electrokinetically-driven microfluidics applied for the concentration, capture, filtration, transportation, and characterization of CTCs. Electrokinetic techniques-electrophoresis, dielectrophoresis, electrorotation, and electrothermal and EOF-have great potential for miniaturization and integration with electronic instrumentation for the development of point-of-care devices, which can become a tool for early cancer diagnostics and for the design of personalized therapeutics. In this contribution, we review the state of the art of electrokinetically-driven microfluidics for cancer cells manipulation.

Recent advances and challenges in the recovery and purification of cellular exosomes.

Exosomes are nanovesicles secreted by most cellular types that carry important biochemical compounds throughout the body with different purposes, playing a preponderant role in cellular communication. Because of their structure, physicochemical properties and stability, recent studies are focusing in their use as nanocarriers for different therapeutic compounds for the treatment of different diseases ranging from cancer to Parkinson's disease. However, current bioseparation protocols and methodologies are selected based on the final exosome application or intended use and present both advantages and disadvantages when compared among them. In this context, this review aims to present the most important technologies available for exosome isolation while discussing their advantages and disadvantages and the possibilities of being combined with other strategies. This is critical since the development of novel exosome-based therapeutic strategies will be constrained to the effectiveness and yield of the selected downstream purification methodologies for which a thorough understanding of the available technological resources is needed.

A new species of Andinopanurgus (Hymenoptera: Andrenidae) from high elevations in southern Peru / Una especie nueva de Andinopanurgus (Hymenoptera: Andrenidae) de las grandes alturas del sur de Perú

We describe and figure a distinctive new species of the bee genus Andinopanurgus Gonzalez and Engel (Andrenidae, Protandrenini) from Apurímac and Cusco in southern Peru. Andinopanurgus vargasllosai Gonzalez and Alvarado, n. sp., occurs at elevations above 4000 m in the Central Andes and is the second species of this genus in Peru. The new species possesses terga with semi-translucent distal margins, a unique feature among Andinopanurgus, and it combines morphological features of the two species groups previously recognized in the genus. To facilitate its recognition, we provide an updated key to species of Andinopanurgus.

Describimos e ilustramos una especie nueva del género Andinopanurgus Gonzalez y Engel (Andrenidae, Protandrenini) procedentes de Apurímac y Cusco, al sur de Perú. Andinopanurgus vargasllosai Gonzalez y Alvarado, n. sp., se encuentra en alturas superiores a los 4000 m en los Andes centrales y es la segunda especie del género registrada para el Perú. La especie nueva posee tergos metasomales con las márgenes distales semi-translúcidas, una característica única dentro de Andinopanurgus, y combina características morfológicas de los dos grupos de especies hasta ahora reconocidos en el género. Con el fin de facilitar la identificación, presentamos una clave actualizada para las especies de Andinopanurgus.

ASSOCIATION BETWEEN EARLY ANATOMIC RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND LONG-TERM OUTCOME IN DIABETIC MACULAR EDEMA: An Independent Analysis of Protocol i Study Data.

PURPOSE: This post hoc analysis explores the relationship between early retinal anatomical response and long-term anatomical and visual outcomes with ranibizumab in center-involved diabetic macular edema. METHODS: Eyes randomized to the ranibizumab plus prompt laser and ranibizumab plus deferred laser treatment arms in the Protocol I study were categorized according to their proportional reduction (<20 vs. ≥20%) in central retinal thickness (CRT) after 12 weeks. Adjusted and unadjusted analyses assessed the association between early (Week 12) anatomical response and long-term (Weeks 52 and 156) anatomical and best-corrected visual acuity outcomes. RESULTS: Of 335 study eyes, 118 showed limited (<20%) and 217 showed strong (≥20%) CRT reduction at Week 12. In unadjusted and adjusted analyses, limited early CRT response was negatively and significantly associated with strong CRT response at Weeks 52 and 156. Sensitivity analyses indicated that this association was robust and unrelated to any "floor effect." In unadjusted analyses, a strong early CRT response was associated with greater long-term improvement in best-corrected visual acuity; after controlling for confounders, the association lost statistical significance. CONCLUSION: Early CRT response to ranibizumab is a significant prognostic indicator of medium- to long-term anatomical outcome in center-involved diabetic macular edema.

THE OASIS MP-1 SUBSTUDY: Characterization of the Effect of Ocriplasmin on Microperimetry Parameters.

PURPOSE: To evaluate the effects of ocriplasmin and symptomatic vitreomacular adhesion resolution on visual fixation and macular sensitivity using microperimetry. METHODS: MP-1 parameters were analyzed from 3 OASIS sites after the use of standardized instruments and testing procedures over 24 months. RESULTS: A total of 27 patients (19 ocriplasmin, 8 sham) were evaluated. Mean distance of the preferred fixation locus to the anatomical center was farther in the sham group at baseline and farther in the sham versus ocriplasmin group throughout the study. Retinal sensitivity values were consistently higher in the ocriplasmin versus sham group after Month 3. Fewer patients in the ocriplasmin group had predominantly eccentric fixation at study end compared with the sham group, which also had an increased number of patients with unstable fixation. Patients with vitreomacular adhesion resolution had lower bivariate contour area, fewer relative scotomas, and higher retinal sensitivity parameters at baseline than those with unresolved vitreomacular adhesion. CONCLUSION: Substudy results suggest that fixation and sensitivity parameters tended to be better in the ocriplasmin group than in the sham group over time. The substudy identified parameters that were distinct between patients with and without vitreomacular adhesion resolution, suggesting that microperimetry warrants further study as a relevant biomarker for visual function.

Early Response to Anti-Vascular Endothelial Growth Factor and Two-Year Outcomes Among Eyes With Diabetic Macular Edema in Protocol T.

PURPOSE: Assess associations of 2-year visual acuity (VA) outcomes with VA and optical coherence tomography central subfield thickness (CST) after 12 weeks of anti-vascular endothelial growth factor treatment for diabetic macular edema in DRCR.net Protocol T. DESIGN: Randomized clinical trial. METHODS: Setting: Multicenter (89 U.S. sites). PATIENT POPULATION: Eyes with VA and CST data from baseline and 12-week visits (616 of 660 eyes randomized [93.3%]). INTERVENTION: Six monthly injections of 2.0 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab; subsequent injections and focal/grid laser as needed for stability. MAIN OUTCOME MEASURES: Change in VA from baseline and VA letter score at 2 years. RESULTS: Twelve-week VA response was associated with 2-year change in VA and 2-year VA letter score for each drug (P < .001) but with substantial individual variability (multivariable R2 = 0.38, 0.29, and 0.26 for 2-year change with aflibercept, bevacizumab, and ranibizumab, respectively). Among eyes with less than 5-letter gain at 12 weeks, the percentages of eyes gaining 10 or more letters from baseline at 2 years were 42% (20 of 48), 31% (21 of 68), and 47% (28 of 59), and median 2-year VA was 20/32, 20/32, and 20/25, in the aflibercept, bevacizumab, and ranibizumab groups, respectively. Twelve-week CST response was not strongly associated with 2-year outcomes. CONCLUSIONS: A suboptimal response at 12 weeks did not preclude meaningful vision improvement (ie, ≥ 10-letter gain) in many eyes at 2 years. Eyes with less than 5-letter gain at 12 weeks often had good VA at 2 years without switching therapies.

A Phase 1, Open-Label, Dose-Escalation Trial to Investigate Safety and Tolerability of Single Intravitreous Injections of ICON-1 Targeting Tissue Factor in Wet AMD.

BACKGROUND AND OBJECTIVE: This phase 1 study evaluated the safety and tolerability of single intravitreous injections (IVIs) of ICON-1 (Iconic Therapeutics, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD). ICON-1 is a modified factor VIIa protein linked with the Fc portion of a human immunoglobulin G1. The molecule binds tissue factor overexpressed on choroidal neovascularization (CNV) in AMD. PATIENTS AND METHODS: Open-label, interventional, dose-escalation trial in 18 patients with CNV due to AMD, with six patients per dose cohort. Patients received a single IVI of ICON-1 at baseline in one of three escalating doses: 60 µg, 150 µg, or 300 µg. Standard anti-vascular endothelial growth factor treatment was allowed at the investigator's discretion at least 2 weeks after the ICON-1 injection; patients were followed up to 24 weeks. Dose escalation was based on the absence of significant safety events. At each study visit, best-corrected visual acuity (BCVA), ophthalmic examination (intraocular pressure, slit-lamp, and dilated fundus examination), and ophthalmic imaging (color fundus photography, fluorescein angiography, and optical coherence tomography) assessments were performed. The systemic pharmacokinetics of ICON-1 and presence of anti-ICON-1 antibodies were also assessed. RESULTS: ICON-1 was safe and well-tolerated up to the highest dose administered, which was 300 µg. Commonly reported adverse events were considered related to the IVI procedure or to the underlying nAMD. No significant systemic levels of ICON-1 or anti-ICON-1 antibodies were detected. Preliminary evidence of biological activity (improved BCVA, reduced central retinal thickness, decreased CNV size, and leakage) was most evident with the 300 µg dose at 1 to 2 weeks after the single ICON-1 injection. CONCLUSION: Intravitreous administration of ICON-1 in single doses up to 300 µg in eyes with neovascular AMD was safe and well-tolerated. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:336-345.].

Early and Long-Term Responses to Anti-Vascular Endothelial Growth Factor Therapy in Diabetic Macular Edema: Analysis of Protocol I Data.

PURPOSE: To determine whether early visual acuity response to ranibizumab in diabetic macular edema is associated with long-term outcome. DESIGN: Post hoc analysis of randomized controlled trial data. METHODS: Pooled data from the ranibizumab plus prompt and deferred laser treatment arms of the Diabetic Retinopathy Clinical Research Network's Protocol I study were used to explore the relationship between early (week 12) and late (weeks 52-156) visual acuity response (mean change from baseline in best-corrected visual acuity [CFB BCVA]; categorized improvement [<5, 5-9, or ≥10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] in BCVA). RESULTS: In the analysis population (340 eyes), <5-, 5- to 9-, and ≥10-letter BCVA improvements occurred in 39.7%, 23.2%, and 37.1% of eyes, respectively, at 12 weeks, and 34.2%, 16.5%, and 49.3% of eyes at 156 weeks. Within each early BCVA response category (<5, 5-9, and ≥10 letters of improvement at 12 weeks), mean CFB BCVA at 52-156 weeks varied by <5 letters from that at 12 weeks. CFB BCVA and <5-letter improvement at 12 weeks showed significant positive and negative association, respectively, with CFB BCVA and ≥10-letter improvement at 52 and 156 weeks. Similar relationships were demonstrated in eyes with baseline BCVA <69 letters, and associations remained significant after multivariate adjustment for potential confounders. CONCLUSIONS: Ranibizumab ± laser therapy resulted in similar rates (∼40%) of suboptimal (<5-letter) and pronounced (≥10-letter) BCVA improvement at 12 weeks. Eyes with suboptimal early BCVA response showed poorer long-term visual outcomes than eyes with pronounced early response (mean improvement 3.0 vs 13.8 letters at 156 weeks).

Modelling of electrokinetic phenomena for capture of PEGylated ribonuclease A in a microdevice with insulating structures.

Synthesis of PEGylated proteins results in a mixture of protein-polyethylene glycol (PEG) conjugates and the unreacted native protein. From a ribonuclease A (RNase A) PEGylation reaction, mono-PEGylated RNase A (mono-PEG RNase A) has proven therapeutic effects against cancer, reason for which there is an interest in isolating it from the rest of the reaction products. Experimental trapping of PEGylated RNase A inside an electrokinetically driven microfluidic device has been previously demonstrated. Now, from a theoretical point of view, we have studied the electrokinetic phenomena involved in the dielectrophoretic streaming of the native RNase A protein and the trapping of the mono-PEG RNase A inside a microfluidic channel. To accomplish this, we used two 3D computational models, a sphere and an ellipse, adapted to each protein. The effect of temperature on parameters related to trapping was also studied. A temperature increase showed to rise the electric and thermal conductivities of the suspending solution, hindering dielectrophoretic trapping. In contrast, the dynamic viscosity of the suspending solution decreased as the temperature rose, favoring the dielectrophoretic manipulation of the proteins. Also, our models were able to predict the magnitude and direction of the velocity of both proteins indicating trapping for the PEGylated conjugate or no trapping for the native protein. In addition, a parametric sweep study revealed the effect of the protein zeta potential on the electrokinetic response of the protein. We believe this work will serve as a tool to improve the design of electrokinetically driven microfluidic channels for the separation and recovery of PEGylated proteins in one single step.

Forming a Consensus: Data and Guidance for Physicians Treating Diabetic Macular Edema.

The diabetic macular edema (DME) treatment paradigm has evolved as the understanding of the disease pathology has grown. Since 2012, four pharmacotherapies have been approved by the U.S. Food and Drug Administration for the treatment of DME. First-line treatment of DME with anti-vascular endothelial growth factor [VEGF] agents has become the gold standard; however, an appreciable percentage of patients do not respond to anti-VEGF therapies. In patients who inadequately respond to anti-VEGF therapies, the underlying disease pathology may be mediated by a multitude of growth factors and inflammatory cytokines. For these patients, corticosteroids are an attractive treatment option because they not only downregulate VEGF, but also an array of cytokines. The phase 3 MEAD and FAME trials demonstrated significant visual acuity improvements associated with dexamethasone and fluocinolone acetonide, respectively, in patients with DME; however, class-specific adverse events, including increased intraocular pressure and cataract development, must be considered before use. A panel of experts gathered during the 2015 annual meeting of the American Academy of Ophthalmology for a roundtable discussion focused on patient selection and adverse event management associated with the use of the 0.19 mg fluocinolone acetonide intravitreal implant.