Color Vision and Microperimetry Changes in Nonexudative Age-Related Macular Degeneration After Risuteganib Treatment: Exploratory Endpoints in a Multicenter Phase 2a Double-Masked, Randomized, Sham-Controlled, Crossover Clinical Trial.

BACKGROUND AND OBJECTIVE: To explore the association between best-corrected visual acuity (BCVA) improvement and changes in microperimetry (MP) and color vision in patients with nonexudative age-related macular degeneration following administration of two 1.0-mg intravitreal doses of risuteganib. PATIENTS AND METHODS: In a phase 2a, prospective, double-masked, sham-controlled study, eyes with nonexudative age-related macular degeneration and Early Treatment Diabetic Retinopathy Study BCVA between 20/40 and 20/200 were randomized to intravitreal risuteganib (1.0 mg) or sham injection. The risuteganib group received a second 1.0-mg dose, and patients in the sham group crossed over to receive 1.0 mg of risuteganib at week 16. Exploratory endpoints included changes in color vision and mesopic MP. RESULTS: Thirty-nine patients (risuteganib, n = 25; sham, n = 14) completed the study. There was a significant (P < .05) correlation between BCVA and the total error score (TES) for both Lanthony and Hue Style. Confusion index was close to the criterion for significance (P = .056) in the risuteganib group. All color vision metrics demonstrated a trend toward improvement in risuteganib responders (BCVA letter gain ≥8 letters) and no change in the nonresponders, with significant differences seen in confusion index between the risuteganib and control group (P = .0493) and between responders and nonresponders (P = .0478). MP showed that risuteganib responders improved in mean sensitivity and change in number of loci ≤11 dB and ≤0 dB, whereas nonresponders worsened. CONCLUSION: All color vision and MP parameters tested trended toward improvement in risuteganib-treated patients and risuteganib responders. Statistically significant improvement was evident in two metrics: confusion index (in risuteganib-treated patients and responders) and number of loci with decreased sensitivity (in responders). A significant correlation between BCVA and both TES Lanthony and TES Hue Style in risuteganib patients provides concurrent evidence of objective and subjective improvement of retinal function. [Ophthalmic Surg Lasers Imaging Retina 2022;53:430-438.].

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.].

Rheological Link Between Polymer Melts with a High Molecular Weight Tail and Enhanced Formation of Shish-Kebabs.

Presence of an ultra high molecular weight (UHMw) fraction in flowing polymer melts is known to facilitate formation of oriented crystalline structures significantly. The UHMw fraction manifests itself as a minor tail in the molar mass distribution and is hardly detectable in the canonical characterization methods. In this study, alternatively, we demonstrate how the nonlinear extensional rheology reveals to be a very sensitive characterization tool for investigating the effect of the UHMw-tail on the structural ordering mechanism. Samples containing a UHMw-tail relative to samples without, exhibit a clear increase in extensional stress that is directly correlated with the crystalline orientation of the quenched samples. Extensional rheology, particularly, in combination with linear creep measurements, thus, enables the conformational evolution of the UHMw-tail to be studied and linked to the enhanced formation of oriented structures.

Synthesis of chlorambucil-tempol adduct and its delivery using fluoroalkyl double-ended poly (ethylene glycol) micelles.

In our pursuit to find potent anticancer drugs, we have covalently bonded free radical tempol to chlorambucil giving a chlorambucil-tempol (CT) adduct in which both of the anticancer active sites in tempol and chlorambucil were left intact. Analysis using NMR, Maldi-TOF, and EPR verified the designed chemical structure. Because the CT adduct is more hydrophobic than chlorambucil, its delivery also was investigated using fluoroalkyl double-ended poly (ethylene glycol) (Rf-PEG) micelles. Results from EPR spectra and(19) F and(1) H NMR spin lattice relaxation times show that the Rf-PEG micelles are able to encapsulate CT into the Rf cores of the micelles.

Light-adjustable lens: development of in vitro nomograms.

PURPOSE: To determine whether digital spatial intensity patterns can be developed to effect precise in vitro correction of myopic, hyperopic, and astigmatic refractive errors in a silicone light-adjustable lens (LAL). Also, to determine whether a new spatial intensity pattern for "lock-in" is effective in vitro. METHODS: A digital interferometer/irradiation system was developed to irradiate LALs and measure the power change following irradiation. Light-adjustable lenses were mounted into a wet cell maintained at 35.0 +/- 0.5 degrees C (simulated ocular temperature) and allowed to equilibrate for a minimum of 2 hours. Ultraviolet light was then applied with spatial light intensity patterns to correct hyperopia, myopia, and astigmatism. Light-adjustable lenses were also treated to effect lock-in with a separate spatial light intensity pattern. Treated lenses were characterized for power change and optical quality. In the case of lock-in, exhaustive chemical extraction was also performed to determine the percentage of remaining macromer. RESULTS: Appropriate digital irradiation spatial intensity patterns were created to develop nomograms for in vitro correction of myopia, hyperopia, and astigmatism in approximate 0.25 D steps. Power changes were reproducible and did not alter optical quality of the LALs. Further, lock-in dosing of the LALs did not alter optical quality or significantly change LAL power. CONCLUSIONS: In vitro nomograms have been developed for a silicone LAL that permit precise correction of myopia, hyperopia, and astigmatism. Furthermore, a spatial light intensity pattern has been devised that effects lock-in without significantly altering LAL power or optical quality.