QUANTITATIVE ANALYSIS OF LONGITUDINAL CHANGES IN MULTIMODAL IMAGING OF LATE-ONSET RETINAL DEGENERATION.

PURPOSE: To quantitatively analyze clinically relevant features on longitudinal multimodal imaging of late-onset retinal degeneration to characterize disease progression. METHODS: Fundus autofluorescence (FAF), infrared reflectance, and optical coherence tomography imaging of 4 patients with late-onset retinal degeneration were acquired over 3 to 15 years (20 visits total). Corresponding regions of interest were analyzed on FAF (reticular pseudodrusen [RPD], "speckled FAF," and chorioretinal atrophy) and infrared reflectance (hyporeflective RPD and target RPD) using quantitative measurements, including contour area, distance to fovea, contour overlap, retinal thickness, and texture features. RESULTS: Cross-sectional analysis revealed a moderate correlation (RPD FAF ∩ RPD infrared reflectance = 63%) between contour area across modalities. Quantification of retinal thickness and texture analysis of areas contoured on FAF objectively differentiated the contour types. A longitudinal analysis of aligned images demonstrates that the contoured region of atrophy both encroaches toward the fovea and grows monotonically with a rate of 0.531 mm/year to 1.969 mm/year (square root of area, n = 5 eyes). A retrospective analysis of precursor lesions of atrophy reveals quantifiable progression from RPD to speckled FAF to atrophy. CONCLUSION: Image analysis of time points before the development of atrophy reveals consistent patterns over time and space in late-onset retinal degeneration that may provide useful outcomes for this and other degenerative retinal diseases.

MASSIVE ADVANCING NONEXUDATIVE TYPE 1 CHOROIDAL NEOVASCULARIZATION IN CTRP5 LATE-ONSET RETINAL DEGENERATION: Longitudinal Findings on Multimodal Imaging and Implications for Age-Related Macular Degeneration.

PURPOSE: To describe longitudinal multimodal imaging findings of nonexudative choroidal neovascularization in CTRP5 late-onset retinal degeneration. METHODS: Four patients with CTRP5-positive late-onset retinal degeneration underwent repeated ophthalmoscopic examination and multimodal imaging. All four patients (two siblings and their cousins, from a pedigree described previously) had the heterozygous S163R mutation. RESULTS: All four patients demonstrated large subretinal lesions in the mid-peripheral retina of both eyes. The lesions were characterized by confluent hypercyanescence with hypocyanescent borders on indocyanine green angiography, faintly visible branching vascular networks with absent/minimal leakage on fluorescein angiography, Type 1 neovascularization on optical coherence tomography angiography, and absent retinal fluid, consistent with nonexudative choroidal neovascularization. The neovascular membranes enlarged substantially over time and the birth of new membranes was observed, but all lesions remained nonexudative/minimally exudative. Without treatment, all involved retinal areas remained free of atrophy and subretinal fibrosis. CONCLUSION: We report the existence of massive advancing nonexudative Type 1 choroidal neovascularization in CTRP5 late-onset retinal degeneration. These findings have implications for age-related macular degeneration. They provide a monogenic model system for studying the mechanisms underlying the distinct events of choroidal neovascularization development, enlargement, progression to exudation, and atrophy in age-related macular degeneration. They suggest that choroidal hypoperfusion precedes neovascularization and that nonexudative neovascularization may protect against atrophy.

Rotational Stability of Toric Intraocular Lenses by Lens Model and Haptic Design: A Systematic Review and Single-Arm Meta-Analysis.

Rotational stability is key for optimizing postoperative visual outcomes as even a small degree of rotation of a toric intraocular lens (IOL) from its target axis can result in a significant reduction of astigmatic correction. This systematic review and meta-analysis evaluated the rotational stability of toric IOLs of different lens models and haptic designs. All published studies and clinical trials that investigate postoperative rotation of toric IOLs were searched and evaluated. Quality of studies was assessed using the Methodological Index for Nonrandomized Studies (MINORS) scale. A single-arm meta-analysis was performed in R4.3.1 software with subgroup analysis performed based on lens model and haptic design. Fifty-one published studies of 4863 eyes were included in the meta-analysis. The pooled mean absolute rotation of all toric IOLs was 2.36° (95% CI: 2.08-2.64). Postoperative rotation is dependent on many aspects of lens material and design. Modern commercially available toric IOLs exhibit exceptional rotational stability.

Stability of Aß-fibril fragments in the presence of fatty acids.

We consider the effect of lauric acid on the stability of various fibril-like assemblies of Aß peptides. For this purpose, we have performed molecular dynamics simulations of these assemblies either in complex with lauric acid or without presence of the ligand. While we do not observe a stabilizing effect on Aß40 -fibrils, we find that addition of lauric acid strengthens the stability of fibrils built from the triple-stranded S-shaped Aß42 -peptides considered to be more toxic. Or results may help to understand how the specifics of the brain-environment modulate amyloid formation and propagation.

Out-of-Register Aß42 Assemblies as Models for Neurotoxic Oligomers and Fibrils.

We propose a variant of the recently found S-shaped Aß1-42-motif that is characterized by out-of-register C-terminal ß-strands. We show that chains with this structure can form not only fibrils that are compatible with the NMR signals but also barrel-shaped oligomers that resemble the ones formed by the much smaller cylindrin peptides. By running long all-atom molecular dynamics simulations at physiological temperatures with an explicit solvent, we study the stability of these constructs and show that they are plausible models for neurotoxic oligomers. After analyzing the transitions between different assemblies, we suggest a mechanism for amyloid formation in Alzheimer's disease.