Spinocerebellar ataxia (SCA) is a neurodegenerative disorder characterized by ataxia and cerebellar atrophy. A number of different mutations gives rise to different types of SCA with characteristic ages of onset, symptomatology, and rates of progression. SCA type 34 (SCA34) is caused by mutations in ELOVL4 (ELOngation of Very Long-chain fatty acids 4), a fatty acid elongase essential for biosynthesis of Very Long Chain Saturated and Polyunsaturated Fatty Acids (VLC-SFA and VLC-PUFA, resp., ≥28 carbons), which have important functions in the brain, skin, retina, Meibomian glands, testes, and sperm. We generated a rat model of SCA34 by knock-in of the SCA34-causing 736T>G (p.W246G) ELOVL4 mutation. Rats carrying the mutation developed impaired motor deficits by 2 months of age. To understand the mechanism of these motor deficits, we performed electrophysiological studies using cerebellar slices from rats homozygous for W246G mutant ELOVL4 and found marked reduction of long-term potentiation at parallel fiber synapses and long-term depression at climbing fiber synapses onto Purkinje cells. Neuroanatomical analysis of the cerebellum showed normal cytoarchitectural organization with no evidence of degeneration out to 6 months of age. These results point to ELOVL4 as essential for motor function and cerebellar synaptic plasticity. The results further suggest that ataxia in SCA34 patients may arise from a primary impairment of synaptic plasticity and cerebellar network desynchronization before onset of neurodegeneration and progression of the disease at a later age.

Purpose: To evaluate whether primary graft failure (PGF) rates and endothelial cell loss (ECL) differ between surgeon-trephined/loaded and eye bank-preloaded Descemet-stripping automated endothelial keratoplasty (DSAEK) grafts. Setting: Tertiary care academic center. Design: Retrospective case series and ex vivo laboratory study. Methods: Single-center review of 69 eyes undergoing DSAEK (2020-2023) divided into 3 groups based on graft preparation and eye bank source: (1) eye bank-preloaded in EndoSerter (PL-ES), (2) eye bank-preloaded in glass tube (PL-GT), and (3) surgeon-trephined/loaded in EndoSerter (SL-ES). The primary clinical outcome was PGF (persistent corneal edema >3 months despite medical therapy). Secondary outcomes included visual outcomes and clinical complications (cystoid macular edema [CME] and rebubbling rate [RR]). The primary outcome of the laboratory study was percentage ECL (%ECL). Results: All lenticules were ≤80 μm. PGF was significantly higher in the PL-ES group (8/20; 40%) and the PL-GT group (4/7; 57%) compared with the SL-ES group (1/42; 2%) ( P < .0001). Grafts requiring rebubbling were more likely to experience PGF ( P = .0176). PGF eyes were regrafted with SL-ES DSAEK; none experienced subsequent PGF. There were no significant differences in CME, RR, corrected distance visual acuity, and spherical equivalent. The ex vivo study included 9 PL-ES, 6 PL-GT, and 6 SL-ES grafts. %ECL was higher in both preloaded groups than SL-ES ( P = .0354), although significance was not demonstrated on post hoc analysis. Fluorescent imaging revealed more cell loss in preloaded grafts. Conclusions: Preloading and storage of DSAEK grafts may affect PGF rates clinically and ECL ex vivo.

Background/Objectives: To investigate visual acuity, refractive outcomes and the predictive accuracy of modern intraocular lens (IOL) power calculation formulas in eyes implanted with two presbyopia-correcting IOLs: trifocal Zeiss AT LISA TRI and the nondiffractive EDOF Teleon Comfort. Methods: This retrospective consecutive chart review included 115 patients who underwent uncomplicated bilateral cataract surgery and received either the LISA TRI (n = 56) or Comfort (n = 59). Biometric measurements were obtained preoperatively, and refractive outcomes were assessed 1, 3, and 6 months postoperatively. Postoperative spherical equivalent (SEQ) was compared to predicted SEQ using the ESCRS calculator and IOLCON platform. Outcome measures included mean prediction error and mean absolute error (MAE). Distance-corrected visual acuity (VA), uncorrected VA, defocus curves, preferred viewing distances, contrast sensitivity, and photopic reading speed were also analyzed. Results: All formulas performed better in the LISA TRI group, with significantly lower MAE and higher proportions of eyes within ±0.50 diopters (D). Systematic prediction error offsets were observed for three formulas (K6, Castrop, Hoffer QST) in the LISA TRI group and for all five formulas in the MF15 group. Refractive stability was achieved by 3 months for the LISA TRI, while 20% of Comfort eyes continued to show SEQ shifts > 0.50 D at 3 months. Defocus equivalent (DEQ) had lower proportions of eyes within ±0.50 D than SEQ. Conclusions: The LISA TRI demonstrated superior predictive accuracy, faster refractive stabilization, and stronger near performance than the Comfort. These findings support the importance of IOL-specific constant optimization and highlight the need for incorporating DEQ into routine refractive outcome evaluation.