Segmental Suture Gonioscopy-Assisted Transluminal Trabeculotomy: Comparison of Superior Versus Inferior Hemisphere Outcomes.

PRCIS: Analysis of efficacy, safety, and risk factors for failure of superior versus inferior 180-degree segmental gonioscopy-assisted transluminal trabeculectomy showed no significant difference between approaches, with novel risk factors for failure identified. PURPOSE: Compare the efficacy, safety, and risk factors for failure of superior versus inferior 180-degree segmental suture gonioscopy-assisted transluminal trabeculotomy (GATT). DESIGN: Multicenter, retrospective interventional cohort study of 297 eyes of 243 glaucomatous patients, which underwent superior or inferior 180-degree suture hemi-GATT surgery combined with phacoemulsification at one of 3 Canadian ophthalmological surgical centres in Calgary, Alberta or Toronto, Ontario. MAIN OUTCOME MEASURES: The primary outcome measure was the hazard ratio (HR) of failure for the "primary success" criteria. "Primary success" was defined as an intraocular pressure (IOP) <18 mm Hg and either 1) IOP reduced by ≥20% from baseline on the same number of IOP-lowering medications or 2) IOP ≤ baseline on fewer medications. Secondary outcome measures included HRs of failure for alternative criteria ("complete success", "qualified success" and "20% IOP reduction"), cross-sectional analysis, and Cox proportional hazard analysis for risk factors associated with increased failure for the complete cohort. RESULTS: Baseline characteristics were similar between groups. The crude and adjusted HR of failure for the "primary success" criteria for superior surgeries relative to inferior surgeries were 1.27 (95% CI = 0.86-1.88) and 1.50 (95% CI = 0.91-2.46), with no statistically significant difference between approaches. Of the secondary criteria, there was statistical significance in favor of inferior surgeries only for crude analysis of the "20% reduction" criteria (1.40/1.27 (95% CI = 1.01-1.92). Increased risk of failure by the "primary success" measure for either intervention was seen with primary open angle glaucoma, advanced disease, and age below 70 years. There were no significant differences in the frequency of postoperative complications between cohorts, which were present in 72 superior (44.4%) and 67 inferior (49.6%; P value = 0.41) eyes; mostly early postoperative hyphema, iritis, and corneal edema. CONCLUSIONS: This retrospective study showed no difference in inferior versus superior 180 degrees of hemi-GATT/phacoemulsification cataract surgeries through the majority of analyses. Nonmodifiable factors including glaucoma type, advanced disease, and younger age were associated with a significantly higher risk of failure in this cohort. Further study is warranted.

Stabilization of refractive error and associated factors following small incision phacoemulsification cataract surgery.

BACKGROUND: Accumulating evidence suggests that refractive stabilization occurs rapidly following small incision cataract surgery. Nonetheless, many guidelines still suggest waiting four to 6 weeks before prescribing corrective lenses. This study was undertaken to supplement the existing literature regarding refractive stabilization, and evaluate multiple contributing factors that could dissuade clinicians from confidently correcting refractive error in the early post-operative course following routine cataract surgeries. METHODS: Adult patients undergoing phacoemulsification cataract surgery with uncomplicated surgeries and post-surgical courses at the Calgary Ophthalmology Centre (Calgary, Alberta, Canada) were included in this prospective observational case series. Exclusion criteria included known corneal dystrophies, infectious keratitis, complicated surgery or toric/multifocal IOLs. Data was collected at weekly intervals for a total of 6 weeks. Collected data included autorefraction, visual acuity, corneal pachymetry, and effective lens position. RESULTS: One hundred six eyes of 104 patients were included in this study. Post-operative sphere, cylinder and spherical equivalent were not significantly different at any post-operative week compared with week six, and 80-86% of patients were within 0.5D of last follow-up spherical equivalent at any week. The secondary outcomes of central corneal thickness, effective lens position and visual acuity did, however, exhibit significant differences between early post-operative weeks and last follow-up values. CONCLUSIONS: These data suggest that refractive error can be effectively measured and corrected as early as one-week post-operatively in the majority of patients, though other measures of post-operative stability including central corneal thickness, effective lens position and visual acuity can require up to 4 weeks to stabilize. Thus a conservative and pragmatic approach may be to wait until 4 weeks post-operatively prior to obtaining refractive correction following uncomplicated phacoemulsification cataract surgery.

Transgenic Expression of Cacna1f Rescues Vision and Retinal Morphology in a Mouse Model of Congenital Stationary Night Blindness 2A (CSNB2A).

Purpose: Congenital stationary night blindness 2A (CSNB2A) is a genetic retinal disorder characterized by poor visual acuity, nystagmus, strabismus, and other signs of retinal dysfunction resulting from mutations in Cacna1f-the gene coding for the pore-forming subunit of the calcium channel CaV1.4. Mouse models of CSNB2A have shown that mutations causing the disease deleteriously affect photoreceptors and their synapses with second-order neurons. This study was undertaken to evaluate whether transgenic expression of Cacna1f could rescue morphology and visual function in a Cacna1f-KO model of CSNB2A. Methods: Strategic creation, breeding and use of transgenic mouse lines allowed for Cre-driven retina-specific expression of Cacna1f in a CSNB2A model. Transgene expression and retinal morphology were investigated with immunohistochemistry in retinal wholemounts or cross-sections. Visual function was assessed by optokinetic response (OKR) analysis and electroretinography (ERG). Results: Mosaic, prenatal expression of Cacna1f in the otherwise Cacna1f-KO retina was sufficient to rescue some visual function. Immunohistochemical analyses demonstrated wild-type-like photoreceptor and synaptic morphology in sections with transgenic expression of Cacna1f. Conclusions: This report describes a novel system for Cre-inducible expression of Cacna1f in a Cacna1f-KO mouse model of CSNB2A and provides preclinical evidence for the potential use of gene therapy in the treatment of CSNB2A. Translational Relevance: These data have relevance in the treatment of CSNB2A and in understanding how photoreceptor integration might be achieved in retinas in which photoreceptors have been lost, such as retinitis pigmentosa, age-related macular degeneration, and other degenerative conditions.

Avian Adeno-Associated Viral Transduction of the Postembryonic Chicken Retina.

PURPOSE: The posthatching chicken is a valuable animal model for research, but molecular tools needed for altering its gene expression are not yet available. Our purpose here was to adapt the adeno-associated viral (AAV) vector method, used widely in mammalian studies, for use in investigations of the chicken retina. We hypothesized that the recently characterized avian AAV (A3V) vector could effectively transduce chick retinal cells for manipulation of gene expression, after intravitreal or subretinal injection. METHODS: A3V encoding enhanced green fluorescent protein (EGFP) was injected intravitreally or subretinally into P1-3 chick eye and left for 7 to 10 days. Retinas were then sectioned or flat-mounted and visualized via laser-scanning confocal microscopy for analysis of expression and imaging of retinal cells. RESULTS: Intravitreal A3V-EGFP injection resulted in EGFP expression in a small percent of retinal cells, primarily those with processes and/or cell bodies near the vitreal surface. In contrast, subretinal injection of A3V-EGFP within confined retinal "blebs" produced high rates of transduction of rods and all types of cones. Some examples of all other major retinal cell types, including horizontal, amacrine, bipolar, ganglion, and Müller cells, were also transduced, although with much lower frequency than photoreceptors. CONCLUSIONS: A3V is a promising tool for investigating chick retinal cells and circuitry in situ. This novel vector can be used for studies in which local photoreceptor transduction is sufficient for meaningful observations. TRANSLATIONAL RELEVANCE: With this vector, the postembryonic chick retina can now be used for preclinical trials of gene therapy for prevention and treatment of human retinal disease.